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Jing Zhong,1 Hua Zhang,1 Jie Wu,2 Bosen Zhang,2,3 Liubing Lan1,2 1Department of Obstetrics, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Ultrasound, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Liubing Lan, Department of Prenatal Diagnostic Center, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email lanliubing@126.comObjective: Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM.Methods: A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed.Results: The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥ 30 years old, body mass index (BMI) in early pregnancy≥ 24.0 kg/m2, history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥ 30 years old (≥ 30 vs < 30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183– 3.878, p=0.012), BMI≥ 24.0 kg/m2 (≥ 24.0 kg/m2 vs 18.5– 23.9 kg/m2, OR: 1.887, 95% CI: 1.041– 3.420, p=0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022– 3.794, p=0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046– 7.863, p=0.041) were associated with GDM.Conclusion: Age of pregnant woman ≥ 30 years old, BMI≥ 24.0 kg/m2, history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM.Keywords: gestational diabetes mellitus, advanced age, overweight, history of adverse pregnancy, history of oral contraceptive use

Xueya Xu,&ast; Weili Lu,&ast; Hua Zhang, Xiaoying Wang, Caixia Huang, Qiuping Huang, Wen Xu, Wei Xu Pharmacy College, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoying Wang; Wei Xu, Pharmacy College, Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, Fuzhou, 350122, People’s Republic of China, Email 2003032@fjtcm.edu.cn; 2000017@fjtcm.edu.cnBackground: The combination of nanoplatform-based chemotherapy and photodynamic therapy (PDT) is a promising way to treat cancer. Celastrol (Cela) exhibits highly effective anti-hepatoma activity with low water solubility, poor bioavailability, non-tumor targeting, and toxic side effects. The combination of Cela-based chemotherapy and PDT via hepatoma-targeting and reactive oxygen species (ROS)-responsive polymeric micelles (PMs) could solve the application problem of Cela and further enhance antitumor efficacy.Methods: In this study, Cela and photosensitizer chlorin e6 (Ce6) co-loaded glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) PMs (Cela/Ce6/GCTR PMs) were prepared and characterized. The safety, ROS-sensitive drug release, and intracellular ROS production were evaluated. Furthermore, the in vitro anti-hepatoma effect and cellular uptaken in HepG2 and BEL-7402 cells, and in vivo pharmacokinetic, tissue distribution, and antitumor efficacy of Cela/Ce6/GCTR PMs in H22 tumor-bearing mice were then investigated.Results: Cela/Ce6/GCTR PMs were successfully prepared with nanometer-scale particle size, favorable drug loading capacity, and encapsulation efficiency. Cela/Ce6/GCTR PMs exhibited a strong safety profile and better hemocompatibility, exhibiting less damage to normal tissues. Compared with Cela-loaded GCTR PMs, the ROS-responsiveness of Cela/Ce6/GCTR PMs was increased, and the release of Cela was accelerated after combination with PDT. Cela/Ce6/GCTR PMs can efficiently target liver tumor cells by uptake and have a high cell-killing effect in response to ROS. The combination of GCTR PM-based chemotherapy and PDT resulted in increased bioavailability of Cela and Ce6, improved liver tumor targeting, and better anti-hepatoma effects in vivo.Conclusion: Hepatoma-targeting and ROS-responsive GCTR PMs co-loaded with Cela and Ce6 combined with PDT exhibited improved primary hepatic carcinoma therapeutic effects with lower toxicity to normal tissues, overcoming the limitations of monotherapy and providing new strategies for tumor treatment. Keywords: ROS-responsive polymeric micelles, photodynamic therapy, hepatoma-targeting, celastrol, combination anti-hepatoma therapy

Xiaohui Zhu,1,2 Dongmei Jiang,1 Hongjie Zhang,3 Ruyuan Cai,3 Yuying Wang,1 Fei Hua2 1Department of Endocrinology, Affiliated Hospital 6 of Nantong University, Yancheng, 224000, People’s Republic of China; 2Department of Endocrinology, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, People’s Republic of China; 3Department of Ophthalmology, Affiliated Hospital 6 of Nantong University, Yancheng, 224000, People’s Republic of ChinaCorrespondence: Fei Hua, Email huafeihf@21cn.comObjective: The study aimed to explore the correlation between retinal nerve fiber layer thickness (RNFLT) with blood biochemical indicators and cognitive dysfunction in patients with type 2 diabetes mellitus (T2DM) and the possible mechanism, thereby providing more theoretical basis for the occurrence and prevention of diabetes related complications.Methods: Eighty T2DM patients treated in our hospital from March 2022 to September 2022 were selected as the study subjects, and the clinical data of the patients were retrospectively analyzed. All patients underwent fundus fluorescein angiography (FFA) to analyze the changes in retinal blood vessels. Patients who met the inclusion criteria were divided as the diabetic retinopathy (DR) group (n=46) and simple diabetes group (n=34). The RNFLT, blood biochemical indexes and changes in cognitive functions of the patients were detected. The correlation between RNFLT with blood biochemical indexes and cognitive dysfunction was analyzed.Results: Compared with the simple diabetes group, patients in the DR group had much lower mean, nasal, inferior and superior thicknesses (P< 0.01). There existed no significant difference in blood pressure, body mass index (BMI), blood lipids (triglycerides, cholesterol, low-density lipoprotein, high-density lipoprotein) between the two groups (P> 0.05). Compared with the simple diabetes group, patients in the DR group had much higher fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin (FINS), insulin resistance (HOMA-IR) index, apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) (P< 0.001). Besides, the DR group had sharply lower scores on the Mini-Mental State Examination (MMSE) scale and higher levels of the Trail Making Test-A (TMT-A) and TMT-B (P< 0.001). Spearman correlation analysis confirmed that the mean RNFLT was negatively correlated with the levels of FBG, HbA1c, HOMA-IR index, TMT-A and TMT-B (P< 0.05), positively correlated with the score of mini-mental state examination (MMSE) (P< 0.05), and was no significant correlation with FINS and ApoB/ApoA1 (P> 0.05).Conclusion: DR patients had significantly reduced RNFLT, elevated levels of blood glucose related indicators, and cognitive dysfunction. There existed a correlation between RNFLT and FBG, HbA1c, HOMA-IR index, TMT-A, TMT-B and MMSE.Keywords: type 2 diabetes mellitus, retinal nerve fiber thickness, blood biochemical indicators, cognitive dysfunction, correlation

Yueming Ding,1 Huiying Zhang,1 Zhiqing Hu,1 Yanjun Sun,1 Yiping Wang,2 Baolong Ding,3 Guofeng Yue,4 Yuan He1,5 1Institute of Medical Humanities, School of Marxism, Nanjing Medical University, Nanjing, People’s Republic of China; 2School of Nursing, Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Pharmacy, Nanjing Medical University, Nanjing, People’s Republic of China; 4School of Health Policy and Management, Nanjing Medical University, Nanjing, People’s Republic of China; 5Research Center for Social Risk Management of Major Public Health Events (Key Research Base of Philosophy and Social Sciences of Universities in Jiangsu), Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yuan He, Institute of Medical Humanities, School of Marxism, School of Nursing, Research Center for Social Risk Management of Major Public Health Events (Key Research Base of Philosophy and Social Sciences of Universities in Jiangsu), Nanjing Medical University, Nanjing, 211166, People’s Republic of China, Email heyuan@njmu.edu.cn Guofeng Yue, School of Health Policy and Management, Nanjing Medical University, Nanjing, 211166, People’s Republic of China, Email gfyue@njmu.edu.cnBackground: Improving health-related quality of life (HRQoL) among hypertensive individuals has emerged as a significant public health issue. However, current research has ignored the individual heterogeneity of perceived social support (PSS) among hypertensive patients. The potential mechanism of delay discounting (DD), living alone, and PSS on HRQoL remains unclear, and further exploration is required.Aim: This study aimed to ascertain PSS profiles among hypertensive patients and examine the hypotheses that DD mediates the relationship between PSS and HRQoL and that this mediating process is moderated by living alone in hypertensive patients.Methods: A cross-sectional study was carried out in Jiangsu, China. In total, 1815 hypertensive patients completed socio-demographic and HRQoL questionnaires, a PSS scale, and a DD task. Data analyses included a latent profile analysis, χ2-test, Spearman correlation analysis, and PROCESS macro for regression analysis.Results: Four potential PSS profiles were identified: lowest (3.2%), moderate–low (26.6%), moderate–high (42.4%), and highest (27.8%). DD mediated the association between PSS and HRQoL. The first half of this mediating process was moderated by living alone.Conclusion: Our findings indicated that PSS, DD, and living alone significantly influence the HRQoL of individuals with hypertension. Healthcare professionals should consider variations in PSS among hypertensive patients and implement interventions to reduce DD by enhancing PSS, in order to improve the HRQoL of this population.Keywords: perceived social support, delay discounting, health-related quality of life, living alone, hypertensive patients, latent profile analysis

Jiayun Jiang,1 Hui Zhang,1 Jiejuan Lai,1 Shiyu Zhang,1 Yanjiao Ou,1 Yu Fu,2,&ast; Leida Zhang1,&ast; 1Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leida Zhang, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email 2518569931@qq.com Yu Fu, Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, Beibei District, Chongqing, 400715, People’s Republic of China, Email fuyu2020@swu.edu.cnPurpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed.Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P< 0.001; Median PFS: 13.0 months vs 2.7 months, P< 0.001). The best overall objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P< 0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P< 0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number > 3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855).Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC.Keywords: unresectable hepatocellular carcinoma, transarterial chemoembolization, lenvatinib, tislelizumab, immunotherapy

Gaoyan Tang, Qianqian Zhang, Fengxia Wang, Hua Zhang, Yuanling Qi Department of Oncology, Weifang People’s Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, 261041, People’s Republic of ChinaCorrespondence: Yuanling Qi, Department of Oncology, Weifang People’s Hospital (The First Affiliated Hospital of Shandong Second Medical University), Weifang, Shandong, 261041, People’s Republic of China, Email wryqyl@163.comBackground: As one of the most common types of primary bone sarcomas in adolescents and young adults, osteosarcoma has a high probability of local invasion and distant metastasis with a poor prognosis.Case Presentation: Here, we report the case of a 34-year-old patient with advanced metastatic osteosarcoma. Considering the high expression of PD-L1 and the inability of the patient to tolerate chemotherapy, anti-PD-1 antibody (sintilimab 200 mg, q3w) and anti-angiogenesis drug (anlotinib 8 mg D1-14, q3w) were administered. The metastatic lesions were treated with local radiotherapy. The patient obtained an 11.7-month-sustained remission period, and he also enjoyed a better quality of life.Conclusion: This case demonstrates that sintilimab plus anlotinib may be a feasible treatment regimen for osteosarcoma patients.Keywords: osteosarcoma, sintilimab, anlotinib, immunotherapy, anti-angiogenesis

Jun Cao,1,2 Hao Zhang,2 Xin Xie,3 Wei Wang4 1Department of Oncology, The Third Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Surgical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 3Department of Nuclear Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 4Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of ChinaCorrespondence: Wei Wang, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China, Tel +8613891841656, Email wei.wang@xjtufh.edu.cnBackground: VPS72 is highly expressed in hepatocellular carcinoma and prostate cancer, participating in various cellular processes such as gene transcription, replication, DNA repair, maintenance of genome integrity, and cancer progression. However, its role in colorectal cancer remains unknown.Methods: Bioinformatic methods were used to analyze gene expression, correlation and patient survival. Western blotting, colony formation assays and animal experiments were used to evaluate the function of VPS72 in colon cancer in vivo and in vitro.Results: VPS72 was highly expressed in colon cancer tissues and correlated with poor overall survival (P< 0.05) and relapse free survival (P< 0.01). Furthermore, patients with III/IV clinical stage (P< 0.001), N1 nodal metastasis (P< 0.001) or N2 nodal metastasis (P< 0.05) status had poor overall survival. Further analysis showed that VPS72 is correlated with proliferation and EMT biomarkers. Western blotting, colony formation assays and animal experiments showed that VPS72 overexpression promoted colon cancer proliferation and EMT progress.Conclusion: Our study found that VPS72 was correlated with poor overall survival in colon cancer patients, and high expressed level of VPS72 promoted colon cancer progression, indicating its role as a potential prognosis biomarker.Keywords: VPS72, colon cancer, biomarker, proliferation, epithelial–mesenchymal transformation

Yishan Duan,1,&ast; Jing Ren,2,&ast; Jing Wang,3,&ast; Suyan Wang,4 Rui Zhang,1 Huohuo Zhang,1 Jinrui Hu,1 Wen Deng,1 Weimin Li,1,3,4 Bojiang Chen1,3 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bojiang Chen; Weimin Li, Email cjhcbj@outlook.com; weimin003@163.comPurpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown.Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness.Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246– 4.060), p = 1.000) and ICU admission (HR=0.436(0.093– 2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296– 1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221– 8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort.Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.Keywords: Coronavirus disease 2019, COVID-19, early antibiotics use, bacterial co-infections, clinical outcomes

Cunchuan Chen,1,2,&ast; Huifang Zhang,1,2,&ast; Xia Feng,1,2 Haipeng Wang1,2 1Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research, Shandong University, Jinan, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haipeng Wang, Email wanghaipeng@sdu.edu.cnBackground: This alteration in the policy of COVID-19 resulted in widespread infections throughout China. Most people only need some antiviral drugs such as lopinavir/ritonavir or Chinese herbal preparations for treatment. In this context, the lack of drug knowledge and inadequate drug availability are evident. This study aims to explore the factors influencing drug use and demand during the COVID-19 epidemic.Methods: This study used quota sampling based on gender, age, and place of residence to perform a cross-sectional survey on a sample of 771 adults. The researchers used chi-square tests to understand differences in drug use and demand across characteristics, and binary logistic regression to analyse the influencing factors.Results: The study revealed that 85.9% of the participants used drugs following the COVID-19 infection. Participants with college and above, (OR=2.49, 95% CI=1.27– 4.88) annual personal income between 30,000 and 80,000CNY (OR=2.19, 95% CI=1.35– 3.55) and over 80,000CNY (OR=1.96, 95% CI=1.05– 3.66) were more knowledgeable about using drugs. Gender, (OR=0.69, 95% CI=0.50– 0.95) age, (OR=2.11, 95% CI=1.15– 3.88) residence, (OR=1.58, 95% CI=1.06– 2.37) chronic disease conditions (OR=0.46, 95% CI=0.27– 0.78) and infection symptoms (OR=0.60, 95% CI=0.38– 0.93) as factors influencing the need for drug delivery services. (P< 0.05).Conclusion: Research has revealed that a significant proportion of infected people in China chose drug treatment during COVID-19. Individuals with severe symptoms use more medication and require more drug delivery and storage. Low-education and low-income populations are lacking in drug knowledge, and older adults with underlying medical conditions are more likely to need drug delivery services. Therefore, governments should prioritize vulnerable groups when formulating drug policies and target drug literacy and guidance. In addition, it is recommended that a drug distribution system be set up within the community so that those in need can have quick and easy access to drugs.Keywords: COVID-19, drug use, drug demand, drug delivery, drug stockpiling

Honggang Zhang,1 Huiling Li,1 Shuangjun Zhao,2 Fangping Bao1,2 1Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 2The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, Zhejiang Province, People’s Republic of ChinaCorrespondence: Fangping Bao, Email baofp@zju.edu.cnAbstract: Remimazolam is a novel ultra-short-acting benzodiazepine with a unique pharmacokinetic profile that makes it an attractive option for use in general anesthesia. This review paper provides an in-depth analysis of remimazolam’s applications in the field of general anesthesia, focusing on its pharmacological properties, clinical efficacy, safety profile, and potential advantages compared to other anesthetic agents. Remimazolam acts on GABAa receptors, offering rapid onset and recovery times due to its unique metabolic pathway involving tissue esterases. Clinical trials have demonstrated its efficacy in procedural sedation and general anesthesia, showing a favorable safety profile with minimal cardiovascular and respiratory depression. Compared to traditional anesthetics such as propofol, remimazolam presents distinct advantages, including predictable pharmacokinetics, reduced risk of prolonged sedation, and a reliable safety margin. These attributes position remimazolam as a promising agent in various clinical settings. The purpose of this review is to synthesize current evidence on remimazolam and discuss its potential to improve clinical outcomes in anesthesia practice.Keywords: remimazolam, clinical efficacy, general anesthesia, safety profile, respiratory depression

Hao Zhang,1 Suping Li,1 Xingming Ma2 1Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 2School of Health Management, Xihua University, Chengdu, 610039, People’s Republic of ChinaCorrespondence: Hao Zhang, Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China, Tel +86-0817-2242705, Email zhanghao_112_sh@126.comObjective: Nanomedicine represents a transformative approach in biomedical applications. This study aims to delineate the application of nanomedicine in the biomedical field through the strengths, weaknesses, opportunities, and threats (SWOT) analysis to evaluate its efficacy and potential in clinical applications.Methods: The SWOT analysis framework was employed to systematically review and assess the internal strengths and weaknesses, along with external opportunities and threats of nanomedicine. This method provides a balanced consideration of the potential benefits and challenges.Results: Findings from the SWOT analysis indicate that nanomedicine presents significant potential in drug delivery, diagnostic imaging, and tissue engineering. Nonetheless, it faces substantial hurdles such as safety issues, environmental concerns, and high development costs. Critical areas for development were identified, particularly concerning its therapeutic potential and the uncertainties surrounding long-term effects.Conclusion: Nanomedicine holds substantial promise in driving medical innovation. However, successful clinical translation requires addressing safety, cost, and regulatory challenges. Interdisciplinary collaboration and comprehensive strategic planning are crucial for the safe and effective application of nanomedicine.Keywords: nanomedicine, drug delivery systems, SWOT analysis, biomedical application, safety, interdisciplinary collaboration

Guangjian Wang,1,&ast; Hui Lian,2,&ast; Qirui Guo,1 Hongmin Zhang,1 Xiaoting Wang1 1Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Health Care, 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: Xiaoting Wang, Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email wangxiaoting@pumch.cnPurpose: We previously proposed a new concept, the “critical unit”, which covers the structural integrity and function of mitochondria and endothelium. Injury of the critical unit plays a key role in the development of critical illnesses. High levels of inflammation may lead to abnormalities of the critical unit, which is an important mechanism for critical illnesses, and both inflammation and critical unit dysfunction may affect patient prognosis. Here we evaluated the correlation between interleukin-6 (IL6) and the critical unit biomarkers in critically ill patients and the impact of both on prognosis.Patients and Methods: This study included adult patients admitted to the intensive care unit for various reasons from January 1st to May 31st, 2023. Baseline characteristics, intensive care unit parameters, and laboratory test and outcome data were obtained from the electronic medical records system. Critical unit parameters were measured using polymerase chain reaction and enzyme-linked immunosorbent assay methods. Correlations were examined between IL6, critical unit parameters, and various outcomes.Results: In critically ill patients, IL6 was closely associated with all the critical unit biomarkers (activated partial thromboplastin time, sphingosine 1-phosphate, mitochondrial DNA, mitochondrial fission 1, and Parkin) and the prognoses of patients. A nomogram was constructed using the critical unit biomarkers to predict the in-hospital mortality of critically ill patients. The area under the curve for the mortality prediction model was 0.708. In sensitivity analyses, the predictive effect was better in the non-surgery and tumor groups compared with the surgery and non-tumor groups, with area under the curve values of 0.885 and 0.891, respectively.Conclusion: Our study innovatively integrated mitochondrial and endothelial markers in the critical unit to comprehensively evaluate patient prognosis, which may be a trend in the future assessment of critically ill patients. There are few such studies, and ours may promote the progress of related research.Keywords: critical unit, IL6, critically ill patients, pro-inflammatory response, prognosis

Licai Miao,1,&ast; Zihao Xu,1,&ast; Junhao Sui,1,&ast; Xiangyu Meng,1,&ast; Shicheng Huo,2 Shu Liu,1 Mengchen Chen,1 Zhong Zheng,1 Xiaobin Cai,3 Hao Zhang1 1Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Shanghai, 200433, People’s Republic of China; 2Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, Navy Medical University, Shanghai, 200003, People’s Republic of China; 3Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Cai, Department of Orthopedics Shanghai Tenth People’s Hospital Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China, Tel +8613122575295, Email caixbjn@163.com Hao Zhang Department of Orthopedics, Changhai Hospital Affiliated to the Navy Military Medical University, Tel +8613917856377, Email zhanghsmmu@126.comPurpose: Skin injury, often caused by physical or medical mishaps, presents a significant challenge as wound healing is critical to restore skin integrity and tissue function. However, external factors such as infection and inflammation can hinder wound healing, highlighting the importance of developing biomaterials with antibiotic and wound healing properties to treat infections and inflammation. In this study, a novel photothermal nanomaterial (MMPI) was synthesized for infected wound healing by loading indocyanine green (ICG) on magnesium-incorporated mesoporous bioactive glass (Mg-MBG) and coating its surface with polydopamine (PDA).Results: In this study, Mg-MBG and MMPI was synthesized via the sol-gel method and characterized it using various techniques such as scanning electron microscopy (SEM), the energy dispersive X-ray spectrometry (EDS) system and X-ray diffraction (XRD). The cytocompatibility of MMPI was evaluated by confocal laser scanning microscopy (CLSM), CCK8 assay, live/dead staining and F-actin staining of the cytoskeleton. The antibacterial efficiency was assessed using bacterial dead-acting staining, spread plate method (SPM) and TEM. The impact of MMPI on macrophage polarization was initially evaluated through flow cytometry, qPCR and ELISA. Additionally, an in vivo experiment was performed on a mouse model with skin excision infected. Histological analysis and RNA-seq analysis were utilized to analyze the in vivo wound healing and immunomodulation effect.Conclusion: Collectively, the new photothermal and photodynamic nanomaterial (MMPI) can achieve low-temperature antibacterial activity while accelerating wound healing, holds broad application prospects.Keywords: infection-related wounds, magnesium-doped bioactive glass, photothermal therapy, photodynamic therapy, immunomodulation

Yanting Hao,1 Hua Zhang,2 Fan Zhang1 1Department of Geriatrics, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Fan Zhang, Department of Geriatrics, Peking University Third Hospital, 49 North Garden Road, Beijing, 100191, People’s Republic of China, Email zfpuh3@126.comPurpose: It has been shown that lower Barthel’s index (BI) at admission is associated with a higher in-hospital mortality. There is a lack of evidence regarding the association between the change in BI during hospitalization and mortality after discharge. Our purpose was to determine whether the BI change during hospitalization is associated with all-cause mortality in older adults with COVID-19 pneumonia.Patients and Methods: We conducted a retrospective cohort study of 330 participants at Peking University Third Hospital during the COVID-19 pandemic period. In order to analyze the time to death data, a Kaplan-Meier survival curve was used. We used restricted cubic splines to analyze the association between BI change and all-cause mortality among COVID-19 pneumonia patients aged over 80 years old. Threshold effect analysis was used to assess the ability of BI change score to predict all-cause mortality.Results: Our study included 330 patients aged over 80 years with COVID-19 pneumonia. The Kaplan-Meier curve for mortality showed significantly worst survival with reduced BI among three groups (χ2= 6.896, P < 0.05). There was a non-linear association between the BI change and all-cause mortality (P for all over < 0.001). The effect sizes on the left and right sides of the inflection point were 0.958 (HR: 0.958, 95% CI 0.932– 0.958, P < 0.05) and 1.013 (HR: 1.013, 95% CI 0.967– 1.062, P > 0.05), respectively.Conclusion: Reduced BI during hospitalization was associated with the highest mortality risk. It is crucial to monitor BI change among COVID-19 pneumonia patients aged over 80 years old.Keywords: COVID-19 pneumonia, activities of daily living, mortality, older adult

Xixi Wu, Yuan Xin, Hengtong Zhang, Liang Quan, Qiang Ao NMPA Key Laboratory for Quality Research and Control of Tissue Regenerative Biomaterial, & Institute of Regulatory Science for Medical Device, & National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, People’s Republic of ChinaCorrespondence: Qiang Ao, Email aoqiang@tsinghua.edu.cnAbstract: Cancer, as the foremost challenge among human diseases, has plagued medical professionals for many years. While there have been numerous treatment approaches in clinical practice, they often cause additional harm to patients. The emergence of nanotechnology has brought new directions for cancer treatment, which can deliver anticancer drugs specifically to tumor areas. This article first introduces the application scenarios of nanotherapies and treatment strategies of nanomedicine. Then, the noteworthy characteristics exhibited by biopolymer materials were described, which make biopolymers stand out in polymeric nanomedicine delivery. Next, we focus on summarizing the state-of-art studies of five categories of proteins (Albumin, Gelatin, Silk fibroin, Zein, Ferritin), nine varieties of polysaccharides (Chitosan, Starch, Hyaluronic acid, Dextran, cellulose, Fucoidan, Carrageenan, Lignin, Pectin) and liposomes in the field of anticancer drug delivery. Finally, we also provide a summary of the advantages and limitations of these biopolymers, discuss the prevailing impediments to their application, and discuss in detail the prospective research directions. This review not only helps readers understand the current development status of nano anticancer drug delivery systems based on biopolymers, but also is helpful for readers to understand the properties of various biopolymers and find suitable solutions in this field through comparative reading. Keywords: drug delivery, nanoformulations, polymer, proteins, polysaccharides

Longyin Zhu,&ast; Juan Cai,&ast; Jia Fang, Lingyu Ran, Huan Chang, Huhai Zhang, Jiamin Zeng, Qin Yang, Chunxiao Fu, Qingping Li, Qianguang Pan, Hongwen Zhao Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comObjective: Analyze risk factors for cardiac surgery-associated acute kidney injury (CSA-AKI) in adults and establish a nomogram model for CSA-AKI based on plasma soluble urokinase-type plasminogen activator receptor (suPAR) and clinical characteristics.Methods: In a study of 170 patients undergoing cardiac surgery with cardiopulmonary bypass, enzyme-linked immunosorbent assay (ELISA) measured plasma suPAR levels. Multivariable logistic regression analysis identified risk factors associated with CSA-AKI. Subsequently, the CSA-AKI nomogram model was developed using R software. Predictive performance was evaluated using a receiver operating characteristic (ROC) curve and the area under the curve (AUC). Internal validation was performed through the Bootstrap method with 1000 repeated samples. Additionally, decision curve analysis (DCA) assessed the clinical applicability of the model.Results: Multivariable logistic regression analysis revealed that being male, age ≥ 50 years, operation time ≥ 290 minutes, postoperative plasma suPAR at 2 hours, and preoperative left ventricular ejection fraction (LVEF) were independent risk factors for CSA-AKI. Employing these variables as predictive factors, a nomogram model was constructed, an ROC curve was generated, and the AUC was computed as 0.817 (95% CI 0.726– 0.907). The calibration curve indicated the accuracy of the model, and the results of DCA demonstrated that the model could benefit the majority of patients.Conclusion: Being male, age ≥ 50 years, operation time ≥ 290 minutes, low preoperative LVEF, and elevated plasma suPAR at 2 hours are independent risk factors for CSA-AKI. The nomogram model established based on these risk factors has high accuracy and clinical value, serving as a predictive tool for assessing the risk of CSA-AKI.Keywords: nomogram, acute kidney injury, prediction model, risk factors, cardiac surgery

Jiawen Kuang,1,&ast; Wei Zhang,1,&ast; Haoran Zhang,2,&ast; Nan Lin,1 Jialie Fang,3 Rui Song,4 Zhaohua Xin,2 Jingyi Wang1 1School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, People’s Republic of China; 2Lingqiao Community Health Center, Pudong New Area, Shanghai, People’s Republic of China; 3Jing’an District Center for Disease Control and Prevention, Shanghai, People’s Republic of China; 4Xiaodongmen Subdistrict Community Health Center, Huangpu District, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyi Wang, School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, 446-2 Zhaojiabang Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86 21 3356 3933 ; +86 21 6416 9553, Email jingyi_wang@fudan.edu.cn Zhaohua Xin, Lingqiao Community Health Center, 1236 Jiangdong Road, Pudong New Area, Shanghai, 200131, People’s Republic of China, Tel/Fax +86 21 5864 2003, Email 115013251@qq.comPurpose: Psychosocial factors have been found to profoundly impact mental health of older adults, but the main focus in the current literature has been on one particular aspect of these factors. This study aimed to identify latent classes of older adults based on four psychosocial factors (loneliness, social isolation, perceived social support, and social capital) and the transition of classes over 6 months. We also sought to assess the predictive role of changes in these classes in relation to depression, anxiety, and stress at 18-month follow-up.Methods: We analyzed longitudinal data from 581 community-dwelling older adults in Shanghai, China. The data were collected at baseline (T0), 6-month follow-up (T1) and 18-month follow-up (T2) between March 2021 and April 2023. Using latent class analysis, we identified three underlying classes (Social Connectors, Subjective Social Isolates, and Social Isolates) of the sample. We also established five transition categories from T0 to T1 (Social Connectors T0-T1, Subjective Social Isolates T0-T1, Social Isolates T0-T1, Good Transition, and Bad Transition) using latent transition analysis. Logistic regression was employed to examine the temporal relationships between these transition categories and subsequent symptoms of depression, anxiety and stress, adjusting for age, sex, education, marital status, family income level, sleep quality, health status and outcome variables at T0.Results: Multivariable associations revealed that compared to older adults with persistent good social environment (Social Connectors T0-T1), those with persistent high levels of loneliness and social isolation and low levels of perceived social support and social capital (Social Isolates T0-T1), and those who shifted towards a poorer social environment (Bad Transition) were more likely to experience depression, anxiety and stress at T2. Sustained subjective social isolation (Subjective Social Isolates T0-T1) was associated with more severe depressive symptoms at T2.Conclusion: Our study indicated that adverse psychosocial environment worsened mental health in older adults. These findings highlight the importance of early identification of older individuals at long-term psychosocial risk and development of tailored interventions to improve their social environment and mental health.Keywords: older adults, psychosocial factors, depression, anxiety, stress

Mengli Li,1,&ast; Tongtong Yin,1,&ast; Jiaying Qi,1 Minhao Shi,1 Fangfang Wang,1 Zhiyu Mao,1 Hui Zhang,1,2 Li Wang1 1School of Nursing, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2School of Nursing, Suzhou Vocational Health College, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang; Hui Zhang, Email li-wang-1@suda.edu.cn; zhanghuichange@sina.comObjective: To explore the cut-off values and health evaluations of upper arm circumference (AC) and calf circumference (CC) on sarcopenia in Chinese community-dwelling older people.Methods: In this cross-sectional study, AC, CC, handgrip strength, muscle mass and gait speed were measured in 1537 Chinese community-dwelling older people in Sub-study 1. Correlation analysis, receiver operator characteristic curve (ROC curve) analysis, and consistency analysis were used for determination of AC and CC cut-off values for sarcopenia diagnosis (sarcopenia-AC and CC). Thereafter, 269 participants accepted additional assessments on physical function, body composition and muscle strength in Sub-study 2. T-test or Mann-Whitney U-test was used to explore the differential effects of sarcopenia-AC and CC on health indicators between sarcopenic and non-sarcopenic participants.Results: In Sub-study 1, the Area Under ROC (AUC) of AC and CC for sarcopenia screening were greater than 0.700 (P< 0.05). The cut-off values, sensitivity and specificity of AC and CC on sarcopenia in males were 25.9 cm (86.0%, 83.6%) and 33.7 cm (90.7%, 81.4%) whereas in females were 26.5 cm (70.8%, 69.7%) and 33.0 cm (86.5%, 69.4%), respectively. In Sub-study 2, the participants with sarcopenia-AC or sarcopenia-CC showed lower muscle strength and lower fat and muscle mass than the ones without (P< 0.05). Additionally, males instead of females with sarcopenia-AC or sarcopenia-CC showed worse performance in time-up and go test and 6-Minute Walk Test (P< 0.05). However, the 30-second chair stand test was not different between participants with and without sarcopenia-AC or sarcopenia-CC in both sexes.Conclusion: We found accurate and Chinese population targeted cut-off values of AC and CC on sarcopenia diagnosis (25.9 cm and 33.7 cm in males; 26.5 cm and 33.0 cm in females) and a good evaluation effect of AC and CC on fat and muscle mass, muscle strength and physical functions in males, not females.Keywords: sarcopenia, upper arm circumference, calf circumference, health assessment

Hongda Zhang,1,&ast; Yifan Qi,1,&ast; Jiayan Chen,1 Guanghao Qin,1 Ling Xu,1 Wei He,1 Sile Yu,1,2 Huixin Che,1 Emmanuel Eric Pazo1 1Department of Ophthalmology, He Eye Specialist Hospital, Shenyang, Liaoning, People’s Republic of China; 2School of Public Health, He University, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huixin Che; Emmanuel Eric Pazo, Department of Ophthalmology, He Eye Specialist Hospital, No. 128 North Huanghe Street, Shenyang, Liaoning, 110034, People’s Republic of China, Email chehuixin@163.com; ericpazo@outlook.comPurpose: The objective of this study was to assess the effectiveness of intense pulsed light (IPL) therapy in individuals diagnosed with glaucoma and dry eye disease (DED).Methods: This randomized control study recruited 22 individuals diagnosed with glaucoma, ranging in age from 33 to 82 years. These participants were undergoing treatment with hypotensive eyedrops and had clinical indications and subjective complaints associated with dry eye. Each patient underwent three sessions of IPL therapy in one eye, while the contralateral eye served as the control eye (CT). The following parameters were assessed at three time points: baseline, week-2, and week-4. These parameters include non-invasive breakup time (NITBUT), tear meniscus height (TMH), conjunctivocorneal epithelial staining score (CS), tear film lipid layer (TFLL), meibomian gland expressibility score (MGEx), Schirmer I test, ocular bulbar redness score (OBRS), and ocular surface disease index (OSDI). Intraocular pressure (IOP), best-corrected visual acuity (BCVA), and corneal endothelial cell count (ECC) were assessed for safety. The clinical trial was registered on 25/12/2023 at ClinicalTrials.gov website (NCT06158984).Results: Comparing baseline and 4-week measurements revealed that the IPL group found significant improvements in NITBUT (IPL: 8.74± 2.60 sec. vs CT: 5.76± 1.75 sec. p< 0.01), TMH (IPL: 0.23± 0.05mm vs CT: 0.19± 0.06mm, p=0.011), C.S. (IPL: 1.14± 0.56 vs CT: 1.95± 1.17, p=0.005), TFLL (IPL: 2.91± 2.91 vs CT:3.36± 0.58, p=0.047), MGEx score (IPL: 1.14± 0.35 vs CT: 1.45± 0.51, p=0.020) and OSDI scores (IPL: 31.77± 15.59 vs 50.59± 21.55, p=0.002) significantly improved. Conversely, other parameters showed no significant improvements (p> 0.05).Conclusion: The progression of ocular surface disease in individuals using topical anti-glaucoma medication may worsen if the condition is not addressed. Nevertheless, IPL therapy has the potential to result in significant improvements in both objective and subjective measures of dry eye. Best-corrected visual acuity, endothelial cell count, and intraocular pressure were determined to be within the permitted limits. No adverse events were reported during the course of the study.Plain Language Summary: The results show that people who use topical medicines to treat glaucoma may get worse eye surface disease if they do not treat the problem. IPL treatment, on the other hand, can make a big difference in both objective and subjective dry eye tests. The vision, endothelial cell count, and the pressure inside the eye were all found to be within normal limits after the IPL treatment. Even though the people in our study had glaucoma and had been taking glaucoma medicine for it for a year and the fact that the symptoms last for a long time may also change the results. Also, DED caused by glaucoma medication is complicated, with a lot of different symptoms and signs, even in the same stage. Also, subjective complaints may not match up with clinical signs. The type, amount, and length of anti-glaucoma drugs may have affected the results.Keywords: glaucoma, intense pulsed light, dry eye, meibomian glands, glaucoma-related dry eye

Wentao Luo,1 Xiuwen Lin,1 Yuchong Chen,2 Wenfeng Luo,3 Huagen Zhang1 1The Third Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of China; 2The Fourth Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000 People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of ChinaCorrespondence: Huagen Zhang, The Third Department of Critical Care Medicine, Meizhou People’s Hospital, Meizhou, Guangdong, 514000, People’s Republic of China, Tel +8613549175546, Email 672825592@qq.comBackground: Metagenomic next-generation sequencing (mNGS) is a high-throughput sequencing technique that identifies a wide array of pathogens directly from clinical specimens. This study evaluates the diagnostic value of mNGS in Pneumocystis jirovecii pneumonia (PJP) and compares its efficacy with traditional detection methods, including Grocott’s Methenamine Silver (GMS) staining, serum (1– 3)-β-D-Glucan (BDG) testing, and Lactate Dehydrogenase (LDH) testing.Methods: Seventy-eight patients hospitalized between January 2022 and March 2023 with suspected pulmonary infections were included. Patients were eligible for mNGS if they exhibited symptoms such as fever, cough, dyspnea, or progressive hypoxemia, and met specific clinical criteria for PJP. Specimens obtained included bronchoalveolar lavage fluid, sputum, and peripheral blood. Positive rates and pathogen distributions detected by mNGS and traditional methods were compared.Results: In the PJP group, 25%, 37.5%, and 9.38% of patients had solid organ tumors, corticosteroid use, and skin diseases, respectively, significantly higher than in the non-PJP group. The sensitivity and specificity of mNGS were both 100%, significantly higher than those of serum BDG (sensitivity 50%, specificity 81.8%) and LDH (sensitivity 9.3%, specificity 91.3%). Significant differences in microbial composition between the PJP and Non-PJP groups were observed. mNGS detected multiple mixed pathogens in 96.88% of PJP cases, with 68.75% exhibiting mixed bacterial and viral infections. Notably, 71% of patients improved following antibacterial treatment based on mNGS results.Conclusion: mNGS technology shows superior sensitivity and specificity in diagnosing PJP and guides precise treatment for complex pulmonary infections.Keywords: mNGS, Pneumocystis jirovecii pneumonia, pulmonary infections, dominant pathogens, sensitivity

Huishan Zhang,1,2,&ast; Jing Lin,3,4,&ast; Yufang Huang,3,4 Yu Chen3,4 1Department of Phase I Clinical Trial Ward, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 2Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 3Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China; 4Cancer Bio-Immunotherapy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 350014, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Chen, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 420 Fuma Road, Fuzhou, Fujian, 350014, People’s Republic of China, Tel +86-62752224 Ext 0596, Email chenyu1980@fjmu.edu.cnPurpose: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) scheduled for neoadjuvant radiotherapy still have a poor prognosis. This study was to explore the prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with locally advanced ESCC after neoadjuvant radiotherapy (NRT).Materials and Methods: Eighty-two consecutive patients with ESCC scheduled for neoadjuvant radiotherapy between 2011 and 2017 were enrolled in this study. SII values (SII = platelet × neutrophil/lymphocyte), prognostic nutritional index values (PNI = albumin concentration (g/L) + 5 × total lymphocyte count (109/L)), platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR) were retrospectively collected and calculated before treatment. The Cut-off Finder application was applied to find out the cut-off points of the SII, NLR, PNI and PLR. A regression model was used to examine prognostic factors for overall survival (OS) rates.Results: The median follow-up was 44 months (3 to 83). Sixty patients (73.17%) underwent surgery as scheduled. This study found that factors improving OS were a lower SII (≤ 916.6 × 109/L) (P=0.040) and neoadjuvant chemoradiotherapy (NCRT) (P=0.034). The patients with a lower SII and NCRT had a better OS (P< 0.001). Moreover, additionally, a higher SII was associated with a lower resectability rate (P=0.035).Conclusion: The SII can predict resectability in ESCC patients following neoadjuvant radiotherapy. Both the SII and neoadjuvant chemoradiotherapy appear to influence OS.Keywords: ESCC, NCRT, SII, resectable

Kaiyue Zhang, Chunnan Li, Peitong Wu, Xiaochen Gao, Xueqin Feng, Jiaming Shen, Nanxi Zhang, Xuesheng Hu, Shuo Wang, Hui Zhang, Jingwei Lv, Jiaming Sun Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jiaming Sun; Jingwei Lv, Changchun University of Chinese Medicine, No. 1035, Boshuo Road, Nanguan District, Changchun, 130117, People’s Republic of China, Tel +0431-86763809, Fax + 8676 3968, Email Sun_jiaming2000@163.com; jingwei-lv@hotmail.comPurpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology.Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques.Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes.Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT’s efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management. Keywords: Zhixiao Tang, pneumonia, network pharmacology, integrated metabolomics, 16HBE, Zebrafish

Heng Yang, Lixia Chen, Danjuan Ye, Ying Wu, Huafang Zhang Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of ChinaCorrespondence: Huafang Zhang, Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, N1 Shangcheng Avenue, Yiwu, Zhejiang, 322000, People’s Republic of China, Email wuyizhangyichi@zju.edu.cnPurpose: The objective of this study was to investigate latent classes of oral health and the factors associated with them in acutely admitted elderly inpatients.Patients and Methods: A cross-sectional study was conducted using purposive sampling to survey Chinese older-adult acutely inpatients. Data was collected utilizing several instruments, including a general information questionnaire, Brief Oral Health Status Examination (BOHSE), Oral Frailty Index-8 (OFI-8), Mini-Nutritional Assessment Short Form (MNA-SF), and Frailty Screening Questionnaire (FSQ). Latent class analysis was applied to identify distinct categories of oral health among elderly inpatients, and multinomial logistic regression was employed to analyze the factors associated with different oral health categories.Results: In this study, a total of 504 elderly patients were ultimately included, leading to the identification of three latent classes of oral health: “oral health-low level group (41.27%)”, “oral health-moderate level group (25.4%)”, and “oral health-high level group (33.33%)”. The findings revealed that patients with advanced age, elevated neutrophil percentage, and higher C-reactive protein (CRP) values were more likely to be classified in the low oral health group. Additionally, individuals experiencing malnutrition and frailty had a higher risk of falling into the low oral health category. Those with comorbidities and oral frailty were more prevalent in the moderate oral health group. At the same time, elderly patients with higher BMI (22.95± 3.043) ratios were more likely to be categorized in the high oral health group.Conclusion: This study sheds light on three distinct latent classes of oral health among acutely admitted elderly inpatients. These findings underscore the importance of healthcare professionals focusing on the assessment and health education of elderly patients’ oral health. Furthermore, personalized interventions should be developed to promote healthy aging, with particularly attention to enhancing oral health outcomes in this population.Keywords: emergency department, oral health, factors, older people, latent class analysis, frailty

Lingling Wang,1 Huiguo Liu,1 Ling Zhou,1 Pengdou Zheng,1 Hai Li,2,3 Huojun Zhang,4,&ast; Wei Liu2,3,&ast; 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huojun Zhang, Email hjzhang@whu.edu.cn; Wei Liu, Email 404793938@tjh.tjmu.edu.cnAbstract: Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.Keywords: intermittent hypoxia, hypoxia-inducible factor 1 alpha, nonalcoholic fatty liver disease, oxidative stress, dyslipidemia, leptin resistance

Yan Li, Qi Li, Guangchao Zhao, Haopeng Zhang, Haixing Zhong, Yi Zeng Department of Anesthesia and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi’an, 710000, People’s Republic of ChinaCorrespondence: Yi Zeng; Haixing Zhong, Department of Anesthesia and Perioperative Medicine, Xijing Hospital, the Fourth Military Medical University, Xi’an, 710000, People’s Republic of China, Tel +8613991267646 ; +8613991946615, Email zengyi1014@163.com; haixing.zhong@139.comBackground: To investigate the effects of nalbuphine on emergency agitation (EA), which affects up to 80% of the children following otolaryngology procedures, in children undergoing cochlear implantation.Methods: A prospective double-blinded randomized controlled clinical trial was conducted between November 2020 and October 2022. Eligible children, aged 6 months to 3 years old, were randomly assigned to either 0.1 mg/kg, 0.15 mg/kg, 0.2 mg/kg nalbuphine or 0.9% saline groups. EA was defined by the Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10. Extubation time, post-anesthesia care unit (PACU) length of stay, severe EA (PAED ≥ 15), peak PAED score, the Faces, Legs, Activity, Cry, and Consolability (FLACC) scale, Ramsay sedation score, and adverse events were also recorded.Results: A total of 104 children were enrolled, with 26 children in each group. Nalbuphine significantly reduced the EA occurrence from 73.1% in the saline group to 38.5%, 30.8%, and 26.9% in the 0.1 mg/kg, 0.15 mg/kg, and 0.2 mg/kg nalbuphine groups, respectively (P < 0.001), without affecting the extubation time and PACU length of stay. More children (34.6%) in the 0.9% saline group experienced severe EA. Higher dose nalbuphine (0.15 mg/kg, 0.2 mg/kg) showed lower peak PAED score, better analgesia and sedation effect compared with 0.1 mg/kg nalbuphine and saline groups. However, 0.2mg/kg nalbuphine caused undesired over-sedation in two (7.7%) children. No other adverse events were reported.Conclusion: Young children undergoing cochlear implantation surgery were at a high risk of EA and postoperative pain, while 0.2 mg/kg nalbuphine might be an ideal candidate for EA and pain prevention when used under close monitoring.Trial Registration: ChiCTR2000040407.Keywords: emergence agitation, nalbuphine, cochlear implantation, postoperative pain

Xiaona He,1 Dan Yang,2 Jing Shao,1,3 Huafen Wang,4 Huafang Zhang1 1Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of China; 2Zhejiang Nursing Association, Hangzhou, 310000, People’s Republic of China; 3Institute of Nursing Research, School of Medicine Zhejiang University, Hangzhou, 310058, People’s Republic of China; 4The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Huafen Wang, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China, Tel +86 13516805833, Email 2185015@zju.edu.cn Huafang Zhang, Department of Nursing, the Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, People’s Republic of China, Tel +89 15924187619, Email wuyizhangyichi@zju.edu.cnBackground: In recent years, research on dysphagia has gained significant traction as one of the key topics of oral health research pertaining to the aged. Numerous academics have studied dysphagia in great detail and have produced numerous excellent scientific research findings.Objective: To review the literature regarding dysphagia in community-dwelling older adults and identify the knowledge and trends using bibliometric methods.Methods: The literature on dysphagia in older adults in the community was gathered from the Web of Science Core Collection (WoSCC), with inclusion criteria specifying English-language publications. The retrieval deadline was November 28, 2022. We extracted the following data: title, year, abstract, author, keywords, institution, and cited literature, and used CiteSpace (version 6.1.R3) to visualize the data through the knowledge map, burst keyword analysis, cluster analysis, and collaborative network analysis.Results: A total of 979 articles and reviews were retrieved. Regarding productivity, the top 2 countries were the United States (n =239) and Japan (n =236). Hidetaka Wakabayashi (n =26) was one of the most prolific writers. The first paper in the frequency ranking of references cited was a white paper: European Society for Swallowing Disorders and European Union Geriatric Medicine Society white paper: oropharyngeal dysphagia as a geriatric syndrome (n =53). “Prevalence” (n =173), “risk factor” (n =119), and “aspiration pneumonia” (n =108) were the most frequently occurring keywords (excluding defining nouns). The study identified reliability, tongue pressure, home discharge, and swallowing function as research hotspots from 2020 to 2022.Conclusion: Prevalence, risk factors, and pneumonia are significant areas of study. Tongue pressure and sarcopenia are research hotspots and potential targets. In the future, research on dysphagia needs to refine strategies for prevention and control, as well as provide tertiary preventative services.Keywords: dysphagia, community, older adults, bibliometric analysis, citespace

Zhou Zhu,1– 3,&ast; Huizi Gong,4,&ast; Mingjuan Liu,1– 3 Hanlin Zhang,1,2 Leyan Yang,1,2 Xinyi Zhang,5 Heyi Zheng,1,2 Yanfeng Li,6 Mingli Li,7 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 6Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 7Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingli Li, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email limingli@pumch.cn Jun Li, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email lijun35@hotmail.comBackground: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses.Methods: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed.Results: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34– 64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg’s sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases.Conclusion: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg’s sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.Keywords: tabes dorsalis, neurosyphilis, ataxia, cerebrospinal fluid

Boyu Li,1,&ast; Meishan Liu,2,&ast; Ying Wang,2 Hong Zhang,2 Lingling Xuan,1 Kewu Huang,2 Zhuoling An1 1Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kewu Huang; Zhuoling An, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongtinan Road, Beijing, People’s Republic of China, Tel/Fax +86 010 85231167 ; Tel/Fax +86 010 85231362, Email kewuhuang@126.com; anzhuoling@163.comPurpose: Vitamin D deficiency (VDD, 25-hydroxyvitamin D < 20 ng/mL) has been reported associated with exacerbation of chronic obstructive pulmonary disease (COPD) but sometimes controversial. Research on severe vitamin D deficiency (SVDD, 25-hydroxyvitamin D < 10 ng/mL) in exacerbation of COPD is limited.Patients and Methods: We performed a retrospective observational study in 134 hospitalized exacerbated COPD patients. 25-hydroxyvitamin D was modeled as a continuous or dichotomized (cutoff value: 10 or 20 ng/mL) variable to evaluate the association of SVDD with hospitalization in the previous year. Receiver operator characteristic (ROC) analysis was performed to find the optimal cut-off value of 25-hydroxyvitamin D.Results: In total 23% of the patients had SVDD. SVDD was more prevalent in women, and SVDD group tended to have lower blood eosinophils counts. 25-hydroxyvitamin D level was significantly lower in patients who were hospitalized in the previous year (13.6 vs 16.7 ng/mL, P = 0.044), and the prevalence of SVDD was higher (38.0% vs 14.3%, P = 0.002). SVDD was independently associated with hospitalization in the previous year [odds ratio (OR) 4.34, 95% CI 1.61– 11.72, P = 0.004] in hospitalized exacerbated COPD patients, whereas continuous 25-hydroxyvitamin D and VDD were not (P = 0.1, P = 0.9, separately). The ROC curve yielded an area under the curve of 0.60 (95% CI 0.50– 0.71) with an optimal 25-hydroxyvitamin D cutoff of 10.4 ng/mL.Conclusion: SVDD probably showed a more stable association with hospitalization in the previous year in hospitalized exacerbated COPD patients. Reasons for lower eosinophil counts in SVDD group needed further exploration.Keywords: association, vitamin D, severe deficiency, hospitalization for exacerbation, COPD

Yuan Xu,1 Jie Song,1 Jie Gao,1 Hongjing Zhang2 1Department of Gastroenterology, Dongying People’s Hospital(Dongying Hospital of Shandong Provincial Hospital Group), Dongying, Shandong, People’s Republic of China; 2Community Health Service Center in Hekou District, Dongying, Shandong, People’s Republic of ChinaCorrespondence: Yuan Xu, Department of Gastroenterology, Dongying People’s Hospital (Dongying Hospital of Shandong Provincial Hospital Group), No. 317 Nanyi Road, Dongying, Shandong, 257091, People’s Republic of China, Email jry0919@sina.comPurpose: Oxidative stress promotes disease progression by stimulating the humoral and cellular immune responses. However, the molecular mechanisms underlying oxidative stress and immune responses in acute pancreatitis (AP) have not been extensively studied.Patients and Methods: We analyzed the GSE194331 dataset and oxidative stress-related genes (OSRGs). We identified differentially expressed immune cell-associated OSRGs (DE-ICA-OSRGs) by overlapping key module genes from weighted gene co-expression network analysis, OSRGs, and DEGs between AP and normal samples. Functional enrichment analysis was performed to investigate the functions of DE-ICA-OSRGs. We then filtered diagnostic genes using receiver operating characteristic curves and investigated their molecular mechanisms using single-gene set enrichment analysis (GSEA). We also explored the correlation between diagnostic genes and differential immune cells. Finally, we constructed a transcription factor-microRNA-messenger RNA (TF-miRNA-mRNA) network of biomarkers.Results: In this study, three DE-ICA-OSRGs (ARG1, NME8 and VNN1) were filtered by overlapping key module genes, OSRGs and DEGs. Functional enrichment results revealed that DE-ICA-OSRGs were involved in the cellular response to reactive oxygen species and arginine biosynthesis. Latterly, a total of two diagnostic genes (ARG1 and VNN1) were derived and their expression was higher in the AP group than in the normal group. The single-gene GSEA enrichment results revealed that diagnostic genes were mainly enriched in macroautophagy and Toll-like receptor signaling pathways. Correlation analysis revealed that CD8 T cells, resting memory T CD4 cells, and resting NK cells were negatively correlated with ARG1, and neutrophils were positively correlated with ARG1, which was consistent with that of VNN1. The TF-miRNA-mRNA regulatory network included 11 miRNAs, 2 mRNAs, 10 transcription factors (TFs), and 26 pairs of regulatory relationships, like NFKB1-has-miR-2909-VNN1.Conclusion: In this study, two immune cell oxidative stress-related AP diagnostic genes (ARG1 and VNN1) were screened to offer a new reference for the diagnosis of patients with AP. Keywords: acute pancreatitis, oxidative stress, diagnosis, immunity

Shuang Xiao,1 Anthony Androulakis,2 William D Skelton,3 Irene L Quan,4 Jinlian Cheng,1 Yan Wang,1 Xueqi Zhu,1 Haiqun Zhang5 1Office of Drug Clinical Trial Institution, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2School of Public Health, University of South Carolina, Columbia, SC, USA; 3D.AC, The Acupuncture Clinic, Columbia, SC, USA; 4Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 5Trauma Orthopaedics, Beijing Fengsheng Special Hospital of Traditional Medical Traumatology and Orthopaedics, Beijing, People’s Republic of ChinaCorrespondence: Jinlian Cheng, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Art Museum Back Street, Dongcheng District, Beijing, People’s Republic of China, Tel +86-010-87906813, Email cjltitan@126.comAim: The aim of this study is to assess the willingness, motivation, satisfaction levels, and expectations of participants engaged in clinical trials, while also exploring factors that influence compliance from the participants’ standpoint. Furthermore, this research aims to enhance the understanding of all stakeholders involved in clinical trials about the needs of participants and to offer evidence-based and pragmatic recommendations for effectively managing clinical trial participants.Methods: An electronic questionnaire covers various aspects of Traditional Chinese Medicine (TCM) clinical trials. The distribution of the electronic questionnaire was facilitated through WeChat groups, WeChat Moments, and individual interactions. Count data was expressed in terms of frequency (or rate), and subsequent analysis was conducted utilizing the standard chi-squared test. A p value≤ 0.05 was considered significant. By drawing a Pareto chart, the priority of factors influencing participants’ willingness to participate in clinical trials was systematically assessed.Results: 88 participants answered the questionnaire. A decline in education level corresponded to a decreasing comprehension of participants’ grasp of “clinical trial” and “clinical trial participant” (p< 0.05). The primary reason for participants’ reservations about joining clinical trials stems from their inadequate comprehension of clinical trial details. The key factors contributing to participants’ reluctance to engage in clinical trials encompass aspects of trial design, the operational procedures, insufficient understanding of clinical trial particulars, concerns about potential harm to their bodies and opposition from family members. Importantly, these areas of participants’ hesitation and unwillingness to partake in clinical trials mirror the factors participants’ dissatisfaction contributing to.Conclusion: We found four factors significantly influencing participants’ willingness to engage and their overall satisfaction: the participant’s profile, trial design, trial institution setup, and the qualifications of the researchers. Derived from these critical factors, this paper presents a series of constructive measures.Keywords: clinical trial, traditional Chinese medicine, compliance, satisfaction, participants

Zi-Lin Chen,1,2 Xiang Ding,3 Lin Zhuo,3 Rong-Hua Li,4 Hong Zhang1,5 1Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 2Xiangya School of Nursing, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 3Organ Transplant Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 4Nuclear Medicine Department, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China; 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaCorrespondence: Hong Zhang, Email Zhong2800@csu.edu.cnBackground: Kidney transplantation is a critical treatment for end-stage renal disease (ESRD), with health-promoting lifestyle (HPL) significantly impacting patient outcomes. HPL involves behaviors like regular exercise, balanced nutrition, stress management, and habit modification. However, few studies have analyzed the HPL of renal transplant recipients, addressing a significant gap in current research.Objective: This study aimed to determine the predictors of HPL in renal transplant recipients using the Chinese Health Promoting Lifestyle Profile (HPLP).Methods: This cross-sectional study enrolled renal transplant recipients completing the revised Chinese HPLP at organ transplant center in a tertiary hospital in Hunan Province of China between May 2022 and July 2022.Results: A total of 450 patients were included, comprising 256 males (56.9%), with a mean age of 44.85 ± 10.57 years. The mean score of self-actualization, health responsibility, interpersonal support, physical activity, stress management, nutrition, and overall HPLP were 15.27 ± 5.03 (possible range: 0– 24), 11.41 ± 4.18 (possible range: 0– 24), 11.61 ± 3.13 (possible range: 0– 18), 7.53 ± 3.79 (possible range: 0– 18), 12.68 ± 3.61 (possible range: 0– 21), 11.17 ± 2.41 (possible range: 0– 15), and 69.66 ± 16.98 (possible range: 0– 120), respectively. Multivariate logistic regression analysis showed that urban residence (OR = 2.061, 95% CI: 1.350– 3.148, P = 0.001), non-smoking after transplantation (OR = 2.010, 95% CI: 1.123– 3.600, P = 0.019) and two post-transplant complications (OR=0.387, 95% CI: 0.218– 0.689, P = 0.001).Conclusion: Although renal transplant recipients exhibit a moderate level of HPL, targeted interventions are essential to improve these behaviors. These interventions should focus especially on individuals from rural households, post-transplant smokers, and those experiencing post-transplant complications, to enhance their quality of life and clinical outcomes.Keywords: health promotion, healthy lifestyle, kidney transplantation, cross-sectional study

Zheping Chen,1,&ast; Changli Gao,1,2,&ast; Yingchao Zhang,1,3 Yongxu Gao,1,4 Le Zhang,1 Shanshan Zhao,1 He Zhang,1 Xin Zhao,1 Yanwu Jin1 1Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Anesthesiology, Laoling People Hospital, Laoling, People’s Republic of China; 3Department of Anesthesiology, Shouguang People Hospital, Weifang, People’s Republic of China; 4Department of Anesthesiology, Jinan Third People’s Hospital, Laoling, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanwu Jin, Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Bei Yuan Street, Jinan, 250033, People’s Republic of China, Tel +86-17660085535, Email jinyanwu_aa@163.comBackground: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine.Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 μg·kg− 1 (RD0.5 Group) or 1.0 μg·kg− 1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 μg·kg− 1·h− 1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery.Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness.Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 μg·kg− 1) may be a more appropriate choice.Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).Keywords: dexmedetomidine, thoracic paravertebral nerve block, neuropathic pain, thoracoscopic surgery

Yidong Cui,1 Qingming Liu,2 Qiqiang Zhang,3 Xuemei Di,3 Hai Zhang3 1Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of China; 2Department of Neurology, Shandong Second Provincial General Hospital, Jinan, 250012, People’s Republic of China; 3Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Hai Zhang, Department of Pharmacy, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, No. 2699 West Gaoke Road, Shanghai, 200092, People’s Republic of China, Tel/Fax +8621-20261401, Email zhxdks2005@126.comBackground: Aconitum carmichaelii (Fuzi) has been conventionally used to cure a variety of ailments, such as pain, cold sensations, and numbness of limb muscles (Bi Zheng) in China. Our prior investigations identified Benzoylaconine (BAC) as a bioactive alkaloid derived from Aconitum carmichaelii, with other studies also demonstrating its significant pharmacological potential.Purpose: This study aimed to explore the potential of BAC as a protective agent against skeletal muscle ischemia-reperfusion (I/R) injury and to elucidate the underlying mechanisms.Methods: In vivo models involved subjecting Sprague-Dawley rats to I/R through femoral artery ligation followed by reperfusion, while in vitro models utilized C2C12 cells subjected to hypoxia/reoxygenation (H/R). CCK-8 assay was used to assess cell viability. TUNEL staining and flow cytometric analysis were used to measure cell apoptosis. Biochemical assay was used to assess skeletal muscle injury and oxidative stress. Immunofluorescence and Western blot were performed to determine protein levels.Results: BAC effectively protected muscle tissue from I/R injury, enhancing cell viability (p< 0.01), elevating SOD levels (p< 0.05), and reducing CK (p< 0.01), LDH (p< 0.01), ROS (p< 0.01), MDA (p< 0.01), and apoptosis-related molecules in vivo and in vitro (p< 0.05, p< 0.01). Mechanistically, BAC increased the expression of IF1, phosphorylated AMPK, facilitated the translocation of nuclear Nrf2, and induced the expression of HO-1 (p< 0.01). Notably, AMPK inhibitor Compound C significantly hindered the ability of BAC to ameliorate H/R-induced cell injury (p< 0.05), oxidative stress(p< 0.01), and apoptosis (p< 0.05), as well as promote Nrf2 nuclear translocation (p< 0.01). Moreover, silencing of IF1 with siRNA abolished BAC-induced activation of AMPK/Nrf2 axis (p< 0.01).Conclusion: Our study provides novel evidence supporting the potential of BAC as a myocyte-protective agent against I/R injury, and we establish a previously unknown mechanism involving the activation of the IF1-dependent AMPK/Nrf2 axis in mediating the protective effects of BAC. Keywords: Benzoylaconine, ischemia-reperfusion injury, oxidative stress, AMPK, IF1

Wang Yi,1,2 Weikai Wang,3 Hua Zhang,2 Ying Wang,2 Yong Zhou,2 Zhangyan Guo,2 Jingmei Li,2 Le Ma,2 Dan Yao,2 Taining Zhang,3 Yanqiang Du,2 Li Liu1 1Department of Neonatology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Pediatric Intensive Care Unit, the Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Pediatric intensive care unit, Gansu Provincial Maternity and Child Health Hospital, Gansu Provincial Central Hospital, Lanzhou, Gansu, People’s Republic of ChinaCorrespondence: Li Liu, Department of Neonatology, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Yanta District, Xi’an, Shaanxi, 710003, People’s Republic of China, Email liuli918@sohu.com Yanqiang Du, Department of pediatric intensive care unit, the Affiliated Children’s Hospital of Xi’an Jiaotong University, No. 69, Xiju Lane, Lianhu District, Xi’an, Shaanxi, 710003, People’s Republic of China, Email duyanqiang_xaetyy@163.comBackground: In Asia, Hanta virus (HTNV) results in severe hemorrhagic fever with renal syndrome (HFRS). The efficacy of sivelestat in treating children with HTNV-induced HFRS remains unclear.Methods: An ambispective cohort study was performed on children diagnosed with HFRS and hospitalized at the Children’s Hospital Affiliated to Xi’an Jiaotong University from August 2018 to 2023. Patients who received neutrophil elastin-inhibitor infusion between August 2019 and August 2023 were assigned to the sivelestat group, while patients who did not were assigned to the control group. The independent sample t test was used for inter-group analysis. The Chi-square test and Fisher’s exact probability test were used for categorical variables. Spearman correlation test was used to evaluate the correlation between two sets of continuous variables. Kaplan-Meier survival curve and Log -Rank test was used to evaluate the difference in cumulative probability of survival between the two groups.Results: No significant differences were observed between the two groups in gender, age, contact history, body mass index, HFRS severity, clinical indexes at admission. Compared to the control group, the sivelestat group exhibited a significant decrease in the interleukin-8 level at 48 h (28.5± 3 vs 34.5± 3.5) and 72 h (21.3± 4.5 vs 31.5± 5.6) (P< 0.05), as well as the ICAM-1 level at 48 h (553± 122 vs 784± 187) and 72 h (452± 130 vs 623± 85) (P< 0.05). The concentration of VCAM-1 in the sivelestat group exhibited a consistent downward trend. Moreover, the level of VCAM-1 was significantly lower than that in the control group at 24 h (1760± 289 vs 2180± 445), 48 h (1450± 441 vs 1890± 267), and 72 h (1149± 338 vs 1500± 396) (P< 0.05). Kaplan-Meier curve analysis revealed a statistically significant difference in the cumulative probability of survival between two groups (P = 0.041). In the secondary outcomes, the sivelestat group demonstrated a decrease in the utilization rate of mechanical ventilation and continuous renal replacement therapy (CRRT).Conclusion: Sivelestat may suppress neutrophil-mediated inflammatory response to reduce endothelial and organ damage, and improve clinical outcomes in children with severe hemorrhagic fever and renal syndrome.Keywords: Sivelestat, hemorrhagic fever with renal syndrome, vascular endothelial injury, inflammatory response, cohort study, children

Nan Mei,1,&ast; Sha Gong,1,&ast; Lizhao Wang,2 Lu Wang,1 Jincheng Wang,1 Jianpeng Li,3 Yingying Bao,4 Huanming Zhang,1 Huaiyu Wang1 1Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Breast Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 3Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 4Institute of Gene and Cell Therapy, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaiyu Wang, Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shannxi, 710061, People’s Republic of China, Email why@xjtufh.edu.cn; whymed@126.comBackground: Multiple myeloma (MM), an incurable plasma cell malignancy. The significance of the relationship between natural killer (NK) cell-related genes and clinical factors in MM remains unclear.Methods: Initially, we extracted NK cell-related genes from peripheral blood mononuclear cells (PBMC) of healthy donors and MM samples by employing single-cell transcriptome data analysis in TISCH2. Subsequently, we screened NK cell-related genes with prognostic significance through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. Following the initial analyses, we developed potential subtypes and prognostic models for MM using consensus clustering and lasso regression analysis. Additionally, we conducted a correlation analysis to explore the relationship between clinical features and risk scores. Finally, we constructed a weighted gene co-expression network analysis (WGCNA) and identified differentially expressed genes (DEGs) within the MM cohort.Results: We discovered that 153 NK cell-related genes were significantly associated with the prognosisof MM patients (P < 0.05). Patients in NK cluster A exhibited poorer survival outcomes compared to those in cluster B. Furthermore, our NK cell-related genes risk model revealed that patients with a high risk score had significantly worse prognoses (P < 0.05). Patients with a high risk score were more likely to exhibit adverse clinical markers. Additionally, the nomogram based on NK cell-related genes demonstrated strong prognostic performance. The enrichment analysis indicated that immune-related pathways were significantly correlated with both the NK subtypes and the NK cell-related genes risk model. Ultimately, through the combined use of WGCNA and DEGs analysis, and by employing Venn diagrams, we determined that ITM2C is an independent prognostic marker for MM patients.Conclusion: In this study, we developed a novel model based on NK cell-related genes to stratify the prognosis of MM patients. Notably, higher expression levels of ITM2C were associated with more favorable survival outcomes in these patients.Keywords: multiple myeloma, NK cell-related genes, NK subtypes, prognostic model, ITM2C

Donghao Wang,1,&ast; Yuting Zhang,1,&ast; Qiming Gan,1,&ast; Xiaofen Su,1,&ast; Haojie Zhang,1,2,&ast; Yanyan Zhou,1 Zhiyang Zhuang,1 Jingcun Wang,1 Yutong Ding,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang; Dongxing Zhao, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13600460056 ; +86-13650901411, Email nfzhanggird@163.com; rieast@163.comObjective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea–hypopnea index (AHI).Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR).Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07– 1.62, P < 0.01) and 1.45 (95% CI = 1.01– 2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02– 3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes.Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.Keywords: obstructive sleep apnea, arousal threshold, apnea–hypopnea index, hypertension, diabetes

Tingting Wang,1 Yang Wang,2 Qingyue Liu,1 Wenbin Guo,1 Hongliang Zhang,1 Liangliang Dong,3 Jiajun Sun1 1Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 2Department of Laboratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 3Department of Respiratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of ChinaCorrespondence: Jiajun Sun, Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, No. 306 Jiankang Road, Linqing, Shandong, People’s Republic of China, Tel +86-13793092818, Email 13793092818@126.comBackground: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population.Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (> 98), mild malnutrition (92– 98), moderate malnutrition (82– 91), and severe malnutrition (≤ 81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect.Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 > 98), the adjusted HR values for GNRI in Q3 (92– 98), Q2 (82– 91), and Q1 (≤ 81) were 1.81 (95% CI: 1.27– 2.58, p=0.001), 1.23 (95% CI: 0.84– 1.79, p=0.296), 2.27 (95% CI: 1.57– 3.29, p< 0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5.Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.Keywords: geriatric nutritional risk index, 90-day mortality, older adults, chronic obstructive pulmonary disease, MIMIC-IV

Jinjie Gao,1 Jiajia Zheng,2 Hua Zhang,3 Jijun Wang,1 Hongmei Jing1 1Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 2Department of Laboratory Medicine, Peking University Third Hospital, Beijing, 100191, People’s Republic of China; 3Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Hongmei Jing, Tel +86-010-82266785, Email hongmeijing@bjmu.edu.cnObjective: We performed a retrospective analysis to investigate the clinical predictors of bacteremia outcome involving Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) after initial empirical antimicrobial therapy among hematological malignancy cases.Methods: This retrospective study was conducted between April 2018 and April 2023. All bloodstream infections (BSIs) caused by E. coli and K. pneumoniae in hospitalized hematological malignancy (HM) patients were identified. Data on patient demographics, clinical characteristics, empirical antimicrobial treatment, outcomes and the antimicrobial susceptibility were collected from medical records. Multivariate analyses were utilized to assess the risk factors for all-cause mortality within 28 days and carbapenem resistance. Optimal cutoffs for continuous predictive variables were evaluated by receiver operating characteristic (ROC) curve analysis.Results: Among 61 individuals diagnosed with bacteremia, 39 cases were caused by E. coli bacteremia, while the remaining 22 were identified as K. pneumoniae bacteremia. Out of these, there were 10 cases of carbapenem-resistant Enterobacteriaceae (CRE) and 12 cases resulted in all-cause mortality within 28 days. Analysis indicated that Pitt score was an independent risk factor for mortality and a cut-off of 2.5 was a reliable predictor with 83.3% sensitivity and 85.7% specificity, respectively. Impaired mental status and elevated body temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on the third day (d3) after antimicrobial treatment were identified as independent risk factors for predicting carbapenem resistance.Conclusion: We found that Pitt score with a cut-off of 2.5 was a reliable predictor for mortality within 28 days in HM bacteremia cases. Impaired mental status and elevated temperature exceeding 38.6°C as well as a procalcitonin (PCT) level over 8.24 ng/mL on d3 after antimicrobial treatment were identified as predictive risk factors to carbapenem resistance.Keywords: antimicrobial resistance, mortality, risk factors, initial clinical response

Min Jiang,1,&ast; Hui Zhang,2,&ast; Wenjun Lu,3 Xuedan Qiu,1 Chenyao Lin,1 Rongqing Zhao,1 Qingcao Li,1 Qiaoping Wu1 1Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China; 2Clinical Laboratory, Ninghai County Chengguan Hospital, Ningbo, Zhejiang Province, People’s Republic of China; 3Intensive Care Units, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingcao Li; Qiaoping Wu, The Affiliated LiHuiLi Hospital of Ningbo University, 1111 Jiangnan Road, Ningbo, Zhejiang Province, 315040, People’s Republic of China, Tel +86-574-55835786, Fax +86-574-55835781, Email lqc_lab@163.com; lhlyywqp@163.comBackground: Klebsiella pneumoniae (KP) is a common nosocomial pathogen. Capsules are an important component of KP’s virulence, among which the K1, K2, K5, K20, K54, and K57 serotypes are predominant and exhibit varying degrees of virulence.Methods: The capsule and virulence genes of 150 carbapenem-resistant Klebsiella pneumoniae (CRKP) and 213 carbapenem-sensitive Klebsiella pneumoniae (CSKP) isolates were examined by polymerase chain reaction (PCR). The isolates were tested for hypermucoviscosity by string tests. Phylogenetic relationships between KP isolates were analyzed using multilocus sequence typing (MLST) and a Galleria mellonella infection model confirmed the differences in virulence.Results: A total of 111 of 363 isolates of KP were detected, the highest detected serotypes were K1, K5, and K2, and CSKP was detected more frequently than CRKP. There was a greater prevalence of K1 and K2 serotypes in CSKP, while in CRKP, K5 serotypes were more prevalent. K1 isolates had the highest detection rates for hypermucoviscosity Klebsiella pneumoniae (hmKP) and hypervirulent Klebsiella pneumoniae (hvKP), and carried the most virulence genes. K54 isolates had the lowest detection rate of hmKP while K5 isolates had the lowest detection rate of hvKP and carried the fewest virulence genes. MLST results for serotypes K1, K20, and K57 showed significant homogeneity, while those for serotypes K2, K5, and K54 showed diversity. The Galleria mellonella infection model showed that the K1 serotype was the most virulent and the K54 serotype was the weakest.Conclusion: CSKP isolates were detected more frequently than CRKP isolates for capsular serotype detection. K1 isolates had the most virulence gene and strongest virulence, K5 isolates carried the fewest virulence genes, and K54 isolates had the weakest virulence. Furthermore, significant homogeneity was observed among K1, K20, and K57 isolates.Keywords: Klebsiella pneumoniae, capsular serotypes, virulence, MLST

Yuwei Ma,1,2,&ast; Tao Jiang,1,2,&ast; Rong Zhang,1 Fei Liu,3 Shilong Song,1,2 Huijun Zhang,4 Jingwen Huang,1 Zelai He1,2 1The First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 2Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical University & Tumor Hospital Affiliated to Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 3Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, People’s Republic of China; 4Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zelai He; Jingwen Huang, Email hezelai@alumni.sjtu.edu.cn; he.ze.lai@163.com; byyfyhjw@163.comIntroduction: Lung cancer’s high incidence and dismal prognosis with traditional treatments like surgery and radiotherapy necessitate innovative approaches. Despite advancements in nanotherapy, the limitations of single-treatment modalities and significant side effects persist. To tackle lung cancer effectively, we devised a temperature-sensitive hydrogel-based local injection system with near-infrared triggered drug release. Utilizing 2D MXene nanosheets as carriers loaded with R837 and cisplatin (DDP), encapsulated within a temperature-sensitive hydrogel-forming PEG-MXene@DDP@R837@SHDS (MDR@SHDS), we administered in situ injections of MDR@SHDS into tumor tissues combined with photothermal therapy (PTT). The immune adjuvant R837 enhances dendritic cell (DC) maturation and tumor cell phagocytosis, while PTT induces tumor cell apoptosis and necrosis by converting light energy into heat energy.Methods: Material characterization employed transmission electron microscopy, X-ray photoelectron spectroscopy, phase transition temperature, and near-infrared thermography. In vitro experiments assessed Lewis cell proliferation and apoptosis using CCK-8, Edu, and TUNEL assays. In vivo experiments on C57 mouse Lewis transplant tumors evaluated the photothermal effect via near-infrared thermography and assessed DC maturation and CD4+/CD8+ T cell ratios using flow cytometry. The in vivo anti-tumor efficacy of MDR@SHDS was confirmed by tumor growth curve recording and HE and TUNEL staining of tumor sections.Results: The hydrogel exhibited excellent temperature sensitivity, controlled release properties, and high biocompatibility. In vitro experiments revealed that MDR@SHDS combined with PTT had a greater inhibitory effect on tumor cell proliferation compared to MDR@SHD alone. Combining local immunotherapy, chemotherapy, and PTT yielded superior anti-tumor effects than individual treatments.Conclusion: MDR@SHDS, with its simplicity, biocompatibility, and enhanced anti-tumor effects in combination with PTT, presents a promising therapeutic approach for lung cancer treatment, offering potential clinical utility.Keywords: 2D Mxene, drug delivery system, hydrogel, lung cancer

Jingxuan Wu,1,2,&ast; Wenzhu Zhang,1,2,&ast; Hong Zhang,1,2,&ast; Xingjia Lu,1,2,&ast; Biqing Luan,1,2,&ast; Qizhi Yang,1,2,&ast; Liang Chen,1,&ast; Wenlin Chen,3,&ast; Fei Ge1,&ast; 1Department of Breast Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China; 2No. 1 School of Clinical Medicine, Kunming Medical University, Kunming, 650000, People’s Republic of China; 3Third Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Ge, Department of Breast Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China, Email ajqnadjd@hotmail.com Wenlin Chen, Third Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650000, People’s Republic of China, Email chenwenlin1@hotmail.comAbstract: Breast cancer is one of the most common malignant tumors affecting women worldwide. Breast cancer is a complex disease characterized by abnormal growth of cells in the breast tissue. Metastasis, the spread of cancer cells from the primary tumor site to distant organs, is a major challenge in the management of breast cancer. Although metastasis to distant sites is a well-known feature of breast cancer, scalp involvement is relatively rare. The occurrence of scalp metastasis signifies an advanced stage of the disease. The 51-year-old female discovered a firm, painless mass in her right breast that had been there for two years. It had been pricking for a month, and the biopsy revealed that the mass was invasive carcinoma of the right breast. Imaging tests suggested that the tumor was malignant. Adjuvant endocrine therapy and postoperative adjuvant chemotherapy were administered following a modified radical resection for breast cancer. Eleven months later, radiation treatment and replace endocrine therapy was used. 32 months following surgery, a scalp tumor was discovered; a pathology biopsy verified the origin of the breast cancer; three months later, bone, brain, and visceral metastases were discovered. After that, she received oral capecitabine treatment and was admitted into the hospital for advanced rescue treatment. She is currently in the disease stability state, her disease is effectively managed, and no new metastatic lesions have been discovered.Keywords: breast cancer, scalp metastasis, chemotherapy, radiotherapy, endocrine therapy, case report

Guangtian Wang,1,2,&ast; Zhihui Li,3,&ast; Gongchen Wang,4,&ast; Qixu Sun,5 Peng Lin,1 Qian Wang,2 Huishu Zhang,6 Yanyan Wang,7 Tongshuai Zhang,8 Feiyun Cui,9 Zhaohua Zhong1,2 1Teaching Center of Pathogenic Biology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Microbiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 3Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 4Department of Vascular Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, People’s Republic of China; 5Department of Gastroenterology, Penglai People’s Hospital, Yantai, Shandong, 265600, People’s Republic of China; 6Teaching Center of Biotechnology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 7Teaching Center of Morphology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 8Department of Neurobiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China; 9Department of Physiology, School of Basic Medical Sciences, Harbin Medical University, Harbin, Heilongjiang, 150081, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaohua Zhong; Feiyun Cui, Email zhongzh@hrbmu.edu.cn; feiyun@hrbmu.edu.cnAbstract: Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment. Keywords: angiogenesis, ischemic stroke, nanoparticles, blood brain barrier, neurogenesis, neuroprotection therapy

Wenbin Li,1,2,&ast; Haohan Zhang,3,&ast; Zuo You,4 Baozhu Guo5 1Department of Clinical Oncology, Qianjiang Hospital Affiliated to Renmin Hospital of Wuhan University, Qianjiang, Hubei, People’s Republic of China; 2Department of Clinical Oncology, Qianjiang Central Hospital of Hubei Province, Qianjiang, Hubei, People’s Republic of China; 3Cancer Center, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Department of Traditional Chinese Medicine, Xianfeng County People’s Hospital, Enshi, Hubei, People’s Republic of China; 5Department of Pain, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuo You, Department of Traditional Chinese Medicine, Xianfeng County People’s Hospital, Enshi, 445600, People’s Republic of China, Email hbzyyouzuo@126.com Baozhu Guo, Department of Pain, Renmin Hospital of Wuhan University, Wuhan, Hubei, 430060, People’s Republic of China, Email 18071120246@163.comAbstract: Emerging studies suggest that long non-coding RNAs (lncRNAs) participate in the mutual regulation of cells in tumor microenvironment, thereby affecting the anti-tumor immune activity of immune cells. Additionally, the intracellular pathways mediated by lncRNAs can affect the expression of immune checkpoints or change the cell functions, including cytokines secretion, of immune and stromal cells in tumor microenvironment, which further influences cancer patients’ prognosis and treatment response. With the in-depth research, lncRNAs have shown great potency as a new immunotherapy target and predict immunotherapy response. The research on lncRNAs provides us with a new insight into developing new immunotherapy drugs and predicting the outcome of immunotherapy. With development of RNA sequencing technology, amounts of lncRNAs were found to be dysregulated in immune and stromal cells rather than tumor cells. These lncRNAs function through ceRNA network or regulating transcript factor activity, thus leading abnormal differentiation and activation of immune and stromal cells. Here, we review the function of lncRNAs in the immune microenvironment and focus on the alteration of lncRNAs in immune and stromal cells, and discuss how these alterations affect tumor growth, metastasis and treatment response.Keywords: lncRNA, immune and stromal cells, tumor microenvironment, differentiation, cytokine secretion

Jian Zhou,1,2,&ast; Housheng Zheng,1,&ast; Huiru Zhang,1 Wenqiang Yu,1 Baoer Li,1 Liang Ye,1 Lu Wang1 1Hyperbaric Oxygen Department, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Wang, Hyperbaric oxygen department, Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-21839715, Email luwangszu@163.com Liang Ye, International Cancer Center, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-26631420, Fax +86-0755-86671943, Email liangyeszu@163.comObjective: MCM5 is a DNA licensing factor involved in cell proliferation and has been previously established as an excellent biomarker in a number of malignancies. Nevertheless, the role of MCM5 in GBM has not been fully clarified. The present study aimed to investigate the potential roles of MCM5 in the treatment of GBM and to elucidate its underlying mechanism, which is beneficial for developing new therapeutic strategies and predicting prognosis.Methods: Firstly, we obtained transcriptomic and proteomic data from the TCGA and CPTAC databases on glioma patients. Employing the DeSeq2 R package, we then identified genes with joint differential expression in GBM tissues subjected to chemotherapy. To develop a prognostic risk score model, we performed univariate and multivariate Cox regression analyses. In vitro knockdown and overexpression of MCM5 were used to further investigate the biological functions of GBM cells. Additionally, we also delved into the upstream regulation of MCM5, revealing associations with several transcription factors. Finally, we investigated differences in immune cell infiltration and drug sensitivity across diverse risk groups identified in the prognostic risk model.Results: In this study, the chemotherapy-treated GBM samples exhibited consistent alterations in 46 upregulated and 94 downregulated genes at both the mRNA and protein levels. Notably, MCM5 emerged as a gene with prognostic significance as well as potential therapeutic relevance. In vitro experiments subsequently validated the role of increased MCM5 expression in promoting GBM cell proliferation and resistance to TMZ. Correlations with transcription factors such as CREB1, CTCF, NFYB, NRF1, PBX1, TEAD1, and USF1 were discovered during upstream regulatory analysis, enriching our understanding of MCM5 regulatory mechanisms. The study additionally delves into immune cell infiltration and drug sensitivity, providing valuable insights for personalized treatment approaches.Conclusion: This study identifies MCM5 as a key player in GBM, demonstrating its prognostic significance and potential therapeutic relevance by elucidating its role in promoting cell proliferation and resistance to chemotherapy.Keywords: glioblastoma, minichromosome maintenance protein 5, chemotherapeutic drug resistance

Houxi Xu,1,2,&ast; Hongqun Zhang,1,3,&ast; Songxian Sun,2,&ast; Jingyuan Zhang,2 Jiege Huo,1,3 Chunxiang Zhou2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing, University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3The Third School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunxiang Zhou, School of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, People’s Republic of China, Email chunxiangzhou@njucm.edu.cn Jiege Huo, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China, Email huojiege@jsatcm.comBackground: The CD1A gene, a key component of the human immune system and part of the CD1 family, plays a crucial role in presenting lipid antigens to T cells. Abnormal CD1A expression is associated with various immune-related diseases and tumors. However, the biological function of CD1A in COAD is unclear.Methods: Multiple databases were systematically employed to conduct an analysis of CD1A expression in pan-cancer and COAD, along with its clinical-pathological features. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses of CD1A were performed using the ‘clusterProfiler’ package. The Protein-protein interaction (PPI) analysis of CD1A was used the STRING database. Additionally, TIMER and ssGSEA tools were used to explore the relationship between CD1A expression in COAD and immune cell infiltration. The study also investigated the association between CD1A expression and N6-methyladenosine (m6A) modification genes in the TCGA COAD cohort and constructed a CD1A-centric competing endogenous RNA (ceRNA) regulatory network.Results: CD1A displays varying expression levels in various tumors, including COAD, and is closely linked to clinical-pathological characteristics. GO analysis suggests that CD1A plays a role in important processes like antigen processing and presentation, leukocyte-mediated immunity, and lymphocyte-mediated immunity. KEGG analysis identifies CD1A’s involvement in key pathways such as the Chemokine signaling pathway and Cytokine-cytokine receptor interaction. PPI analysis highlights CD1A’s interactions with CD207, CD1C, CD1E, FOXP3, and ITGB2. ssGSEA analysis indicates a significant relationship between CD1A expression and the infiltration of various immune cells in COAD. Significant associations were found between CD1A and m6A modification genes in COAD. Furthermore, a CD1A-centered ceRNA regulatory network has been constructed.Conclusion: CD1A emerges as a potential biomarker for the diagnosis and treatment of COAD, showing a strong association with tumor immune infiltration, m6A modification, and the ceRNA network.Keywords: CD1A, COAD, immune infiltration, m6A, ceRNA

Guo Chen,1 Duoduo Yu,2 Yichen Wang,1 Zou Ma,1 Mengna Bi,1 Lisha Lu,1 Shangshang Zhang,1 Jiaxin Liu,1 Hu Chen,1 Hai Shen,2 Huiwu Zhang,2 Xiaobing Luo,2 Yan Si,1 Peng Zhang1 1Department of Geriatric Orthopedics(1), Sichuan Provincial Orthopedic Hospital, Chengdu, Sichuan, 610041, People’s Republic of China; 2Sichuan Provincial Orthopedic Hospital, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Peng Zhang, Tel +86-19980487275, Email yicoal@yeah.netPurpose: The aim of this study is to investigate the effects of a preoperative combined with postoperative moderate-intensity progressive resistance training (PRT) of the operative side in patients with hip osteoarthritis (HOA) who are undergoing total hip arthroplasty (THA). The study seeks to evaluate the impact of this combined intervention on muscle strength, gait, balance, and hip joint function in a controlled, measurable, and objective manner. Additionally, the study aims to compare the outcomes of this combined intervention with those of preoperative or postoperative muscle strength training conducted in isolation.Methods: A total of 90 patients with HOA scheduled for unilateral primary THA were randomly assigned to three groups: Pre group (preoperative PRT), Post group (postoperative PRT), and Pre& Post group (preoperative combined with postoperative PRT) focusing on hip flexion, extension, adduction, and abduction of operated side. Muscle strength, gait parameters, balance, and hip function were assessed at specific time points during a 12-month follow-up period.Results: All three groups showed significant improvements in muscle strength, with the Pre& Post group demonstrating the most pronounced and sustained gains. Gait velocity and cadence were significantly improved in the Pre& Post group at 1-month and 3-month postoperative follow-ups compared to the other groups. Similarly, the Pre& Post group exhibited superior balance performance at 3-month and 12-month postoperative follow-ups. The Harris Hip Score also showed better outcomes in the Pre& Post group at all follow-up intervals.Conclusion: Preoperative combined with postoperative moderate-intensity PRT in HOA patients undergoing THA led to superior improvements in muscle strength, gait, balance, and hip joint function compared to preoperative or postoperative PRT alone. This intervention shows significant promise in optimizing postoperative rehabilitation and enhancing patient outcomes following THA.Keywords: exercise therapy, muscle strength, progressive resistance training, total hip arthroplasty, gait variability

Chenlu Ma,1 Wen Zhang,1 Shu Da,2 Huan Zhang,3 Xichao Zhang1 1Faculty of Psychology, Beijing Normal University, Beijing, 100875, People’s Republic of China; 2School of Psychology, Nanjing Normal University, Nanjing, 210024, People’s Republic of China; 3Academy of Global Innovation & Governance, University of International Business and Economics, Beijing, 100029, People’s Republic of ChinaCorrespondence: Xichao Zhang, Faculty of Psychology, Beijing Normal University, No. 19 XinJieKouWai Street, HaiDian District, Beijing, 100875, People’s Republic of China, Email xchzhang@bnu.edu.cnPurpose: Environmental uncertainty has reached unprecedented levels in recent years. While there is substantial knowledge about the connection between environmental uncertainty and organizational outcomes, limited attention has been devoted to investigating its impact on employees’ depression and anxiety symptoms. Grounded in job demands-resources theory, this study aims to explore the relationship between environmental uncertainty and employees’ depression and anxiety symptoms, and it further investigates the mediating role of work pressure and the moderating role of union practices.Methods: In September 2022, we undertook a cross-sectional survey study, gathering data from 1081 employees across various enterprises situated in Liaoning, China. Throughout this timeframe, notable global occurrences heightened the awareness of environmental uncertainty. Following the exclusion of participants who did not provide information on the main variables, the final valid sample comprised 940 employees. To test all hypotheses, a series of confirmatory factor analyses and path-analytic procedures were conducted using Mplus 7.0.Results: Our results confirm that environmental uncertainty, as a high job demand, increases employees’ work pressure, thereby elevating rates of anxiety and depression; the indirect relationship between environmental uncertainty and employees’ anxiety and depression through work pressure is stronger when union practices are lower.Conclusion: Our findings indicate the detrimental impact of environmental uncertainty on employees’ mental health, and highlight the roles of work pressure and union practices. In light of this, organizations should take steps to mitigate employees’ perceptions of environmental uncertainty and establish mental health programs, in cooperation with union practices, to protect employees’ mental well-being.Keywords: environmental uncertainty, anxiety, depression, union practices, work pressure

Sijie Jiang,1– 4 Shaobing Xie,1– 4 Zhihai Xie,1– 4 Weihong Jiang,1– 4 Hua Zhang1– 4 1Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2Hunan Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 4Anatomy Laboratory of Division of Nose and Cranial Base, Clinical Anatomy Center of Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Weihong Jiang; Hua Zhang, Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital of Central South University, 87 Xiangya Road, Kaifu District, Changsha, 410008, People’s Republic of China, Tel/Fax +86731-89753045, Email jiangwh68@126.com; entxy@126.comBackground: Elevated serum uric acid is crucial in the pathophysiology of chronic inflammatory diseases. However, its impact on chronic rhinosinusitis (CRS) recurrence risk is unknown. This study investigates the association between elevated serum uric acid and the risk of CRS recurrence.Methods: A retrospective cohort study was conducted on 1004 CRS patients (including 638 males and 366 females) who received functional endoscopic sinus surgery. All patients were followed up for more than 2 years, and categorized into subgroups based on phenotype, gender, and postoperative recurrence. Cox regression analysis was performed to evaluate the associations between serum uric acid and the risk of CRS recurrence.Results: After categorization, 104 males had hyperuricemia, and 54 females presented hyperuricemia. The rate of recurrent CRS in the hyperuricemia group was significantly higher compared to the non-hyperuricemia group in both males and females (P< 0.05). In both male and female patients, the rate of hyperuricemia and uric acid levels were elevated in the recurrent CRS group in comparison with the non-recurrent CRS group (P< 0.05). Unadjusted and adjusted Cox regression analysis demonstrated that serum uric acid was an independent risk factor for CRS recurrence (P< 0.05). The receiver operator characteristic curve showed that serum uric acid was a potential biomarker for predicting the recurrence of CRS and its phenotypes in both genders (P< 0.05).Conclusion: There is a close relationship between elevated serum uric acid and the recurrence risk of CRS and its phenotypes, suggesting that serum uric acid may be a novel biomarker for predicting recurrent CRS.Keywords: chronic rhinosinusitis, uric acid, hyperuricemia, biomarker, recurrence

Quan Hu,1,&ast; Yingxiao Li,2,&ast; Zhaochen Lin,3 Hao Zhang,4 Haoyue Chen,4 Cui Chao,3 Chuanliang Zhao5 1Department of Neurosurgery, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 2Department of Gynecology, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 3Hydrogen Medical Research Center, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 4Department of Rehabilitation Medical Center, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China; 5Department of Orthopedics, the Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanliang Zhao, Department of Orthopedics, The Affiliated Taian City Central Hospital of Qingdao University, Tai’an City, Shandong, 271000, People’s Republic of China, Tel +8615621539631, Email zhaochuanliang2003@163.comAbstract: Hydrogen, which is a novel biomedical molecule, is currently the subject of extensive research involving animal experiments and in vitro cell experiments, and it is gradually being applied in clinical settings. Hydrogen has been proven to possess anti-inflammatory, selective antioxidant, and antiapoptotic effects, thus exhibiting considerable protective effects in various diseases. In recent years, several studies have provided preliminary evidence for the protective effects of hydrogen on spinal cord injury (SCI). This paper provides a comprehensive review of the potential molecular biology mechanisms of hydrogen therapy and its application in treating SCI, with an aim to better explore the medical value of hydrogen and provide new avenues for the adjuvant treatment of SCI.Keywords: hydrogen, spinal cord injury, selective antioxidant, anti-inflammatory

Wenyan Sun,1,&ast; Xuetong Zhao,2– 4,&ast; Nicola Dalbeth,5,&ast; Robert Terkeltaub,6 Lingling Cui,1 Zhen Liu,1 Lin Han,1 Can Wang,1 Hui Zhang,1,7 Yiming Bao,2– 4 Changgui Li,1,7 Jie Lu1,7 1Shandong Provincial Key Laboratory of Metabolic Diseases, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2National Genomics Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation, Beijing, 100101, People’s Republic of China; 3CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Science and China National Center for Bioinformation, Beijing, People’s Republic of China; 4University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 5Department of Medicine, University of Auckland, Auckland, New Zealand; 6VA San Diego VA Healthcare Center, University of California San Diego, San Diego, CA, USA; 7Institute of Metabolic Diseases, Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Lu, Shandong Provincial Key Laboratory of Metabolic Diseases and Qingdao Key Laboratory of Gout, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Email 13127006046@163.com Changgui Li, Shandong Provincial Key Laboratory of Metabolic Diseases, Shandong Provincial Clinical Research Center for Immune Diseases, the Affiliated Hospital of Qingdao University, Qingdao, 266003, People’s Republic of China, Email changguili@vip.163.comObjective: This study aimed to understand predictors of inadequate response (IR) to low-dose febuxostat treatment based on clinical variables.Methods: We pooled data from 340 patients of an observational cohort and two clinical trials who received febuxostat 20 mg/day for at least 3 months. IR was defined as failure to reach the target serum urate level (sUA< 6 mg/dL) at any time point during 3 months treatment. The potential predictors associated with short- or mid-term febuxostat IR after pooling the three cohorts were explored using mixed-effect logistic analysis. Machine learning models were performed to evaluate the predictors for IR using the pooled data as the discovery set and validated in an external test set.Results: Of the 340 patients, 68.9% and 51.8% were non-responders to low-dose febuxostat during short- and mid-term follow-up, respectively. Serum urate and triglyceride (TG) levels were significantly associated with febuxostat IR, but were also selected as significant features by LASSO analysis combined with age, BMI, and C-reactive protein (CRP). These five features in combination, using the best-performing stochastic gradient descent classifier, achieved an area under the receiver operating characteristic curve of 0.873 (95% CI [0.763, 0.942]) and 0.706 (95% CI [0.636, 0.727]) in the internal and external test sets, respectively, to predict febuxostat IR.Conclusion: Response to low-dose febuxostat is associated with early sUA improvement in individual patients, as well as patient age, BMI, and levels of TG and CRP.Keywords: gout, febuxostat, urate-lowering therapy, machine learning model