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Guangjiang Wang, Yuan Guo Department of Ophthalmology, The Fourth Hospital of Baotou, Baotou City, Inner Mongolia Autonomous Region, 014030, People’s Republic of ChinaCorrespondence: Yuan Guo, Department of Ophthalmology, The Fourth Hospital of Baotou, No. 1, Aogen Road, Qingshan District, Baotou City, Inner Mongolia Autonomous Region, 014030, People’s Republic of China, Email guoyuantfhb@outlook.comBackground: Type 2 diabetes mellitus (T2DM) is associated with diabetic retinopathy (DR). The complement system maintains the normal physiologic microenvironment of the retina. The relationship between serum complement levels and clinical features of DR remains unclear.Methods: Clinical characteristics of 252 patients with T2DM including 101 with non-DR (NDR), 79 with nonproliferative DR (NPDR), and 72 with proliferative DR (PDR) were prospectively analyzed. Serum complement levels were compared between NDR and DR patients. The correlation between clinical characteristics and complement levels in DR patients was analyzed. A multifactorial logistic analysis was constructed to predict the risk of developing DR in T2DM.Results: Serum C4, CFB, CFI, C3 and C5 levels were higher in DR patients than in NDR patients (all P < 0.05). In T2DM patients, C3 and C4 levels were higher in PDR patients than in DR patients (all P < 0.05), and MBL levels were not statistically different between the two cohorts (P > 0.05). These complement components or fragments were positively correlated with the duration of diabetes, glycosylated hemoglobin (HbA1c), and triglycerides (TG) (all P < 0.05). C3, C5, the duration of diabetes, HbA1c, and TG were the independent risk factors for DR in T2DM patients. The ROC model showed good value for predicting the risk of developing DR in T2DM with an area under the curve of 0.887.Conclusion: Serum complements C3 and C5 are predictive factors for DR in patients with T2DM. The prediction model constructed by the clinical characteristics of patients with T2DM and complement can better distinguish between NDR and DR, and can be used as a potential biomarker for assessing the risk of developing DR.Keywords: Complement system, diabetic retinopathy, clinical features, complement factors

Wanling Li,1,2,&ast; Shufang Shi,2,&ast; Yajie Shi,2 Xiaofang Feng,2 Yueqin Li,2 Yuli Guo,2 Jiajia Xu,2 Liping Cui,2 Mei Wang1 1Department of Comprehensive Medical, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Nursing, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, 030032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Wang, Department of Comprehensive Medical, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, People’s Republic of China, Tel/Fax +86-0351-8379512, Email wm69520@126.com Liping Cui, Department of Nursing, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, 99 Longcheng Street, Taiyuan, Shanxi, 030032, People’s Republic of China, Tel/Fax +86-13934154909, Email sxtylsj-1@163.comBackground: Elderly patients, due to their complex medical conditions and extensive care needs, are at risk of experiencing low-quality or fragmented care during transitions between different healthcare settings. After transitioning from hospital to home, inadequate self-care abilities may result in further health deterioration and increased risks of adverse outcomes. Currently, China lacks effective transitional support services from hospital to home, hindering the smooth transition for elderly patients. Therefore, understanding the specific care needs of elderly patients during this period provides a scientific basis for establishing reasonable transitional support services.Objective: This study aims to explore the transitional care needs of elderly patients during the hospital-to-home transition, as perceived by key stakeholders—patients, caregivers, and nurses—using Shanxi Province as a case example.Methods: A descriptive phenomenological method was employed in this study. Purposeful sampling selected 10 elderly patients, 5 caregivers, and 5 nursing staff from a tertiary hospital in Shanxi Province, China, for semi-structured in-depth interviews. The Colaizzi’s analysis was used in data analysis.Results: The transitional care needs of elderly patients from hospital to home can be summarized into four themes: the need to enhance self-care abilities, the need for professional guidance, the need for social and psychological support, and the need for healthcare service resources.Conclusion: Elderly patients have diverse care needs during the hospital-to-home transition, which require urgent attention and support. To address these needs, healthcare professionals should conduct comprehensive assessments during the patients’ hospitalization, accurately identifying care issues and implementing team-based interventions. By fulfilling these needs, healthcare providers can ensure that elderly patients are well-prepared psychologically, possess sufficient knowledge and self-care skills, and have access to comprehensive support services from hospitals and communities as they transition from professional hospital care to home self-care.Keywords: elderly patients, transitional care, needs, stakeholders, qualitative study

Jiamin Fang,1 Hao Liang,2 Shilong Lu,1 Huilian Liao,3 Mingming Xu,4 Yumei Chen,5 Yanfen Li,6 Lijuan Dong,7 Yingui Guo,8 Zhixia Jiang,1 Lin Wei9 1State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Nursing, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Nursing, Shunde Hospital of Guangzhou University of Traditional Chinese Medicine, Shunde, People’s Republic of China; 4Department of Nursing, ShenZhen Traditional Chinese Medicine Hospital, ShenZhen, People’s Republic of China; 5Department of External Service Dept, Foshan Hospital of Traditional Chinese Medicine, Foshan, People’s Republic of China; 6Department of Nursing, Huizhou Hospital of Traditional Chinese Medicine, Huizhou, People’s Republic of China; 7Department of Nursing, Zhongshan Hospital of Traditional Chinese Medicine, Zhongshan, People’s Republic of China; 8Department of Nursing, Dongguan Traditional Chinese Medicine Hospital, Dongguan, People’s Republic of China; 9State Key Laboratory of Traditional Chinese Medicine Syndrome/Department of Nursing, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong People’s Republic of ChinaCorrespondence: Lin Wei, State Key Laboratory of Traditional Chinese Medicine Syndrome/Department of Nursing, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, 55 N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Email weilin22@gzucm.edu.cnPurpose: Although preoperative C-Reactive Protein to Albumin Ratio(CAR) is one of the important indicators for surgical risk assessment, the relationship between preoperative CAR and postoperative outcomes in older patients undergoing non-cardiac surgery is still unclear. Therefore, the purpose of this study is to explore the relationship between preoperative CAR and adverse postoperative outcomes in older patients undergoing non-cardiac surgery.Patients and Methods: We conducted a secondary analysis of data from the multicenter, prospective, longitudinal study called Early-Warning model of Perioperative Adverse Events for Elderly Patients (EPAE). A total of 2511 individuals from seven centers in Guangdong province were included in this study. The CAR was the latest blood counts measured within 3 days prior to surgery. The primary outcome of interest in this study was Clavien–Dindo grade III (CD3) complications. Secondary outcomes included: overall morbidity, reoperation and readmission. This cohort compared baseline characteristics and clinical data between different groups based on the quartile of CAR. Multivariate logistic regression and restricted cubic spline analysis (RCS) were used to explore the relationship between CAR and adverse postoperative outcomes. Further, the subgroup analyses were also conducted.Results: Among the 2511 older patients enrolled in the study, 1524 individuals (60.7%) were females and the median age at admission was 69.0 years (65.0, 73.0). Multivariate logistic regression analysis and sensitivity analysis both revealed that high CAR is associated with a high incidence of CD3 complications, overall morbidity, and reoperation (P < 0.05). Furthermore, the restricted cubic spline analysis shows a non-linear relationship between CAR and overall morbidity (cut-off value = 0.034, P for nonlinear < 0.001). No significant interaction was found in the subgroup analyses (P for interaction > 0.05).Conclusion: In older patients with non-cardiac surgery, high CAR was significantly associated with adverse postoperative outcomes, including CD3 complications, overall morbidity and reoperation.Keywords: C-reactive protein to albumin ratio, older patients, adverse postoperative outcomes

Jifeng Li, Yifei Zeng, Mengjie Wang, Yongxin Liu, Yubo Guo, Wenjie Zhao, Qiao Huang, Dongxiao Zhang Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Dongxiao Zhang, Department of Galactophore Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Art Museum Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +8617864190977, Email Tzdx_thinking@126.comPurpose: Granulomatous lobular mastitis (GLM) has seen a rising incidence, though its pathogenesis remains unclear, posing challenges for treatment and contributing to high recurrence rates with conventional therapies. While the role of inflammatory and immune factors in GLM has been recognized, a comprehensive clinical evaluation of these markers is still lacking. This study aims to identify potential diagnostic markers and therapeutic targets by comparing immune markers and cytokine levels in GLM patients and healthy controls.Methods: Conducted at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from July 2023 to May 2024, this study enrolled 30 GLM patients and 15 healthy female controls in a 2:1 ratio. Serum levels of immune markers and cytokines were analyzed to explore their potential association with GLM.Results: The study population comprised 30 GLM patients with a mean age of 33.40 ± 4.12 years and 15 healthy female controls with a mean age of 32.13 ± 6.19 years. Significantly elevated levels of C-reactive protein (CRP), Immunoglobulin A (IgA), Complement Component 3 (C3), Complement Component 4 (C4), Compliment Component 1q (C1q), Alpha1-antit-rypsin (AAT), α 1-acidglycoprotein (AGP), Anti-histone antibodies (Anti-HIS), Anti-Ro52 antibodies (Anti-Ro52), Anti-double stranded DNA antibodies (Anti-dsDNA), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-α (TNF-α) were observed in GLM patients compared to controls (all P < 0.05). Subgroup analysis revealed higher levels of CRP, C3, C1q, AAT, and AGP in patients with larger mass areas and those with erythema nodosum (all P < 0.05). No significant differences were found in subgroups based on disease duration or recurrence (both P > 0.05).Conclusion: Serum levels of CRP, IgA, AAT, AGP, Anti-HIS, Anti-Ro52, Anti-dsDNA, C3, C4, C1q, IL-6, IL-10, and TNF-α may serve as diagnostic and prognostic indicators for GLM, with CRP, AAT, AGP, and C1q being particularly indicative of disease severity. These markers offer potential therapeutic targets for GLM.Keywords: granulomatous lobular mastitis, peripheral serology, immune markers, cytokine

Ruixue Zhang,1 Hui Xu,1 Xiaoxue Zhang,1 Hui Xiong,2 Fei Tang,3 Liping Lv,3 Xiangdong Mu,4 Wei Tian,5 Yueguang Cheng,6 JianRong Lu,6 Xiuhong Nie,7 Yang Guo,8 Yingying Liu,9 Zhi Zhang,10 Lianjun Lin1 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Interventional Pulmonology, Anhui Province Chest Hospital, Hefei, People’s Republic of China; 4Department of Respiratory, Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 5Department of Geriatrics, Jishuitan Hospital, Beijing, People’s Republic of China; 6Department of Emergency, Jingmei Group General Hospital, Beijing, People’s Republic of China; 7Department of Respiratory, Xuanwu Hospital, Beijing, People’s Republic of China; 8Department of Endoscopic Diagnosis &treatment, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 9CapitalBio Technology Co., Ltd, Beijing, People’s Republic of China; 10Bio Biological Group Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Lianjun Lin, Department of Geriatrics, Peking University First Hospital, No. 8 Xishiku Avenue, Beijing, 100034, People’s Republic of China, Email 06474@pkufh.comPurpose: The detection of pathogenic microorganisms plays a significant role in the diagnosis and management of pneumonia that are responsible for a substantial number of deaths worldwide. However, conventional microbiological tests (CMT) have low accuracy and are time-consuming. In this study, we aim to evaluate the clinical value of Chips for Complicated Infection Detection (CCID) in detecting pneumonia pathogens.Patients and Methods: This study was conducted at nine hospitals in China from January 2021 to September 2022. Respiratory samples from adult pneumonia patients were collected from each patient. CMT and CCID were performed in parallel to identify the pathogens.Results: A total of 245 patients were included, with 73% being elderly. CCID identified pathogenic microbes in 78.0% of patients and conventional microbiological tests (CMT) in 57.1% of the patients (p< 0.001). The overall positive and negative percent agreements between CCID and CMT for pathogen detection were 90.07% and 38.46%, respectively. 38.8% of patients were diagnosed with mixed infections with at least two pathogens by CCID. Bacterial infections identified by CCID accounted for 60.0% of 245 patients, with the top 3 being Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium, respectively. K. pneumoniae was the most common pathogen in elderly patients, with a significantly higher prevalence compared to non-elderly patients (p = 0.0011). Among the 197 patients who had used antibiotics before sample collection, the positive rate of CCID was significantly higher than that of CMT (p < 0.001).Conclusion: This study indicates that compared to CMT, this novel chip has significant advantages in detecting pathogens in pneumonia patients, especially in the elderly.Keywords: pneumonia, elderly, pathogens, chip, LAMP

Yingli Wang,1,2,&ast; Yalin Jiang,2,&ast; Meiling Xie,1,2,&ast; Bin Qi,2 Kunpeng Pu,2 Wenjie Du,2 Qingqing Zhang,2 Mengmeng Ma,2 Ziyong Chen,2 Yongxia Guo,2 Hui Qian,2 Kaiqin Wang,2 Tulei Tian,2 Lin Fu,3 Xiaofei Zhang2 1Bengbu Medical University Graduate School, Bengbu, Anhui, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Fu, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China, Tel +86 551 6516 7923, Email fulindev@126.com Xiaofei Zhang, Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, 236800, People’s Republic of China, Email zhangxiaofeibz@163.comBackground: Leucine-rich α-2 glycoprotein 1 (LRG1) is associated with various inflammatory lung diseases. Nevertheless, the connection between LRG1 and adult community-acquired pneumonia (CAP) individuals was still not well understood. Through a prospective cohort study, the correlations of serum LRG1 with severity and prognosis were evaluated in CAP patients.Methods: The study encompassed 327 patients who received the diagnosis of CAP. We collected fasting venous blood and clinical features. Serum LRG1 was detected by ELISA. CAP severity was assessed using various scoring systems. The prognostic outcomes were observed through follow-up visits.Results: The level of serum LRG1 at admission was gradually increased with CAP severity scores. Serum LRG1 level shown positive associations with inflammatory indices, including C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Linear and logistic regression analyses suggested that serum LRG1 at admission was positively associated with severity scores and the risk of death in CAP patients. Serum LRG1 in combination with CAP severity scores significantly increased the predictive powers for severity and death compared with single serum LRG1 or severity scores.Conclusion: The study revealed positive connections of serum LRG1 levels with severity and poor prognosis in CAP patients, suggesting LRG1 partakes into the physiological processes of CAP. Serum LRG1 may be regarded as a potential biomarker in predicting the severity and death among CAP patients.Keywords: community-acquired pneumonia, LRG1, severity, outcomes, cohort study

Chaoping Ma,1,&ast; Weisong Jiang,2,&ast; Juan Li,1,&ast; Wenwu Sun,2,&ast; Jiyuan Zhang,1 Peixian Xu,1 Yiran Guo,1 Ning Ning,2 Jiaoyan Li,2 Bing Zhao,2 Enqiang Mao,2 Chengjin Gao1 1Departments of Emergency, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, People’s Republic of China; 2Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengjin Gao; Enqiang Mao, Email gaochengjin@xinhuamed.com.cn; maoeq@yeah.netIntroduction: In critically ill patients, the stress hyperglycemia ratio (SHR) was significantly associated with mortality. However, the relationship between SHR and mortality in septic patients is still unclear.In this study, patients with sepsis from two Chinese academic centers were identified and divided into quartiles based on SHR levels.Methods: Multivariable regression analysis will be used to determine associations between SHR and clinical outcomes in sepsis patients.The Kaplan-Meier curve was used to predict mortality in various groups of septic patients.Results: A total of 1835 septic patients were included in the study.The in-hospital, 30-day, and 60-day mortality rates for all septic patients were 22.8%, 18.7%, and 21.7%, respectively. Increased SHR was significantly associated with hospital mortality in multivariate regression analysis.These results were further confirmed in the adjusted analysis, where the hospital mortality and the 60-day mortality of the highest SHR quartile were significantly increased compared to the lowest SHR quartile. However, the highest SHR quartile was not associated with 30-day mortality.In addition, the risk of in-hospital mortality, 30-day mortality and 60-day mortality showed a consistent upward trend with increasing SHR quartile. The survival curve showed that the worst prognosis was in the fourth SHR quartile.Discussion: In conclusion, SHR was significantly associated with hospital mortality in patients with sepsis. This finding indicates that the SHR may be useful in identifying septic patients at higher risk of hospital mortality.Keywords: sepsis, stress hyperglycemia ratio, mortality, Hyperglycemia

Yongru Chen,1 Chongyue Chen,1 Wei Chen,2,3 Wei Gai,4 Yafeng Zheng,4 Yuxin Guo,4 Zhaoning Wang,1 Yongsong Chen,1 Zhiming Cai1,5,6 1The First Affiliated Hospital of Shantou University, Shantou, Guangdong, People’s Republic of China; 2Department of Urology, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, International Cancer Center, Shenzhen University School of Medicine, Shenzhen, People’s Republic of China; 3Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen, People’s Republic of China; 4WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China; 5BGI Genomics, BGI Shenzhen, Shenzhen, People’s Republic of China; 6Carson International Cancer Center, Shenzhen University, Shenzhen, People’s Republic of ChinaCorrespondence: Zhiming Cai, Carson International Cancer Center of Shenzhen University, No. 1066, Xueyuan Road, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86 136 0253 0322, Email caizhiming2000@163.com Yongsong Chen, The First Affiliated Hospital of Shantou University, No. 57, Changping Road, Shantou, Guangdong Province, People’s Republic of China, Tel +86 0754-88905000, Email yongsongchen@126.comPurpose: This study aimed to evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) in sepsis patients who received early empirical antibiotic treatment.Patients and Methods: A retrospective analysis was conducted on clinical data from sepsis patients diagnosed in the Emergency Intensive Care Unit (EICU) between April 2019 and May 2023. All patients underwent standard conventional microbiological testing. Patients were categorized into either the mNGS group or the control group based on whether they underwent mNGS tests. Baseline variables were matched using propensity scores.Results: Out of 461 sepsis patients screened, 130 were included after propensity matching, with 65 patients in each group. Despite prior antibiotic treatment, 57 cases (87.69%) in the mNGS group had positive mNGS results, exceeding the culture detection rate (52.31%). Besides, a higher proportion of patients in the mNGS group experienced antibiotic adjustments compared to the control group (72.31% vs 53.85%). Mortality rates were also compared based on the duration of antibiotic exposure before mNGS sampling. Patients exposed to antibiotics for less than 24 hours had a lower mortality rate compared to those exposed for over 8 days (22.22% vs 42.86%). COX multivariate analysis identified mNGS testing, underlying diseases, lymphocyte percentage, infection site (respiratory and bloodstream) as independent risk factors for mortality in sepsis patients.Conclusion: With increased antibiotic exposure time, the positive rate of culture testing significantly decreased (44.44% vs 59.52% vs 35.71%, P = 0.031), whereas the positive rate of mNGS remained stable (77.78% vs 88.10% vs 92.86%, P = 0.557). mNGS demonstrated less susceptibility to antibiotic exposure. Early mNGS detection positively impacted the prognosis of sepsis patients.Keywords: metagenomic next-generation sequencing, sepsis, antibiotic management, clinical value, prognosis

Lihao Zhang,1 Yan Su,2 Qian Wang,1 Yan Wang,1 Yikun Guo1 1Department of Neurology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of China; 2Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, People’s Republic of ChinaCorrespondence: Yikun Guo, Department of Neurology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, 68&num; Middle Gehu Road, Changzhou, Jiangsu Province, 213000, People’s Republic of China, Tel +86-519-81087079, Fax +86-519-81087711, Email guoyikun000@163.comObjective: To explore the role of white matter hyperintensities (WMH) in predicting early neurological deterioration (END) in patients with embolic stroke of undetermined source (ESUS) without reperfusion therapy.Methods: In a retrospective analysis, 111 acute ESUS patients not treated with reperfusion therapy were enrolled. WMH severity was evaluated using the Fazekas scale, with patients categorized into mild (Fazekas score ≤ 2) or moderate-to-severe (Fazekas score ≥ 3) WMH groups. Clinical data were compared between the groups, and END was monitored within 72 hours of hospital admission. The association between WMH and END was assessed using binary logistic regression.Results: Patients with moderate-to-severe WMH were significantly older (p = 0.001) and more likely to have a history of stroke (28.6% vs 10.5%, p = 0.017) compared to the mild WMH group. The END group (n=16) presented with higher baseline NIHSS scores and a greater prevalence of moderate-to-severe WMH (p < 0.05). Binary logistic regression identified moderate-to-severe WMH (OR = 4.012, 95% CI: 1.080– 14.906, p = 0.038), smoking (OR = 4.368, 95% CI: 1.171– 16.293, p = 0.028), and diabetes mellitus (OR = 3.986, 95% CI: 1.007– 15.789, p = 0.049) as independent predictors of END in ESUS patients.Conclusion: Moderate-to-severe WMH is an independent risk factor for END in ESUS patients not receiving reperfusion therapy, highlighting the importance of considering WMH in the clinical evaluation and management of stroke patients.Keywords: white matter hyperintensities, early neurological deterioration, embolic stroke of undetermined source, risk factors

Lingling Ding,1,&ast; Guowan Zheng,1– 3,&ast; Aoni Zhou,4 Fahuan Song,1– 3 Lei Zhu,5 Yefeng Cai,6 Yehao Guo,1 Tebo Hua,7 Yunye Liu,1 Wenli Ma,1 Yiqun Hu,1– 3 Yawen Guo,1– 3 Chuanming Zheng1– 3 1Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Zhejiang Provincial Clinical Research Center for Malignant Tumor, Hangzhou, Zhejiang, 310000, People’s Republic of China; 3Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou, Zhejiang, 310000, People’s Republic of China; 4Hangzhou Normal University, Hangzhou, Zhejiang, 311121, People’s Republic of China; 5Department of Thyroid Surgery, The Fifth Hospital Affiliated to Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 6Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 7Department of Thyroid Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yawen Guo; Chuanming Zheng, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, People’s Republic of China, Email mingdoc@163.com; gyw20072644@126.comBackground: The incidence of papillary thyroid cancer (PTC) has been increasing annually; however, early diagnosis can improve patient outcomes. Pyroptosis is a programmed cell death modality that has received considerable attention recently. However, no studies have reported using pyroptosis-related genes in PTC diagnosis.Methods: Analyzed 33 pyroptosis-related genes in PTC transcriptome data from the Gene Expression Omnibus database. Subsequently, used the Least Absolute Shrinkage and Selection Operator (LASSO) model to construct a PTC molecular diagnostic model. Furthermore, confirmed differences in the expression of five genes between PTC and non-tumor tissues using immunohistochemistry. Collected 338 PTC and control samples to construct a five-gene PTC diagnostic model, which was then validated using a training set and underwent correlation analysis with immune cell infiltration. Additionally, validated the biological functions of the core gene NOD1 in vitro.Results: The five-gene PTC diagnostic model demonstrated good diagnostic value for PTC. Moreover, identified three reliable subtypes of pyroptosis and found that NOD1 is involved in tumor-suppressive microenvironment formation. Notably, patients with high NOD1 expression had lower Progression-Free Survival (PFS). Additionally, NOD1 expression was positively correlated with immune markers such as CD47, CD68, CD3, and CD8. Lastly, inhibiting NOD1 showed significant anti-PTC activity in vitro.Conclusion: Our results suggest that pyroptosis-related genes can be used for PTC diagnosis, and NOD1 could be a promising therapeutic target.Keywords: pyroptosis-related genes, papillary thyroid cancer, PTC, immune cell infiltration, bioinformatic, diagnosis model

Jianrong Zhang,1,&ast; Yiyu Tang,1 Shaoting Feng,1,&ast; Io Nam Wong,2,&ast; Yue Guo,1 Jun Zhang,1 Jiancong Chen,1 Daya Yang,1 Kunsong Zhang,1 Wenbao Yao,1 Rong Li,1 Yaying Bai,1 Shuqin Ding,1 Ming Kuang,1 Haipeng Xiao,1 Dan Xu1,3,&ast; 1Department of Medical Education, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2General Practice Research, Faculty of Medicine, Macau University of Science & Technology, Taipa, 999078, Macau; 3General Practice Research, Curtin School of Population Health/Curtin Medical School, Faculty of Health Sciences, Curtin University, Perth, WA, Australia&ast;These authors contributed equally to this workCorrespondence: Ming Kuang; Shuqin Ding, Email kuangm@mail.sysu.edu.cn; dingshq@mail.sysu.edu.cnIntroduction: The rising demand for knowledge updates and technological innovations in China has made clinical placement teaching challenging. Reforms for innovative teaching models through pilot classes have shown to improve students’ academic performance. This novel integration led to the announcement of healthcare collaboration in the Guangdong-Hong-Kong-Macao Greater Bay Area for projects within China’s “Global-Innovation-Hub” zones. First Affiliated Hospital (FAH) of Sun Yat-sen University (SYSU) in Guangzhou and the Faculty of Medicine (FMD) of Macau University of Science & Technology (MUST) in Macau have developed an inaugural project for FMD/MUST medical students to perform pre-internships at FAH-SYSU. This study aimed to reflect on students’ experiences with collaborative teaching and learning through medical curricular integration in the “Global-Innovation-Hub” zones designed by both institutions for developing integrated curriculum.Methods: FMD/MUST students attended medical clerkships at FAH-SYSU using a system-integrated curriculum in China’s “Global-Innovation-Hub” zones, allowing different education systems at different locations. Post-clerkship surveys ranked teaching models in conjunction with written reflections in response to post-clerkship questionnaires for all participating students. The teaching models were defined by the way supervisors’ interaction with students, and written reflections in response to the post-clerkship questionnaire were descriptively and semantically analysed.Results: The top-ranked teaching models include first “Student-led consultation under supervision in observers’ chair with discussion”, second “Observe consultation and discuss with the teacher in-between patients in observers’ chair” and third “Student-led consultation under supervision in consultants’ chair with discussion”. The post-clerkship questionnaires showed positive outcomes.Conclusion: This study demonstrates the successful delivery of collaborative teaching and learning through medical curricular integration in China’s “Global-Innovation-Hub” zones. This integration enables the development of a consistent and student-preferred teaching model being introduced into clinical placement curriculum. The unique location of China’s “Global-Innovation-Hub” zones in the Guangdong-Hong-Kong-Macao Greater Bay Area allows this integration to significantly improve students’ clinical reasoning learning.Keywords: Guangdong-Hong Kong-Macao Greater Bay Area, Global Innovation Hub, teaching model integration, clinical placement teaching, clinical reasoning learning

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Maolin Hou,1,&ast; Jinghua Chen,2,&ast; Le Yang,3,&ast; Lei Qin,3 Jie Liu,4 Haibo Zhao,5 Yujin Guo,6 Qing-Qing Yu,6 Qiujie Zhang5 1Department of Internal Medicine, Siziwangqi People’s Hospital, Wulancabu, 011800, People’s Republic of China; 2Department of Oncology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, 250000, People’s Republic of China; 3Department of Gastrointestinal Surgery, Jining, 272000, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250000, People’s Republic of China; 5Department of Oncology, Jining, 272000, People’s Republic of China; 6Department of Clinical Pharmacology, Jining, 272000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Zhang, Department of Oncology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email zhangqiujie86@163.com Qing-Qing Yu, Department of Clinical Pharmacology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email yuqingqing_lucky@163.comIntroduction: Gastric cancer, the fifth most common malignant tumor in the world, poses a serious threat to human health. However, the role of fatty acid metabolism (FAM) in gastric cancer remains incompletely understood. We aim to provide guidance for clinical decisions by utilizing public database of gastric adenocarcinoma to establish an FAM-related gene subtypes via machine learning algorithm.Methods: The intersection of FMGs from KEGG, Hallmark, and Reactome bioinformatics databases and the DEGs of the TCGA-STAD cohort was used to decompose the gene matrix related to establish FAM-related gene subtypes by NMF. Comparison of immune infiltrating differences between subtypes using ESTIMATE and Cibersort algorithms. The multifactor Cox regression to identify independent risk genes for patient prognosis based on the subtypes. A prognostic model including independent risk genes was built using random survival forest and Cox regression. IHC validation in gastric cancer and adjacent tissues confirmed the above gene expression level.Results: 71 DEGs related to FMGs of STAD were identified, which was used to established the FAM-related gene subtypes, C1 and C2. The immune infiltrating analysis showed that most immune features of C2 were significantly upregulated compared to C1. The independent risk genes were CGβ 8, UPK1B, and OR51G based on the subtypes. A gastric cancer prognostic model consisting of independent risk genes was constructed and patients were classified into high-risk and low-risk groups with survival differential analysis. Finally, IHC showed that CGβ 8 and UPK1B expression were upregulated in gastric cancer, while OR51G2 did not detect differences in expression.Conclusion: The study developed a machine learning-based gastric cancer prognosis risk model using FMGs. This model effectively stratifies patients according to their risk levels and provides valuable insights for clinical decision-making, enabling accurate evaluation of patient prognosis.Keywords: Gastric cancer, fatty acid metabolism-related genes, machine learning, genomics, signature

Yanli Guo,1,&ast; Dinggui Huang,2,&ast; Jingxia Sun,3,&ast; Zhenwei Zhai,3,&ast; Hewei Xiao,4,&ast; Weiguang Hao,5 Qiu Wang,3 Jianhao Huang,3 Miaomiao Jin,1 Wensheng Lu3,&ast; 1Department of Endocrinology, Heji Affiliated Hospital of Changzhi Medical College, Changzhi, Shanxi, 046011, People’s Republic of China; 2Project Fund Supervision Center, Health Commission of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 4Scientific Research Cooperation Department, Guangxi Academy of Medical Sciences, People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 5Department of Endocrinology, Tongde Hospital, Yuncheng, Shanxi, 044000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.comAim: This study aimed to assess the efficacy of antithyroid drugs (ATDs) and radioactive iodine-131 (RAI) therapies in reducing the risk of major adverse cardiovascular events (MACEs) and all-cause mortality in patients with hyperthyroidism complicated with type 2 diabetes mellitus (T2DM).Methods: Between January 2013 and December 2021, 540 subjects were included in the analysis. All participants were followed up for 9 years, with a median of 54 months (2451 person-years). The subjects were categorized into two groups: the ATDs group (n = 414) and the RAI group (n = 126). According to the free triiodothyronine (FT3) tertiles, the patients receiving RAI were further grouped as follows: low-level (≤ 4.70 pmol/L, n = 42), moderate-level (4.70– 12.98 pmol/L, n = 42), and high-level (≥ 12.98 pmol/L, n = 42). The efficacy of ATDs and RAI therapies in reducing the risk of MACEs and all-cause mortality was assessed.Results: Of the 540 participants, 163 experienced MACEs (30.19%), 25 (15.34%) of whom died. Multivariate Cox regression analyses revealed that RAI was associated with a 38.5% lower risk of MACEs (P = 0.016) and a 77.1% lower risk of all-cause mortality (P = 0.046). Stratified analyses indicated that RAI had a protective effect on MACEs in patients aged ≥ 60 years (P = 0.001, P for interaction = 0.031) and patients with a duration of diabetes mellitus ≥ 6 years (P = 0.013, P for interaction = 0.002). Kaplan‒Meier analysis revealed a lower cumulative incidence of MACEs and all-cause mortality in the RAI group (log-rank, all P < 0.05). Moreover, the ROC curve suggested an optimal FT3 cut-off value of 5.4 pmol/mL for MACE (P < 0.001).Conclusion: Our findings suggested that RAI therapy effectively reduced the risk of MACEs and all-cause mortality in elderly patients with hyperthyroidism combined with T2DM.Keywords: hyperthyroidism, type 2 diabetes mellitus, radioactive iodine-131, major adverse cardiovascular events, all-cause mortality

Yiwei Wang,1 Yanzhi Guo,1 Yang Zhang,1 Shouyue Huang,1 Yisheng Zhong1,2 1Author Affiliations Department of Ophthalmology, Ruijin Hospital Affiliated Medical School, Shanghai Jiao tong University, Shanghai, 200025, People’s Republic of China; 2Author affiliations Department of Ophthalmology, Wuxi Branch of Ruijin Hospital Affiliated Medical School, Shanghai Jiao tong University, Wuxi, People’s Republic of ChinaCorrespondence: Yisheng Zhong; Shouyue Huang, Email yszhong68@126.com; yachtjj@hotmail.comAbstract: Glaucoma is the leading cause of irreversible blindness worldwide. It is an ocular disease characterized by an increase in intraocular pressure or, in some cases, normal intraocular pressure, which leads to optic nerve damage and progressive constriction of the visual field (VF). Primary Open-Angle Glaucoma (POAG) and Primary Angle-Closure Glaucoma (PACG) represent the predominant forms of glaucoma. Numerous hypotheses have been posited to elucidate the pathogenic mechanisms underlying these conditions. There is an emerging understanding of the distinct pathological processes that differentiate the various types of glaucoma. While some similarities in the mechanisms between PACG and POAG have been suggested, evidence indicates that there are also significant differences between the two. This review synthesizes the similarities and differences in the etiology of optic neuropathy caused by POAG and PACG, considering their respective pathophysiological mechanisms, the morphology of the optic disc and surrounding tissues, genetic characteristics, optical coherence tomography angiography, optical coherence tomography, and structural and functional features from VF examinations. These characteristics may contribute to a deeper comprehension of the underlying pathogenesis of glaucoma and enhance the management of different types of this ocular condition.Keywords: pathophysiology, lamina cribrosa, optic nerve head, visual field

Jing Wang,1,&ast; Lei Tian,2,&ast; Weilong Zhang,1,&ast; Shuhan Tang,1 Wei Zhao,1 Yu Guo,1 Chaoling Wu,1 Yuansheng Lin,1 Xiaoyan Ke,1 Hongmei Jing1 1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Health Management Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyan Ke; Hongmei Jing, Email xykbysy@163.com; hongmeijing@bjmu.edu.cnBackground: The application of rituximab has significantly enhanced the overall survival rates in patients with diffuse large B-cell lymphoma (DLBCL). Regrettably, a significant number of patients still progress to relapse/refractory DLBCL (rrDLBCL).Methods: Herein, we employed targeted sequencing of 55 genes to investigate if gene mutations could predict the progression to rrDLBCL. Additionally, we compared the mutation profiles at the time of DLBCL diagnosis with those found in rrDLBCL cases.Results: Our findings highlighted significantly elevated mutation frequencies of TP53, MEF2B and CD58 in diagnostic biopsies from patients who progressed to relapse or refractory disease, with CD58 mutations exclusively observed in the rrDLBCL group. In assessing the predictive power of mutation profiles for treatment responses in primary DLBCL patients, we found that the frequency of CARD11 mutations was substantially higher in non-response group as compared with those who responded to immunochemotherapy. In addition, we revealed mutations in HIST2H2AB, BCL2, NRXN3, FOXO1, HIST1H1C, LYN and TBL1XR1 genes were only detected in initial diagnostic biopsies, mutations in the EBF1 gene were solely detected in the rrDLBCL patients.Conclusion: Collectively, this study elucidates some of the genetic mechanisms contributing to the progression of rrDLBCL and suggests that the presence of CD58 mutations might serve as a powerful predictive marker for relapse/refractory outcomes in primary DLBCL patients.Keywords: targeted sequencing, mutation profile, relapse/refractory disease, diffuse large B-cell lymphoma

Wei-Li Xia,1,&ast; Xiao-Hui Zhao,2,&ast; Yuan Guo,1 Hong-Tao Hu,1 Hai-Liang Li1 1Department of Interventional Radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of China; 2Department of Interventional Radiology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hai-Liang Li, Department of interventional radiology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, 127 Dongming Road, Zhengzhou, Henan Province, 450008, People’s Republic of China, Tel +86 13903861969, Fax +0371 65587181, Email lihailianggy@163.comBackground and Objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS.Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed.Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients’ 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02).Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.Keywords: hepatocellular carcinoma, transarterial chemoembolization, portal vein tumor thrombus, 125I seed, arterioportal shunts

Hanzhi Chen,1,&ast; Leting Zhou,1,&ast; Meilin Yan,1,&ast; Cheng Li,1 Bin Liu,1 Xiaobin Liu,1 Weiwei Shan,1 Ya Guo,2 Zhijian Zhang,1 Liang Wang1 1Department of Nephrology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Key Laboratory of Advanced Process Control for Light Industry (Ministry of Education), Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Zhang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email zzjwxyy@163.com Liang Wang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangliang_wuxi@126.comBackground: End-stage kidney disease (ESKD) patients often face complications like anemia, malnutrition, and cardiovascular issues. Serological tests, which are uncomfortable and not frequently conducted, assist in medical assessments. A non-invasive, convenient method for determining these test results would be beneficial for monitoring patient health.Objective: This study develops machine learning models to estimate key serological test results using non-invasive cellular bioelectrical impedance measurements, a routine procedure for ESKD patients.Methods: The study employs two machine learning models, Support Vector Machine (SVM) and Random Forest (RF), to determine key serological tests by classifying cell bioelectrical indicators. Data from 688 patients, comprising 3,872 biochemical–bioelectrical records, were used for model validation.Results: Both SVM and RF models effectively categorized key serological results (albumin, phosphorus, parathyroid hormone) into low, normal, and high. RF generally outperformed SVM, except in classifying calcium levels in women.Conclusion: The machine learning models effectively classified serological test results for maintenance hemodialysis patients using cellular bioelectrical indicators, therefore can help in making judgments about physicochemical indicators using electrical signals, thereby reducing the frequency of serological tests.Keywords: serological test results, cellular bioelectrical indicators, machine learning, End-stage kidney disease

Sherin George Shaji,1 Pratikkumar Patel,1 Umar-Farouk Mamani,1 Yuhan Guo,1 Sushil Koirala,1 Chien-Yu Lin,1 Mohammed Alahmari,1 Evanthia Omoscharka,2 Kun Cheng1 1Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA; 2Department of Pathology, University Health/Truman Medical Center, School of Medicine, University of Missouri-Kansas City, Kansas, MO, USACorrespondence: Kun Cheng, Email chengkun@umkc.eduIntroduction: The tumor microenvironment (TME) of pancreatic cancer is highly immunosuppressive and characterized by a large number of cancer-associated fibroblasts, myeloid-derived suppressor cells, and regulatory T cells. Stimulator of interferon genes (STING) is an endoplasmic reticulum receptor that plays a critical role in immunity. STING agonists have demonstrated the ability to inflame the TME, reduce tumor burden, and confer anti-tumor activity in mouse models. 2’ 3’ cyclic guanosine monophosphate adenosine monophosphate (2’ 3’-cGAMP) is a high-affinity endogenous ligand of STING. However, delivering cGAMP to antigen-presenting cells and tumor cells within the cytosol remains challenging due to membrane impermeability and poor stability.Methods: In this study, we encapsulated 2’ 3’-cGAMP in a lipid nanoparticle (cGAMP-LNP) designed for efficient cellular delivery. We assessed the properties of the nanoparticles using a series of in-vitro studies designed to evaluate their cellular uptake, cytosolic release, and minimal cytotoxicity. Furthermore, we examined the nanoparticle’s anti-tumor effect in a syngeneic mouse model of pancreatic cancer.Results: The lipid platform significantly increased the cellular uptake of 2’ 3’-cGAMP. cGAMP-LNP exhibited promising antitumor activity in the syngeneic mouse model of pancreatic cancer.Discussion: The LNP platform shows promise for delivering exogenous 2’ 3’-cGAMP or its derivatives in cancer therapy.Keywords: 2’ 3’-cGAMP, cold tumor, innate immunotherapy, lipid nanoparticle, cytosolic delivery

Xinchao Jiang,1,&ast; Yinyin Guo,2,&ast; Mei Fang,1 Xin Wang,3 Biao Zhang,4 Yi Song,1 Jianxue Qian1 1Department of Pain Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 2Department of Oncology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 3Department of Nephrology, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China; 4Department of Intensive Care, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianxue Qian; Yi Song, Department of Pain Medicine, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, 39 Xiashatang Road, Wuzhong District, Suzhou, Jiangsu, People’s Republic of China, Tel/Fax +86 0512-69388313 ; +86 0512-69388412, Email szxqjx@126.com; 376063583@qq.comObjective: Knee osteoarthritis (KOA) is a chronic condition characterized by persistent pain that can lead to severe disability. In this study, we primarily investigated the analgesic effect of Huojing decoction on MIA-induced knee arthritis.Methods: The network pharmacology method was employed to acquire target information of Huojing decoction and KOA. MIA was intratibially injected to induce KOA pain in rats. Huojing decoction was then administered once daily via intragastric administration for 14 days. Pain level was assessed by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The levels of inflammatory cytokines were determined by ELISA and PCR. TRPV1 and CGRP were detected through immunohistochemistry. The protein expression of TrkA, MKK3/6 and p38 was assessed by Western blot.Results: Mechanical allodynia and thermal hyperalgesia were observed in KOA rats. The expression levels of inflammatory cytokines were significantly decreased after Huojing decoction infusion of KOA rats. TRPV1 and CGRP were reduced with treatment. Furthermore, the protein expressions of TrkA, MKK3/6 and p38 in the DRG of rats were significantly decreased.Conclusion: Our data suggested that Huojing decoction can alleviate inflammation in KOA pain rats. Additionally, it can inhibit the expression of TrKA, MKK3/6 and p38 signaling pathways, indicating its analgesic effect on KOA pain rats. Keywords: huojing decoction, analgesic effect, knee osteoarthritis, dorsal root ganglion, TrkA/MKK3/6/p38 pathway

Zhuo-Ren Zhou, Yong Guo Department of Health Care, Guangdong Women and Children Hospital, Guangzhou, 511400, People’s Republic of ChinaCorrespondence: Yong Guo, Department of Health Care, Guangdong Women and Children Hospital, Guangzhou, 511400, People’s Republic of China, Tel +86 2039151521, Email geyong084@163.comObjective: This study aimed to assess the growth of full-term infants with different sizes at birth and examine catch-up and catch-down growth in their first year.Methods: This retrospective population-based cohort study was based on the Guangdong Provincial Women and Children Health Information System. 194797 full-term singleton live births were extracted. Measurements for weight and length were taken at birth, 6 months, and 12 months. The size-for-gestational age was categorized as small (SGA, < 10th centile), appropriate (AGA, 10th-90th centiles), or large (LGA, > 90th centile) based on the international newborn size for gestational age and sex INTERGROWTH-21st standards. Catch-up and catch- down growth were defined as a change in standard deviation in z-score greater than 0.67 in the growth curves.Results: Of the 194797 full-term singletons, the average gestational age was 39.28 ± 1.03 weeks, and the average weight of the newborns was 3205 ± 383 grams. 15632 infants were identified as SGA (8.0%) and 12756 were LGA (6.5%). At 1 year of age, catch-up growth in weight was observed in 63.0% of SGA infants, 29.5% of AGA infants, and 5.4% of LGA infants. Conversely, catch-down growth occurred in 3.3% of SGA infants, 17.8% of AGA infants, and 54.7% of LGA infants. The proportions of catch-up growth in length for SGA, AGA, and LGA infants within the first year were 31.4%, 22.5%, and 17.1%, respectively. Catch-up or catch-down growth predominantly occurred before 6 months of age. However, from 6 to 12 months, there was no significant variation in WAZ among children with different birth sizes.Conclusion: In their first year of life, full-term singleton live births tend towards regression to the mean in their postnatal weight and length. The average delay in the growth of LGA is compensated by an increase in it of the SGA. Early monitoring and intervention are crucial for optimizing growth in infants with different birth sizes.Keywords: growth status, infant, birth weight, catch-up growth

Yan Guo,1,&ast; Jing-Jing Pan,2,&ast; Wen Zhu,1 Mu-Zi Wang,3 Tian-Yu Liu,4 Xiao-Xin Wang,5 Qian-Qian Wu,1 Yi-Xin Cheng,1 Yi-Sen Qian,1 Xiao-Guang Zhou,1 Yang Yang1 1Department of Neonatology, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neonatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Department of Neonatology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, People’s Republic of China; 4Department of Neonatology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, People’s Republic of China; 5Department of Pediatrics, Shandong Tumor Hospital, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Guang Zhou; Yang Yang, Department of Neonatology, Children’s Hospital of Nanjing Medical University, 72 Guangzhou Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email gzzhouxg@163.com; yy860507@126.comObjective: This prospective study is to explore the role of specific circRNAs in predicting the development of bronchopulmonary dysplasia (BPD).Methods: From July 1, 2021 to December 1, 2021, peripheral blood samples were collected from 62 premature infants with gestational age (GA) ≤ 32 weeks on the 7th, 14th, and 28th day after birth. Then, on the 28th day, the included infants were divided into the BPD group and the non-BPD group according to the definition of BPD. Serum exosomal circRNAs from peripheral blood were identified, sequenced, and compared between the BPD and non-BPD groups at different time points. Specific differentially expressed circRNAs were further verified from another 42 enrolled premature infants (GA ≤ 32 weeks). The classical lung biological markers in serum were also measured simultaneously.Results: Hsa_circ_0001359 in serum exosomes showed continuous differential expression between the BPD group and the non-BPD group on the 7th, 14th, and 28th day. Compared with that, classical lung biological markers like IL-6, IL-33, KL-6, and ET-1 did not exhibit continuous differences. Moreover, the expression of hsa_circ_0001359 on day 7 had a higher predictive value in predicting BPD (area under curve:0.853, 95% CI:0.738– 0.968; adjusted odds ratio:6.033, 95% CI:2.373– 13.326). The calibration curve further showed the mean absolute error = 0.033, mean squared error = 0.00231, and quantile of absolute error = 0.058.Conclusion: Hsa_circ_0001359 in serum exosomes is a promising marker for predicting BPD in preterm infants with gestational age ≤ 32 weeks.Keywords: bronchopulmonary dysplasia, circular RNAs, high-throughput sequencing, preterm infants

Zhihong Cheng,1,&ast; Song Feng,1,2,&ast; Linfeng Yang,1 Jing Huang,3 Xilei Chen,4 Yang Guo,1 Yu Xiang,1 Bin Peng1 1Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Neurosurgery, Dazhou Third People’s Hospital, Dazhou, Sichuan, People’s Republic of China; 3Innovation Center for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 4Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Peng, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, No. 234 Fujiang Road, Shunqing District, Nanchong, Sichuan, People’s Republic of China, Tel/Fax +86-817-2242781, Email binpeng01@sina.comPurpose: The spinal nerve ligation (SNL) model is a typical peripheral neuropathic pain model. During its construction, the removal of paraspinal muscles and transverse processes typically occurs, resulting in additional trauma that may potentially affect the pathophysiologic process of neuropathic pain. This study aimed to investigate the feasibility of establishing a more reliable SNL model using an oblique lateral approach.Methods: 36 adult male Sprague-Dawley rats were randomly divided into three groups: the traditional SNL (T-SNL) group, the new SNL (N-SNL) group (where the left L5 spinal nerve was ligated with a titanium clip via an oblique lateral approach), and the sham-operated (Sham) group. The operation time, Intraoperative bleeding, the number of rats that died, gait behavior, mechanical and cold pain threshold were recorded and measured. Stereology technology was used to calculate the number of microglia in spinal dorsal horn, and the Enzyme-linked immunosorbent assay (ELISA) technology was used to detect the expression of TNF-α and IL-1β in spinal cord as well as C-reactive protein (CRP) in serum in order to assess the effect of surgery on animal inflammation.Results: Compared with the T-SNL group, operative time and intraoperative bleeding were significantly decreased in the N-SNL group. Within 14 days postoperation, one rat in the N-SNL group was died, two rats in the T-SNL group were died. Compared with the Sham group, the N-SNL group showed obvious spontaneous pain behavior, decreased the pain thresholds, the number of microglia and the expression of TNF-α and IL-1β were significantly increased, and there was no significant difference in these indexes compared with T-SNL group. There was no significant difference in serum CRP levels among the three groups.Conclusion: This study suggests that the oblique lateral approach SNL model is a reliable NP model with the advantages of good reproducibility, accessibility, and low trauma.Keywords: animal model, mechanical pain threshold, hyperpathia, microglial, peripheral nerve injury, inflammatory

Yi Zhang,&ast; Yiqing Guo,&ast; Chao Gong, Junzuo Fu, Lianhua Chen Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junzuo Fu; Lianhua Chen, Department of Anesthesiology, Shanghai General Hospital of Nanjing Medical University, No. 100 Haining Road, Shanghai, 200080, People’s Republic of China, Tel +86-21-63240090, Email Fujunzuo021@163.com; emily19941010@126.comBackground: The positive roles of deep muscle relaxation in abdominal surgeries and transversus abdominis plane block (TAPB) in the postoperative analgesia. This study aimed to discuss the effects of TAPB on abdominal muscle relaxation, the intraoperative diaphragmatic, and the respiratory functions.Methods: The patients were randomly divided into the TAPB group who received single-shot TAPB bilaterally (n=30), and the control group who did not receive TAPB (n=30). Both groups keep the same steps for other procedures in the surgeries and anesthesia. Four time points for monitoring were defined: The moment when pneumoperitoneum pressure stabilized following endotracheal intubation and anesthetic induction (T0), appearance of the first incisure in the pressure-volume (P-V) loop (T1), appearance of the second incisure in the P-V loop (T2), and the moment with single stimulation (SS) =20% (T3). Primary observation parameters were SS1 measured by muscle relaxation monitoring at T1, and SS2 at T2. Secondary observation parameters included surgeon’s satisfaction with surgical field and respiratory dynamics at the four time points.Results: The two groups were comparable in age, gender, BMI, ASA grade, and operation time. The TAPB group had a dramatic reduction in the total dose of intraoperative sufentanil (0.73± 0.21 ug/kg) compared with the control group (0.87± 0.18 ug/kg) (P=0.023); Other use of drug did not differ between the two groups. The two groups did not differ significantly in SS at either T1 (SS1) or T2 (SS2). In either group, surgeon’s satisfaction with surgical field at T1 and T2 decreased dramatically compared with T0 and T3 (all P< 0.05). At each time point, the respiratory dynamics and the surgeon’s satisfaction with surgical field did not differ significantly between the two groups.Conclusion: TAPB reduced the use of intraoperative analgesics without altering the degree of abdominal relaxation, or affecting surgeon’s satisfaction with surgical field in the patients receiving laparoscopic colorectal surgery.Keywords: Transversus abdominis plane block, deep muscle relaxation, analgesia, laparoscopic colorectal surgery

Qingqing Ma,1,2,&ast; Guoju Luo,1,&ast; Fei Wang,1,&ast; Haolong Li,1 Xiaomeng Li,1,3 Yongmei Liu,1 Zhan Li,1 Ye Guo,1 Yongzhe Li1 1Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Medical Laboratory Innovation Unit, Chinese Academy of Medical Sciences, Shenyang, People’s Republic of China; 3Department of Clinical Laboratory, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Guo; Yongzhe Li, Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuai-Fu-Yuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email 4227582@163.com; yongzhelipumch@126.comPurpose: This study investigated potential predictive models associated with natural killer (NK) cell mitochondrial membrane potential (MMP or ΔΨm) in predicting death among critically ill patients with COVID-19.Patients and Methods: We included 97 patients with COVID-19 of different severities attending Peking Union Medical College Hospital from December 2022 to January 2023. Patients were divided into three groups according to oxygen and mechanical ventilation use during specimen collection and were followed for survival and death at 3 months. The lymphocyte subpopulation MMP was detected via flow cytometry. We constructed a joint diagnostic model by integrating identified key indicators and generating receiver operating curves (ROCs) and evaluated its predictive performance for mortality risk in critically ill patients.Results: The NK-cell MMP median fluorescence intensity (MFI) was significantly lower in critically ill patients who died from COVID-19 (p< 0.0001) and significantly and positively correlated with D-dimer content in critically ill patients (r=0.56, p=0.0023). The random forest model suggested that fibrinogen levels and NK-cell MMP MFI were the most important indicators. Integrating the above predictive models for the ROC yielded an area under the curve of 0.94.Conclusion: This study revealed the potential of combining NK-cell MMP with key clinical indicators (D-dimer and fibrinogen levels) to predict death among critically ill patients with COVID-19, which may help in early risk stratification of critically ill patients and improve patient care and clinical outcomes.Keywords: COVID-19, mortality prediction, NK cell, mitochondrial membrane potential, fibrinogen, D-dimer

Yanxia Guo,&ast; Zhihua Yao,&ast; Yan Feng, Dan Wang, Yizheng Wang, Jingyan Lin Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyan Lin, Email linjingyan@nsmc.edu.cnBackground: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy.Methods: Seventy-five patients aged ≥ 65 years and American Society of Anesthesiologists (ASA) class I–III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate.Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088– 0.108] mg/kg vs 0.162 [0.153– 0.171] mg/kg; 0.258 [0.249– 0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264– 0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167– 0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101– 0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups.Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.Keywords: painless gastroscopy, elderly patients, median effective dose, fentanyl, remimazolam tosilate

Chengxue He,1,2,&ast; YanHui Guo,3,&ast; Nina Zhou,2,&ast; Zhen Wang,4,&ast; Teli Liu,2 Xiaoxia Xu,2 Feng Wang,2 Hua Zhu,2 Zhi Yang,1,2 Xianteng Yang,1,5 Lei Xia2 1Medical College, Guizhou University, Guiyang, GuiZhou Province, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals (National Medical Products Administration), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 3Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Hepato-Pancreato-Biliary Surgery, Sarcoma Center, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 5Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, GuiZhou Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Xia; Zhi Yang, Tel +86 010-88197852 ; +86 010-88196196, Email xialei9012288@126.com; pekyz@163.comBackground: In recent years, PD-L1 has been primarily utilized as an immune checkpoint marker in cancer immunotherapy. However, due to tumor heterogeneity, the response rate to such therapies often falls short of expectations. In addition to its role in immunotherapy, PD-L1 serves as a specific target on the surface of tumor cells for targeted diagnostic and therapeutic interventions. There is an absence of a fully developed PD-L1-targeted diagnostic and therapeutic probe for clinical use, which constrains the exploration and clinical exploitation of this target.Methods and Results: In this study, we engineered a PD-L1-targeted probe with multimodal imaging and dual therapeutic functionalities utilizing organic melanin nanoparticles. Functionalization with the WL12-SH peptide endowed the nanoprobe with specific targeting capabilities. Subsequent radiolabeling with 89Zr (half-life: 100.8 hours) and chelation of Mn2+ ions afforded the probe the capacity for simultaneous PET and MRI imaging modalities. Cellular uptake assays revealed pronounced specificity, with -positive cells exhibiting significantly higher uptake than -negative counterparts (p < 0.05). Dual-modal PET/MRI imaging delineated rapid and sustained accumulation at the neoplastic site, yielding tumor-to-non-tumor (T/NT) signal ratios at 24 hours post-injection of 16.67± 3.45 for PET and 6.63± 0.64 for MRI, respectively. We conjugated the therapeutic radionuclide 131I (half-life: 8.02 days) to the construct and combined low-dose radiotherapy and photothermal treatment (PTT), culminating in superior antitumor efficacy while preserving a high safety profile. The tumors in the cohort receiving the dual-modality therapy exhibited significantly reduced volume and weight compared to those in the control and monotherapy groups.Conclusion: We developed and applied a novel -targeted multimodal theranostic nanoprobe, characterized by its high specificity and superior imaging capabilities as demonstrated in PET/MRI modalities. Furthermore, this nanoprobe facilitates potent therapeutic efficacy at lower radionuclide doses when used in conjunction with PTT. Keywords: theranostics, PET/MRI, melanin nanoparticles, photothermal therapy

Lin Sun,1,2,&ast; Xu Zhao,1 Yunting Guo,1,&ast; Xiaomin Hou,3– 5 Jieru Li,6 Xiaoxia Ren,7 Lin Dong,1 Ruifeng Liang,1 Jisheng Nie,1 Yiwei Shi,2 Xiaojiang Qin1,2,4,5,8 1School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4China Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, China; 5Environmental Exposures Vascular Disease Institute, Taiyuan, Shanxi, People’s Republic of China; 6Department of Foreign Languages, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 8Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojiang Qin, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86-18735379826, Email sph@sxmu.edu.cn Yiwei Shi, Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86-13835193132, Email chinasyw225@163.comPurpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity.Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤ 50 mmHg) and non-mild (PASP > 50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve.Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628).Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.Keywords: smoking index, NT-proBNP, pulmonary hypertension, chronic lung disease, predictive value

Yuanhang Pan,1,&ast; Di Zhao,1,&ast; Xinbo Zhang,1,&ast; Na Yuan,1 Lei Yang,1 Yuanyuan Jia,2 Yanzhao Guo,3 Ze Chen,1 Zezhi Wang,1 Shuyi Qu,1 Junxiang Bao,4 Yonghong Liu1 1Department of Neurology, Xijing Air Force Medical University, Xi’an, People’s Republic of China; 2Encephalopathy Department No.2, Baoji Hospital of Traditional Chinese Medicine, Baoji, People’s Republic of China; 3Encephalopathy Department No.10, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, People’s Republic of China; 4Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Liu, Department of Neurology, Xijing hospital, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 13991236602, Email liuyhong@fmmu.edu.cn Junxiang Bao, Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 02984711241, Email baojunx@fmmu.edu.cnBackground: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1.Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early.Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP).Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA.Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices.Keywords: obstructive sleep apnea, narcolepsy, machine learning, prediction model, sleep disorder

Yanling Li,&ast; Li Ji,&ast; Tian Liu, Guang Xu, Kaihe Wang, Leixin Mu, Yuying Guo, Qun Ma School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Ma, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email maqun99@126.comBackground: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection.Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD.Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group.Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.Keywords: multidrug-resistant Pseudomonas aeruginosa infection, combination therapy, PK/PD model, Qiguiyin decoction, levofloxacin

Xi Wang,1 Xinxin Liu,1 Yaoyao Guo,1,2 Tingting Gong,1 Wenmin Lu,1,3 Meihua Han,1 Yifei Guo,1 Xiangtao Wang1 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2College of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 3College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, People’s Republic of ChinaCorrespondence: Xiangtao Wang, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing, 100193, People’s Republic of China, Tel +86-10-57833266, Email xtaowang@163.comBackground: Breast cancer is a heterogeneous disease globally accounting for approximately 1 million new cases annually. Chemotherapy remains the main therapeutic option, but the antitumor efficacy needs to be improved.Methods: Two multifunctional nanoparticles were developed in this paper using oleic acid and mPEG2k-PCL2k as the drug carriers. Squamocin (Squ) was employed as a chemotherapeutic agent. Resiquimod (R848) or ginsenoside Rh2 was co-encapsulated in the nanoparticles to remold the immunosuppressive tumor microenvironment, and IR780 was coloaded as a photosensitizer to realize photothermal therapy.Results: The obtained Squ-R848-IR780 nanoparticles and Squ-Rh2-IR780 nanoparticles were uniformly spherical and approximately (162.200 ± 2.800) nm and (157.300 ± 1.1590) nm, respectively, in average diameter, with good encapsulation efficiency (above 85% for each drug), excellent stability in various physiological media and high photothermal conversion efficiency (24.10% and 22.58%, respectively). After intravenous administration, both nanoparticles quickly accumulated in the tumor and effectively enhanced the local temperature of the tumor to over 45 °C when irradiated by an 808 nm laser. At a low dose of 0.1 mg/kg, Squ nanoparticles treatment alone displayed a tumor inhibition rate of 55.28%, pulmonary metastasis inhibition rate of 59.47% and a mean survival time of 38 days, which were all higher than those of PTX injection (8 mg/kg) (43.64%, 25 days and 37.25%), indicating that Squ was a potent and effective antitumor agent. Both multifunctional nanoparticles, Squ-Rh2-IR780 nanoparticles and Squ-R848-IR780 nanoparticles, demonstrated even better therapeutic efficacy, with tumor inhibition rates of 90.02% and 97.28%, pulmonary metastasis inhibition rates of 95.42% and 98.09, and mean survival times of 46 days and 52 days, respectively.Conclusion: The multifunctional nanoparticles coloaded with squamocin, R848 and IR 780 achieved extraordinary therapeutic efficacy and excellent antimetastasis activity and are thus promising in the future treatment of breast tumors and probably other tumors.Keywords: breast cancer, multifunctional nanoparticle, antitumor efficacy, antimetastasis, combined therapy

Xiaoxue Lang,1 Xiangtao Wang,1 Meihua Han,1 Yifei Guo1– 4 1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Beijing, People’s Republic of ChinaCorrespondence: Yifei Guo, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing, 100193, People’s Republic of China, Tel +86 18810811910, Email ffguo@163.comAbstract: Until now, there has been a lack of effective strategies for cancer treatment. Immunotherapy has high potential in treating several cancers but its efficacy is limited as a monotherapy. Chemoimmunotherapy (CIT) holds promise to be widely used in cancer treatment. Therefore, identifying their involvement and potential synergy in CIT approaches is decisive. Nano-based drug delivery systems (NDDSs) are ideal delivery systems because they can simultaneously target immune cells and cancer cells, promoting drug accumulation, and reducing the toxicity of the drug. In this review, we first introduce five current immunotherapies, including immune checkpoint blocking (ICB), adoptive cell transfer therapy (ACT), cancer vaccines, oncolytic virus therapy (OVT) and cytokine therapy. Subsequently, the immunomodulatory effects of chemotherapy by inducing immunogenic cell death (ICD), promoting tumor killer cell infiltration, down-regulating immunosuppressive cells, and inhibiting immune checkpoints have been described. Finally, the NDDSs-mediated collaborative drug delivery systems have been introduced in detail, and the development of NDDSs-mediated CIT nanoparticles has been prospected. Keywords: chemoimmunotherapy, chemotherapy, immunotherapy, NDDSs

Yuanfei Li,1,&ast; Yong Yang,1,&ast; Yafeng Zheng,2,&ast; Yang Gao,3 Guoliang Shu,4 Wei Gai,2 Yuxin Guo,2 Xianghui Deng1 1Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 2WillingMed Technology (Beijing) Co., Ltd, Beijing, People’s Republic of China; 3Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China; 4Department of General Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianghui Deng, Department of Critical Care Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People’s Republic of China, Tel +8613974833075, Email 853275395@qq.comAbstract: The liver receives blood from both the hepatic artery and portal vein. Hepatic infarction is rare in clinical practice as both the hepatic artery and portal vein can supply blood to the liver. Here, we reported a case of a 75-year-old man who underwent radical laparoscopic surgery for rectal cancer and subsequently developed hepatic infarction. The patient experienced severe infection, as well as circulatory and respiratory failure on the third day after surgery. The patient presented with high fever, chest tightness, shortness of breath, decreased blood oxygen saturation and blood pressure. The leukocyte count decreased from 8.10 × 10^9/L to 1.75 × 10^9/L. Procalcitonin (PCT) levels increased from 1.02 ng/mL to 67.14 ng/mL, and eventually reaching levels over 200 ng/mL. Enhanced abdominal computed tomography (CT) confirmed the presence of hepatic infarction, but no thrombosis was observed in the hepatic artery or portal vein. Metagenomic next-generation sequencing (mNGS) identified hypervirulent Klebsiella pneumoniae (hvKp) in the patient’s blood and ascites, one day earlier than the detection results using traditional culture methods. The patient was diagnosed with hepatic infarction combined with septic shock caused by hvKp. This case emphasizes that in the high-risk group of thrombosis, infection can trigger exacerbated hepatic infarction events, particularly in cases after surgical procedures. For severely ill patients with infectious diseases who are admitted to the ICU with worsening symptoms, it is important to collect appropriate samples and send them for pathogen detection using mNGS in a timely manner. This may aid in early intervention and improve clinical outcomes.Keywords: hepatic infarction, mNGS, hypervirulent Klebsiella pneumoniae, septic shock

Qiang Tan, Ming Chen, Hongmei Yang, Yao Guo, Xiaoyi Zou Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People’s Republic of ChinaCorrespondence: Qiang Tan, Department of Cardiology, Qinhuangdao First Hospital, Hebei Medical University, Qinhuangdao, Hebei Province, People’s Republic of China, Email qhdtanqiang@aliyun.comBackground: Subclinical hypothyroidism (SH) increases the risk of cardiovascular events, however the influence of SH on prognosis of ejection fraction preserved heart failure (HFpEF) is not fully understood.Methods: In this prospective observational study, patients with HFpEF were divided into euthyroidism group (n = 413) and SH group (n = 79). Patients were followed up for at least 30 months to examine the association between SH and cardiovascular events in patients with HFpEF. The primary end point was composite cardiovascular events (cardiovascular death and re-hospitalization). The patients underwent flow-mediated dilation (FMD) measurement by ultrasound in order to value endothelial function.Results: The rate of composite cardiovascular events was higher in SH group than in euthyroidism group (54.49% and 26.36%, respectively; p < 0.001). The higher risk of cardiovascular events in SH group was primarily due to a higher risk of re-hospitalization compared to euthyroidism group (45.56% and 20.58%, respectively; p < 0.001). The rate of cardiovascular death was higher in SH group than in euthyroidism group (13.92% and 5.81%, respectively; p = 0.017). Cox proportional hazards regression showed that SH (hazard ratios [HR] 1.921, 95% confidence interval [CI] 1.139– 3.240), level of TSH (HR 1.025, 95% CI 1.010– 1.054), age (HR 1.017, 95% CI 1.002– 1.034), LVEF (HR 0.975, 95% CI 0.953– 0.996), atrial fibrillation (HR 1.581, 95% CI 1.083– 2.307), eGFR (HR 0.987, 95% CI 0.978– 0.997), and NYHA cardiac function (HR 2.342, 95% CI 1.649– 3.326) were independent predictors of cardiovascular events in patients with HFpEF (all P < 0.05).Conclusion: Subclinical hypothyroidism was associated with increased cardiovascular events and death in patients with HFpEF.Keywords: subclinical hypothyroidism, ejection fraction preserved heart failure, endothelial function, flow-mediated dilation, cardiovascular events

Zihan Yang,1,&ast; Miaomiao Zhang,2,&ast; Yan Guo,3 Rui Wang,4 Fei Xie5 1First Department of Foot and Ankle Surgery, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China; 2Emergency Department, Tianjin Haihe Hospital, Tianjin, People’s Republic of China; 3Administration Department, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China; 4School of Nursing, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 5Nursing Department, Tianjin Hospital, Tianjin University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Xie, Email 15265827878@163.comObjective: To investigate the current situation, trending subjects, and future directions in the field of burnout among nurses, and to serve as a resource for researchers conducting related research.Methods: The bibliometric analysis was carried out using R package “bibliometrix”, bibliometric online analysis platform (https://bibliometric.com/) and VOSviewer (1.6.18).Results: The leading countries that had a significant impact on this field were the USA and China. University of Pennsylvania was the most influential institution. Journal of Nursing Management was the top productive journal. Critical care, oncology care, acute care, and infectious disease care were more likely to lead to symptoms of burnout among nurses. “Mental health”, “job satisfaction”, “stress”, and “COVID-19” were the current hot topics in this field.Conclusion: Our study not only provides a thorough outline to assist researchers in understanding the leading countries, institutions, journals, and potential collaborators, but it also examines the current and upcoming trends in this field and inspires researchers to select research directions.Keywords: burnout, nurse, mental health, COVID-19, hotspots, trends

Zhishuo Zhang,1,&ast; Lujia Tang,1,&ast; Yiran Guo,1 Xin Guo,2 Zhiying Pan,2 Xiaojing Ji,1,&ast; Chengjin Gao1,&ast; 1Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China; 2School of Information Science and Technology, Sanda University, Shanghai, Pudong District, 201209, China&ast;These authors contributed equally to this workCorrespondence: Xiaojing Ji; Chengjin Gao, Email jixiaojing@xinhuamed.com.cn; gaochengjin@xinhuamed.com.cnBackground: As of 30 April 2023, the COVID-19 pandemic has resulted in over 6.9 million deaths worldwide. The virus continues to spread and mutate, leading to continuously evolving pathological and physiological processes. It is imperative to reevaluate predictive factors for identifying the risk of early disease progression.Methods: A retrospective study was conducted on a cohort of 1379 COVID-19 patients who were discharged from Xin Hua Hospital affiliated with Shanghai Jiao Tong University School of Medicine between 15 December 2022 and 15 February 2023. Patient symptoms, comorbidities, demographics, vital signs, and laboratory test results were systematically documented. The dataset was split into testing and training sets, and 15 different machine learning algorithms were employed to construct prediction models. These models were assessed for accuracy and area under the receiver operating characteristic curve (AUROC), and the best-performing model was selected for further analysis.Results: AUROC for models generated by 15 machine learning algorithms all exceeded 90%, and the accuracy of 10 of them also surpassed 90%. Light Gradient Boosting model emerged as the optimal choice, with accuracy of 0.928 ± 0.0006 and an AUROC of 0.976 ± 0.0028. Notably, the factors with the greatest impact on in-hospital mortality were growth stimulation expressed gene 2 (ST2,19.3%), interleukin-8 (IL-8,17.2%), interleukin-6 (IL-6,6.4%), age (6.1%), NT-proBNP (5.1%), interleukin-2 receptor (IL-2R, 5%), troponin I (TNI,4.6%), congestive heart failure (3.3%) in Light Gradient Boosting model.Conclusion: ST-2, IL-8, IL-6, NT-proBNP, IL-2R, TNI, age and congestive heart failure were significant predictors of in-hospital mortality among COVID-19 patients.Keywords: COVID-19, machine learning, prognosis model, ST2, IL-8, TNI, IL-6, IL-2R, congestive heart failure

Chen Bai, Mingcan Xu, Yan Guo, Yanwu Jin, Xin Zhao Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People’s Republic of ChinaCorrespondence: Yanwu Jin; Xin Zhao, Department of Anesthesiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247, Beiyuan Road, Jinan, Shandong, 250033, People’s Republic of China, Email jinyanwu_aa@163.com; lujnzx@sohu.comAbstract: Remimazolam is a novel ultrashort-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A (GABAA) receptors to exert sedative effects. Remimazolam has the properties of controllable sedation, rapid onset, and a short duration of action, along with minor depression of circulation and respiration. Remimazolam has been approved for clinical use since 2020 in Japan, and it has been applied for procedural sedation, general anesthesia induction and maintenance, and sedation in ICU patients, and has been proven to be safe and effective. Currently, no consensus has been reached on the clinical application of remimazolam in pediatric patients. This review introduces the clinical research progress and limitations of remimazolam in recent years, aiming to supply scientific guidance and a theoretical reference for the application of remimazolam in pediatric anaesthesia.Keywords: remimazolam, sedation, pediatric patient, clinical anesthesia

Ying Chen,1,2,&ast; Wen-Xia Li,1,2,&ast; Jia-Hua Wu,1,2 Geng-Hang Chen,2 Chun-Min Yang,1,2 Hai Lu,1,2 Xi Wang,3 Shu-Sen Wang,4 Heng Huang,5 Li Cai,6 Li Zhao,7 Rou-Jun Peng,8 Ying Lin,9 Jun Tang,3 Jian Zeng,10 Le-Hong Zhang,11 Yong-Li Ke,12 Xian-Ming Wang,13 Xin-Mei Liu,14 An-Qin Zhang,15 Fei Xu,4 Xi-Wen Bi,4 Jia-Jia Huang,4 Ji-Bin Li,16 Dan-Mei Pang,17 Cong Xue,4 Yan-Xia Shi,4 Zhen-Yu He,18 Huan-Xin Lin,18 Xin An,4 Wen Xia,4 Ye Cao,16 Ying Guo,16 Ruo-Xi Hong,4 Kui-Kui Jiang,4 Yong-Yi Zhong,4 Ge Zhang,19 Piyawan Tienchaiananda,20 Masahiro Oikawa,21 Zhong-Yu Yuan,4 Qian-Jun Chen22,23 1Department of Breast Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, People’s Republic of China; 2Department of Breast Surgery, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Breast Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 4Department of Medical Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 5Department of Breast Oncology, Lianjiang People’s Hospital, Lianjiang, People’s Republic of China; 6Department of Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, People’s Republic of China; 7Department of Breast Oncology, Guangzhou First People Hospital, Guangzhou, People’s Republic of China; 8Department of Integrated Therapy in Oncology, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 9Department of Breast Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 10Department of Breast Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 11Department of Breast Oncology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 12Department of Breast Oncology, General Hospital of PLA Guangzhou Military Area, Guangzhou, People’s Republic of China; 13Department of Breast Oncology, Shenzhen Second People’s Hospital, Shenzhen, People’s Republic of China; 14Department of Breast Oncology, Haikou People’s Hospital, Haikou, People’s Republic of China; 15Department of Breast Oncology, Maternal and Child Health Care Hospital of Guangdong Province, Guangzhou, People’s Republic of China; 16Department of Good Clinical Practice, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 17Department of Medical Oncology, Foshan First People’s Hospital, Foshan, People’s Republic of China; 18Department of Radiotherapy, Sun Yat-sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China; 19Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong; 20Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Rangsit University, Rajavithi Hospital, Bangkok, Thailand; 21The Department of Breast Surgery, New-wa-kai Oikawa Hospital, Fukuoka, Japan; 22State Key Laboratory of Traditional Chinese Medicine Syndrome/Departments of Gynecologic Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 23State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian-Jun Chen, 55N, Neihuanxi Road, Guangzhou, Guangdong, 510006, People’s Republic of China, Tel +86 1868883505, Email cqj55@163.com Zhong-Yu Yuan, 651 Dongfeng Road, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86 13798027658, Email yuanzhy@sysucc.org.cnPurpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not.Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into “consistent” (standard acceptable dose) and “inconsistent” (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes.Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the “inconsistent” dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the “inconsistent” dose of anthracycline and taxane did not affect DFS compared with the “consistent” dose. Moreover, in the capecitabine group, the “inconsistent” anthracycline dose did not affect DFS compared with the “consistent” dose. However, patients with “consistent” taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06).Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.Keywords: adjuvant chemotherapy, capecitabine, SYSUCC-001, triple-negative breast cancer, TNBC

Meng-Ru Zhang,1,2,&ast; Lin-Lin Fang,3,&ast; Yang Guo,1 Qin Wang,1 You-Jie Li,1 Hong-Fang Sun,1 Shu-Yang Xie,1 Yan Liang1 1Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 2Department of Clinical Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China; 3RemeGen Co., Ltd, YanTai, ShanDong, 264000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Liang; Shu-Yang Xie, Department of Biochemistry and Molecular Biology, School of Basic Medicine, Binzhou Medical University, YanTai, ShanDong, 264003, People’s Republic of China, Tel/Fax +86 535 6913335 ; +86 535 6913166, Email 18766567201@163.com; xieshuyang@bzmc.edu.cnAbstract: Cancer immunotherapy has emerged as a novel therapeutic approach against tumors, with immune checkpoint inhibitors (ICIs) making significant clinical practice. The traditional ICIs, PD-1 and PD-L1, augment the cytotoxic function of T cells through the inhibition of tumor immune evasion pathways, ultimately leading to the initiation of an antitumor immune response. However, the clinical implementation of ICIs encounters obstacles stemming from the existence of an immunosuppressive tumor microenvironment and inadequate infiltration of CD8+T cells. Considerable attention has been directed towards advancing immunogenic cell death (ICD) as a potential solution to counteract tumor cell infiltration and the immunosuppressive tumor microenvironment. This approach holds promise in transforming “cold” tumors into “hot” tumors that exhibit responsiveness to antitumor. By combining ICD with ICIs, a synergistic immune response against tumors can be achieved. However, the combination of ICD inducers and PD-1/PD-L1 inhibitors is hindered by issues such as poor targeting and uncontrolled drug release. An advantageous solution presented by stimulus-responsive nanocarrier is integrating the physicochemical properties of ICD inducers and PD-1/PD-L1 inhibitors, facilitating precise delivery to specific tissues for optimal combination therapy. Moreover, these nanocarriers leverage the distinct features of the tumor microenvironment to accomplish controlled drug release and regulate the kinetics of drug delivery. This article aims to investigate the advancement of stimulus-responsive co-delivery nanocarriers utilizing ICD and PD-1/PD-L1 inhibitors. Special focus is dedicated to exploring the advantages and recent advancements of this system in enabling the combination of ICIs and ICD inducers. The molecular mechanisms of ICD and ICIs are concisely summarized. In conclusion, we examine the potential research prospects and challenges that could greatly enhance immunotherapeutic approaches for cancer treatment.Keywords: antitumor therapy, immunogenic cell death, co-delivery, immune-checkpoint inhibitors, stimulus-responsive nanocarriers

Wenxian Fu,1– 4 Xinyi Li,1– 4 Sifan Ji,1– 4 Tingting Yang,1,3– 5 Lu Chen,1,3– 5 Yaru Guo,1,3– 5 Kongliang He1– 5 1Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China; 2School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230022, People’s Republic of China; 3Anhui Mental Health Center, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China; 4Psychiatry Department, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China; 5Psychological Counseling department, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of ChinaCorrespondence: Kongliang He, Affiliated Psychological Hospital of Anhui Medical University, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China, Tel +8613966721862, Email hefei413@126.comObjective: Non-suicidal self-injury (NSSI) behavior is very common in adolescents with depression, and childhood trauma is considered one of the distal risk factors for its exacerbation. Rumination caused by adverse traumatic experiences, which can be transferred through NSSI behavior, can alleviate symptoms of depression in adolescents. The current research focuses on the relationship between the three, further exploring whether rumination is a mediator in the relationship between childhood trauma and NSSI behavior on the basis of previous studies, and provides some suggestions for future early intervention for adolescents with depression.Methods: A total of 833 adolescent patients with depression who met the DSM-5 criteria for depressive episode were recruited from 12 hospitals in China. The Chinese version of the Function Assessment of Self-mutilation, Childhood Trauma Questionnaire, and Rumination Inventory were used as research tools.Results: The scores of childhood trauma and rumination in adolescents with depression in the NSSI group were higher than those in the non-NSSI group. A Pearson’s correlation analysis showed that childhood trauma was positively correlated with rumination (r=0.165, P< 0.01), different types of childhood trauma were significantly positively correlated with rumination and its three factors, and these results were statistically significant. Rumination partially mediated the relationship between childhood trauma and NSSI behavior in depressed adolescent patients (effect size=0.002), and the effect in female participants (effect size=0.003), was greater than that in male participants (effect size=0.002).Conclusion: Childhood trauma and rumination were key factors for NSSI behavior in adolescents with depression. Childhood trauma not only has a direct effect on NSSI behavior in adolescent depression, but also plays an indirect effect on NSSI behavior through rumination.Keywords: adolescents, childhood trauma, rumination, non-suicidal self-injury

Kaifang Yao,1,&ast; Zhihan Chen,1,&ast; Yanwei Li,1 Baomin Dou,1 Zhifang Xu,1– 3 Yajing Ma,1 Simin Du,1 Jiangshan Wang,1 Jiangjiang Fu,1 Qi Liu,1 Zezhi Fan,1 Yangyang Liu,1– 3 Xiaowei Lin,1– 3 Yuan Xu,1– 3 Yuxin Fang,1– 3 Shenjun Wang,1– 3 Yi Guo1,3,4 1Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 2School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China; 3National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin City, People’s Republic of China; 4School of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Guo; Shenjun Wang, School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China, Tel +86 22-5959-6290, Email guoyi_168@163.com; shenjunwang@163.comPurpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia.Patients and Methods: We injected complete Freund’s adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1−/− mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1.Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1−/− ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated.Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.Keywords: acupuncture, TRPA1, ST36, inflammation, immune, analgesia

Xin Huang, Yueying Chen, Fanglu Zhong, Bin Gui, Yugang Hu, Yuxin Guo, Qing Deng, Qing Zhou Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of ChinaCorrespondence: Qing Zhou; Qing Deng, Department of Ultrasound, Renmin Hospital of Wuhan University, 238&num; Jiefang Road, Wuhan, 430060, People’s Republic of China, Email qingzhou@whu.edu.cn; wudadq@163.comBackground: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types.Methods: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs’ impact.Results: The Ce6@aPD-L1 NBs effectively induced reactive oxygen species generation, leading to tumor cells death. In mice, they demonstrated a remarkable enhancement of immune responses compared to control groups. These immune responses encompassed immunogenic cell death induced by sonodynamic therapy and PD-1/PD-L1 blockade, activating dendritic cells maturation and effectively stimulating CD8+T cells.Conclusion: Ce6@aPD-L1 NBs facilitate tumor-targeted delivery, activating anti-tumor effects through direct sonodynamic therapy action and immune system reactivation in the tumor microenvironment. Ce6@aPD-L1 NBs exhibit substantial potential for achieving synergistic anti-cancer effects in PCa.Keywords: Ce6, nanobubbles, ultrasound, sonodynamic therapy, immunotherapy

Rui Jing,1 Hui Dong,1 Kun Huang,2 Zhong Liu,1 Ran Xue,1 Yiran Dong,1 Mei Jiao,3 Na Li,4 Yumei Guo,5 Yun Liu,6 Wenqian Zhang,1 Hongyun Sun1 1Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China; 2Tuberculosis Control Division, Licheng Center for Disease Control and Prevention, Jinan, People’s Republic of China; 3Department of Sexually Transmitted Diseases and AIDS Prevention and Control, Lixia Center for Disease Control and Prevention, Jinan, People’s Republic of China; 4Tuberculosis and Vector Control Division, Shizhong Center for Disease Control and Prevention, Jinan, People’s Republic of China; 5Department of Infectious Diseases and Endemic Disease Control, Huaiyin Center for Disease Control and Prevention, Jinan, People’s Republic of China; 6AIDS Prevention and Control Department, Tianqiao Center for Disease Control and Prevention, Jinan, People’s Republic of ChinaCorrespondence: Wenqian Zhang; Hongyun Sun, Institute for Tuberculosis Control, Jinan Center for Disease Control and Prevention, Jinan, People’s Republic of China, Tel +86 0531-81278897 ; +86 0531 81278873, Email wqzh618@gmail.com; jncdcxxtb@jn.shandong.cnPurpose: This study aimed to investigate awareness of tuberculosis control among post-treatment tuberculosis patients, in order to provide a basis for future preventive and control work in this population.Patients and Methods: A cross-sectional descriptive study was conducted on post-treatment patients with tuberculosis in seven districts of Jinan City between July 2021 and December 2022. A face-to-face or telephone interviews using structured questionnaires for the research subjects were conducted by data collectors. Analyses were carried out first for all subjects, and then separately for male and female subjects.Results: A total of 837 valid questionnaires were collected, of which 495 were males and 342 were females. The awareness rate of the core TB knowledge was 82.46%. The ≥ 65 year group in the total group (OR=0.43, 95% CI: (0.28, 0.68)), male (OR=0.47, 95% CI: (0.27, 0.83)) and female group (OR=0.40, 95% CI: (0.19, 0.86)) was lower than that of the control group. Educational level and monthly income are the main factors of TB cognition in total group. People with university or higher education (OR=2.05, 95% CI: (1.38, 3.05)) and with a monthly income of ≥ 6,000 (OR=1.89, 95% CI: (1.10, 3.25)) had a higher awareness rate. The group with current residence in the city was more aware than the reference group.Conclusion: In the future, the communication of the main transmission route, suspicious symptoms, and cure of TB needs to be strengthened for the post-treatment TB patients. The elderly, those with secondary school education or below, agricultural workers and low-income people are the groups with weak knowledge of TB, and they are also the groups that need to be focused on health education. The above information should be focused on the above groups of people in order to educate them in a way that is easily acceptable to them.Keywords: pulmonary tuberculosis, awareness rate, completed treatment patients, layered analysis

Lina Guo,1 Jaclene A Zauszniewski,2 Gege Zhang,1 Xiaoyu Lei,1 Mengyu Zhang,1 Miao Wei,1 Keke Ma,1 Caixia Yang,1 Yanjin Liu,3 Yuanli Guo1 1Department of Neurology, National Advanced Stroke Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 3Department of Nursing, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Yuanli Guo, Email gylzd@163.comObjective: To explore distinct longitudinal trajectories of resourcefulness among initial ischemic stroke patients from diagnosis to 12 months, and to identify whether sociodemographic factors, disease-related factors, self-efficacy, family function, and social support can predict patterns in the trajectories of resourcefulness.Methods: A prospective longitudinal study was conducted. Initial ischemic stroke patients who met inclusion and exclusion criteria were followed up when still in hospital (Preparing for discharge, Baseline, T1), at 1 month (T2), at 3 months (T3), at 6 months (T4), at 9 months (T5) and 12 months (T6) (± 1 week) after discharge. General information, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), General Self-Efficacy Scale (GSES), General Family Functioning Subscale (FAD-GF), and Social Support Rate Scale (SSRS) were used in T1. The Resourcefulness Scale© was evaluated at 6 time points. Growth mixture modeling was used to identify trajectory patterns of resourcefulness. Logistic regression was used to identify predictors of resourcefulness trajectories.Results: Three longitudinal trajectories of resourcefulness were identified and named as the high-stable class (38.9%, n=71), fluctuation class (41.2%, n=75), and low-stable class (19.9%, n=36), respectively. Dwelling areas (x2= 6.805, P= 0.009), education (x2= 44.865, P= 0.000), monthly income (x2= 13.063, P= 0.001), NIHSS scores (x2= 44.730, P= 0.000), mRS scores (x2= 51.788, P= 0.000), Hcy (x2= 9.345, P= 0.002), GSES (x2= 56.933, P= 0.000), FAD-GF (x2= 41.305, P= 0.000) and SSRS (x2=52.373, P= 0.000) were found to be statistically significant for distinguishing between different resourcefulness trajectory patterns. Lower education (OR=0.404), higher NIHSS(OR=6.672) scores, and higher mRS(OR=21.418) scores were found to be risk factors for lower resourcefulness, whereas higher education(OR=0.404), GSES(OR=0.276), FAD-GF(OR=0.344), and SSRS(OR=0.358) scores were identified as protective factors enhancing resourcefulness.Conclusion: This study obtained three patterns of trajectories and identified their predictive factors in initial ischemic stroke. The findings will assist health care professionals in identifying subgroups of patients and when they may be at risk of low resourcefulness and provide timely targeted intervention to promote resourcefulness.Keywords: initial ischemic stroke, resourcefulness, longitudinal study, social ecology theory, predictive factors, nursing care

Changshun Yan,1 Yankai Guo,2 Guiqiu Cao1 1Department of Cardiology, Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, The Xinjiang Uygur Autonomous Region, People’s Republic of China; 2Department of Pacing Electrophysiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, The Xinjiang Uygur Autonomous Region, People’s Republic of ChinaCorrespondence: Guiqiu Cao, Tel +8613199954310, Email guiyueshisan@163.comBackground: Coronary slow flow phenomenon (CSFP) is a phenomenon in which distal vascular perfusion is delayed on angiography, but coronary arteries are not significantly narrowed and there is no other organic cardiac disease. Patients with CSFP may be repeatedly readmitted to the hospital because of chest pain or other symptoms of precordial discomfort, and there is a risk of adverse events. In order to investigate the risk factors affecting the readmission of CSFP patients, a prediction model was constructed with the aim of identifying patients at risk of readmission at an early stage and providing a reference for further clinical intervention.Methods: In this study, we collected clinical data from 397 CSFP patients between June 2021 and January 2023 in Xinjiang Medical University Hospital. Telephone follow-up clarified whether the patients were readmitted to the hospital. A predictive model for readmission of CSFP patients was constructed using multifactorial logistic regression. Nomogram was used to visualize the model and bootstrap was used to internally validate the model. ROC, DCA and Calibration curve were plotted to evaluate the calibration and discriminative ability of the column line graphs, respectively. Calibration and resolution of the column line graphs, respectively.Results: A total of 34 of 397 CSFP patients experienced readmission. Smoking history, creatine kinase isoenzyme-MB, total cholesterol, and left ventricular ejection fraction were the predictors of readmission in patients with CSFP. The area under the curve of the Nomogram model was 0.87, which indicated that the model had good predictive ability and differentiation, and the DCA and Calibration curves also indicated that the model had good consistency and was clinically useful.Conclusion: A readmission prediction model for patients with CSFP may facilitate early identification of patients at potential risk for readmission and timely interventional therapy to improve patient prognosis.Keywords: coronary slow flow phenomenon, readmission, predictive model

Yanping Guo,1 Zhangbin Yu,2 Huiying Tu,2 Biying Zheng,1 Jiamin Li,1 Ying Liu1 1Department of Pediatrics, Peking University Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 2Department of Neonatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Yanping Guo; Ying Liu, Tel +86-15919990131 ; +86-13902992158, Email guoyanping1223@163.com; 13902992158@139.comBackground and Objectives: To examine the correlation between the concentration of vitamin D (VD) in venous blood at approximately 4 weeks of age (± 4 weeks of age) and neonatal outcomes in preterm infants (birth weight < 1500 g or gestational age < 32 weeks) in two neonatal intensive care units (NICUs) located in Shenzhen, China.Methods and Study Design: Preterm infants were split into two groups based on their VD concentration at ± 4 weeks of age: VD insufficiency (VDI) group (≤ 20 ng/mL) and VD sufficient (VDS) group (> 20 ng/mL). Binary logistic regression analysis was used to examine relationships between outcomes and VDI.Results: Of 230 infants in total, 119 (51.7%) were assigned to the VDI group and 111 to the VDS group (48.3%). No correlation was found between serum VD at ± 4 weeks of age and gestational age (p> 0.05). The starting point of the two groups for oral VD intake did not differ significantly (p> 0.05). At ± 4 weeks of age, oral VD dose (P< 0.05) was greater in the VDS group. Gestational diabetes mellitus was associated with VDI (OR=1.94, 95% CI 1.01– 3.75, p=0.047) after controlling for this risk. Following correction for gestational age and oral VD dosage at ± 4 weeks old, VDI was also linked to a significant risk of retinopathy of prematurity (OR=2.00, 95% CI 1.08– 3.68, p< 0.027).Conclusion: Preterm newborns (gestational age < 32 weeks or birth age < 1500 g) in NICUs in Shenzhen, China continue to have significantly high VDI. Higher VDI is associated with gestational diabetes mellitus and retinopathy of prematurity.Keywords: very preterm birth, very low birth weight infant, vitamin D, 4 weeks of age, outcome

Jiakang Chen,1,&ast; Kasim Allel,2– 4,&ast; Chuyue Zhuo,1,&ast; Wenwei Luo,5 Nanhao He,1 Xu Yang,1 Yingyi Guo,1 Jiong Wang,1 Likang Yao,1 Jiahui Li,1 Yexin Lin,1 Ruiyang Tu,6 Laith Yakob,2,3 Chao Zhuo1 1State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Disease Control, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; 3Antimicrobial Resistance Centre, London School of Hygiene & Tropical Medicine, London, UK; 4Institute for Global Health, University College London, London, UK; 5Department of Clinical Laboratory, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 6Department of Science and Technology Studies, University College London, London, UK&ast;These authors contributed equally to this workCorrespondence: Chao Zhuo, State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiang Road, Guangzhou, Guangdong, People’s Republic of China, Email chaosheep@gzhmu.edu.cnIntroduction: Although Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) significantly contribute to bloodstream infections, their economic repercussions remain largely unquantified.Data Source and Methods: We performed a retrospective analysis of inpatients diagnosed with Escherichia coli or Klebsiella pneumoniae bacteremia in a tertiary hospital from January 2020 to December 2022 in Guangzhou, China. We employed the chi-square test to examine ESBL risk factors and utilized propensity score matching (PSM) to negate baseline confounding factors, assessing economic burden through disability-adjusted life years (DALYs), hospital costs and productivity losses. We employed mediation analysis to eliminate confounding factors and better identify ESBL sources of burden related.Results: We found 166 ESBL-EC/KP BSI patients (52.2% of the total examined 318 patients). Post-PSM analysis revealed that ESBL-producing EC/KP will reduce the effectiveness of empirical medication by 19.8%, extend the total length of hospitalization by an average of 3 days, and increase the patient’s financial burden by US&dollar;2047. No significant disparity was found in overall mortality and mean DALYs between the groups. Mediation analysis showed that the link between ESBL and hospital costs is predominantly, if not entirely, influenced by the appropriateness of empirical antibiotic treatment and length of hospital stay.Conclusion: Patients with BSI due to ESBL-producing ESBL-EK incur higher costs compared to those with non-ESBL-EK BSI. This cost disparity is rooted in varying rates of effective empirical antimicrobial therapy and differences in hospital stay durations. A nuanced approach, incorporating a thorough understanding of regional epidemiological trends and judicious antibiotic use, is crucial for mitigating the financial impact on patients.Keywords: Escherichia coli, Klebsiella pneumoniae, bacteremia, ESBL, risk factors, medical costs

Yanni Tan,1,&ast; Yameng Li,2,&ast; Xiuxian Huang,3,&ast; Zhenwei Zhai,3,&ast; Qiu Wang,3,&ast; Yanli Guo,4 Junjun Li,5 Wensheng Lu3,&ast; 1Department of Endocrinology and Respiratory of the Third People’s Hospital of Nanning, Nanning, Guangxi, 530003, People’s Republic of China; 2Medical Department of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Endocrinology and Metabolism of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China; 4Yuncheng Vocational and Technical University, Yuncheng, Shanxi, 044000, People’s Republic of China; 5Hospital Dean’s Office of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wensheng Lu, Department of Endocrinology and Metabolism, Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email Lwswxqz@163.com Junjun Li, Hospital Dean’s Office of Guangxi Academy of Medical Sciences and the People’s Hospital of Guangxi Zhuang Autonomous Region, No. 6, Taoyuan Road, Nanning, Guangxi, 530021, People’s Republic of China, Email lijunjun6225@163.comObjective: To explore the relationship between red blood cell distribution width to albumin (RDW/ALB) ratio (RAR) and the risk of rehospitalization and rehospitalization all-cause mortality in middle-aged and elderly survivors with sepsis based on an ambispective longitudinal cohort from the Intensive Care Unit (ICU).Methods: Between 2017 and 2022, 455 adults who survived the first-episode severe sepsis without recurrence for at least 3 months were included in this study. All participants were followed up every 4 weeks for 12 months. According to the tertiles of RAR, participants were divided into three groups: low-level (≤ 0.36, n = 152), moderate-level (0.37– 0.44, n = 152), and high-level (≥ 0.45, n = 151). The relationship between RAR and the risk of rehospitalization and rehospitalization all-cause mortality was evaluated.Results: Out of 455 participants, 156 experienced rehospitalization (34.3%), of which 44 (28.2%) died. Receiver operating characteristic (ROC) analysis showed that the RAR cut-off values for rehospitalization and rehospitalization all-cause mortality were 0.4251 and 0.4743, respectively. Multivariate Cox regression analysis indicated that the RAR was positively associated with rehospitalization (P = 0.011) and all-cause mortality (P = 0.006). Compared with the low-level, the high-level RAR presented a higher dose-dependent rehospitalization risk (P = 0.02) and rehospitalization all-cause mortality (P = 0.044). The stratified analysis displayed that compared to the low-level, with the RAR increasing by 1.0, the risk for rehospitalization increased 3.602-fold in aged < 65 patients (P = 0.002) and 1.721-fold in female patients (P = 0.014). Kaplan–Meier survival analysis implied a significant positive association between the RAR and the cumulative incidence of rehospitalization and rehospitalization all-cause mortality (log-rank, all P < 0.001).Conclusion: RAR has a reliable predictive value for the risk of rehospitalization and rehospitalization all-cause mortality in patients with sepsis. Consequently, monitoring RAR for at least 1 year after surviving sepsis in female patients aged < 65 in clinical practice is critical.Keywords: sepsis, red blood cell distribution width, albumin, rehospitalization, rehospitalization all-cause mortality

Shujie Wang,1,2 Chunyan Shao,2 Xingkai Zhao,1 Yizhe Guo,1 Houhui Song,2 Lida Shen,3 Zhenlei Zhou,1 Zhen Li4,5 1College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China; 2College of Animal Science and Technology & College of Veterinary Medicine, Zhejiang Agriculture and Forestry University, Hangzhou, Zhejiang, 311300, People’s Republic of China; 3College of Mechanical and Electrical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu, 210016, People’s Republic of China; 4College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China; 5State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology and Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Nanjing, Jiangsu, 210008, People’s Republic of ChinaCorrespondence: Zhenlei Zhou, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China, Tel +86 (25) 84395505, Email zhouzl@njau.edu.cn Zhen Li, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, People’s Republic of China, Tel/Fax +86 (25) 84399827, Email lizhen@njau.edu.cnIntroduction: Hydroxylapatite (HAp) is a biodegradable bone graft material with high biocompatibility. However, the clinical application of HAp has been limited due to the poor absorption rate in vivo.Methods: In this study, carbonated hydroxylapatite (CHAp) with a chemical composition similar to natural bone was synthesized. HAp and CHAp scaffolds were fabricated by 3D printing. Each material was designed by two types of scaffold model with a maximum width of 8 mm and a thickness of 2 mm, ie, structure I (round shape) and structure II (grid shape). Then, the HAp scaffolds were loaded with lutein. These scaffolds were implanted into the 8 mm bone defect on the top of the rabbit skull within 3 hours in the morning. The curative effects of the scaffolds were assessed two months after implantation.Results: The 3D printed scaffolds did not cause severe inflammation or rejection after implantation. It showed that the porous structures allow bone cells to enter into the scaffolds. Furthermore, CHAp scaffolds were more biocompatible than HAp scaffolds, and showed a higher level of degradation and new bone formation after implantation. Structure II scaffolds with a smaller mineral content degraded faster than structure I, while structure I had better osteoconductive properties than structure II. Besides, the addition of lutein significantly enhanced the rate of new bone formation.Discussion: The uniqueness of this study lies in the synthesis of 3D printed CHAp scaffolds and the implantation of CHAp in rabbit bone defects. The incorporation of suitable carbonate and lutein into HAp can enhance the osteoinductivity of the graft, and CHAp has a faster degradation rate in vivo, all of which provide a new reference for the research and application of apatite-based composites.Keywords: bone, 3D printing, hydroxylapatite, lutein, repair

Yue Wu,1 Siqi Cheng,1 Shaoyuan Lei,2 Dongxiao Li,3 Zhongzhong Li,4 Yansu Guo1,2,5 1Beijing Geriatric Healthcare Center, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Evidence-Based Medicine, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Neurology, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, People’s Republic of China; 4Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Beijing Municipal Geriatric Medical Research Center, Beijing, People’s Republic of ChinaCorrespondence: Yansu Guo, Beijing Geriatric Healthcare Center, Xuanwu Hospital, Capital Medical University, Changchun Street 45, Beijing, People’s Republic of China, Email gys188@163.comBackground: There is growing evidence that an antioxidant diet is a protective factor against frailty. However, few studies have examined the effect of comprehensive dietary antioxidants on frailty symptoms. The aim of this study was to examine the relationships between the composite dietary antioxidant index (CDAI) and frailty and the underlying mechanisms involved.Methods: Based on the National Health and Nutrition Survey (NHANES) 2003– 2018, this study included 11,277 older persons aged ≥ 60 years. In this study, frailty was defined as having a total score > 0.21 on the 49-item frailty index. Six dietary antioxidants were selected for use in calculating the CDAI. A weighted multiple logistic regression model with subgroup analysis and restricted cubic splines (RCSs) were used to examine the association between the CDAI and frailty. To examine the role of oxidative stress, mediation analyses were also conducted.Results: The association between the CDAI score and frailty risk was significant according to the multivariate model. Compared with participants in tertile 1, participants in both tertile 2 and tertile 3 had lower odds of developing frailty symptoms (OR=0.86; 95% CI=0.75– 0.97; P=0.02; and OR=0.81; 95% CI=0.70– 0.93; P=0.003). According to the subgroup analyses, the differences in interactions were not statistically significant. There was also a potential nonlinear relationship between the CDAI score and frailty risk. The serum albumin concentration and uric acid concentration had significant mediating effects on the association between the CDAI score and frailty index, with 19.25% (P=0.002) and 21.26% (P < 0.001) of the total, respectively.Conclusion: Frailty is negatively associated with the CDAI score, which may be partially mediated by oxidative stress.Keywords: frailty, CDAI, NHANES, elderly adults