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Xiangjun Chen,* Weiwei Li,* Qing Fan, Xiao Liu, Xuanxiang Zhai, Xiaoyi Shi, Wenting Li, Wei Hong School of Pharmacy, Shandong Engineering Research Center of New-Type Drug Loading & Releasing Technology and Preparation, Binzhou Medical University, Yantai, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Hong; Wenting Li, Email hongwei_sy@bzmc.edu.cn; liwenting1003@163.comIntroduction: Pseudomonas aeruginosa (P. aeruginosa)-induced pneumonia is marked by considerable infiltration of inflammatory cells and biofilm formation, which causes acute and transient lung inflammation and infection. Nevertheless, the discovery of alternative preventative and therapeutic methods is essential due to the high mortality rates in clinical settings and the resistance of P. aeruginosa infection to multiple medications.Purpose: In this research, we constructed amphiphilic Janus nanoparticles (JNPs, denoted as SSK1@PDA/CaP@CIP), loaded with hydrophobic SSK1, a β-galactosidase (β-gal)-activated prodrug for reducing macrophages, and hydrophilic ciprofloxacin (CIP), a classic antibiotic for treating infection. SSK1@PDA/CaP@CIP was designed to effectively attenuate inflammation, eradicate biofilms, and combat planktonic P. aeruginosa.Results: As expected, SSK1@PDA/CaP@CIP was able to target the infection site and demonstrated outstanding efficacy in treating P. aeruginosa strain PAO1-induced pneumonia by regulating macrophage infiltration to reduce inflammation and removing planktonic bacteria and biofilms to control infection. Additionally, the primary organs did not exhibit any discernible pathological changes following treatment with SSK1@PDA/CaP@CIP, which indicates superior biocompatibility throughout the treatment course.Discussion: In conclusion, our investigation introduced a promising approach to the treatment of pneumonia associated with PAO1.Keywords: Pseudomonas aeruginosa, pneumonia, inflammatory responses, β-galactosidase (β-gal)-activated prodrug, amphiphilic Janus nanoparticles

Huizhong Hu, Yuanjie Qiu, Nirui Shen, Huan Chen, Jia Zhang, Yan Wang, Xiangyu Shi, Manxiang Li Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Manxiang Li, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China, Tel\Fax +86-029-85324053, Email manxiangli@hotmail.comPurpose: Although low-carbohydrate and low-fat diets improve weight loss, cardiovascular disease, and diabetes, the relationship between these dietary patterns, highlighting macronutrient sources, and chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to assess the association between low-carbohydrate diets (LCDs) and low-fat diets (LFDs) and the odds of COPD and mortality among people with COPD in the National Health and Nutrition Examination Survey.Patients and Methods: Clinical data were extracted from the 2007– 2008, 2009– 2010, and 2011– 2012 National Health and Nutrition Examination Survey (NHANES) cycles that met the inclusion criteria. Multivariable logistic regression was used to evaluate the associations between LCD and LFD scores and COPD, and multivariable Cox proportional hazards regression and restricted cubic spline (RCS) regression were used to assess the relationship between all-cause mortality and LCD and LFD scores.Results: Comparing extreme tertiles, multivariable-adjusted odds ratio (OR) were 1 (reference), 1.09 (95% CI, 0.77– 1.55), 1.84 (95% CI, 1.09– 3.09) (P = 0.045 for trend) for unhealthy LFD scores. After multivariate adjustment, a per 5-point increase in unhealthy LCD score was associated with a 21% higher risk of total mortality (hazard ratio, 1.21; 95% CI, 1.03– 1.43); while a per 5-point increase in healthy LFD scores was associated with a 21% lower risk of total mortality (HR, 0.79; 95% CI, 0.67– 0.94).Conclusion: Higher unhealthy LFD score was associated with an increased odds of COPD. Unhealthy LCD scores were significantly associated with higher total mortality, whereas healthy LFD scores were associated with lower total mortality in patients with COPD.Keywords: low-carbohydrate diet, low-fat diet, chronic obstructive pulmonary disease, mortality, NHANES

Xiaoqin Ji,1,* Xuebing Shi,2,* Jun Hu,3 Wanrong Jiang,3 Bin Zhou,3 Houlong Zhou,3 Xi Yuan,3 Yikun Li,3 Hua Huang,3 Jiasheng Wang,3 Wei Ding,3 Yong Wang,4 Xiangdong Sun3 1Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Radiation Oncology, Nanjing Jiangbei Hospital, Nanjing, People’s Republic of China; 3Department of Radiation Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 4Department of Outpatient Clinic, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong Wang; Xiangdong Sun, Email 292917354@qq.com; sunxd_81@126.comPurpose: The objective of this study was to compare the clinical outcomes of stereotactic body radiation therapy (SBRT) in elderly patients aged 65 or older with clinical stage I–II non-small-cell lung cancer (NSCLC), specifically examining the differences between centrally located lung tumors and peripherally located lung tumors.Methods: From April 2009 to January 2020, a total of 136 patients with 136 tumors (65 central, 71 peripheral; NSCLC) at an early stage (T1-3N0M0) were treated with SBRT at a single institution. Central/peripheral location was assessed retrospectively on planning CT scans. A propensity score matching analysis was utilized to compare the two groups. In addition, the prognosis and related toxicity were compared between the two study arms.Results: A total of 33 central tumors and 33 peripheral tumors were matched and analyzed. The results showed no significant differences in overall survival (OS) and progression-free survival (PFS) between the two groups. The 2-year OS was 71.88% (95% CI, 57.87%-89.27%) in the central lung cancer group, while it was 93.94% (95% CI, 86.14%-100.00%) in the peripheral lung cancer group (P=0.462). The 2-year PFS was 43.75% in the central lung cancer group, while it was 78.79% in the peripheral lung cancer group (P=0.279). Further subgroup analysis indicated that the location of peripheral tumor have a positive impact on OS in patients with adenocarcinoma. The occurrence of local failure, regional failure, or distant failure was comparable between central and peripheral tumors. There was no statistically significant difference in toxicity between the central and the peripheral tumor groups.Conclusion: The outcomes of SBRT for central tumors versus peripheral lung tumors in elderly patients with early-stage NSCLC were similar. SBRT demonstrated a similar level of safety in terms of toxicity for both central and peripheral lung tumors.Keywords: Non-small cell lung cancer, stereotactic body radiation therapy, central lung cancer, elderly patients, propensity score matching

Doyoung Kwak,1 Yuanjie Liang,2 Xu Shi,3 Xi Tan2 1Department of Electrical & Computer Engineering, Texas A&M University, College Station, TX, USA; 2Novo Nordisk Inc, Plainsboro, NJ, USA; 3Department of Biostatistics, University of Michigan, Ann Arbor, MI, USACorrespondence: Xi Tan, Email mxtz@novonordisk.comPurpose: Observational research provides valuable insights into treatments used in patient populations in real-world settings. However, confounding is likely to occur if there are differences in patient characteristics associated with both the exposure and outcome between the groups being evaluated. One approach to reduce confounding and facilitate unbiased comparisons is inverse probability of treatment weighting (IPTW) using propensity scores. Machine learning (ML) and entropy balancing can potentially be used in generating propensity scores for IPTW, but there is limited literature on this application. We aimed to assess the feasibility of applying these methods for reducing confounding in observational studies. These methods were assessed in a study comparing cardiovascular outcomes in adults with type 2 diabetes and established atherosclerotic cardiovascular disease taking once-weekly glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors.Methods: We applied advanced methods to generate the propensity scores compared to the original logistic regression method in terms of covariate balance. After calculating weights, a weighted Cox proportional hazards model was used to calculate the sample average treatment effect. Support Vector Classification, Support Vector Regression, XGBoost, and LightGBM were the ML models used. Entropy balancing was also performed on features identified in the original cardiovascular outcomes study.Results: Accuracy (range: 0.71 to 0.73), area under the curve (0.77 to 0.79), precision (0.53 to 0.60), recall (0.66 to 0.68), and F1 score (0.60 to 0.64) were similar between all of the advanced propensity score methods and traditional logistic regression. Among ML models, only XGBoost achieved balance in all measured baseline characteristics between the two treatment groups, closely approximating the performance of the original logistic regression. Entropy balancing weights provided the best performance among all models in balancing baseline characteristics, achieving near perfect balancing.Conclusion: Among the advanced methods examined, entropy balancing weights performed the best for optimizing balancing and can produce similar results compared to traditional logistic regression.Keywords: propensity score, machine learning, entropy balancing, type 2 diabetes, glucagon-like peptide-1 receptor agonists

Zhaorong Gao,1– 3 Zhen Guo,1– 3 Yongbo Song,1– 3 Xiujing Shi,1– 3 Yingzuo Zhao,1– 3 Conghui Liu1– 3 1Qingdao Eye Hospital of Shandong First Medical University, Eye Institute of Shandong First Medical University, Qingdao, People’s Republic of China; 2State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao Eye Hospital of Shandong First Medical University, Qingdao, People’s Republic of China; 3School of Ophthalmology, Shandong First Medical University, Qingdao, People’s Republic of ChinaCorrespondence: Zhen Guo, Qingdao Eye Hospital of Shandong First Medical University, Eye Institute of Shandong First Medical University, 5 Yanerdao Road, Qingdao, Shandong, 266071, People’s Republic of China, Fax +86532 8761 0087, Email guoz@sdfmu.edu.cnPurpose: With girls typically exhibiting higher rates of myopia than boys, however, the mechanisms behind this gender difference remain unclear. This study aims to investigate the gender disparities in the relationship between myopia, sleep duration, physical activity, and BMI.Patients and Methods: A total of 3138 primary and secondary school students were included. Mplus 8.3 was used to perform the multiple mediation analysis.Results: Sleep duration was indicated to directly affect myopia (β=0.273, 95% CI=0.184− 0.356) and through physical activity, BMI, physical activity and BMI three significantly mediation pathways, respectively. In terms of gender, the mediating direct effect of sleep duration on myopia of boys was 66.96%, which is much higher than that of girls’ 50.91%. And the mediating indirect effect of sleep duration on myopia through physical activity and BMI are 32.65% and 12.10% respectively among girls, both of which are significantly higher than that of boys.Conclusion: The study found that there are significant differences in the impact of sleep duration on myopia in children and adolescents of different genders. In this regard, while paying attention to the sleep duration of children and adolescents, special attention should also be paid to the indirect impact of girls’ physical activity and BMI on myopia, and targeted measures should be formulated according to children of different genders to effectively protect the eye health of children and adolescents.Keywords: myopia, children and adolescents, sleep duration, physical activity, BMI, gender difference

Caige Li,1,2 Yu Xue,1 Yiwei Liu,1 Kangning Zheng,1 Yuting Gao,1,3 Yi Gong,1 Junlan Lu,1 Yuman Zhang,1 Jingmin Ji,1 Zhiqin Zhang,1 Xinli Shi1 1Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of ChinaCorrespondence: Xinli Shi, Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, 3 Xingyuan Road, Shijiazhuang, Hebei, 050200, People’s Republic of China, Tel +86-0311-89926237, Email sxlsunshine@sina.comIntroduction: Yes-associated protein 1 (YAP1) is a crucial molecule in the Hippo pathway. The impact of hepatocyte-specific Yap1 knockout (Yap1LKO) on hepatic lipid droplets (LD) and pePLIN2 in metabolic fatty liver has not been reported. This study aims to explore whether Yap1LKO could offer a protective effect in a liver injury model.Methods: Three-week-old Yap1LKO and Yap1Flox mice were given aristolochic acid I (AAI) combined carbon tetrachloride (CCL4) establish liver injury model. Eight-week-old Yap1LKO and Yap1Flox mice were fed with a high-fat diet for 18 weeks to establish obesity-related liver injury model. Further biochemical, histomorphological, immunohistochemical, and lipidomic analyses were performed on serum and liver tissues of these mice to elucidate the effects of hepatocyte-specific Yap1 knockout on hepatic lipid metabolism.Results: Yap1LKO reduced triglyceride (TG) content and PLIN2 expression level in the liver during the intervention of AAI combined CCl4. Moreover, Yap1LKO improved lipid metabolism homeostasis in the liver by increasing the beneficial lipid molecules and reducing the harmful lipid molecules through lipidomics. Finally, Yap1LKO reduced TG content in the serum and liver, hepatic vacuolar degeneration, and hepatic PLIN2 expression level in mice fed with a high-fat diet (HFD).Conclusion: Yap1LKO is protective in regulating liver and blood TG when induced with toxic substances AAI combined CCl4 and a high-fat diet.Keywords: yes-associated protein, hepatocyte-specific Yap1 knockout, perilipin-2, lipidomic, triglyceride

Hao Wang,1 Yinbo Xiao,1 Yumeng Cai,1 Yang Zhou,1 Longyun Chen,1 Jianbin Guo,2 Xiaohua Shi,1 Zhiyong Liang1 1Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Zhiyong Liang; Xiaohua Shi, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, Tel +86 10-69159353 ; +86 10-69159365, Email liangzy@pumch.cn; shixiaohua3762@foxmail.comIntroduction: This study used single-center data to analyze the clinicopathological features of site-specific endometrial cancer.Methods: Patients with endometrial carcinoma who had undergone surgery at Peking Union Medical College Hospital, China, between March 2016 and January 2022 were enrolled. Clinical information and pathological characteristics were summarized, and microsatellite status was analyzed using the immunohistochemical method. Patient prognoses were measured in terms of the rates of overall survival and progression-free survival.Results: The mean patient age was 49 years (ranging: from 25 to 76 years old), and there was no difference in clinicopathological features between endometrioid and type II endometrial carcinoma in LUSC. The ER and PR expression ratios were 80.4% and 64.3%, respectively, in this LUSC cohort, and the MMR deficiency ratio was 33.9%, including 39.6% in endometrioid carcinoma and 15.4% in type II endometrial carcinoma. Combined MSH2&MSH6 loss was more common than combined MLH1&PMS2 being unexpressed (16.1% vs 12.5%), and dMMR patients differed significantly from the pMMR group in terms of vascular invasion (P=0.003). The combination of chemotherapy and radiotherapy did not provide a statistically significant improvement in prognosis compared to chemotherapy alone.Conclusion: The results of this study showed that LUSC patients tended to be younger and their tumors had less expression of hormone markers. The biological behavior of both endometrioid cancer and type II EC may be similar when EC occurs in this area. Furthermore, this type of tumor also showed a higher incidence of vascular invasion, and the combination of chemotherapy and radiotherapy did not provide significant improvement. Thus, successful treatment of LUSC tumors requires aggressive surgical intervention and a more effective postoperative treatment approach.Keywords: endometrial cancer, lower uterine segment, prognosis

Xuliang Shi,1,&ast; Miaomiao Hou,1,&ast; Xiaoyan Chen,2 Ya Zhu3 1College of Education, Hebei University, Baoding, Hebei Province, 071002, People’s Republic of China; 2Department of Applied Social Sciences, The Hong Kong Polytechnic University, Hong Kong; 3Center for Mental Health Education and Counseling, Guangdong University of Science and Technology, Dongguan, Guangdong Province, 523083, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuliang Shi, Associate professor at the College of Education, Hebei University, Baoding, 071002, People’s Republic of China, Email shixl163@163.comObjective: This longitudinal study examined the reciprocal relationship between sleep disturbances with non-suicidal self-injury and whether self-compassion mediates these associations.Methods: A total of 5785 freshmen were sampled from a large-scale health-related cohort among Chinese college students at the baseline. This study spanned six waves with a six-month interval between each wave. Data from the last four waves were used because self-compassion or non-suicidal self-injury was not measured in the first two waves. The cross-lagged panel models were used to examine the longitudinal dynamic relationships between sleep disturbances, self-compassion, and non-suicidal self-injury.Results: The results showed that all the auto-regressive paths were significant. For the cross-lagged paths, there was a reciprocal relation between sleep disturbances and self-compassion. Importantly, self-compassion played a longitudinal mediating role in the prediction from sleep disturbances to non-suicidal self-injury (indirect effect = 0.007 to 0.009, all p values < 0.001).Conclusion: Psychological interventions targeting improved sleep quality and self-compassion may hold great promise for reducing the incidence of non-suicidal self-injury.Keywords: sleep disturbances, self-compassion, NSSI, longitudinal design

Lantian Xie,1,&ast; Yan Chen,1,&ast; Lifan Zhang,1– 3 Lidan Zhao,4 Tao Li,5 Xiaochun Shi,1,2 Xiaoqing Liu1– 3 1Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China; 4Department of Rheumatology and Clinical Immunology, Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Psychological Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Email shixch7722@163.com; liuxq@pumch.cnObjective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients.Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI.Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment.Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients′ compliance with LTBI screening and TPT.Keywords: rheumatic diseases, latent tuberculosis infection, tuberculosis preventive treatment, knowledge, attitudes

Yunpeng Cui,1 Qiwei Wang,1 Chuan Mi,1 Bing Wang,1 Yuanxing Pan,1 Yunfei Lin,1 Rui He,2 Liying Sun,3 Bo Zheng,4 Xuedong Shi1 1Department of Orthopaedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Plastic Surgery and Burn, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Clinical Pharmacology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuedong Shi, Department of Orthopedic, Peking University First Hospital, Beijing, People’s Republic of China, Email pku_ortho@163.comBackground: This retrospective cohort study explores a practical approach to acquiring pathogenic microorganisms in patients with bone and joint infections.Methods: From Aug 2018 to Mar 2022, 68 consecutive patients (87 cultures) with bone and joint infection were recruited in this study. All cultures followed the Peking University First Hospital Procedure of Culturing Pathogenic microorganisms for bone and joint infection. Tissue samples were obtained through fluoroscopy-guided biopsy or open debridement. Tissue samples were divided into manual homogenization (MH), manual mixture (MM), and pathological examination. The baseline, antibiotic exposure, laboratory, surgical, and microbial data were reviewed. Independent sample T-test, Mann–Whitney U-test, and Chi-square test were used to detect the difference between patients who received different processing measures.Results: The average age was 55.8± 2.4 years old. Thirty-nine patients were male. The total positive culture rate of the manual homogenization group was 80.5% (70/87). Thirty-five patients had mixed infections with more than one microorganism cultured. Staphylococci accounted for 60.23% of all microorganisms. Staphylococcus aureus (18.2%) and Staphylococcus epidermidis (15.9%) were the two most common bacteria cultured in this study. Patients with positive culture in the manual mixture group had significantly higher WBC (p = 0.006), NE% (p = 0.024), ESR (p = 0.003), CRP (p = 0.020) and IL6 (0.050) compared to patients with negative culture. After tissue homogenization, only ESR is still statistically different. Patients without SIRS had a low positive culture rate (59.4%). Tissue homogenization could significantly increase the positive culture rate of patients without SIRS. Pre-culture antibiotic exposure was not an independent risk factor for culture results.Conclusion: Peking University First Hospital Procedure for Culturing Pathogenic microorganisms for Bone and Joint Infections was a practical approach for obtaining pathogenic microorganisms.Keywords: bone and joint infection, systemic inflammatory response syndrome, antibiotic, tissue homogenization

Sijia Liu,1,2,&ast; Ting Yang,1,2,&ast; Qingsong Jiang,1,2 Liang Zhang,1,2 Xinhui Shi,1,2 Xin Liu,3 Xiaoli Li1,2 1Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, People’s Republic of China; 3Medical Research Center, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoli Li; Xin Liu, Email lixiaoli@cqmu.edu.cn; liux0704@tmmu.edu.cnAbstract: Sepsis is a disorder of the immune response to infection or infectious factors with high morbidity and mortality in clinical settings. The lactylation of lysine residues, fueled by lactate, plays a pivotal role in its pathophysiology. In conducting a literature review on sepsis-related research, we employed a systematic approach to ensure comprehensiveness and accuracy. Initially, we conducted an extensive literature search through the PubMed database, utilizing a range of keywords including “sepsis”, “lactate”, “lactylation”, and “epigenetic modification”. The aim was to capture the most recent research related to the pathophysiological mechanisms of sepsis, metabolic disorders, and the role of lactylation. The results of the literature review revealed a close link between sepsis and metabolic dysfunction, particularly the pivotal role of lactylation in regulating immune responses and inflammatory processes. Lactate, not only an energy metabolic byproduct produced during glycolysis, affects the activity of various proteins, including those involved in immune regulation and cell signaling, through lactylation. In the context of sepsis, changes in the levels of lactylation may be closely associated with the severity and prognosis of the disease. In summary, lactylation, as an emerging type of epigenetic modification, provides a new perspective for the diagnosis and treatment of sepsis. Future research needs to further elucidate the exact mechanisms of lactylation in sepsis and explore its potential as a therapeutic target.Plain Language Summary: The annual incidence and mortality rates associated with sepsis are on the rise, and to date, no medications or therapies have been proven effective in clinical practice. Glycolysis plays a pivotal role in regulating lactylation, a process derived from lactate generated by cellular glucose metabolism. In the context of sepsis, elevated lactate levels are indicative of a poor prognosis. It is imperative to delve into the mechanisms underlying lactylation alterations during sepsis to enhance our comprehension of its complex pathophysiology and to pinpoint innovative therapeutic targets for the condition. Keywords: sepsis, lactate, lactylation, epigenetic modification

Boyong Qiu,1,2,&ast; Siyu Qiao,2,&ast; Xiujuan Shi,2 Lin Shen,2 Bing Deng,2 Zilin Ma,2 Duan Zhou,2 Yihong Wei2 1Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, The First Affiliated Hospital of Henan University of CM, Zhengzhou, Henan, People’s Republic of China; 2Cardiovascular Department, Longhua Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yihong Wei; Duan Zhou, Email weiyihong2022@shutcm.edu.cn; zhouduan@126.comBackground: In China, Shen’ge formula (SGF), a Traditional Chinese Medicine blend crafted from ginseng and gecko, holds a revered place in the treatment of cardiovascular diseases. However, despite its prevalent use, the precise cardioprotective mechanisms of SGF remain largely uncharted. This study aims to fill this gap by delving deeper into SGF’s therapeutic potential and underlying action mechanism, thus giving its traditional use a solid scientific grounding.Methods: In this study, rats were subjected to abdominal aortic constriction (AAC) to generate pressure overload. Following AAC, we administered SGF and bisoprolol intragastrically at specified doses for two distinct durations: 8 and 24 weeks. The cardiac function post-treatment was thoroughly analyzed using echocardiography and histological examinations, offering insights into SGF’s influence on vital cardiovascular metrics, and signaling pathways central to cardiac health.Results: SGF exhibited promising results, significantly enhanced cardiac functions over both 8 and 24-week periods, evidenced by improved ejection fraction and fractional shortening while moderating left ventricular parameters. Noteworthy was SGF’s role in the significant mitigation of myocardial hypertrophy and in fostering the expression of vital proteins essential for heart health by the 24-week mark. This intervention markedly altered the dynamics of the Akt/HIF-1α/p53 pathway, inhibiting detrimental processes while promoting protective mechanisms.Conclusion: Our research casts SGF in a promising light as a cardioprotective agent in heart failure conditions induced by pressure overload in rats. Central to this protective shield is the modulation of the Akt/HIF-1α/p53 pathway, pointing to a therapeutic trajectory that leverages HIF-1α promotion and p53 nuclear transport inhibition. Keywords: Shen’ge formula, heart failure, hypertrophy, apoptosis, angiogenesis

Ying Wang, Shaohua Bi, Xiaoqing Shi, Liying Dai Division of Neonatology, Anhui Provincial Children’s Hospital, Hefei, Anhui, 230051, People’s Republic of ChinaCorrespondence: Liying Dai, Division of Neonatology, Anhui Province Children’s Hospital, No. 39, Wangjiang East Road, Baohe District, Hefei, Anhui, 230051, People’s Republic of China, Email dailiying1101@163.comAbstract: Optical Genome Mapping (OGM) technology has garnered growing interest for the identification of chromosomal structural variations (SVs), particularly complex ones that are implicated in genetic diseases in humans. In this study, we performed genetic diagnostics on a neonatal patient who presented with feeding difficulties, hypotonia, and an atrial septal defect. We utilized a combination of trio-whole exome sequencing and OGM for our analysis. The results revealed an unbalanced translocation between maternal chromosomes 4 and 6 in the proband, ogm[GRch38]t(4:6)(q35.2;q25.3), resulting in a 2.8 Mb deletion at the 4q35 terminal and a 10.2 Mb duplication at the 6q25 terminal. In summary, this study highlights how OGM, in conjunction with other genetic approaches, can unveil the genetic etiology of complex clinical syndromes. Neonatal patients often exhibit low specific phenotypes, underlining the significance of SV detection.Keywords: optical genome mapping, unbalanced translocation, copy number variations, neonatal diseases

Xiangwen Shi,1,2,&ast; Haonan Ni,3,&ast; Linmeng Tang,4,&ast; Mingjun Li,2 Yipeng Wu,2 Yongqing Xu3 1Graduate School, Kunming Medical University, Kunming, People’s Republic of China; 2Laboratory of Yunnan Traumatology and Orthopedics Clinical Medical Center, Yunnan Orthopedics and Sports Rehabilitation Clinical Medical Research Center, Department of Orthopedic Surgery, 920th Hospital of Joint Logistics Support Force of PLA, Kunming, People’s Republic of China; 3First People’s Hospital of Huzhou, the First affiliated Hospital of Huzhou University, Huzhou, People’s Republic of China; 4Department of Radiology, the Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Xu, Department of Orthopedic Surgery, 920th Hospital of Joint Logistics Support Force, 212 Daguan Road, Xi Shan District, Kunming, Yunnan, 650031, People’s Republic of China, Email xuyongqingkm@163.net Yipeng Wu, Department of Orthopedic Surgery, 920th Hospital of Joint Logistics Support Force, 212 Daguan Road, Xi Shan District, Kunming, Yunnan, 650031, People’s Republic of China, Email 20201497@kmmu.edu.cnObjective: Osteomyelitis is a challenging disease in the field of bone infections, with its immune and molecular regulatory mechanisms still poorly understood. The aim of this study is to explore the value and potential mechanisms of cuproptosis-related genes (CRGs) in Staphylococcus aureus (S. aureus)-infected osteomyelitis from an immunological perspective.Methods: Initially, three transcriptomic datasets from public databases were integrated and analyzed, and consistent expression of CRGs in S. aureus-infected osteomyelitis was identified. Subsequently, immune infiltration analysis was performed, and M2 macrophage-related CRGs (M2R-CRGs) were further identified. Their potential molecular mechanisms were evaluated using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA). Finally, distinct osteomyelitis subtypes and diagnostic models based on characteristic M2R-CRGs were constructed.Results: Through correlation analysis with immune cell infiltration, three characteristic M2R-CRGs (SLC31A1, DLD, and MTF1) were identified. Further analysis using unsupervised clustering and immune microenvironment analysis indicated that cluster 1 might activate pro-inflammatory responses, while cluster 2 was shown to exhibit anti-inflammatory effects in osteomyelitis. Compared to Cluster A, Cluster B demonstrated higher levels and a greater diversity of immune cell infiltrations in CRG-related molecular patterns, suggesting a potential anti-inflammatory role in osteomyelitis. A diagnostic model for S. aureus-infected osteomyelitis, based on the three M2R-CRGs, was constructed, exhibiting excellent diagnostic performance and validated with an independent dataset. Significant upregulation in mRNA and protein expression levels of the three M2R-CRGs was observed in rat models of S. aureus-infected osteomyelitis, aligning with bioinformatic results.Conclusion: The M2R-CRGs (SLC31A1, DLD, and MTF1) may be considered characteristic genes for early diagnosis and personalized immune therapy in patients with S. aureus-infected osteomyelitis.Keywords: osteomyelitis, cuproptosis, Staphylococcus aureus, M2 macrophage, immune infiltration, diagnosis

Xin Zheng,&ast; Qiaoqing Zhang,&ast; Weijuan Su, Wei Liu, Caoxin Huang, Xiulin Shi, Xuejun Li Department of Endocrinology and Diabetes, Xiamen Diabetes Institute, Fujian Province Key Laboratory of Translational Research for Diabetes, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiulin Shi; Caoxin Huang, Email shixiulin2002@163.com; cxhuang@xmu.edu.cnPurpose: Nutrient intake for pregnant women with gestational diabetes mellitus (GDM) is important to ensure satisfactory birth outcomes. This study aims to explore the dietary profiles of patients with GDM, compare the results with the Chinese dietary guidelines or Dietary Reference Intakes (DRIs) from China and investigate the relationship between maternal dietary intake and pregnancy outcomes.Patients and Methods: A total of 221 patients with GDM in the second trimester were included in the cohort. Dietary intake data were collected using a 24-hour recall method for three consecutive days. The pregnancy outcomes of these participants were subsequently monitored. Both univariate logistic regression and multivariate logistic regression analyses were conducted to explore the associations between dietary intake variables or general characteristics variables and adverse pregnancy outcomes.Results: Participants with adverse pregnancy outcomes showed a lower intake of iodine and vitamin D, a lower percentage of dietary energy intake from carbohydrates and a higher percentage of dietary energy intake from fats, compared to participants without adverse pregnancy outcomes. The gestational weight gain and family history of diabetes were associated with an increased risk of adverse pregnancy outcomes. Conversely, regular exercise, the intake of iodine and Vitamin D, and the percentage of dietary energy intake from carbohydrates were associated with a decreased risk.Conclusion: The daily diet of pregnant women with GDM in China did not meet the dietary guidelines or DRIs. The low intake of Vitamin D and iodine, the low dietary carbohydrate ratio, family history of diabetes, lack of exercise, and high gestational weight gain were associated with increased risk of adverse pregnancy outcomes in pregnant women with GDM.Keywords: gestational diabetes, nutrient intake, dietary reference intakes, pregnancy outcomes, adverse pregnancy outcome

Qinzheng Chen,1 Zhen He,1 Yaxin Wang,2 Xuanjin Yang,2 Nana Liu,2 Suhan Zhang,2 Liangkun Ma,2 Xuezhong Shi,1 Xiaocan Jia,1 Yongli Yang,1 Yin Sun,2 Yuan He3 1Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, People’s Republic of China; 3National Human Genetic Resources Center, National Research Institute for Family Planning, Beijing, People’s Republic of ChinaCorrespondence: Yin Sun, Department of Obstetrics and Gynecology, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences (CAMS) and PUMC, Beijing, 100730, People’s Republic of China, Email yinsun_pumch@163.com Yongli Yang, Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China, Email ylyang377@zzu.edu.cnPurpose: To assess the impact of maternal pre-pregnancy body mass index (BMI) on longitudinal fetal growth, and the potential mediation effect of the maternal fasting plasma glucose in first trimester.Methods: In this retrospective cohort study, we collected pre-pregnancy BMI data and ultrasound measurements during pregnancy of 3879 singleton pregnant women who underwent antenatal examinations and delivered at Peking Union Medical College Hospital. Generalized estimation equations, linear regression, and logistic regression were used to examine the association between pre-pregnancy BMI with fetal growth and adverse neonatal outcomes. Mediation analyses were also used to examine the mediating role of maternal fasting plasma glucose (FPG) in first trimester.Results: A per 1 Kg/m² increase in pre-pregnancy BMI was associated with increase fetal body length Z-score (β 0.010, 95% CI 0.001, 0.019) and fetal body weight (β 0.017, 95% CI 0.008, 0.027). In mid pregnancy, pre-pregnancy BMI also correlated with an increase Z-score of fetal abdominal circumference, femur length (FL). Pre-pregnancy BMI was associated with an increased risk of large for gestational age and macrosomia. Mediation analysis indicated that the associations between pre-pregnancy BMI and fetal weight in mid and late pregnancy, and at birth were partially mediated by maternal FPG in first trimester (mediation proportion: 5.0%, 8.3%, 1.6%, respectively).Conclusion: Maternal pre-pregnancy BMI was associated with the longitudinal fetal growth, and the association was partly driven by maternal FPG in first trimester. The study emphasized the importance of identifying and managing mothers with higher pre-pregnancy BMI to prevent fetal overgrowth.Keywords: body mass index, fetal growth, adverse neonatal outcomes, fasting plasma glucose, mediation analysis, cohort study

Qiumiao Chen,1 Bin Qin,2 Manqing Zhang,2 Yumei Zhou,2 Xiaotong Shi,2 Yubo Xie1,3 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, College of Stomatology, Hospital of Stomatology, Guangxi Medical University, Nanning, People’s Republic of China; 3Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Yubo Xie; Xiaotong Shi, Email xybdoctor@163.com; Hbb38@163.comBackground: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB).Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 μg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events.Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05).Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.Keywords: remimazolam, dexmedetomidine, difficult airways, awake tracheal intubation

Ailin Zhao, Li Zhang, Xiaomei Shi Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 250001, People’s Republic of ChinaCorrespondence: Xiaomei Shi, Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324 of Jing Wu Road, HuaiYin District, Jinan, Shandong Province, 250001, People’s Republic of China, Tel +86 15552519354, Email shixm11xm@163.comObjective: To investigate the current nursing practice environment in Jinan, Shandong Province, and to identify the factors influencing the practice environment.Methods: This study is a cross-sectional study for nurses. From October to December 2022, using the clustering and stratified sampling methods, 2426 nurses from internal Medicine, Surgery, Obstetrics and Gynecology, Outpatient Department and Intensive Care Department of the Provincial Hospital of Shandong Medical University were selected and then investigated and analyzed using the revised Nurse Practice Environment Assessment Scale.Results: The overall mean evaluation of the practice environment scored 75.13± 19.87, with a minimum value of 59.74 and a maximum value of 95.82. The items with higher scores were “the hospital has systematic training for new nurses”, “the work system is perfect”, and “the hospital can provide continuing education for nurses in accordance with the needs of their positions”. The items with lower scores were “nurses enjoy legal benefits”, “nurses have the opportunity to participate in hospital management decisions”, and “nurses have the opportunity to participate in hospital internal management”. The results of the multiple linear regression analysis of the factors influencing nurses’ practice environment showed that gender, education, position, and years of work were independent influences on nurses’ practice environment scores (p < 0.05), and they explained 48.127% of the variation in the total scores of the nurses’ practice environment scale. The estimated values (β) of sex, education, cheif nurse, nurses staff, work experience (year), and whether the only child variables were 3.141, 3.237, 2.713, 5.471, 2.074 and 0.732, respectively.Conclusion: The nurse practice environment still needs to be improved, mainly in terms of hospital management participation, human resource allocation and salary distribution system.Keywords: nurse, practice environment, cross-sectional survey, factor

Ye Liu,1,&ast; Lifan Zhang,1– 4,&ast; Yan Chen,1,&ast; Guiren Ruan,1– 3 Yuchen Liu,1 Shi Chen,1 Lantian Xie,1 Fengying Wu,1 Xiaochun Shi,1– 3 Xiaoqing Liu1– 4 1Division of Infectious Diseases, Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 3Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Clinical Epidemiology Unit, Peking Union Medical College, International Clinical Epidemiology Network, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaochun Shi; Xiaoqing Liu, Division of Infectious Diseases, Department of Internal Medicine, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shuaifuyuan No. 1, Beijing, 100005, People’s Republic of China, Email shixch7722@163.com; liuxq@pumch.cnBackground: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB.Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis.Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61– 93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584– 644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430– 1570], and the incidence density was 240 per 100,000 person-years[95% CI:144– 375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273– 49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122– 7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 − 33.070), anemia (aHR=2.565, 95% CI:1.015– 6.479) and T-SPOT.TB level≥ 300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365– 12.892) were independent risk factors for ATB development in LTBI patients.Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥ 300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.Keywords: latent tuberculosis infection, active tuberculosis, incidence, risk factors

Yaxin Wei,1 Min Zhu,2 Yan Man,1 Hongyi Xiao,3 Guimin Dong,3 Xinyuan Shi,1 Fanceng Ji3 1School of Anesthesiology, Weifang Medical University, Weifang, 261053, People’s Republic of China; 2Department of Gynecology, Weifang People’s Hospital, Weifang, 261041, People’s Republic of China; 3Department of Anesthesiology, Weifang People’s Hospital, Weifang, 261041, People’s Republic of ChinaCorrespondence: Fanceng JiDepartment of Anesthesiology, Weifang People’s Hospital, No. 151 Guangwen Street, Kuiwen District, Weifang, 261041, People’s Republic of China, Tel +86-13563698838, Email jifanceng@163.comPurpose: To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery.Patients and Methods: 141 cases of gynaecological daycase surgery patients in Weifang People’s Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded.Results: The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05).Conclusion: Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.Keywords: flumazenil, remimazolam, gynecologic day surgery, postoperative PONV

Jun Feng, Liya Zhang, Jihong Tang, Bingbing Zhang, Xiao Xiao, Xiaoyan Shi Department of Neurology, Children’s Hospital of Soochow University, Suzhou, Jiangsu, 215025, People’s Republic of ChinaCorrespondence: Liya Zhang; Jihong Tang, Email zhliyasz@163.com; tjhsuzhou@163.comObjective: To evaluate the efficacy and safety of lacosamide (LCM) monotherapy in the treatment of self-limited epilepsy with centrotemporal spikes (SeLECTS).Methods: In this study, 89 children with SeLECTS who were treated with LCM monotherapy in the Children’s Hospital Affiliated to Soochow University from June 2019 to June 2021 were included. Clinical seizures and spike wave index (SWI) on video EEG during slow-wave sleep were evaluated before and after treatment. The role of LCM monotherapy in improving SWI, controlling clinical seizures and improving cognition was analyzed, and corresponding adverse reactions were documented.Results: There were 52 males and 37 females in this group, with an average age of 7.6 ± 2.1 years. The total effective rate was 93.83% and at 18 months of treatment, the cumulative control rate was 85.19%, the retention rate was 91.01% and the effective rate in terms of EEG spike index was 72.92%, all of which showed a high rate; there was no statistically significant difference in intelligence quotient before and after treatment (P > 0.05). In addition, it was found in the study that the earlier the age of onset, the less obvious the improvement in SWI after LCM treatment; the lower the baseline seizure frequency, the more significant the improvement in SWI after LCM treatment.Conclusion: LCM monotherapy had curative effect and adverse reactions for SeLECTS, with no negative impact on cognition. These significant findings indicate that LCM is likely to become a widely prescribed ASM for the treatment of SeLECTS. Meanwhile, the onset age and baseline seizure frequency had certain value in judging prognosis and predicting curative effect.Keywords: lacosamide, epilepsy, self-limited epilepsy with centrotemporal spikes, efficacy, safety

Gengyao Hu,1,&ast; Yuanhang Pan,1,&ast; Na Yuan,1,&ast; Zhixian Yang,2 Xiuyu Shi,3 Sha Ma,4 Shan Li,4 Xiaohua Hou,5 Fei Liu,5 Dongmei Li,6 Junxiang Bao,7 Yonghong Liu1 1Department of Neurology, Xijing Hospital, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China; 2Department of Pediatrics, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Pediatrics, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 4Department of Neurology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 6Department of Dentistry for Special Services, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China; 7Department of Aerospace Hygiene, Fourth Military Medical University (Air Force Medical University), Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Liu, Email liuyhong@fmmu.edu.cnBackground: Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the electroclinical manner, therapeutic regimen, and prognosis of SRFMM.Methods: Twenty-three patients who were diagnosed with SRFMM by clinical manifestation, video-electroencephalography (EEG) and electromyography over bilateral masseter and temporalis muscles were enrolled. Clinical and electrophysiological evaluation as well as follow-up information were recorded and analyzed.Results: The cohort involved 4 infants and 19 adults with a mean onset age of 43.5 years for SRFMM, among whom 19 were male. Twenty-one patients complained of tongue injuries and disturbed night-time sleep. SRFMM in 4 patients were ascribed to oral aripiprazole, brainstem ischemia and brain trauma. In 62 SRFMM episodes, 93.5% occurred in NREM sleep and 6.5% in REM sleep, and all events were associated with EEG arousals. In 13 patients with or without clonazepam, the motor events gradually disappeared, and the rest turned to be sporadic.Conclusion: SRFMM is a characteristic parasomnia manifested by tongue biting and accompanying facial mandibular myoclonus, leading to disrupted sleep. Besides adults, infants can also experience SRFMM with spontaneous remission. Most patients respond well to clonazepam, eventually with favorable prognosis.Keywords: sleep-related facial mandibular myoclonus, tongue biting, movement disorder, SRFMM

Kui Zhang,1,&ast; Yan Liu,2,&ast; Zhenrui Zhao,1 Xuewen Shi,1 Ruihao Zhang,1 Yixiang He,1 Huaibin Zhang,1 Wenji Wang3 1The First Clinical Medical College of Lanzhou University, Lanzhou, People’s Republic of China; 2Department of Gynecology, First Affiliated Hospital of Xi ‘an Medical College, Xi’ an, People’s Republic of China; 3Department of Orthopedics, the First Hospital of Lanzhou University, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenji Wang, The First Hospital of Lanzhou University, Lanzhou, 730000, People’s Republic of China, Tel +8613893221698, Email ldyyjzwwj@outlook.comBackground: Polyvinyl alcohol/Chitosan hydrogel is often employed as a carrier because it is non-toxic, biodegradable, and has a three-dimensional network structure. Meanwhile, Magnesium-doped nano-hydroxyapatite(Mg-nHA) demonstrated high characterization to promote the osteogenic differentiation of bone marrow derived mesenchymal stem cell(BMSCs). Therefore, in order to develop a porous hydrogel scaffold for the application of bone tissue engineering, an appropriate-type Mg-nHA hydrogel scaffold was developed and evaluated.Methods: A composite hydrogel containing magnesium-doped nano-hydroxyapatite (Mg-nHA/PVA/CS) was developed using a magnetic stirring-ion exchange method and cyclic freeze-thaw method design, with polyvinyl alcohol and chitosan as the main components. Fourier transform infrared spectra (FTIR), electron energy dispersive spectroscopy (EDS), X-ray photoelectron spectrometer (XPS) and scanning electron microscopy (SEM) were employed to analyze the chemical structure, porosity, and elemental composition of each hydrogels. The equilibrium swelling degree, moisture content, pH change, potential for biomineralization, biocompatibility, the osteogenic potential and magnesium ion release rate of the composite hydrogel were also evaluated.Results: SEM analysis revealed a well-defined 3D spatial structure of micropores in the synthesised hydrogel. FTIR analysis showed that doping nanoparticles had little effect on the hydrogel’s structure and both the 5% Mg-nHA/PVA/CS and 10% Mg-nHA/PVA/CS groups promoted amide bond formation. EDS observation indicated that the new material exhibited favourable biomineralization ability, with optimal performance seen in the 5% Mg-nHA/PVA/CS group. The composite hydrogel not only displayed favourable water content, enhanced biocompatibility, and porosity (similar to human cancellous bone), but also maintained an equilibrium swelling degree and released magnesium ions that created an alkaline environment around it. Additionally, it facilitated the proliferation of bone marrow mesenchymal stem cells and their osteogenic differentiation.Conclusion: The Mg-nHA/PVA/CS hydrogel demonstrates significant potential for application in the field of bone repair, making it an excellent composite material for bone tissue engineering. Keywords: magnesium-doped nano-hydroxyapatite, polyvinyl alcohol, chitosan, hydrogel, physical crosslinking

Xiaoyi Shi, Yifang Sun, Xiaolan Ding Department of Dermatology, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiaolan Ding, Department of Dermatology, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +8613522658992, Fax +861088325474, Email Lancyding@126.comBackground: Coronavirus disease 2019 (COVID-19) has given rise to several new onset or exacerbated dermatologic disorders including vitiligo. However, the relationship between COVID-19 infection or its associated vaccines and vitiligo progression is unclear.Aim: We investigate the impact of COVID-19 infection and its associated vaccines on vitiligo progression.Methods: A cross-sectional study was performed among patients who visited Department of Dermatology, Peking University People’s Hospital between 2022.1 and 2023.6. Detailed information including demographic characteristics, vitiligo clinical features, information on COVID-19 infection and vaccination and disease progression was collected by an electronic questionnaire.Results: Overall, 314 patients with vitiligo completed the questionnaire. 47.5% were males, with an average age of 25.5± 15.9 years. 266 (84.7%) patients had received COVID-19 vaccination, and 70.3% of the patients reported progression of vitiligo after vaccination, mostly within 3 months. 55.6% of the patients had disease progression after the second dose of vaccine. 270 patients experienced COVID-19 infection, and 30.7% of these patients had progression of vitiligo after infection, most of the progression occurred within 1– 2 months. 184 patients (68.2%) interrupted treatment. Analysis results indicated patients in active stage had a higher risk for vitiligo progression after COVID-19 infection and vaccination.Keywords: COVID-19, infection, vaccination, vitiligo, disease progression

Yifan Yang,1,&ast; Huayu Yang,1,&ast; Zongli Diao,2 Xu Liu,2 Lan Yao,1 Liyan Wang,2 Xiaotian Shi,1 Xu Li,1 Qing Ma1 1Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Nephrology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Ma, Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, 95, Yong-an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +86 10 63137641, Fax +86 10 63138730, Email maqing3@163.comPurpose: Frailty is an important geriatric syndrome associated with aging and adverse events, especially in patients with severe infection. To help guide prognosis for elderly patients undergoing maintenance hemodialysis (MHD) who experience acute infection, this study investigated whether baseline (pre-infection) frailty may be associated with adverse outcomes in elderly patients undergoing MHD who suffer SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection.Patients and Methods: Patients (aged ≥ 60 y) receiving MHD had been assessed for overall frailty and the 5 frailty components based on the Fried Frailty Phenotype scale within 3 months prior to SARS-CoV-2 infection.Results: There were 59 and 98 patients in the frail and non-frail groups, respectively. Three months after SARS-CoV-2 infection, 21 (13.4%) and 45 (28.7%) patients had died or were in hospital. The multivariate COX proportional risk model suggested that the all-cause mortality rate in patients judged overall frail or with low activity was significantly higher compared with that of the non-frail (P = 0.049; 0.003). The multivariate logistic regression analysis showed that hospitalization 3 months after SARS-CoV-2 infection was associated with both overall frailty and low activity (OR 2.276, 95% CI: 1.034– 5.010, P = 0.041; OR 2.809, 95% CI: 1.311– 6.020, P = 0.008, respectively).Conclusion: Overall frailty and specifically low activity were significantly associated with all-cause mortality and hospitalization in this elderly MHD population after SARS-CoV-2 infection. Early assessment of frailty and effective interventions are recommended to improve the prognosis of patients receiving MHD who are at higher risk of acute infection.Keywords: SARS-CoV-2, COVID-19, hemodialysis, frailty, elderly, prognosis

Qiaona Jiang,1,&ast; Xiaofei Zhang,1,&ast; Xiaohui Lu,2 Yanzhe Li,3 Chenghao Lu,1 Jinghui Chi,1 Yanyan Ma,1 Xiaomei Shi,1 Lili Wang,1 Shen Li3 1Department of Psychiatry, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Psychiatry, Qingdao Mental Health Center, Qingdao, People’s Republic of China; 3Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Wang, Department of Psychiatry, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +00-86-022-88188796, Email tjadyywll@163.com Shen Li, Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, No. 13, Liulin Road, Hexi District, Tianjin, 300222, People’s Republic of China, Tel +00-86-022-88188875, Email lishen@tmu.edu.cnObjective: Tardive dyskinesia (TD) is a severe rhythmic movement disorder caused by long-term antipsychotic medication in chronic patients with schizophrenia (SCZ). We aimed to investigate the association between polymorphisms in oxidative stress-related genes (GSTM1, SOD2, NOS1, and NOS3) and adenosine receptor gene (ADORA2A), as well as their interactions, with the occurrence and severity of TD, and cognitive impairments in a Chinese Han population of SCZ patients.Methods: Two hundred and sixteen SCZ patients were recruited and divided into TD group (n=157) and non-TD group (n=59). DNA extraction was performed by a high-salt method, followed by SNP genotyping using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The severity of TD, psychopathology and cognitive functioning were assessed using the Abnormal Involuntary Movement Scale (AIMS), the Positive and Negative Syndrome Scale (PANSS) and the Repeated Battery for Assessment of Neuropsychological Status (RBANS), respectively.Results: The combination of GSTM1-rs738491, NOS1-rs738409 and ADORA2A-rs229883 was identified as the best three-point model to predict TD occurrence (p=0.01). Additionally, GSTM-rs738491 CC or NOS3-rs1800779 AG genotypes may be protective factors for psychiatric symptoms in TD patients. TD patients carrying the NOS1-rs738409 AG or ADORA2A-rs229883 TT genotypes exhibited poorer cognitive performance.Conclusion: Our findings suggest that the interaction of oxidative stress-related genes and adenosine receptor gene may play a role in the susceptibility and severity of TD in Chinese Han SCZ patient. Furthermore, these genes may also affect the psychiatric symptoms and cognitive function of TD patients.Keywords: tardive dyskinesia, schizophrenia, oxidative stress, adenosine receptor, polymorphisms, cognitive impairments

Jie Huang,1,&ast; Wenqiang Zhu,1,&ast; Qiangzhi Duan,2,&ast; Chaomang Zhu,1 Xueling Shi,1 Hongyu Zhao,1 Peng Cai,1 Duojie Li1 1Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 2Department of Radiotherapy, The 2nd Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Duojie Li, Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China, Tel/Fax +86-139-5633-2626, Email liduojie@163.comPurpose: To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM).Patients and Methods: This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥ 3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR).Results: The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B.Conclusion: For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.Keywords: breast cancer, human epidermal growth factor receptor type 2, brain metastasis, pyrotinib, radiation therapy, hyperfractionated radiotherapy

Zhiguang Fan,1 Xiaoli Shi,2 Chunjie Hu,3 Liya Zhu,4 Zhe Wang5 1Department of Psychology, Shaoxing University, Zhejiang, 312000, People’s Republic of China; 2School of Education, Jilin International Studies University, Changchun, 130000, People’s Republic of China; 3The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of China; 4School of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of China; 5School of Pharmacology, Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of ChinaCorrespondence: Zhe Wang, Email megaton0514@gmail.comBackground: Individuals who initiate the concealment of their adverse or distressing thoughts from others can trigger off negative psychological experiences and social isolation, and lead to poorer health. Therefore, this study aimed to analyze the psychometric properties of the Self-Concealment Scale (SCS) in Chinese older adults.Methods: A questionnaire was administered to 1085 elderly people using convenience sampling and snowball sampling. Scales used included the SCS, Distress Disclosure Index (DDI), Revised Cheek and Buss Shyness Scale (RCBS), Social Interaction Anxiety Scale (SIAS), Social Phobia Scale (SPS), UCLA Loneliness Scale (ULS-8), and Kessler Psychological Distress Scale (K10).Results: The SCS consisted of 10 items with a one-dimensional structure, explaining 55.66% of the variance. The factor loading values for each item ranged from 0.68 to 0.75, and the covariance ranged from 0.46 to 0.57. Confirmatory factor analysis showed good model fit (χ 2/df=2.829, RMSEA=0.057, CFI=0.981, IFI=0.981, TLI=0.974, PNFI=0.712, PGFI=0.719). The criterion-related validity test found that the SCS was significantly and positively correlated with the RCBS, SIAS, SPS, ULS-8, K10, depression, and anxiety; and the SCS was significantly and negatively correlated with the DDI. The Cronbach’s α coefficient value for the scale was 0.923; the split-half reliability coefficient value was 0.923. In addition, the SCS had cross-gender consistency.Conclusion: The SCS has good reliability and validity in older adults and can be used as a valid tool to assess self-concealment among older people.Keywords: older adult, self-concealment, reliability, validity

Yi Zhou,1 Biao Hua,2 Xiaoyang Shi,1 Shaoying Du,1 Jing Yuan,1 Yan Wang1 1School of Nursing, Hebei University, Baoding, Hebei, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Hebei University, Baoding, Hebei, People’s Republic of ChinaCorrespondence: Yan Wang, School of Nursing, Hebei University, No. 342 Yuhuadong Road, Lianchi District, Baoding, Hebei, 071000, People’s Republic of China, Tel/Fax +86 3125075605, Email chjanwy@163.com Biao Hua, Department of Neurology, Affiliated Hospital of Hebei University, No. 212 Yuhuadong Road, Lianchi District, Baoding, Hebei, 071000, People’s Republic of China, Email huabiao19890120@163.comPurpose: To investigate the level of exercise intention and its associated factors among persons post-stroke using the Theory of Planned Behavior.Patients and Methods: In this cross-sectional study, a total of 333 participants admitted to the neurology units of a tertiary care hospital in China with a confirmed diagnosis of stroke were recruited. A self-administered instrument based on the Theory of Planned Behavior was used to determine the exercise intention and its associated factors among persons post-stroke.Results: The results revealed that only 128 participants had exercise intention after discharge with a prevalence of 38.4%. Multivariable linear regression analysis revealed that monthly income, living situation, subjective norms, attitude, and perceived behavioral control were significant predictors of exercise intention of persons post-stroke. Perceived behavioral control and living situation were the most relevant factors of exercise intention.Conclusion: The level of exercise intention among persons post-stroke was found to be low. Perceived behavioral control and living situation were particularly important and contributed to exercise intention. Healthcare professionals’ adequate guidance on exercise should be provided, with a focus on educating both patients and their family members, especially spouses, to promote exercise intention in persons post-stroke.Keywords: exercise intention, stroke, exercise adherence, Theory of Planned Behavior

Jianv Wang,1,&ast; Hongye Liao,1,&ast; Jieming Ban,2 Sen Li,2 Xia Xiong,1 Qingqing He,1 Xinyu Shi,2 Hongping Shen,2 Sijin Yang,2 Changzhen Sun,2 Li Liu1 1Department of Dermatology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China; 2Drug Research Center of Integrated Traditional Chinese and Western Medicine, National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changzhen Sun, Drug Research Center of Integrated Traditional Chinese and Western Medicine, National Traditional Chinese Medicine Clinical Research Base, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel/Fax +86-136-9949-2406, Email sunchangzhen@swmu.edu.cn Li Liu, Department of Dermatology, the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel/Fax +86-193-3860-9127, Email liuli@swmu.edu.cnBackground: Near-infrared cyanine dyes have high sensitivity and spatial resolution imaging capabilities, but they also have unavoidable drawbacks such as photobleaching, low water solubility, fluorescence quenching, and toxic side effects. As an effective biologic drug carrier, albumin combines with cyanine dyes to form albumin@dye nanoparticles. These nanoparticles can alleviate the aforementioned issues and are widely used in tumor imaging and photothermal therapy.Methods: Herein, a newly synthesized near-infrared dye IR-817 was combined with bovine serum albumin (BSA) to create BSA@IR-817 nanoparticles. Through the detection of fluorescence emission and absorption, the optimal concentration and ratio of BSA and IR-817 were determined. Subsequently, dynamic light scattering (DLS) measurements and scanning electron microscopy (SEM) were used for the physical characterization of the BSA@IR-817 nanoparticles. Finally, in vitro and in vivo experiments were conducted to assess the fluorescence imaging and photothermal therapeutic potential of BSA@IR-817 nanoparticles.Results: IR-817 was adsorbed onto the BSA carrier by covalent conjugation and supramolecular encapsulation, resulting in the formation of dispersed, homogeneous, and stable nanoparticles with a particle size range of 120– 220 nm. BSA@IR-817 not only improved the poor water solubility, fluorescence quenching, and toxic side effects of IR-817 but also enhanced the absorption and fluorescence emission peaks in the near-infrared region, as well as the fluorescence in the visible spectrum. In addition, BSA@IR-817 combined with laser 808 irradiation was able to convert light energy into heat energy with temperatures exceeding 50 °C. By creating a mouse model of subcutaneous melanoma, it was discovered that the tumor inhibition rate of BSA@IR-817 was greater than 99% after laser irradiation and that it achieved nearly complete tumor ablation without causing significant toxicity.Conclusion: Our research, therefore, proposes the use of safe and effective photothermal nanoparticles for the imaging, diagnosis, and treatment of melanoma, and offers a promising strategy for future biomedical applications.Keywords: albumin, cyanine dyes, near-infrared imaging, photothermal therapy, melanoma

Lu Han,1,2,&ast; Yaping Zhang,2– 4,&ast; Li Li,2,&ast; Qun Zhang,2 Zhihao Liu,2,3 Haiqing Niu,1,2 Jing Hu,2 Zhou Ding,2 Xiao Shi,2 Xiaoping Qian1,2 1Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, People’s Republic of China; 4Department of Pathology, The First People’s Hospital of Yangzhou, Yangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Qian, Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-13951743162, Fax +86-25-68182342, Email xiaopingqian@nju.edu.cnPurpose: Exploring the expression and prognosis of mismatch repair proteins and PD-L1 in colorectal cancer.Patients and Methods: A total of 272 patients with surgically resected CRC were enrolled in the study from January 2018 to May 2022 at Nanjing Drum Tower Hospital (The Affiliated Hospital of Nanjing University Medical School). Surgically resected samples were collected from patients along with general, clinicopathological, and imaging data for each patient. Immunohistochemistry (IHC) was used to detect expression of MSH2, MSH6, MLH1, and PMS2 proteins in tumor tissue. X-squared (X2) testing was performed to investigate the correlation between expression of MMR proteins and PD-L1 in CRC tumor tissues and clinicopathological characteristics. Correlation analysis was also used to compare the deletion of four MMR proteins in CRC tumor tissues. A survival curve and Log rank test were used to investigate the relationship between the expression of MMR proteins and PD-L1 with regard to CRC patient prognosis and survival.Results: MMR protein expression deletion was correlated with tumor location, the degree of tissue differentiation, and TNM stage (P< 0.05). PD-L1 expression was correlated with TNM stage (P

Jihai Chen,1,2 Lijun Wei,2 Xiaoxia Zhu,2 Wenli Xu,2 Yuxin Zou,2 Xinyu Qi,2 Jia Fang,2 Xiaodong Wang,2 Xiaolan Shi,1 Yunlu Sheng,2 Guoxian Ding,2 Xiaojun Ouyang,1 Yu Duan2 1Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Nanjing, 210024, People’s Republic of China; 2Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Yu Duan, Department of Geriatric Endocrinology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email duanyujsph@163.com Xiaojun Ouyang, Department of Geriatric, Geriatric Hospital of Nanjing Medical University, Luojia Road 30, Nanjing, 210024, People’s Republic of China, Email xiaojun_ouyang@aliyun.comBackground and Aims: Sarcopenia is a common disease in the elderly, and the thyroid hormone (TH) might participate in the pathogenesis of sarcopenia. However, the results of previous studies were not completely consistent. We performed this study to investigate the association between THs and sarcopenia in a Chinese elderly euthyroid population.Subjects and Methods: A total of 309 Chinese elderly euthyroid subjects with an average age of 85.19 ± 7.8 years were enrolled. Participants were divided into four groups (non-sarcopenia, possible sarcopenia, sarcopenia and serve sarcopenia) according to the consensus update of AWGS in 2019. Serum levels of TT3, FT3, TT4, FT4, TSH, rT3 and TBG were measured. Muscle mass was measured by multifrequency bioelectrical impedance analysis, hand grip (HG) was represented by spring-type dynamometer, and gait speed (GS) was determined by 6-metre walk test. The FRAIL scale was used to assess frailty.Results: Compared to the non-sarcopenia group, the sarcopenia group showed a significant increase in age and FRIAL score, while FT3 and TT3 levels decreased significantly. Partial correlation analysis (adjusted by age, gender and the scores of FRIAL scale) indicated that FT3, TT3 and TSH had significant positive correlations with HG, and there also was a significant positive correlation between TT3 and GS. In addition, after adjusting for age, gender, BMI, ALT, sCr, and score on the FRAIL scale, the multivariate linear regression analysis showed that TT3 was positively associated with muscle strength and negatively associated with sarcopenia risk.Conclusion: There is an association between the low TT3 level and sarcopenia. Therefore, maintaining higher T3 concentrations within the normal range appears to be beneficial for sarcopenia in the elderly. In addition, due to the fluctuation of FT3, TT3 is a more stable and practical indicator to evaluate the relationship between sarcopenia and thyroid hormone in the elderly euthyroid population.Graphical Abstract: Keywords: sarcopenia, thyroid hormone, elderly, muscle strength

Kang Zou,1,2,&ast; Shu Huang,3,4,&ast; Wensen Ren,1,2,&ast; Huan Xu,1,2 Wei Zhang,1,2 Xiaomin Shi,1,2 Lei Shi,1,2 Xiaolin Zhong,1,2 Yan Peng,1,2 Muhan Lü,1,2 Xiaowei Tang1,2 1Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, People’s Republic of China; 3Department of Gastroenterology, Lianshui County People’ Hospital, Huaian, People’s Republic of China; 4Department of Gastroenterology, Lianshui People’ Hospital of Kangda College Affiliated to Nanjing Medical University, Huaian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaowei Tang; Muhan Lü, Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Street Taiping No. 25, Region Jiangyang, Luzhou, Sichuan Province, 646099, People’s Republic of China, Tel +86 8303165200, Fax +86 83061641541, Email solitude5834@hotmail.com; lvmuhan@swmu.edu.cnPurpose: The aim of this study is to develop and validate a predictive model for the prediction of in-hospital mortality in patients with acute pancreatitis (AP) based on the intensive care database.Patients and Methods: We analyzed the data of patients with AP in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and Electronic Intensive Care Unit Collaborative Research Database (eICU-CRD). Then, patients from MIMIC-IV were divided into a development group and a validation group according to the ratio of 8:2, and eICU-CRD was assigned as an external validation group. Univariate logistic regression and least absolute shrinkage and selection operator regression were used for screening the best predictors, and multivariate logistic regression was used to establish a dynamic nomogram. We evaluated the discrimination, calibration, and clinical efficacy of the nomogram, and compared the performance of the nomogram with Acute Physiology and Chronic Health Evaluation II (APACHE-II) score and Bedside Index of Severity in AP (BISAP) score.Results: A total of 1030 and 514 patients with AP in MIMIC-IV database and eICU-CRD were included in the study. After stepwise analysis, 8 out of a total of 37 variables were selected to construct the nomogram. The dynamic nomogram can be obtained by visiting https://model.sci-inn.com/KangZou/. The area under receiver operating characteristic curve (AUC) of the nomogram was 0.859, 0.871, and 0.847 in the development, internal, and external validation set respectively. The nomogram had a similar performance with APACHE-II (AUC = 0.841, p = 0.537) but performed better than BISAP (AUC = 0.690, p = 0.001) score in the validation group. Moreover, the calibration curve presented a satisfactory predictive accuracy, and the decision curve analysis suggested great clinical application value of the nomogram.Conclusion: Based on the results of internal and external validation, the nomogram showed favorable discrimination, calibration, and clinical practicability in predicting the in-hospital mortality of patients with AP.Keywords: acute pancreatitis, medical information mart for intensive care-IV, MIMIC-IV, electronic intensive care unit collaborative research database, eICU-CRD, dynamic nomogram

Xiaotian Shi, Shan Wang, Jieqiong Hu, Fei Chen, Heng Zhang, Yifan Yang, Xv Li, Qing Ma Department of Geriatrics, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Qing Ma, Email maqing3@163.comObjective: Determine the relationship of renal function with frailty using different formulas for estimated glomerular filtration rate (eGFR).Methods: Individuals who were 60-years-old or more (n=507) were recruited from August 2020 to June 2021, and the FRAIL scale was used to classify them as non-frail or frail. The three equations used to compute the eGFR were based on serum creatinine (eGFRcr), cystatin C (eGFRcys), or SCr+CysC (eGFRcr-cys). Renal function was classified using eGFR and defined as normal (≥ 90 mL/min/1.73m2), mild damage (59– 89 mL/min/1.73m2), or moderate damage (≤ 60 mL/min/1.73m2). The relationship of frailty with renal function was analyzed. A subset of participants (n=358) was used to analyze changes in eGFR from 1 January 2012 to 31 December 2021 according to frailty and using the different eGFR equations.Results: There were significant differences between the eGFRcr-cys and eGFRcr values in the frail group (P< 0.05), but not the non-frail group; however, the differences between the eGFRcr-cys and eGFRcys values were significant in the frail and non-frail groups (P< 0.001). Based on each eGFR equation, the prevalence of frailty increased as eGFR decreased (P< 0.001), but there was no significant relationship after adjusting for age or the age-adjusted Charlson co-morbidity index. There were temporal declines in eGFR in all three frailty groups (robust, pre-frail, and frail), especially in the frail group (2.226 mL/min/1.73m2 per year; P< 0.001).Conclusion: For older individuals who are frail, the eGFRcr value may not provide accurate estimates of renal function. Frailty is associated with a rapid decline in kidney function.Keywords: elderly, frailty, kidney function, serum creatinine, cystatin C

Xuesong Wang,1,&ast; Guang Zuo,1,&ast; Jun Liu,1,2 Juncha Zhang,1,2 Xuliang Shi,1,2 Xisheng Fan,1,2 Xuxin Li,1 Yuanbo Gao,1 Hao Chen,1 Cun-Zhi Liu,3 Yanfen She1,2 1School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei International Joint Research Center for Dominant Diseases in Chinese Medicine and Acupuncture, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Liu; Yanfen She, School of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, No. 3 Xingyuan Road, Luquan Districtt, Shijiazhuang City, Hebei Province, 050200, People’s Republic of China, Email 822053583@qq.com; sheyanfen@163.comObjective: Dysmenorrhea is a common clinical condition and some studies shown that the skin temperature of some acupoints changes in primary dysmenorrhea (PD) patients. This study aimed to evaluate the changes in skin temperature at specific acupoints in PD patients and healthy subjects.Methods: The literature for assessing skin temperature at acupoints in PD patients and healthy subjects was searched in eight databases. The literatures obtained from the search was independently screened by two authors, and the quality of the included articles was evaluated using the consensus checklist of the Thermographic Imaging in Sports and Exercise Medicine (TISEM) and the Newcastle–Ottawa Scale (NOS) scale. The skin temperature of the relevant acupoints or the difference between the left and right acupoints of the same name was used as the outcome during any period of menstruation. Finally, the meta-analysis was performed using RevMan 5.4.1 software to evaluate the changes in skin temperature in the related acupoints.Results: Seven eligible studies were included, which included 328 patients with PD and 279 healthy subjects. The results of the meta-analysis revealed a significant difference in skin temperature around the Sanyinjiao (SP6)(MD: 0.04, 95% CI: 0.00, 0.08), Xuehai (SP 10)(MD: − 0.07, 95% CI:-0.11, − 0.02) and Taixi (KI 3)(MD: 0.06, 95% CI:0.01, 0.11) acupoints between PD and healthy subjects. PD patients also showed a difference in skin temperature at the Taixi (KI 3)(MD: 0.14, 95% CI:0.04, 0.24), Shuiquan (KI 5)(MD: 0.11, 95% CI: 0.03,0.19), Taichong (LR 3)(MD: − 0.10, 95% CI: − 0.19,-0.01), Diji (SP 8)(MD: − 0.09, 95% CI: − 0.16, − 0.01), and Xuehai (SP 10)(MD: − 0.14, 95% CI: − 0.23, − 0.06) acupoint areas at different times of menstruation compared to that of healthy subjects, as revealed by the subgroup analysis.Conclusion: Primary dysmenorrhea patients showed some differences in the skin temperature of the special acupoints are as Sanyinjiao (SP6), Diji (SP 8), Xuehai (SP 10), Shuiquan (KI 5), Taichong (LR 3), and Taixi (KI 3) compared with healthy subjects.Registration Number: CRD42022381387.Keywords: acupuncture points, acupoints, acupoint sensitization, skin temperature, thermography, meta-analysis, systematic review

Weiqiang Xiao,1,&ast; Xiaokun Wang,1,&ast; Yuanye Qu,1 Mingyue Sun,1 Yanmin Chang,1 Wenjiao Li,1 Yong Shen,1,2 Xiufang Shi,3 Min Jing,1 Qingxia Xu1,4 1Department of Clinical Laboratory, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Institute of Biophysics, Chinese Academy of Sciences, Foshan, People’s Republic of China; 3School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 4Zhengzhou Key Laboratory for Diagnosis of Digestive System Tumor Markers, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingxia Xu; Xiufang Shi, Email zlyyxuqingxia0575@zzu.edu.cn; xfshi@zzu.edu.cnBackground: Emergence of blaKPC and blaNDM co-harboring Klebsiella pneumoniae has escalated the threat of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to healthcare. It remains unknown the prevalence and molecular characteristics of CRKP co-producing KPC and NDMs carbapenemases in Henan.Methods and Results: Twenty-seven CRKP strains isolated from different times were selected randomly in affiliated cancer hospital of Zhengzhou University from January 2019 to January 2021, among which one KPC-2 and NDM-5 positive CRKP named K9 was isolated from an abdominal pus sample of a 63-year-old male patient with leukemia. Sequencing of K9 determined that K9 belonged to ST11-KL47, which is resistant to antibiotics such as meropenem, ceftazidime-avibactam and tetracycline. K9 carried two different plasmids that contained blaNDM− 5 and blaKPC− 2. Both plasmids were shown to be novel hybrid plasmids and IS 26 played an important role in generation of two plasmids. Gene blaKPC-2 was flanked by the NTEKPC-Ib-like genetic structure (IS 26-ΔTn 3-ISKpn8-blaKPC-2-ISKpn6-IS 26) and was located on a conjugative IncFII/R/N type hybrid plasmid.Conclusion: The resistance gene blaNDM− 5 located on a region organized as IS 26-blaNDM– 5-ble-trpF-dsbD-ISCR1-sul1-aadA2-dfrA12-IntI1-IS 26 was carried by a phage-plasmid. We described a clinical CRKP co-producing KPC-2 and NDM-5 and emphasized an urgent need to control their further spread.Keywords: carbapenem-resistant Klebsiella pneumoniae, KPC-2, NDM-5, beta-lactamases, hybrid plasmid, IS 26

Feifei Lu,1,2,&ast; Wentao Xu,2,&ast; Xiaoye Shi,2,&ast; Honglu Yu,2,&ast; Xingshun Qi1,2 1College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, 110167, People’s Republic of China; 2Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning, 110840, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingshun Qi, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, Liaoning Province, 110840, People’s Republic of China, Email xingshunqi@126.comBackground: Until now, there is little evidence regarding clinical efficacy of 14-day vonoprazan-based bismuth quadruple therapy (BQT) for Helicobacter pylori (H. pylori) eradication.Methods: Overall, 65 treatment-naïve patients with H. pylori infection who received 14-day vonoprazan-based BQT regimen (VBCA, n=17) or pantoprazole-based BQT regimen (PBCA, n=48) for H. pylori eradication were retrospectively included.Results: Neither successful H. pylori eradication (88.2% versus 91.7%, p=1.000) nor adverse event (52.9% versus 64.6%, p=0.397) was significantly different between VBCA and PBCA groups.Conclusion: Vonoprazan seems to be as effective and safe as pantoprazole during a 14-day BQT regimen in treatment-naïve patients with H. pylori infection.Keywords: Helicobacter pylori, vonoprazan, pantoprazole, bismuth quadruple therapy, efficacy

Yanan Liu, Shuo Zhang, Rongrong Hu, Chao Li, Gang Chen, Xiaoxiao Shi, Yan Liu, Ke Zheng, Hang Li, Yubing Wen, Xuemei Li, Xuewang Li, Peng Xia, Yan Qin Department of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Peng Xia; Yan Qin, Department of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Tel +86 01069155058, Email 7-xp@163.com; qinyanbeijing@126.comPurpose: There are increasing reports of atypical membranous nephropathy (AMN) cases with similar pathological characteristics to secondary membranous nephropathy (SMN) without definite underlying causes. Although rituximab has become a first-line option in treating idiopathic membranous nephropathy (IMN), the efficacy and safety of rituximab-based regimen for AMN is not clear.Patients and Methods: This is a retrospective, single-center study. AMN patients who received rituximab-based therapy were included. IMN patients treated with rituximab during the same period were selected as the control group matched by gender, sex, baseline urinary protein and albumin levels. Baseline data and follow-up data were collected.Results: A total of 20 AMN patients and 40 IMN patients were included. The baseline levels of urinary protein were comparable between the two groups [6.77 (IQR 3.34, 11.49) g/24 h vs 6.47 (IQR 3.4, 10.76) g/24 h, P=0.944]. The baseline levels of serum albumin were 26.15± 6.71 g/L and 26.8± 5.54 g/L (P=0.689) respectively. The cumulative remission rate for rituximab-based treatment at the 12th month was lower in AMN group than IMN group [13 (65%) vs 36 (90%), P=0.045]. In AMN group, non-responders showed a higher level of proteinuria and a worse renal function at baseline than those of responders. There was no significant difference in the overall adverse events or serious adverse events between the two groups.Conclusion: In our study, AMN patients obtained proteinuria remission in a lower percentage compared with IMN patients. In general, rituximab-based therapy is effective in AMN patients with an acceptable safety profile.Keywords: rituximab, atypical membranous nephropathy, idiopathic membranous nephropathy, efficacy

Fengli Huang,1,&ast; Qun Zhang,2,&ast; Jie Xiao,3,&ast; Xin Zhang,1 Xingzhi Han,3 Xiao Shi,3 Jing Hu,2 Li Li,2 Xiaoping Qian1,2 1Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Oncology, Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 3Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoping Qian, Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-13951743162, Fax +86-25-68182342, Email xiaopingqian@nju.edu.cnPurpose: Recent studies have shown that traditional Chinese medicine (TCM), such as gambogic acid (GA), is involved in the regulation of tumor immune microenvironment and can be combined with other anti-tumor treatment strategies. Here, we used GA as an adjuvant to construct a nano-vaccine to improve the anti-tumor immune response of colorectal cancer (CRC).Materials and Methods: We used a previously reported two-step emulsification method to obtain poly (lactic-co-glycolic acid) /GA nanoparticles (PLGA/GA NPs), and then CT26 colon cancer cell membrane (CCM) was used to obtain CCM-PLGA/GA NPs. This novel nano-vaccine, CCM-PLGA/GA NPs, was co-synthesized with GA as an adjuvant and neoantigen provided by CT26 CCM. We further confirmed the stability, tumor targeting, and cytotoxicity of CCM-PLGA/GA NPs. The regulatory effect on the tumor immune microenvironment, the anti-tumor efficacy, and the combined anti-tumor efficacy with anti-PD-1 monoclonal Antibodies (mAbs) of this novel nano-vaccine was also detected in vivo.Results: We successfully constructed the CCM-PLGA/GA NPs. In vitro and in vivo tests showed low biological toxicity, as well as the high tumor-targeting ability of the CCM-PLGA/GA NPs. Besides, we revealed a remarkable effect of CCM-PLGA/GA NPs to activate the maturation of dendritic cells (DCs) and the formation of a positive anti-tumor immune microenvironment.Conclusion: This novel nano-vaccine constructed with GA as the adjuvant and CCM providing the tumor antigen can not only directly kill tumors by enhancing the ability of GA to target tumors, but also indirectly kill tumors by regulating tumor immune microenvironment, providing a new strategy for immunotherapy of CRC.Keywords: cancer immunotherapy, gambogic acid, nano-vaccine, tumor immune microenvironment, colorectal cancer

Xiangwen Shi,1,2,&ast; Linmeng Tang,3,&ast; Haonan Ni,1,&ast; Mingjun Li,1 Yipeng Wu,1,2 Yongqing Xu2 1Kunming Medical University, Kunming, People’s Republic of China; 2Laboratory of Yunnan Traumatology and Orthopedics Clinical Medical Center, Yunnan Orthopedics and Sports Rehabilitation Clinical Medical Research Center, Department of Orthopedic Surgery, 920th Hospital of Joint Logistics Support Force of PLA, Kunming, People’s Republic of China; 3Bone and Joint Imaging Center, Department of Medical Imaging, the First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongqing Xu; Yipeng Wu, Department of Orthopedic Surgery, 920th Hospital of Joint Logistics Support Force, 212 Daguan Road, Xi Shan District, Kunming, Yunnan, 650100, People’s Republic of China, Email docxuyongqing@sina.com; 20201497@kmmu.edu.cnObjective: Staphylococcus aureus (SA)-induced osteomyelitis (OM) is one of the most common refractory diseases in orthopedics. Early diagnosis is beneficial to improve the prognosis of patients. Ferroptosis plays a key role in inflammation and immune response, while the mechanism of ferroptosis-related genes (FRGs) in SA-induced OM is still unclear. The purpose of this study was to determine the role of ferroptosis-related genes in the diagnosis, molecular classification and immune infiltration of SA-induced OM by bioinformatics.Methods: Datasets related to SA-induced OM and ferroptosis were collected from the Gene Expression Omnibus (GEO) and ferroptosis databases, respectively. The least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) algorithms were combined to screen out differentially expressed-FRGs (DE-FRGs) with diagnostic characteristics, and gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to explore specific biological functions and pathways. Based on these key DE-FRGs, a diagnostic model was established, and molecular subtypes were divided to explore the changes in the immune microenvironment between molecular subtypes.Results: A total of 41 DE-FRGs were identified. After screening and intersecting with LASSO and SVM-RFE algorithms, 8 key DE-FRGs with diagnostic characteristics were obtained, which may regulate the pathogenesis of OM through the immune response and amino acid metabolism. The ROC curve indicated that the 8 DE-FRGs had excellent diagnostic ability for SA-induced OM (AUC=0.993). Two different molecular subtypes (subtype 1 and subtype 2) were identified by unsupervised cluster analysis. The CIBERSORT analysis revealed that the subtype 1 OM had higher immune cell infiltration rates, mainly in T cells CD4 memory resting, macrophages M0, macrophages M2, dendritic cells resting, and dendritic cells activated.Conclusion: We developed a diagnostic model related to ferroptosis and molecular subtypes significantly related to immune infiltration, which may provide a novel insight for exploring the pathogenesis and immunotherapy of SA-induced OM.Keywords: osteomyelitis, ferroptosis, molecular subtype, immune infiltration, biomarker

Yuan Cheng,1,2 Junxiang Li,1 Xiaosi Zhang,1 Yalan Li,3 Xiaojun Shi,1 Rui Shi,1 Tangyou Mao,1 Fushun Kou,1,4 Lei Shi1 1Gastroenterology Department, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, People’s Republic of China; 2School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210046, People’s Republic of China; 3School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 4Center for IBD Research, Department of Gastroenterology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, People’s Republic of ChinaCorrespondence: Lei Shi, Department of Gastroenterology, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, 1st Section, Fangxingyuan, Fangzhuang, Fengtai District, Beijing, 100078, People’s Republic of China, Email b01350@bucm.edu.cn Fushun Kou, Center for IBD Research, Department of Gastroenterology, The Shanghai Tenth People’s Hospital, Tongji University, No. 301 Yanchang Road, Shanghai, 200072, People’s Republic of China, Email koufuhsun@126.comPurpose: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by mucosal inflammation, which may develop into ulcerative colitis-associated carcinogenesis (UCAC) with disease progression. Qingchang Wenzhong Decoction (QCWZD) is a classic and effective prescription for the clinical treatment of UC. QCWZD has been shown to alleviate intestinal mucosal injury in acute and chronic UC models. This study aimed to explore and then verify the pharmacological mechanisms of QCWZD in UC and UCAC therapy.Methods: In this study, approaches including microarray analysis, network pharmacology, and biological verification are employed to clarify the mechanism of QCWZD in the treatment of UC and UCAC. TCMSP, Swiss Target Prediction, and Similarity Ensemble Approach were used to investigate the active ingredients and targets of QCWZD. UC and UCAC valid targets were identified by the microarray data in the GEO database (GSE38713 and GSE47908). The core targets were obtained by PPI network and enriched by GO and KEGG. DSS and AOM/DSS mouse models were adopted to verify the above analysis results.Results: The enrichment analysis showed that the therapeutic targets of QCWZD enriched in blood circulation, cell adhesion molecules, and pathways of inflammation and cancer such as IL-17 signaling pathway and toll-like receptor signaling pathway were involved in the multiple synergies of QCWZD on UC and UCAC treatment. The results of experiments demonstrated that QCWZD can exert its effects on protecting the intestinal mucosal barrier, regulating inflammation and improving intestinal fibrosis in UC and UCAC and the main mechanism of QCWZD in treatment of UC and UCAC may be related to the activation of the IL-17, NF-κB and TLR4 signaling pathways.Conclusion: Our results indicated that QCWZD treated UC and UCAC via multiple targets and pathways and the IL-17, NF-κB and TLR4 signaling pathways may be highly involved in this process.Keywords: QCWZD, ulcerative colitis, ulcerative colitis-associated carcinogenesis, colitis-associated cancer, intestinal fibrosis

Hongyu Meng,1,2,&ast; Ruixi Li,3,&ast; Yuankang Xie,1,&ast; Zhaohong Mo,2 Hang Zhai,2 Guangquan Zhang,3 Guohui Liang,4 Xianjie Shi,3 Boxuan Zhou1,2 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 4School of Clinical Medicine, Henan University, Kaifeng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Boxuan Zhou; Xianjie Shi, Email zhoubx3@mail2.sysu.edu.cn; shixianjie301@126.cmBackground: Circular RNAs (circRNAs) are becoming vital biomarkers and therapeutic targets for malignant tumors due to their high stability and specificity in tissues. However, biological functions of circRNAs in hepatocellular carcinoma (HCC) are still not well studied.Methods: Gene Expression Omnibus (GEO) database and qRT-PCR were used to evaluate expression of circROBO1 (hsa_circ_0066568) in HCC tissues and cell lines. CCK-8, colony formation, EdU staining, flow cytometry for cell cycle analysis, and xenograft model assays were performed to detect the circROBO1 function in vitro and in vivo. RNA pull-down, RNA immunoprecipitation (RIP), and Luciferase reporter assays were used to investigate the relationship among circROBO1, miR-130a-5p, and CCNT2. More importantly, we developed nanoparticles made from poly lactic-co-glycolic acid (PLGA) and polyethylene glycol (PEG) chains as the delivery system of si-circROBO1 and then applied them to HCC in vitro and in mice.Results: circROBO1 was obviously upregulated in HCC tissues and cell lines, and elevated circROBO1 was closely correlated with worse prognosis for HCC patients. Functionally, knocking down circROBO1 significantly suppressed HCC cells growth in vitro and in mice. Mechanistically, circROBO1 acted as a competing endogenous RNA to downregulate miR-130a-5p, leading to CCNT2 expression upregulation. Furthermore, miR-130a-5p mimic or CCNT2 knockdown reversed the role of circROBO1 overexpression on HCC cells, which demonstrated that circROBO1 promoted HCC development via miR-130a-5p/CCNT2 axis. In addition, we developed nanoparticles loaded with si-circROBO1, named as PLGA-PEG (si-circROBO1) NPs, which significantly prevented the proliferation of HCC cells, and did not exhibit apparent toxicity to major organs in vivo.Conclusion: Our findings firstly demonstrate that circROBO1 overexpression promotes HCC progression by regulating miR-130a-5p/CCNT2 axis, which may serve as an effective nanotherapeutic target for HCC treatment.Keywords: nanoparticles, hepatocellular carcinoma, circROBO1, cell proliferation, drug delivery

Yanan Duan,1 Ye Zhou,2 Yiqing Peng,2 Xiuling Shi,2 Cunxu Peng2 1Jining Medical University, Jining, Shandong Province, 272002, People’s Republic of China; 2Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong Province, 272029, People’s Republic of ChinaCorrespondence: Cunxu Peng, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Rencheng District, Jining City, Shandong Province, People’s Republic of China, Tel +86 13385405627, Fax +86 0530-6533898, Email 18678766751@163.comPurpose: Infertility is highly correlated with inflammation. We sought to evaluate the independent relationships between each inflammatory marker in women with infertility.Patients and Methods: This cross-sectional study included 1028 infertile patients who were hospitalized at Jining Medical University between January 2016 and December 2022. NLR and PLR were the independent and dependent variables measured at baseline, respectively. Age, body mass index (BMI), and menstrual status were covariates. Based on BMI, the study population was split into two groups: Low-BMI and High-BMI.Results: A stratified analysis revealed that the overweight group had significantly higher levels of WBC, platelet count, lymphocyte count, neutrophil count and NLR. Comparing the overweight group to the normal weight group, the levels were noticeably higher in the overweight group. Significantly positive correlations between NLR and PLR were found in both univariate and multiple regression analyses.Conclusion: There was a significant positive correlation between NLR and PLR in infertility patients. These results will help in the search for biomarkers of infertility and in the development of infertility prediction models.Keywords: infertility, inflammation marker, PLR, NLR, lymphocyte count

Jie Ren,1,&ast; Jingzhou Wang,2,&ast; Xingchen Yao,1 Yue Wu,1 Ming Shi,1 Xiangjun Shi,3 Xinru Du1 1Department of Orthopaedics, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China; 2Department of Orthopaedics, Beijing Daxing District People’s Hospital, Beijing, 102600, People’s Republic of China; 3Department of Hematology, Beijing Chao-yang Hospital, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinru Du, Department of orthopaedics, Beijing Chao-yang Hospital, No. 8 of Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 13683156652, Email duxinru@163.comObjective: To explore the role of sclerosteosis (SOST) gene expression in the occurrence and development of multiple myeloma (MM) complicated with sarcopenia.Methods: Analysis of the SOST expression in skeletal muscle tissue of patients with MM using high-throughput sequencing combined with transcriptomics; observation of morphological changes of the mouse C2C12 myoblasts co-cultured with SP2/0 myeloma cells in Transwell; observation of the SOST expression in the C2C12 myoblasts using the immunofluorescence labeling method; and assessment of the changes in exercise capacity of mice with MM using ethology; and the measurement of the SOST expression in muscles of mice using immunohistochemistry.Results: The transcription level of the SOST gene in the muscle tissue was significantly higher in patients with MM and sarcopenia than in patients with MM without sarcopenia and elderly patients with sarcopenia; the area of C2C12 mouse myoblasts co-cultured with SP2/0 myeloma cells was 167,904 ± 8653.7 pix; this was significantly lower than the area of 402,994 ± 13,575.0 pix in the control group (CG); the fluorescence intensity of SOST in the cells of the experimental group (EG) was 159,389 ± 10,534 AU; this was significantly higher than the intensity of 26,338 ± 6059 AU in the CG; the differences in results of the coat-hanger test, the tail suspension test, the weight-bearing forced swimming test, and the grip strength test between the tumor-bearing mice in the EG and the CG were statistically significant; and the quantitative result of SOST expression in the muscle tissue of the EG mice was 11,515 ± 1573 pix; this was significantly higher than the result of 3399 ± 798.8 pix in the CG.Conclusion: The SOST gene expression was significantly higher in muscle of mice in EG than in CG; and increased SOST gene expression might be a pathogenesis of MM complicated with sarcopenia.Keywords: multiple myeloma, SOST, multiple myeloma mouse model, ethology, sarcopenia, myoblast differentiation

Weiran Hu,1,2,&ast; Hongqiang Wang,1,2,&ast; Xiaonan Wu,1,3 Xinge Shi,1,2 Haohao Ma,1,2 Kai Zhang,1,2 Yanzheng Gao1,2 1Department of Spine and Spinal Cord Surgery, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Spine and Spinal Cord Surgery, People’s Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Spine and Spinal Cord Surgery, People’s Hospital of Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanzheng Gao, Department of Spine and Spinal Cord Surgery, Henan Provincial People’s Hospital, No. 7, Wei Wu Road, Zhengzhou, 450003, People’s Republic of China, Email gaoyanzhengspine@163.comStudy Design: Retrospective cohort study.Objective: This study aimed to investigate the characteristics of microflora in patients with deep spinal surgical site infection (SSI) after prophylactic use of vancomycin powder (VP).Methods: A retrospective analysis was performed on patients after spinal surgery. Patients were grouped according to whether VP use and only patients with deep SSI were included in this study. General information of the patients, the dose of vancomycin, bacterial culture results, drug sensitivity test results, and SSI treatment methods were recorded. The differences of microflora between the two groups were analyzed, and the sensitivity of bacteria in the +VP group to antibiotics was analyzed.Results: The infection rate in the +VP group was 4.9% (56/1124) vs 6.3% (93/1476) in the No-VP group (P < 0.05). The proportion of Gram-positive bacteria (GPB) in the +VP SSIs was 55.4% vs.74.1% in the No-VP group (P < 0.05). The percentage of Gram-negative bacteria (GNB) in the +VP SSIs was 46.4% vs.30.1% in the No-VP group (P < 0.05). More dose of VP cannot decrease the SSI, but the proportion of GNB in VP > 1g SSIs was higher (59.0% vs 32.4%, P < 0.05). In the +VP SSIs, all of the GNB cultured were sensitive to meropenem, and linezolid covered most of the GPB cultured.Conclusion: Local use of vancomycin powder can reduce the incidence of SSI, but this may lead to changes in the bacterial flora. Once the SSI occurs, the case of GNB infection may be increased. The more dose of VP cannot decrease SSI but may increase the rate of GNB in the +VP SSIs. Once infections still occur after VP use, antibiotics covering GNB may be added. These findings may help guide choice of empiric antibiotics while awaiting culture data.Keywords: surgery site infection, microflora, spine, vancomycin

Jinkun Xia,1,2,&ast; Haoran Ding,1,&ast; Shujun Liu,3 Ran An,1,2 Xiaolei Shi,1– 3 Ming Chen,1 Haozhen Ren1– 3 1Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Institute of Hepatobiliary Surgery, Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haozhen Ren; Ming Chen, Email renhaozhen1984@163.com; chenming@njglyy.comAbstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system worldwide, and there is a lack of effective treatment for late-stage HCC. Recent experimental studies have demonstrated that dysfunction of the intestinal flora has a significant impact on hepatocarcinogenesis. The pathophysiological link between the intestine, its microbiota, and the liver has been described as the “gut-liver axis”. Dysbiosis of the intestinal flora and increased permeability of the intestinal wall are closely associated with liver pathology through the immune response. The “gut-liver axis” theory has been applied to the clinical study of the pathogenesis and treatment of HCC. The intestinal fungal community, as part of the gut microbiome, has a significant impact on human health and disease, while relatively little research has been done in HCC. In this study, we performed a comprehensive analysis of the expression and potential biological functions of the fungal recognition receptors C-type lectin receptors (CLRs) (Dectin-1, Dectin-2, Dectin-3, and Mincle) in HCC. We found that CLRs were downregulated in HCC, and their expressions were correlated with the clinical prognosis of HCC patients. Further studies suggested that the expression of CLRs were significantly correlated with immune infiltration and immunotherapy efficacy in HCC. Based on previous studies and our findings, we hypothesize that intestinal fungal communities and CLRs-triggered antifungal immunity have a key role in the pathogenesis of HCC, and these findings may provide new perspectives and targets for HCC immunotherapy.Keywords: hepatocellular carcinoma, mycobiome, fungus, immunity, C-type lectin receptor, gut-liver axis

Yunpeng Cui,1 Chuan Mi,1 Bing Wang,1 Bo Zheng,2 Liying Sun,3 Yuanxing Pan,1 Yunfei Lin,1 Xuedong Shi1 1Department of Orthopaedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Clinical Pharmacology, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuedong Shi, Department of Orthopaedics, Peking University First Hospital, No. 7 Xishiku Street, Xicheng District, Beijing, 100032, People’s Republic of China, Tel +86 28-010-83572970, Email pku_ortho@163.comObjective: This study aimed to investigate the effects of manual homogenization on the sensitivity of microbiological culture for patients with pyogenic spondylitis.Methods: From October 2018 to March 2021, patients undergoing fluoroscopy-guided biopsy or open debridement due to pyogenic spondylitis were recruited. Their demographic data and baseline characteristics were recorded. Tissue samples were obtained through fluoroscopy-guided biopsy or open debridement. Tissue samples were divided into three parts: manual homogenization (MH), manual mixture (MM), and pathological examination. Sterile normal saline was set as the negative control to exclude false-positive culture results. The Chi-square test was used to detect the difference of microbiological culture results.Results: Twenty-four consecutive patients (33 tissue cultures) with pyogenic spondylitis treated in our department between October 2018 and March 2021 were recruited in this study. The average age was 61.7± 3.2 years old and 10 patients were female. The MH group had a significantly higher positive rate compared with the MM group in aerobic conditions: 78.8% (26 isolates) vs 54.5% (18 isolates), P=0.037 and anaerobic condition: 63.6% (21 isolates) vs 39.4% (13 isolates), P=0.049. The results of subgroup analyses showed that MH could improve the culture sensitivity for patients with previous antibiotics use and without paravertebral abscesses but not reach a significant level on statistics.Conclusion: Based on the present study, manual homogenization could improve the sensitivity of microbiological cultures for patients with pyogenic spondylitis.Keywords: tissue culture, pyogenic spondylitis, manual homogenization, blood culture bottle

Xiaorui Shi,1 Xinan Wang,1 Rong Huang,1 Chu Tang,1 Chong Hu,1 Pengbo Ning,1 Fu Wang1– 3 1Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi’an, 710071, People’s Republic of China; 2Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis, School of Pharmacy, Shaanxi Institute of International Trade & Commerce, Xianyang, Shaanxi, 712046, People’s Republic of China; 3School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaCorrespondence: Fu Wang; Pengbo Ning, Email fwang@xidian.edu.cn; pbning@xidian.edu.cnBackground: Micro- and nano-sized plastics (MPs and NPs) have become an environmental issue of global concern due to their small size, strong bio-permeability and high specific surface area. However, few studies have assessed the effect of polystyrene MPs and NPs on human lung cells. In this research, we evaluated the cytotoxicity and genotoxicity of polystyrene (PS) MPs and NPs with different sizes (2 μm and 80 nm) and surface modification (carboxy and amino functionalized polystyrene, pristine polystyrene) in A549 cells.Methods: The zeta potential and hydrodynamic particle size of five types of PS plastic solutions were measured by dynamic light scattering, and their morphology and degree of aggregation were observed by scanning electron microscopy. After incubation of the PS plastics with A549 cells, the uptake and toxicity of the cells were assessed by fluorescence microscopy, laser scanning confocal microscopy, flow cytometry, MTT, micronucleus formation assay, and reactive oxygen species.Results: The cytotoxicity and genotoxicity of A549 cells caused by nano-level PS is more serious than that of micro-level. Compared with unmodified PS-NPs, more surface-functionalized PS-NPs were found inside the cells, especially the accumulation of PS-NH2. Cell viability and the induction of micronuclei (MN) are appreciably impacted in a dose-dependent way. Compared with pristine PS-NPs, functionalized PS-NPs showed stronger cell viability inhibitory ability, and induced more MN scores.Conclusion: This study shows that the intrinsic size properties and surface modification of PS plastics, the interaction between PS plastics and the receiving medium, intracellular accumulation are critical factors for evaluating the toxicological influences of PS plastics on humans.Graphical Abstract: Keywords: microplastics, nanoplastics, surface functionalization, cytotoxicity, genotoxicity, oxidative damage

Yalan Bi,1 Xiaohua Shi,2 Dian Chen,1 Yi Zhao1 1Department of Dermatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Yi Zhao, Department of Dermatology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing, People’s Republic of China, Tel/Fax +86 010 56119127, Email zhaoyimd@tsinghua.edu.cnPurpose: To investigate the clinical value of CD133 and CD44 as putative cancer stem cell markers in distinguishing between basal cell carcinoma (BCC) and trichoblastomas (TB).Patients and Methods: Tumor samples from 24 BCC and 23 TB patients were retrospectively retrieved for immunohistochemical staining of CD133 and CD44. The results were interpreted using a semiquantitative scoring system (H score). A receiver operating characteristic (ROC) curve was developed to identify an optimal cutoff value for differentiating between BCC and TB.Results: Expression of CD133 was significantly higher in BCC patients than in TB patients (median H score: 30 [IQR: 12.5– 56.3] vs 0 [IQR: 0– 2], P < 0.001). However, there was no significant difference in CD44 expression between the two groups (median H score: 105 [IQR: 63.8– 155.0] vs 60 [IQR: 30– 120], P = 0.095). The ROC analysis of CD133 immunostaining yielded an area under the curve (AUC) of 0.881 (95% CI: 0.756– 1.000) for differentiating between BCC and TB by using a H score of 7 as the cut-off value (98.5% sensitivity and 87.0% specificity). By contrast, immunostaining of CD44 showed a lower diagnostic value, with an AUC of 0.642 (95% CI: 0.476– 0.808) at the optimal cut-off value of 85 (62.5% sensitivity and 73.9% specificity). The positive and negative predictive values were 88.5% and 95.2% for CD133 and 71.4% and 65.4% for CD44, respectively. Additionally, CD133 expression was significantly associated with mitotic activity in BCC patients (r = 0.549, P = 0.005).Conclusion: Our study expanded upon previous studies of CD133 and CD44 expressions in skin tumors, suggesting that CD133, but not CD44, may serve as a novel biomarker for differential diagnosis of BCC, although future studies using a larger number of patients are needed to justify it further.Keywords: basal cell carcinoma, BCC, trichoblastomas, TB, differential diagnosis, CD133, CD44, immunohistochemistry, receiver operating characteristic, ROC

Anqi Zhang,1,&ast; Fuyuan Yang,2,&ast; Lei Gao,1,&ast; Xiaoyan Shi,3 Jiyuan Yang1 1Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China; 2School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, People’s Republic of China; 3Department of Gynaecology and Obstetrics, First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiyuan Yang, Department of Oncology, First Affiliated Hospital of Yangtze University, Jingzhou, People’s Republic of China, Tel +86 189 7216 1658, Fax +86 716-8062633, Email Yangjiyuanchina@163.comAbstract: Radiation pneumonitis is a common and serious complication of radiotherapy for thoracic tumours. Although radiotherapy technology is constantly improving, the incidence of radiation pneumonitis is still not low, and severe cases can be life-threatening. Once radiation pneumonitis develops into radiation fibrosis (RF), it will have irreversible consequences, so it is particularly important to prevent the occurrence and development of radiation pneumonitis. Immune checkpoint inhibitors (ICIs) have rapidly altered the treatment landscape for multiple tumour types, providing unprecedented survival in some patients, especially for the treatment of non-small cell lung cancer (NSCLC). However, in addition to its remarkable curative effect, ICls may cause immune-related adverse events. The incidence of checkpoint inhibitor pneumonitis (CIP) is 3% to 5%, and its mortality rate is 10% to 17%. In addition, the incidence of CIP in NSCLC is higher than in other tumour types, reaching 7%– 13%. With the increasing use of immune checkpoint inhibitors (ICls) and thoracic radiotherapy in the treatment of patients with NSCLC, ICIs may induce delayed radiation pneumonitis in patients previously treated with radiation therapy, or radiation activation of the systemic immune system increases the toxicity of adverse reactions, which may lead to increased pulmonary toxicity and the incidence of pneumonitis. In this paper, the data about the occurrence of radiation pneumonitis, immune pneumonitis, and combined treatment and the latest related research results will be reviewed.Keywords: radiation pneumonitis, immune pneumonitis, pneumonitis after combination therapy, treatment and management of pneumonitis