Search

Xiang He,1– 3,* Qin Ran,2,3,* Xiaolan Li,2,3,* Anying Xiong,2,3 Lei Zhang,2,3 Manling Jiang,2,3 Lingling Bai,2 Dan Peng,2 Junyi Wang,2,3 Baoqing Sun,1 Guoping Li1– 3 1National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 2Laboratory of Allergy and Precision Medicine, Chengdu Institute of Respiratory Health, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, 610031, People’s Republic of China; 3Department of Respiration, Chengdu third People’s hospital Branch of National Clinical Research Center for Respiratory Disease, Affiliated Hospital of ChongQing Medical University, Chengdu, 610031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guoping Li; Baoqing Sun, Email lzlgp@163.com; sunbaoqing@vip.163.comIntroduction: Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment (TME), and their polarization state significantly influences patient outcomes. This study investigates the inhibitory effects of β-glucan extracted from Candida albicans on lung cancer progression, focusing on its impact on TAM polarization and the induction of ferroptosis, a form of regulated cell death.Methods: Utilizing both in vivo animal models and in vitro cellular assays, we assessed the impact of β-glucan on tumor growth, cellular proliferation, and migration. We evaluated TAM polarization by analyzing the expression of M1 and M2 markers and identified differentially expressed genes (DEGs) related to ferroptosis. The role of ferroptosis in TAM polarization was further confirmed by assessing the protein levels of ACSL4 and GPX4, intracellular ferrous ion levels, and lipid peroxides.Results: β-glucan treatment significantly reduced tumor size and weight, along with cellular proliferation and migration, suggesting a potent suppressive effect on lung cancer cell growth. β-glucan promoted an M1-like phenotype in TAMs, as evidenced by increased CD86 expression and decreased CD206 expression, and modulated cytokine mRNA levels. RNA sequencing analysis post β-glucan treatment identified a substantial number of DEGs enriched in the ferroptosis pathway. The induction of ferroptosis by β-glucan was further confirmed through the significant upregulation of ACSL4 and downregulation of GPX4, alongside increased intracellular ferrous ion levels and lipid peroxides. The ferroptosis inhibitor Fer-1 abrogated these effects, highlighting the specificity of β-glucan-mediated polarization.Conclusion: These results collectively provide novel insights into the immunotherapeutic potential of β-glucan from Candida albicans and its role in modulating TAM polarization and lung cancer growth, offering a promising avenue for cancer treatment strategies.Keywords: β-glucan, lung cancer, TAMs, macrophage polarization, ferroptosis, C. albicans

Wenxin Wu,1,* Kai Chang,2,3,* Liying Bai1 1School of Humanities and Social Sciences, Fuzhou University, Fuzhou, People’s Republic of China; 2Institute of Education, Xiamen University, Xiamen, People’s Republic of China; 3College of Chemistry, Fuzhou University, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liying Bai, School of Humanities and Social Sciences, Fuzhou University, 2 Wulongjiang North Avenue, Fuzhou, 350108, People’s Republic of China, Email bxuer@fzu.edu.cnBackground: The mental health of graduate students is increasingly turning into one of the main issues in global health. Understanding the antecedents of graduate students’ mental health and finding ways to improve the situation are crucial for the students and the entire educational system.Purpose: This study explores the relationship between supervisor narcissism and graduate students’ mental health. Additionally, the study examines the mediating effects of mentorship styles (relationship-oriented and task-oriented) and the moderating role of student’s proactive personality.Methods: This study conducted a three-wave survey, with each wave administered at four-month intervals, involving 547 graduate students. They completed questionnaires on supervisor narcissism, mentorship styles, proactive personality, and mental health. SPSS 26.0 was used to test our hypotheses.Results: This study indicated that: (1) Supervisor narcissism was negatively associated with graduate students’ mental health, fully mediated by relationship-oriented and task-oriented mentorships; (2) Graduate students’ proactive personalities moderated the relationship between these mentorship styles and their mental health; (3) Graduate students’ proactive personalities moderated the indirect effect of supervisor narcissism on students’ mental health through these mentorship styles.Conclusion: This study reveals the detrimental mechanisms through which supervisor narcissism affects graduate students’ mental health. It also demonstrates that enhancing students’ proactive personalities can mitigate these adverse effects. These findings provide empirical evidence within the context of higher education. Practical implications are provided for supervisors, students, and university administrators, emphasizing the importance of effectively matching supervisors with students and promoting students’ proactive personalities. These measures are essential for improving the mental health of graduate students.Keywords: supervisor narcissism, mental health, mentorship style, proactive personality

Ke Wang, Xuelu Wang, Chenying Xu, Lina Bai Operating Room, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Xuelu Wang; Chenying Xu, Operating Room, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 2699 West Gaoke Road, Pudong New Area, Shanghai, People’s Republic of China, 200092, Email wangxuelu@51mch.com; xuchenying@51mch.comObjective: Reasonable surgical scheduling management is crucial to optimize the utilization rate of operating room. This study aims to understand the context, frontier and hot spots of surgical scheduling management research, in order to provide reference for surgical scheduling optimization.Methods: Literature on operation scheduling management collected in Web of Science core collection database was searched from the database establishment to June 21, 2023. HisCite Pro 2.1 software was used to analyze the publication time, countries, research institutions, journals, authors, keywords and highly cited papers.Results: A total of 1383 literatures were included, and research institutions in the United States, Canada and other countries played a leading role in this field. Among them, the combination of machine algorithm and system model optimization to improve the accuracy of surgical duration prediction is the future research focus in this field.Conclusion: Improving operation efficiency is one of the key issues in operating room management. Managers should find the best operation scheduling plan from a more detailed and comprehensive perspective to improve operation efficiency.Keywords: surgery, schedule, manage

Kunping Cui,1 Yi Mao,2 Shuang Feng,3 Haixia Luo,2 Jiao Yang,2 Lang Bai1 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Intensive Care Unit, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of China; 3Ultrasonic Medicine, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of ChinaCorrespondence: Lang Bai, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980602254, Email pangbailang@163.comPurpose: The mortality rate from pulmonary tuberculosis (PTB) complicated by severe community-acquired pneumonia (SCAP) in the intensive care unit (ICU) remains high. We aimed to develop a rapid and simple model for the early assessment and stratification of prognosis in these patients.Patients and Methods: All adult patients with PTB complicated by SCAP admitted to the ICU of a tertiary hospital in Chengdu, Sichuan, China between 2019 and 2021 (development cohort) and 2022 (validation cohort) were retrospectively included. Data on demographics, comorbidities, laboratory values, and interventions were collected. The outcome was the 28-day mortality. Stepwise backward multivariate Cox analysis was used to develop a mortality risk prediction score model. Receiver operating characteristic (ROC) and calibration curves were used to evaluate the model’s predictive efficiency. Decision curve analysis (DCA) was used to validate the model’s clinical value and impact on decision making.Results: Overall, 357 and 168 patients were included in the development and validation cohorts, respectively. The Pulmonary Tuberculosis Severity Index (PTSI) score included long-term use of glucocorticoid, body mass index (BMI) < 18.5 kg/m2, diabetes, blood urea nitrogen (BUN) ≥ 7.14 mmol/L, PO2/FiO2 < 150 mmHg, and vasopressor use. The area under the ROC curve (AUC) values were 0.817 (95% CI: 0.772– 0.863) and 0.814 for the development and validation cohorts, respectively. The PTSI score had a higher AUC than the APACHE II, SOFA, and CURB-65 score. The calibration curves indicated good calibration in both cohorts. The DCA of the PTSI score indicated the high clinical application of the model compared with the APACHE II and SOFA scores.Conclusion: This prognostic tool was designed to rapidly evaluate the 28-day mortality risk in individuals with PTB complicated by SCAP. It can stratify this patient group into relevant risk categories, guide targeted interventions, and enhance clinical decision making, thereby optimizing patient care and improving outcomes.Keywords: pulmonary tuberculosis, severe community-acquired pneumonia, mortality risk prediction, intensive care unit

Zhiyuan Wang,1,&ast; Ruilin Wang,1,&ast; Xiaoyu Li,1,&ast; Lin Bai,1 Pingan Fan,1 Yuanyuan Tang,2 Xin Li,3 Yangmu Huang,4 Xiaoyan Nie,1,5 Sheng Han,1,5 Luwen Shi,1,5 Jing Chen1,5 1Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2Bidding Management Office, Suqian First Hospital, Suqian, Jiangsu, People’s Republic of China; 3Department of Clinical Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4School of Public Health, Peking University, Beijing, People’s Republic of China; 5International Research Center for Medicinal Administration, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Chen, Email jingchen@bjmu.edu.cnBackground: Although affordable generics could probably contribute to the solution of rapidly increasing pharmaceutical expenditure, those drugs are prescribed at a lower rate in China. Physicians’ perception and knowledge of generics have a great influence on their prescribing behavior.Objective: This study aimed to identify factors that affect physicians’ generic prescribing behavior based on the theory of planned behaviors (TPB).Methods: Data were collected by both electronic and paper-based surveys from 1297 Chinese physicians, and 1047 surveys were retained. The structural equation model (SEM) was employed to investigate the relationship between four behavioral constructs, namely, attitudes, subjective norms, perceived control of behaviors, and intentions.Results: About 50% of Chinese physicians had a positive attitude towards generic drugs that had passed the “Consistency Evaluation of Quality and Efficacy of Generic Drugs” (high-quality generic drugs), but their knowledge of generic drugs was relatively inadequate. The path coefficients for the effect of attitudes, subjective norms, and perceived behavioral control on behavioral intention were 0.285, 0.366, and 0.322 respectively. The path coefficients for the effect of behavioral intention and perceived behavioral control on prescribing behavior were 0.009 and 0.410 respectively.Conclusion: Physicians’ attitudes, subjective norms, and perceived behavioral control were significant positive correlation predictors of behavioral intention. Subjective norms and perceived behavior control had a greater impact than attitude on physicians’ prescribing intention. However, the generic prescribing behavior is not under the volitional control of Chinese physicians. Physicians’ prescribing practice is likely affected by perceived strong control over prescribing generic drugs.Keywords: generic prescribing behavior, perception, structural equation model, theory of planned behaviors

Xiaoyu Zhou,1– 3 Fei Du,1– 3 Wei Peng,4 Li Bai,5 Leyi Peng,1– 3 Xiaorong Hou1– 3 1College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Medical Data Science Academy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Chongqing Engineering Research Center for Clinical Big Data and Drug Evaluation, Chongqing, 400016, People’s Republic of China; 4The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, People’s Republic of China; 5Hospital of Zigong Mental Health Central, Sichuan, 643021, People’s Republic of ChinaCorrespondence: Xiaorong Hou, Chongqing Medical University, No. 1, Medical College Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Email xiaoronghou@cqmu.edu.cnPurpose: Long-term care facilities are increasingly challenged with meeting the diverse healthcare needs of the elderly population, particularly concerning medication management. Understanding medication information literacy and behavior among this demographic is imperative. Therefore, this qualitative study aims to explore medication information literacy and develop distinct medication profiles among elderly long-term care residents.Material and Methods: In this study, we conducted in-depth semi-structured interviews with 32 participants aged 65 or older residing in a long-term care facility. The interviews were designed to explore participants’ understanding of medication information, medication management practices, and experiences with healthcare providers. Thematic analysis was employed to analyze the interview data, allowing for the identification of common patterns and themes related to medication-taking behavior among the elderly residents.Results: The thematic analysis revealed four distinct medication behavior profiles among the elderly long-term care residents: (1) Proactive Health Self-Managers, (2) Medication Information Adherents, (3) Experience-Based Medication Users, and (4) Nonadherent Medication Users. These findings provide valuable insights into the diverse approaches to medication management within long-term care facilities and underscore the importance of tailored interventions to support the specific needs of each profile.Conclusion: This study highlights the necessity for tailored medication education and support to optimize medication management for the elderly. With the aging population expansion, addressing the unique medication challenges within long-term care facilities becomes increasingly critical. This research contributes to ongoing endeavors to enhance healthcare services for the elderly, striving for safer and more effective medication-taking behavior.Keywords: medication information literacy, medication profile, long-term care facility, qualitative study, elderly

Kunping Cui,1,&ast; Yi Mao,2,&ast; Shuang Feng,3 Haixia Luo,2 Jiao Yang,2 Ruyi Xu,1 Lang Bai1 1Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 2Intensive Care Unit, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of China; 3Ultrasonic Medicine, Public Health Clinical Center of Chengdu, Chengdu, Sichuan, 610000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lang Bai, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980602254, Email pangbailang@163.comPurpose: Age is considered a vital factor in intensive care units (ICUs) because of its association with physiological frailty, comorbidities, and immune system function. Previous studies have examined the association between age and prognosis in patients with tuberculosis (TB) or sepsis; however, the association between age and prognosis in ICU patients with TB complicated by sepsis is rare. This study aimed to assess the association between age and the prognosis of patients in the ICU with TB complicated by sepsis.Patients and Methods: Data from the ICU of the Public Health Clinical Center of Chengdu were analyzed using the multivariable Cox regression model, stratified analysis with interaction, restricted cubic spline (RCS), and threshold effect analysis to investigate the association between age and 28-day all-cause mortality in patients with TB complicated by sepsis.Results: In total, 520 patients diagnosed with TB and sepsis were enrolled (120 women [23.1%]; median age, 64 years). The association between age and risk of death exhibited a J-shaped curve on the RCS (P for nonlinearity = 0.001). In the threshold analysis, the hazard ratio for the risk of death was 1.104 (95% confidence interval, 1.05– 1.16) in participants aged ≥ 66.2 years. The risk of death increased by 10.4% with every 1-year increase in age in patients with TB complicated by sepsis. No significant association was found between age and 28-day all-cause mortality in patients aged < 66.2 years.Conclusion: A nonlinear relationship was observed between age and short-term all-cause mortality in patients in the ICU with TB complicated by sepsis. Patients with a higher age at admission may have a higher risk of death and require focused attention, close monitoring, and early treatment to reduce mortality.Keywords: sepsis, tuberculosis, age, 28-day all-cause mortality, intensive care unit

Yujing Zhang,1,&ast; Haiqian Wang,2,&ast; Lei Bai,1 Xiaodong Li,1 Li Liu,1 Liang Wang3 1Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 2Department of Outpatient, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 3Department of Interventional Therapy and Vascular Surgery, Dongguan People’s Hospital, Dongguan, 523059, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Wang, Department of Interventional Therapy and Vascular Surgery, Dongguan People’s Hospital, Dongguan, 523059, People’s Republic of China, Email nx.vascular@hotmail.comObjective: To establish the endovascular repair and prognosis of patients with aorto-iliac aneurysm and Brucella abortus infection.Methods: From September 2018 to September 2021, seven cases of Brucella abortus infection with aorto-iliac aneurysm were treated by the endovascular aneurysm repair (EVAR) procedure. Clinical and imaging data were collected to evaluate the therapeutic results, including body temperature, blood culture, imaging manifestations, stent patency and endoleak during the postoperative and follow-up periods.Results: Except for one patient who died of acute hematemesis and hematochezia just after the admission, seven patients were treated successfully. The aneurysms were completely excluded, and all stent grafts were patent. Patients were followed up for 12– 32 months, with an average follow-up of 18.5 ± 9.1 months. There were no cases of endoleak, infection recurrence, gluteal muscle ischemia or spinal cord ischemia during the follow-up period.Conclusion: It is feasible to treat Brucella abortus-infected aneurysms with the EVAR procedure. The results were optimistic in the short and medium-term. The application of sensitive antibiotics before and after the operation is the cornerstone of endovascular therapy. However, the long-term results require further follow-up.Keywords: Brucella abortus infection, aorto-iliac aneurysm, endovascular aneurysm repair, bacterial infection, zoonosis, mycotic aneurysm

Ning Ma,1 Liwei Bai,2 Qiang Lu1 1Department of Endocrinology, First Hospital of Qinhuangdao, Hebei, Qinhuangdao, 066000, People’s Republic of China; 2Qinhuangdao Hospital for Maternal and Child Health, Hebei, Qinhuangdao, 066000, People’s Republic of ChinaCorrespondence: Qiang Lu, Department of Endocrinology, First Hospital of Qinhuangdao, Hebei, Qinhuangdao, 066000, People’s Republic of China, Tel +86 13933909066, Email 13933909066@126.comPurpose: This study seeks to assess the potential of early pregnancy Triglyceride Glucose Index (TyG), triglyceride to High-Density Lipoprotein Cholesterol ratio (TG/HDL-c), Low-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol ratio (LDL-C/HDL-C), and Total Cholesterol to High-Density Lipoprotein Cholesterol ratio (TC/HDL-C) in predicting Gestational Diabetes Mellitus (GDM).Patients and Methods: A total of 1073 adults singleton pregnant women were enrolled from June 2017 to September 2019. Complete anthropometric data and lipid profiles were measured in the first trimester (before 12 weeks gestation) and a 75g oral glucose tolerance test (OGTT) at 24– 28 weeks was performed. Based on OGTT results, participants were categorised into Normal Glucose Tolerance (NGT) group (n=872) and GDM group (n=201). General data, laboratory test results, and surrogate insulin resistance indicators such as TyG index, TG/HDL-C, LDL-C/HDL-C, and TC/HDL-C were documented and compared. To compare differences between the two groups, t-test was used, Spearman correlation analysis and linear regression analysis were performed to establish associations between these indicators and insulin resistance in GDM. Receiver Operating Characteristic (ROC) curves were generated to compare the thresholds of these indicators for predicting GDM during pregnancy and to quantify overall diagnostic accuracy.Results: Individuals with GDM had higher TyG, TG/HDL-C, and LDL-C/HDL-C levels (P < 0.001), but with no significant difference observed in TC/HDL-C. All four ratios were positively correlated with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), yet only TyG emerged as an independent risk factor for HOMA-IR. The Area under the Curve (AUC) of TyG index (0.692) was comparable to that of HOMA-IR (0.703). The cut-off points for TyG index, TG/HDL-C, and HOMA-IR in predicting GDM were 7.088, 0.831, and 1.8, respectively. HOMA-IR exhibited the highest sensitivity (79.1%), while TyG index (64.3%) and TG/HDL-C ratio (64.3%) demonstrated better specificity compared to HOMA-IR (56.3%). LDL-C/HDL-C and TC/HDL-C offered no discernible predictive advantage.Conclusion: Early pregnancy TyG index and TG/HDL-C can aid in identifying pregnant women at risk for GDM, potentially facilitating early and effective intervention to improve prognosis. TyG index exhibited superior predictive capability compared to TG/HDL-C.Keywords: TyG, gestational diabetes mellitus, glucose and lipid metabolism, insulin resistance

Xiaojing Li,1 Liwei Bai,2 Ziru Niu,3 Qiang Lu3 1Department of Obstetrics, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of China; 2Department of Obstetrics, Qinhuangdao Hospital for Maternal and Child Health, Qinhuangdao, Hebei, 066000, People’s Republic of China; 3Department of Endocrinology, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Qiang Lu, Department of Endocrinology, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of China, Tel +86-13933909066, Email 13933909066@126.comPurpose: The objective of this study was to explore whether neck circumference can serve as an early predictor of the risk of Gestational Diabetes (GDM).Patients and Methods: A total of 318 singleton pregnant women who underwent routine prenatal examinations at Qinhuangdao Maternal and Child Health Hospital from September 2017 to September 2020 were selected and categorized into the GDM group and the normal glucose tolerance group (NGT) based on the results of the oral glucose tolerance test (OGTT) conducted during the second trimester. The general information and laboratory test results were compared and analyzed. Inter-group comparison was conducted using the t-test, and multivariate logistic regression analysis was employed to analyze the independent risk factors of GDM. The predictive threshold of various indicators for GDM occurrence during pregnancy was determined using the subject’s work curve.Results: The GDM group exhibited significantly higher levels of pre-pregnancy weight, pre-pregnancy BMI, neck circumference, waist circumference, hip circumference, triglycerides (TG), uric acid (UA), TG/HDL-C ratio, and waist-hip ratio compared to the NGT group. Additionally, HDL cholesterol (HDL-C) levels were significantly lower in the GDM group, and blood glucose levels at each point of the OGTT were markedly higher compared to the NGT group (P< 0.05). Multivariate logistic regression analysis revealed that neck circumference (OR=1.239, P< 0.001) and early pregnancy TG (OR=1.842, P< 0.001) were independent risk factors for GDM. The receiver operating characteristic analysis demonstrated that the optimal critical value of neck circumference for predicting GDM was 32.6 cm, with a sensitivity of 50% and specificity of 74.3%.Conclusion: The neck circumference during early pregnancy was found to be related to GDM, and the predictive cutoff point of 32.6 cm for neck circumference could be employed as a simple index to predict GDM in early pregnancy.Keywords: neck circumference, gestational diabetes, obesity, predictive indicators

Jing Liao,1,2 Mengyao Jiang,1,2 Jiaxiu Liu,1,2 Xiaoyu Zhou,1,2 Zuyue Zhang,3 Qingmao Rao,4 Li Bai,5 Xiaorong Hou1,2 1College of Medical Informatics, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Medical Data Science Academy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Chengdu Blood Center, Chengdu, 610041, People’s Republic of China; 4Educational Affairs Office, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610065, People’s Republic of China; 5Hospital of Zigong Mental Health Central, Zigong, Sichuan, People’s Republic of ChinaCorrespondence: Xiaorong Hou, Email xiaoronghou@cqmu.edu.cnBackground: E-consultation medical services have become popular globally, which offers patients more options, regardless of time or location. However, research indicates a prevalent issue with the communication quality in e-consultations, leading to sub-optimal patient experiences.Objective: This study aims to design an evaluation system for e-consultation quality. The developed scale guides operators in improving services and users in assessing their experience. It aids in selecting e-consultation services, saving costs, and assisting doctors in making informed decisions.Methods: This study combines existing scales, literature analysis, and expert consultation to form preliminary evaluation indicators. Fourteen experts were invited using stratified purposive sampling. Two rounds of Delphi method were conducted to exclude indicators that did not meet basic conditions. The final evaluation system was determined through expert discussions and revisions. The Analytic Hierarchy Process (AHP) quantified indicator weights.Results: Both rounds of the questionnaire saw compelling response rates of 100% (14 out of 14) and 92.86% (13 out of 14), respectively. Meanwhile, the Expert Authority Coefficient (Cr) was recorded at 0.89 and 0.88, respectively, while the Kendall Consistency Coefficient (Kendall W) for all level indicators fluctuated between 0.133 and 0.37 (P< 0.05). The ultimate indicator system formulated includes three primary indicators, ten secondary indicators, and thirty-two tertiary indicators. The highest to lowest weighted first-level indicators were ‘Joint Decision-Making between Doctors and Patients’ (0.6232), ‘Patient Responsiveness’ (0.2395), and “Interpersonal Relationship between Doctors and Patients” (0.1373). Weights for the second-level and third-level indicators were also determined.Conclusion: A scientific scale for e-consultation quality evaluation has been created, which effectively captures the essence of online medical communication and patient experiences. It enriches the theoretical framework for evaluating e-consultation quality, broadens perspectives in Internet medicine, provides practical guidance for network medical service managers and users and the development of the “Internet + medical health” service model.Keywords: e-consultation, quality assessment scale, doctor-patient relationship, medical staff, user perception

Chunye Dai,1,&ast; Xuelu Wang,1,&ast; Chenying Xu,1 Lina Bai,1 Yuehong Li2 1Operating Room, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Nursing Department, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenying Xu, Tel +86 021-20261099, Email xuchenying@51mch.comBackground: The COVID-19 pandemic used to be a major public health emergency which affected people worldwide, and it affected individuals’ body, mood, work and lifestyle to some extent. The pregnant woman affected by the unstable hormone will be more sensitive than normal ones. Long-term depression and anxiety could feedback on their body and lead to a host of pregnancy complications. Because pregnant women who choose cesarean section are awake during the perioperative period, to ensure safety, the degree of cooperation about psychology and behavior is relatively high, so we should know the psychological state of such a group of people.Objective: This study aims to explore psychological experience and influential factors of pregnant women who decided elective caesarean section after the COVID-19 pandemic.Methods: This is a cross-sectional study carried out in a hospital in Shanghai, according to the inclusion and exclusion criteria, we selected pregnant women who selected elective cesarean section as the study objects, all participants provided informed consent and completed questionnaires, including sociodemographic questionnaire, Generalized Anxiety Disorder scale (GAD-7) and General Well-Being Schedule (GWBS). Software SPSS 23.0 was used to analyze and explore the influencing factors.Results: Eligible 595 questionnaires were included in the study, the mean score of GAD-7 was 4.855 ± 3.254 and 90.699 ± 13.807 of GWBS. Generalized linear regression analysis revealed several factors that were statistically significant with the two scales, including birthplace, average monthly income, number of abortion and pregnancy complication (p < 0.01).Conclusion: The COVID-19 infection status and symptoms around infection have no statistical difference in anxiety level and general well-being after they experience the COVID-19 pandemic. However, through this study, we found some influencing factors that worth further exploration. In the future, we will expand the sample size to explore the different situation of multi-center, and we hope provide psychological nursing interventions based on existing results to offer a better delivery experience.Keywords: public health emergency, cesarean section, pregnant woman, psychological experience

Lin Zhang, Chao Xu, Lin Bai, Lin Li, Jinyan Guo, Yanyi Li Department of Intensive Care Unit, Heilongjiang Provincial Hospital, Harbin, Heilongjiang, 150036, People’s Republic of ChinaCorrespondence: Yanyi Li, Tel +8615304513567, Email shengicu@126.comBackground: Intensive care unit (ICU) patients with sepsis who experience severe lymphopenia are at a higher risk of mortality, and they serve as a more accurate indicator of bacteremia compared to traditional infection markers.Aim: Our study aimed to examine the influence of severe lymphopenia on ICU mortality and outcomes in sepsis patients, while also evaluating the clinical significance of comprehensive nursing intervention in preventing severe lymphopenia.Methods: Patients with sepsis in the ICU at our hospital between January 2015 and January 2021 were split into a control group and a test group.The control group received regular nursing care, while the test group was provided with comprehensive nursing care in addition to the control group. The results encompassed mortality rates of 28 days, mortality rates of 1 year, and lengths of stay in the ICU.Results: Our attention was directed towards day 4 absolute lymphocyte counts, taking into account the receiver operating characteristic (ROC) outcome. Patients with severe lymphopenia were older, more patients with 2 above comorbidities, higher co-infection rates and SOFA score. In addition, patients with severe lymphopenia required longer days stay in ICU (P< 0.001), and presented with higher 28-day mortality (P=0.038) and 1-year mortality (P=0.004). Patients in control group have a higher incidence of severe lymphopenia (P=0.006), 28-day mortality (P=0.015) and 1-year mortality (P=0.019) compared with the test group.Conclusion: Comprehensive nursing intervention can prevent the occurrence of severe lymphopenia, improve patients satisfaction and reduce mortality.Keywords: sepsis, lymphopenia, comprehensive nursing, survival, intensive care unit, ICU

Bin Zhang,1,&ast; Yanyan Song,1,&ast; Qian Ma,2,&ast; Jian Yang,1 Lei Bai1 1Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Anesthesiology, Tumor Hospital, General Hospital of Ningxia Medical University, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Bai, Email baileibl02h@126.comObjective: To investigate the changes and significance of perioperative expression levels of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-related lipocalin (NGAL), and heme oxygenase-1 (HO-1) in patients with acute kidney injury (AKI) after cardiac valve replacement under cardiopulmonary bypass.Methods: A total of 80 patients were divided into the AKI group and non-AKI group based on the postoperative occurrence of AKI. The expression levels of urinary KIM-1, NGAL, serum creatinine, urea nitrogen, and HO-1 were compared between the two groups before surgery and at 12 h, 24 h, and 48 h after surgery.Results: There were 22 patients with postoperative AKI (AKI group), the incidence of postoperative AKI were 27.5%, and there were 58 patients without AKI (non-AKI group). There was no significant difference in general clinical data between the two groups (P > 0.05). Compared between AKI group and preoperative group, KIM-1, NGAL, HO-1, blood creatinine, and BUN levels were significantly increased, with significant differences (P < 0.05). Compared with non-AKI groups, KIM-1, NGAL, HO-1, blood creatinine, and blood urea nitrogen levels increased at all time points, but the difference was not significant (P > 0.05). Compared with AKI group and non-AKI group, KIM-1, NGAL, HO-1, blood creatinine, and BUN levels increased significantly, the differences were statistically significant (P < 0.05).Conclusion: AKI can easily occur after cardiac valve replacement and postoperative expression levels of KIM-1, NGAL, and HO-1 can be early warning indicators of postoperative AKI.Keywords: acute kidney injury, cardiac valve replacement, heme oxygenase-1, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin

Zhongbao Wang,1 Yunshao Zheng,2 Yunli Fan,2 Yunming Fan,2 Xianbiao Su,2 Bingrui Wang,2 Jing Li,2 Diancai Chen,2 Fengxia Sun,2 Shen Li,2 Jiashu Ma,1 Xianwei Li,2 Ludong Bai,2 Ranran Li2 1Department of Psychiatry, Jining Medical University, Jining, People’s Republic of China; 2Department of Psychiatry, Shandong Mental Health Center, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Ranran Li, Department of Psychiatry, Shandong Mental Health Center, Shandong University, 49 East Wenhua Road, Jinan, Shandong, 250014, People’s Republic of China, Tel +86 18678777190, Email dtlrr113@126.comBackground: Most antipsychotic drugs are dopamine receptor antagonists that usually lead to abnormal increases in prolactin concentrations and the development of hyperprolactinemia (HPRL), which in turn causes sexual dysfunction in patients. Peony-Glycyrrhiza Decoction (PGD) enhanced dopamine D2 receptors (DRD2) and dopamine transporter (DAT) and significantly reversed the expression of DRD2 and DAT. Therefore, we hypothesized that PGD might effectively improve hyperprolactinemia and alleviate sexual dysfunction in patients.Methods: We performed an 8-week randomized controlled study on 62 subjects with schizophrenia who were randomized into two groups. The experimental group was treated with the PGD intervention, and the control group did not receive treatment. The primary outcome indicators were the levels of sex hormones and the total Arizona Sexual Experience Scale (ASEX) score.Results: There was a significant difference in PRL levels between the two groups at weeks 4 and 8. From the beginning to the end of the experiment, there was a significant increase in PRL levels in the control group, while there was no significant change in the experimental group. The ASEX scale assessed sexual function in both groups, and patients in the experimental group showed an improvement in sexual function at week 8. During the experiment, the two groups found no differences between Positive and Negative Syndrome Scale (PANSS) scores and Treatment Emergent Symptom Scale (TESS) scores.Conclusion: PGD significantly improved the patient’s sexual function but was less effective in reducing prolactin levels and may prevent further increases in prolactin levels.Keywords: hyperprolactinemia, antipsychotics, Peony-Glycyrrhiza Decoction, schizophrenia, sexual function, adverse effects

Xue Song,1 Jiaqi Wang,2 Lu Bai,1 Wei Zou3 1The First Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 2The Second Clinical Medical College, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China; 3First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of ChinaCorrespondence: Wei Zou, The First Clinical Medical College, Heilongjiang University of Chinese Medicine, 26 Heping Road, Xiangfang District, Harbin, Heilongjiang, People’s Republic of China, Email kuangzou1965@163.comBackground: Migraine is a serious global health concern that imposed a huge economic burden on social health care. Over the past few decades, the analgesic effects of acupuncture have been widely recognized, and there is a growing body of research on acupuncture for migraine. Citation analysis is a branch of bibliometrics that helps researchers analyze and identify historical or landmark studies within the scientific literature. Currently, there is no analysis of the 100 most highly cited publications on acupuncture for migraine.Methods: The 100 most highly cited publications on acupuncture for migraine were screened using the Science Citation Index Expanded of the Web of Science Core Collection database. CiteSpace and VOSviewer programs were used for bibliometric analysis.Results: A total of 493 publications on acupuncture for migraine were identified. 100 of the most highly cited publications on acupuncture for migraine were published from 1984– 2020. These publications were cited 6142 times with an h-index of 44 and 84% were original articles. The highest frequency of citations was 416. A total of 335 authors were involved in the study with 37 lead authors. 212 institutions from 20 countries contributed to the 100 most highly cited publications. The most published studies came from the United States (n=36), followed by China (n=27) and Germany (n=26). The Technical University of Munich published the largest number of papers (n = 15). Top-cited publications mainly came from the Headache (n=13, citations=582). Neuroimaging is gradually emerging as a hot topic of research.Conclusion: This is the first bibliometric analysis to offer a thorough list of the 100 most highly cited papers on acupuncture for migraine, demonstrating significant progress and emerging trends in this field to assist researchers in determining the direction for further research.Keywords: acupuncture, bibliometric analysis, citation analysis, migraine, CiteSpace, VOSviewer

Xingyi Wang, Lishuang Bai, Xiao Ma, Li-Shan Yang Emergency Department, General Hospital of Ningxia Medical University, Yinchuan, 750000, People’s Republic of ChinaCorrespondence: Li-Shan Yang, Email nyfyyls@126.comAbstract: Arsenic and its compounds are widely found in nature. They are often absorbed into the human body through the respiratory tract, skin and digestive tract, and distributed throughout the body through the blood. It is more common in coal burning arsenic poisoning and drinking water arsenic poisoning. In recent years, arsenic poisoning related to industrial production has also been reported. Two cases of hydrogen arsenide poisoning related to industrial production were reported and analyzed in order to improve the treatment level.Keywords: hydrogen arsenide poisoning, blood purification, special effect antidote, cluster therapy

Luyuan Bai,1 Weiye Liang,1 Yongqian Wang,2 Ning Fan,1 Qi zhang,3 Yun Bian,1 Fude Yang1 1Peking University Huilongguan Clinical Medical School, Beijing Huilongguan Hospital, Beijing, People’s Republic of China; 2Office of Scientific Research, Peking University Health Science Center, Beijing, People’s Republic of China; 3Department of Psychology, Wuxi Mental Health Center, Wuxi, People’s Republic of ChinaCorrespondence: Fude Yang; Yun Bian, Peking University Huilongguan Clinical Medical School, 7, Nandian Road, Huilongguan, Changping District, Beijing, 100096, People’s Republic of China, Tel +86-010-83024456 ; +86-010-83024572, Email yangfd_200@163.com; ihqihqajjq@163.comObjective: This study aims to explore the ability of betahistine to inhibit weight gain and abnormal lipid metabolism in patients with chronic schizophrenia.Methods: A comparison study of betahistine or placebo therapy was conducted for 4 weeks in 94 patients with chronic schizophrenia, who were randomly divided into two groups. Clinical information and lipid metabolic parameters were collected. Positive and Negative Syndrome Scale (PANSS) was used to assess psychiatric symptoms. Treatment Emergent Symptom Scale (TESS) was used to evaluate treatment-related adverse reactions. The differences in lipid metabolic parameters before and after treatment between the two groups were compared.Results: Repeated measures analysis of variance (ANOVA) revealed that after 4 weeks of betahistine/placebo treatment, the interaction effect of time and group was statistically significant on low-density lipoprotein cholesterol (F = 6.453, p = 0.013) and waist-to-hip ratio (F = 4.473, p = 0.037), but did not reveal any significant interaction effect of time and group on weight, body mass index or other lipid metabolic parameters, as well as the time main effect and group main effect (all p > 0.05). Betahistine had no significant impact on PANSS, and no side effects related to betahistine were detected.Conclusion: Betahistine may delay metabolic abnormalities in patients with chronic schizophrenia. It does not affect the efficacy of the original antipsychotics. Thus, it provides new ideas for the treatment of metabolic syndrome in patients with chronic schizophrenia.Keywords: schizophrenia, lipid metabolism, betahistine, histamine, H3-receptor antagonist

Liangzhi Zhang,1 Hui Li,1,2 Lulu Bai,1,2 NaiChun Ji1 1Department of Sports Health Research Center, Xi ‘an Medical University, Xi’an City, People’s Republic of China; 2Department of Knee Surgery, Hong Hui Hospital, Xi’an Jiaotong University, Xi’an City, People’s Republic of ChinaCorrespondence: Hui Li, Department of Sports Health Research Center, Xi ‘an Medical University, Xinwang Road, Xi’an City, 710021, Shaanxi Province, People’s Republic of China, Tel/Fax +86-18092901809, Email lhxahhyy@163.comBackground: Increasingly, patient satisfaction after total knee arthroplasty (TKA) is being recognized as an important measure of health-care quality in osteoarthritis (OA) patients. But satisfaction after TKA has not yet been reported in Kashin-Beck disease (KBD). We aim to examine satisfaction and clinical efficacy of TKA in the treatment of OA and KBD.Methods: Retrospectively review of 37 KBD patients (45 knees) and 52 OA patients (58 knees) who underwent TKA from January 2015 to January 2017. Data of outcome measures such as Knee Society knee score (KSKS) and function score (KSFS), Western Ontario and McMaster Universities Arthritis Index (WOMAC), and radiographic evaluation were collected preoperatively and during the last follow-up. Satisfaction was compared using the 2011 Knee Society Scoring System.Results: There were no differences in age, gender, BMI and Follow-up time. KBD patients had significantly worse preoperative range of motion, KSKS, and mechanical lateral distal femoral angle (mLDFA) compared with OA patients (P < 0.05). At the last follow-up, the KSKS, KSFS, WOMAC score, and radiographic parameters of all patients significantly improved (P < 0.05), but the satisfaction was higher in KBD patients than in OA (P < 0.05). Further analysis showed that KSFS, WOMAC total, pain, stiffness, and function scores were significantly worse for KBD (P < 0.05).Conclusion: Patient satisfaction was greater but clinical outcomes were inferior in KBD than in OA. This study also demonstrated that TKA is an effective surgical procedure for KBD, but how to improve functional outcomes needs to be further studied.Keywords: Kashin-Beck disease, osteoarthritis, total knee arthroplasty, satisfaction

Yunming Tian,1 Wei-Zeng Huang,2 Lei Zeng,3 Li Bai,1 Fei Han,4,* Yuhong Lan1,* 1Department of Radiation Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong Province, People’s Republic of China; 2Department of Medical Oncology, Huizhou First Hospital, Huizhou, Guangdong Province, People’s Republic of China; 3Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jixiang Province, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Han, Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China, Email hanfeisysucc@126.com Yuhong Lan, Department of Radiation Oncology, Hui Zhou Municipal Central Hostpital, Huizhou, Guangdong Province, People’s Republic of China, Email lanyuhonghzyy@126.comObjective: To investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).Methods: A cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan–Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors.Results: In total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age > 50 years, lactate dehydrogenase > 245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms.Conclusion: High rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.Keywords: failure patterns, intensity-modulated radiotherapy, nasopharyngeal carcinoma, surveillance

Xuerun Peng,1,&ast; Zhipeng Zhao,1,&ast; Liwen Liu,2 Lan Bai,1 Rongsheng Tong,1 Hao Yang,3 Lei Zhong1 1Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, People’s Republic of China; 2Department of Obstetrics and Gynecology, Fengrun District People’s Hospital, Tangshan, Hebei, 063000, People’s Republic of China; 3POWERCHINA Chengdu Engineering Corporation Limited, Chengdu, Sichuan, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zhong, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, People’s Republic of China, Email zhl7235301@163.com Hao Yang, POWERCHINA Chengdu Engineering Corporation Limited, Chengdu, 610072, Sichuan, People’s Republic of China, Email yanghao@chidi.com.cnAbstract: Indoleamine 2.3-dioxygenases (IDO1/2) and tryptophan 2.3-dioxygenase (TDO) are the initial and rate-limiting enzymes in tryptophan metabolism, which play an essential role in mediating immunosuppression in tumor microenvironment. Accumulating evidence has indicated that both IDO1 and TDO are highly expressed in many malignant tumors, and their expression is generally associated with reduced tumor-infiltrating immune cells, increased regulatory T-cell infiltration, as well as cancer progression and poor prognosis for malignancies. A large number of IDO1 and TDO inhibitors have been screened or synthesized in the last two decades. Thus far, at least 12 antagonists targeting IDO1 and TDO have advanced to clinical trials. In this account, we conducted a comprehensive review of the development of IDO1 and TDO inhibitors in cancer immunotherapy, particularly their clinical research progress, and presented the current challenges and corresponding solutions.Keywords: indoleamine 2, 3-dioxygenase, tryptophan-2, 3-dioxygenase, tryptophan metabolism, cancer immunotherapy, immune tolerance

Weitong Song,1 Lu Bai,1 Yuya Yang,1 Yongchao Wang,2 Pingxiang Xu,1,3 Yuming Zhao,1 Xuelin Zhou,1,3 Xiaorong Li,1,3 Ming Xue1,3 1Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, People’s Republic of China; 3Beijing Laboratory for Biomedical Detection Technology and Instrument, Beijing, People’s Republic of ChinaCorrespondence: Ming Xue, Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Youanmen, Beijing, 100069, People’s Republic of China, Tel +8610-83950416, Fax +8610-83911520, Email xuem@ccmu.edu.cnPurpose: We designed a novel isoliquiritigenin (ISL) loaded micelle prepared with DSPE-PEG2000 as the drug carrier modified with the brain-targeting polypeptide angiopep-2 to improve the poor water solubility and low bioavailability of ISL for the treatment of acute ischemic stroke.Methods: Thin film evaporation was used to synthesize the ISL micelles (ISL-M) modified with angiopep-2 as the brain targeted ligands. The morphology of the micelles was observed by the TEM. The particle size and zeta potential were measured via the nanometer particle size analyzer. The drug loading, encapsulation and in vitro release rates of micelles were detected by the HPLC. The UPLC-ESI-MS/MS methods were used to measure the ISL concentrations of ISL in plasma and main tissues after intravenous administration, and compared the pharmacokinetics and tissue distributions between ISL and ISL-M. In the MCAO mice model, the protective effects of ISL and ISL-M were confirmed via the behavioral and molecular biology experiments.Results: The results showed that the drug loading of ISL-M was 7.63 ± 2.62%, the encapsulation efficiency was 68.17 ± 6.23%, the particle size was 40.87 ± 4.82 nm, and the zeta potential was − 34.23 ± 3.35 mV. The in vitro release experiments showed that ISL-M had good sustained-release effect and pH sensitivity. Compared with ISL monomers, the ISL-M could significantly prolong the in vivo circulation time of ISL and enhance the accumulation in the brain tissues. The ISL-M could ameliorate the brain injury induced by the MCAO mice via inhibition of cellular autophagy and neuronal apoptosis. There were no the cellular structural damages and other adverse effects for ISL-M on the main tissues and organs.Conclusion: The ISL-M could serve as a promising and ideal drug candidate for the clinical application of ISL in the treatment of acute ischemic stroke.Keywords: isoliquiritigenin, micelle, brain distribution, pharmacokinetics, ischemic stroke, MCAO

Gang Wang,1,&ast; Le Xiao,1,&ast; Hongye Ren,2 Kenneth Simonsen,2 Jingdong Ma,3 Xiangdong Xu,4 Ping Guo,5 Zhiren Wang,6 Ludong Bai,7 Elin Heldbo Reines,2 Lene Hammer-Helmich2 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 2Medical Affairs, H. Lundbeck A/S, Valby, Denmark; 3Medical Affairs, Lundbeck China, Beijing, People’s Republic of China; 4Department of Psychiatry, Xinjiang Mental Health Center, Xinjiang, People’s Republic of China; 5Department of Psychosomatic Disorders, The 3rd People’s Hospital of Huzhou City, Huzhou, People’s Republic of China; 6Department of Science & Technology, Beijing Huilongguan Hospital, Beijing, People’s Republic of China; 7Department of Psychiatry, Shandong Mental Health Center, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Elin Heldbo Reines, Medical Affairs, H. Lundbeck A/S, Ottiliavej 9, Valby, 2500, Denmark, Tel +45 30832313, Email er@lundbeck.comBackground: Major depressive disorder (MDD) affects > 163 million people worldwide and is a leading cause of disability in China. Functional impairment occurs alongside cognitive symptoms, anxiety, and depression, reducing quality of life and productivity in patients with MDD.Purpose: The multimodal antidepressant vortioxetine has demonstrated efficacy in relieving depressive and functional symptoms of MDD in randomized controlled trials (RCTs). The RELIEVE China study aimed to investigate the real-world effectiveness of vortioxetine in China.Patients and Methods: This was an observational, prospective cohort study in patients with MDD initiating treatment with vortioxetine at physician’s discretion in China. Participants were followed up for 24 weeks and assessed at 3 time points: baseline, week 8, and week 24. The primary objective was to assess the change from baseline to weeks 8 and 24 in functional impairment as measured by Sheehan Disability Scale (SDS) total score. Additional assessments included SDS subdomains, measures of depression severity, anxiety, and cognition. The safety and tolerability of vortioxetine were also examined.Results: In total, 859 patients were included in the analysis. A consistent and significant improvement in functional impairment was observed during the study, with baseline mean SDS total score (16.7 points) decreasing by 5.42 (SE, 0.22) and 8.71 (SE, 0.226) points at week 8 and week 24, respectively (P< 0.0001). Improvements in other functioning, cognitive, and anxiety assessments were also observed (all P< 0.0001). A total of 74.7% of patients had responded, and 63.9% had reached remission at week 24. The tolerability profile of vortioxetine in this real-world population was consistent with the established tolerability profile for this drug.Conclusion: This study demonstrated the short- and long-term effectiveness and tolerability of vortioxetine for patients with MDD in a real-world setting in China. These findings are consistent with the efficacy and safety profile observed during RCTs.Keywords: China, cognition, functioning, major depressive disorder, real-world evidence, vortioxetine

We consider the testing and estimation of change-points, locations where the distribution abruptly changes, in a sequence of observations. Motivated by this problem, in this contribution we first investigate the extremes of Gaussian fields with trend, which then help us to give the asymptotic p-value approximations of the likelihood ratio statistics from change-point models., 1. Introduction Change-point problems appear to have arisen originally in problems of quality control, where one observes the output of a production process sequentially and wants to signal any departure [...]

1. In order to compare the difference between different derivatisations for amino acids determination of foie gras via, reversed phase high performance liquid chromatography (HPLC), O-phthalaldehyde and 9-fluorenyl-methyl chloroformate (OPA-FMOC group), phenylisothiocyanate (PITC group) and 6-Aminoquinolyl-N-hydrox-ysuccinimidyl Carbamate (AQC group) were applied to derivatisation reagent in this current experiment. The determination results of automatic amino acid analyser were applied, and 17 amino acids were detected by these three derivatisation methods. 2. The running times of OPA-FMOC group, PITC group and AQC group were 18, 45 and 35 min, respectively. There was a large difference between the results of OPA-FMOC group and results from the automatic amino acid analyser, although the difference between the results from PITC and the automatic amino acid analyser was minimal. 3. In conclusion, the running time of OPA-FMOC group was shorter than that of PITC group and AQC group; the accuracy of the former was better than the OPA-FMOC group and AQC group for the determination of amino acid of foie gras. [ABSTRACT FROM AUTHOR]

The Jiuwandashan–Yuanbaoshan area, which is located in the western Jiangnan orogenic belt, has experienced frequent tectonic and magmatic events, and contains extensive Neoproterozoic Sn–polymetallic deposits. The Jialong Sn–polymetallic deposit is located in the northeastern part of the Neoproterozoic Yuanbaoshan granite and superimposed Sirong ductile shear zone and represents the first Caledonian Sn–polymetallic deposit discovered in this area. In this study, we investigated the mechanisms of Caledonian Sn mineralisation using the numerous types of fluid inclusions that formed during the main mineralisation stage. Liquid-rich inclusions (Wa-type) have a wide range of homogenisation temperatures (180–302 °C) and a bimodal distribution of salinities (8–10 and 21–22 wt% NaClequiv). Gas-rich inclusions (Wb-type) have homogenisation temperatures of 379–383 °C and salinities of 4.34–4.49 wt% NaClequiv. The homogenisation temperatures of CO2-rich liquid inclusions (Ca-type) are 222–248 °C, and the salinities are 11.32–13.45 wt% NaClequiv, indicating the fluid underwent significant boiling. δ18Owater values vary from 1.1 to 5.3‰ VSMOW, with δD = −65 to −35‰ VSMOW. The ore-forming fluid has the characteristics of a typical metamorphic hydrothermal fluid. There is a significant difference in δ34S values between the mafic–ultramafic and granitic rocks in the study area, indicate the ore-forming materials were derived mainly from metamorphosed sedimentary rocks of the Sibao Group. The Jialong Sn–polymetallic deposit is a typical example of Caledonian Sn mineralisation, but there was no coeval magmatism, although the Sirong ductile shear zone was active during the period of Sn mineralisation. During the Caledonian activity of the Sirong ductile shear zone, ductile shear deformation resulted in the generation of metamorphic fluids from distal Neoproterozoic strata. This fluid migrated to the northwest under the influence of a pressure gradient, underwent decompression-driven boiling and precipitated Sn and other elements. KEY POINTS: The ore-forming fluid of Caledonian tin mineralisation in the Jiuwandashan–Yuanbaoshan area is derived from metamorphic fluid generated by ductile shear deformation. The mineralisation of the Jialong Sn–polymetallic deposit primarily derives from the sedimentary metamorphic rocks of the Sibao Group. Boiling of metamorphic fluid is the main metallogenic mechanism of the Jialong Sn–polymetallic deposit. [ABSTRACT FROM AUTHOR]

This study investigated the development of a novel composite modified asphalt incorporating PDA-MoS2 into styrene-butadiene-styrene (SBS) modified asphalt. The successful synthesis of PDA-MoS2 was confirmed through various characterization techniques. The incorporation of PDA-MoS2 into SBS modified asphalt resulted in significant improvements in performance properties. With a PDA-MoS2 content of 0.7 wt%, the modified asphalt showed a notable 15.1% rise in softening point and a 24% drop in penetration in comparison to the control SBS modified asphalt. Dynamic Shear Rheometer tests revealed a 2.4-fold increase in the rutting factor at 60°C. Multiple Stress Creep Recovery tests demonstrated enhanced rutting resistance, with a 72.2% reduction in nonrecoverable creep compliance at 0.1 kPa stress level. Electrochemical measurements showed improved corrosion resistance, evidenced by lower current densities and higher charge transfer resistance. Microstructural analysis revealed well-dispersed PDA-MoS2 particles forming a compact network structure within the asphalt matrix. The hydrophilicity of the modified asphalt increased, with a 35.3% decrease in water contact angle. The synergistic effect between PDA-MoS2, SBS, and asphalt components, facilitated by enhanced interfacial interactions and chemical bonding, contributed to the observed performance improvements. The results indicate that PDA-MoS2 has the potential to improve the characteristics of SBS modified asphalt as a modifier. [ABSTRACT FROM AUTHOR]

Bioactive metabolites play a crucial role in shaping interactions among diverse organisms. In this study, we identified cyclo(Pro-Tyr), a metabolite produced by Bacillus velezensis, as a potent inhibitor of Botrytis cinerea and Caenorhabditis elegans, two potential cohabitant eukaryotic organisms. Based on our investigation, cyclo(Pro-Tyr) disrupts plasma membrane polarization, induces oxidative stress and increases membrane fluidity, which compromises fungal membrane integrity. These cytological and physiological changes induced by cyclo(Pro-Tyr) may be triggered by the destabilization of membrane microdomains containing the [H+]ATPase Pma1. In response to cyclo(Pro-Tyr) stress, fungal cells activate a transcriptomic and metabolomic response, which primarily involves lipid metabolism and Reactive Oxygen Species (ROS) detoxification, to mitigate membrane damage. This similar response occurs in the nematode C. elegans, indicating that cyclo(Pro-Tyr) targets eukaryotic cellular membranes. Cyclo(Pro-Tyr), a metabolite from Bacillus velezensis, inhibits Botrytis cinerea and Caenorhabditis elegans by disrupting membrane polarization, inducing oxidative stress, and increasing membrane fluidity. These effects trigger lipid metabolism and ROS detoxification, targeting eukaryotic membranes. [ABSTRACT FROM AUTHOR]

Bowei Chen,1,&ast; Xiaohong Liu,1,&ast; Yunan Li,1 Tianhe Shan,1 Liya Bai,1 Chunyu Li,2 Yinsong Wang1 1School of Pharmacy, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), Tianjin Medical University, Tianjin, 300070, People’s Republic of China; 2Department of Integrated Traditional Chinese and Western Medicine, International Medical School, Tianjin Medical University, Tianjin, 300070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yinsong Wang; Chunyu Li, Email wangyinsong@tmu.edu.cn; lichunyu@tmu.edu.cnBackground: Breast cancer is a common malignancy in women. Conventional clinical therapies for breast cancer all display moderate clinical efficacies and limitations. It is urgent to explore the novel and combined therapeutic strategies for breast cancer to meet clinical demand.Methods: An iRGD tumor-penetrating peptide-modified nano-delivery system (denoted as iRGD-PSS@PBAE@JQ1/ORI nanoparticles) based on a marine sulfated polysaccharide was developed by codelivery of JQ1 (BET inhibitor) and oridonin (ORI, bioactive diterpenoid derived from traditional Chinese medicine herb). The iRGD-PSS@PBAE@JQ1/ORI NPs, surface modified with iRGD peptide conjugated propylene glycol alginate sodium sulfate (iRGD-PSS). The antitumor efficacy was evaluated both in vitro and in vivo.Results: The prepared iRGD-PSS@PBAE@JQ1/ORI NPs effectively enhanced the tumor targeting and cellular internalization of JQ1 and ORI. Thus, JQ1 exerted the reversal effect on immune tolerance by decreasing the expression of PD-L1, while ORI displayed multiple antitumor effects, such as antiproliferation, inhibition of intracellular ROS production and inhibition of lactic acid secretion.Conclusion: Our data revealed that iRGD peptide could significantly improve the cellular internalization and tumor penetration of the nano-delivery system. The combination of JQ1 and ORI could exert synergistic antitumor activities. Taken together, this study provides a multifunctional nanotherapeutic system to enhance the anti-tumor efficiency against breast cancer.Keywords: iRGD peptide-modified nano-delivery system, marine sulfated polysaccharide, JQ1, oridonin, synergistic antitumor activity, breast cancer

Ning Yu, Xuefang Liu, Dandan Shi, Long Bai, Tianfu Niu, Ya Liu Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of ChinaCorrespondence: Ya Liu, Department of Anaesthesiology and Intensive Care, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050004, People’s Republic of China, Email md2006liuya@aliyun.com; liuya6660707@163.comBackground: The molecular mechanism of septic shock is unknown. We studied the pathogenesis of septic shock and provide a novel strategy for treating and improving the prognosis of septic shock.Methods: Gluten-Sensitive Enteropathy (GSE) 131761, GSE119217, GSE26378 datasets were downloaded from the Gene Expression Omnibus (GEO) database. The three datasets included 204 septic shock samples and 48 normal samples. The R packages “affy” and “limma” were employed to identify the differently expressed genes (DEGs) between septic shock and normal samples. Weighted gene co-expression network analysis (WGCNA) was performed to search for modules that play an important role in septic shock. Functional annotation of DEGs and construction and analysis of hub genes were used to explore the pathomechanism of septic shock. The receiver operating characteristic (ROC) curves were obtained using MedCalc software. The drug molecules that could regulate hub genes associated with septic shock were searched for in the CMap database. An animal model of septic shock was constructed to analyze the role of these hub genes.Results: The merged series contained 321 up-regulated and 255 down-regulated genes. WGCNA showed the brown module had the highest correlation with the status of septic shock. GO and KEGG enrichment analysis results of the brown module genes showed they were mainly enriched in “leukocyte differentiation”, “Ras-proximate-1 (Rap1) signaling pathway”, and “cytokine–cytokine receptor interaction”. Through construction and analysis of a protein–protein interaction (PPI) network, cluster of differentiation 63 (CD63) and complement component 3a receptor 1 (C3AR1) were identified as hub genes of septic shock. The area under curve (AUC) of C3AR1 for the septic shock is 0.772 (P< 0.001), and the AUC of CD63 for the septic shock is 0.871 (P< 0.001). Small molecule drugs were filtered by the number of instances (n> 3) and P-values < 0.05, including “monensin”, “verteporfin”, “ikarugamycin”, “tetrahydroalstonine”, “cefamandole”, “etoposide”. In the animal model, the relative expression levels of interleukin-6 (IL-6), Tumor Necrosis Factor-? (TNF-?), and lactic acid were significantly higher in the septic shock group compared with the control group. Results of Real Time Quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) analysis for CD63 and C3AR1 showed that their relative expression levels were significantly lower in the septic shock group compared with the control group (P< 0.05).Conclusion: CD63 and C3AR1 are significant hub genes of septic shock and may represent potential molecular targets for future studies of septic shock.Keywords: septic shock, CD63, C3AR1, hub genes, animal model