ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

Objective To investigate the therapeutic efficacy of Yiqi Huoxue Tongmai Decoction(a modified priscription derived from Buyang Huanwu Decoction)combined with western medicines in the treatment of patients with pulmonary hypertension due to left heart disease(PH-LHD)of qi deficiency and blood stasis syndrome,and to explore its effect on endothelial function.Methods Eighty patients with PH-LHD of qi deficiency and blood stasis syndrome who were admitted to Shangluo Central Hospital from March 2022 to December 2023 were randomly divided into a study group and a control group,with 40 patients in each group.The control group was given routine treatment with western medicine,and the study group was treated with Yiqi Huoxue Tongmai Decoction on the basis of treatment for the control group,three weeks constituting a course of treatment.Before and after intervention,the two groups of patients were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,pulmonary circulation indicators[mean pulmonary arterial pressure(mPAP)and pulmonary capillary wedge pressure(PCWP)],cardiopulmonary exercise testing(CPET)indicators[peak heart rate,peak systolic blood pressure,peak diastolic blood pressure,maximal oxygen uptake(VO2max),peak oxygen pulse],vascular endothelial function indicators[serum nitric oxide(NO)and endothelin 1(ET-1)]and the scores of quality of life.After treatment,the clinical efficacy and incidence of adverse reactions of the patients between the two groups were compared.Results(1)After three-week of intervention,the total effective rate of the study group was 90.00%(36/40),while that of the control group was 72.50%(29/40),and the comparison between the two groups(tested by chi-square test)showed that the efficacy of the study group was significantly superior to that of the control group(P<0.05).(2)After intervention,the primary symptom scores,secondary symptom scores and total TCM syndrome scores of the two groups of patients were all decreased compared with those before intervention(P<0.05),and the decrease of the scores in the study group was significantly superior to that in the control group(P<0.01).(3)After intervention,the levels of pulmonary circulation indicators of mPAP and PCWP in the two groups were all decreased compared with those before intervention(P<0.05),and the decrease in the study group were significantly superior to that in the control group(P<0.01).(4)After intervention,the CPET indicators of peak heart rate,peak systolic blood pressure and peak diastolic blood pressure in the two groups were all decreased(P<0.05),while the VO2max and peak oxygen pulse rate were all increased compared with those before intervention(P<0.05),and the decrease of peak heart rate,peak systolic blood pressure and peak diastolic blood pressure as well as the increase of VO2max and peak oxygen pulse rate in the study group was significantly superior to that in the control group(P<0.05 or P<0.01).(5)After intervention,the vascular endothelial function indicator of serum ET-1 level in the two groups was decreased compared with that before intervention(P<0.05),and the serum NO level was increased compared with that before intervention(P<0.05),and the decrease of serum ET-1 level and the increase of serum NO level in the study group were significantly superior to those in the control group(P<0.01).(6)After intervention,the scores of six dimensions of 36-Item Short-Form Health Survey(SF-36),including mental health,role-emotional,social functioning,role-physical,vitality,and general health in the patients of the two groups were increased compared with those before intervention(P<0.05),and the increase in the study group was significantly superior to that of the control group(P<0.05 or P<0.01).(7)The incidence of adverse reactions in the study group was 20.00%(8/40)and that was 15.00%(6/40)in the control group,and the comparison between the two groups showed that the difference was not statistically significant(P>0.05).Conclusion Yiqi Huoxue Tongmai Decoction combined with western medicines is effective on enhancing the clinical efficacy for the intervention of patients with PH-LHD of qi deficiency and blood stasis syndrome,and can improve the patients'cardiopulmonary function,vascular endothelial function and improve the quality of life,with higher safety.

Rapid developments in biotechnology have led researchers to seek new method to improve the efficiency and accuracy of biomedical research and drug development,promoting interdisciplinary integration.Recent advancements in artificial intelligence(AI)technologies have brought unprecedented opportunities to this field.The integration of various AI models allows researchers to better utilize multi-omics data,identify disease phenotypes,interpret animal behavior,assess treatment effects,improve experimental designs,reduce the use of experimental animals,enhance animal facility management,and improve animal welfare.This article reviews the advancements in AI biomedical research over the past decade and discusses its contributions to disease phenotype identification,the selection and design of experimental animal models,animal behavior analysis,and animal facility management.It also points out the challenges related to data standardization,AI model selection and interpretability,the extrapolation process from AI models to animal experiments and clinical practice,as well as ethical considerations in using AI in sensitive areas involving human genetics and personalized medicine.This review aims to help researchers and practitioners in relevant fields understand the current state and opportunities of AI development,thus providing support for its broader application.

Metformin is a common oral hypoglycemic drug, which has an important role in improving insulin resistance and regulating the level of glucolipid metabolism.With the widespread use of metformin in recent years, new evidence suggests that it also regulates multiple biological processes such as autophagy, inflammation, angiogenesis, and fibrosis, which may provide the theoretical basis for the use of metformin in ocular disease.Current studies have implicated that metformin has great potential in ocular therapy in preclinical and clinical applications, especially for patients with diabetic retinopathy, where metformin has an important role in delaying disease progression by inhibiting hyperglycemia-induced retinal inflammation, oxidative injury, and vascular endothelial growth factor signaling pathway.For nondiabetic ocular disease, metformin ameliorated the disease course by modulating cellular metabolism, improving oxidative stress and autophagy, and downregulating pro-inflammatory cytokines.Considering the multifaceted roles beyond glucose-lowering effects, as the advantage of safety profile and low cost, metformin has the potential as a novel therapeutic strategy for the treatment of ocular disease.This article reviews the research progress on the application of metformin in ocular diseases.

Metformin is a common oral hypoglycemic drug, which has an important role in improving insulin resistance and regulating the level of glucolipid metabolism.With the widespread use of metformin in recent years, new evidence suggests that it also regulates multiple biological processes such as autophagy, inflammation, angiogenesis, and fibrosis, which may provide the theoretical basis for the use of metformin in ocular disease.Current studies have implicated that metformin has great potential in ocular therapy in preclinical and clinical applications, especially for patients with diabetic retinopathy, where metformin has an important role in delaying disease progression by inhibiting hyperglycemia-induced retinal inflammation, oxidative injury, and vascular endothelial growth factor signaling pathway.For nondiabetic ocular disease, metformin ameliorated the disease course by modulating cellular metabolism, improving oxidative stress and autophagy, and downregulating pro-inflammatory cytokines.Considering the multifaceted roles beyond glucose-lowering effects, as the advantage of safety profile and low cost, metformin has the potential as a novel therapeutic strategy for the treatment of ocular disease.This article reviews the research progress on the application of metformin in ocular diseases.

Rapid developments in biotechnology have led researchers to seek new method to improve the efficiency and accuracy of biomedical research and drug development,promoting interdisciplinary integration.Recent advancements in artificial intelligence(AI)technologies have brought unprecedented opportunities to this field.The integration of various AI models allows researchers to better utilize multi-omics data,identify disease phenotypes,interpret animal behavior,assess treatment effects,improve experimental designs,reduce the use of experimental animals,enhance animal facility management,and improve animal welfare.This article reviews the advancements in AI biomedical research over the past decade and discusses its contributions to disease phenotype identification,the selection and design of experimental animal models,animal behavior analysis,and animal facility management.It also points out the challenges related to data standardization,AI model selection and interpretability,the extrapolation process from AI models to animal experiments and clinical practice,as well as ethical considerations in using AI in sensitive areas involving human genetics and personalized medicine.This review aims to help researchers and practitioners in relevant fields understand the current state and opportunities of AI development,thus providing support for its broader application.

Backgrounds Insomnia is frequent in schizophrenia and is found to be negatively affected by stressful life events,psychotic symptoms and depressive disorder,while the relationship among the four remains understudied in community-dwelling patients with schizophrenia.Objective To analyze the effect of stressful life events on insomnia in community-dwelling patients with schizophrenia,and to explore the mediation effect of psychotic symptoms and depression,so as to provide references for the intervention of insomnia in community-dwelling patients with schizophrenia.Methods From April to June 2023,a sample of 1 105 patients with schizophrenia attending 48 community health centers in Chengdu,Sichuan province and fulfilling the International Classification of Diseases,tenth edition(ICD-10)diagnostic criteria were included.All subjects were assessed using Stressful Life Event Scale(SLEs),Athens Insomnia Scale(AIS),Psychosis Screening Questionnaire(PSQ),and Patient Health Questionnaire Depression Scale(PHQ-9).Spearman correlation analysis was used to determine the correlation among the scales.Then the mediation model was constructed using Smart PLS 4.0,and tested with partial least squares algorithm and Bootstrap techniques.Results 332 patients(30.05%)with community schizophrenia were found to have insomnia.AIS scores in patients with schizophrenia were positively correlated with the scores on SLEs,PSQ and PHQ-9(r=0.165,0.322,0.554,P<0.01).Stressful life events indirectly contributed to insomnia through both separate mediation path and chained mediation path of psychotic symptoms and depressive disorder,and the indirect effect size of 0.102,0.372 and 0.190 was obtained,accounting for 10.46%,38.15%and 19.49%,respectively.Conclusion The stressful life events not only directly exert an impact on insomnia,but also indirectly contribute to insomnia through both the separate and chained mediation effect of psychotic symptoms and depressive disorder.

[Abstract] [Objective] To establish a new centrifugal-membrane hybrid plasmapheresis (CMHP) model, and observe its clinical efficacy, safety and advantages in the treatment of hyperlipidemia by comparing with centrifugation therapeutic plasma exchange (cTPE). [Methods] A retrospective analysis was performed on 47 patients with hyperlipidemia treated in our department from August 2021 to September 2023, with a total of 60 treatments. They were divided into two groups: CMHP group with 37 patients and 46 treatments; cTPE group included 10 patients with 14 treatments. In the CMHP group, the plasma was separated by a blood cell separator and the plasma components were separated by a two-stage membrane plasma component separator. In the cTPE group, the plasma was separated by a blood cell separator for therapeutic plasma exchange. The clinical efficacy, safety and advantages of the two groups were compared. [Results] The reduction ratios of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) before and after treatment in CMHP group were 68.56%[59.81%, 73.42%], 65.80%[55.55%, 75.98%] and 46.57%[36.02%, 54.83%] and 66.67%[43.48%, 76.24%] respectively, with statistically significant difference (P<0.001). The decrease ratios of TC, TG and HDL-C before and after treatment in cTPE group were 42.52%[29.67%, 49.85%], 52.32%[38.43%, 67.07%] and 22.36%[8.51%, 33.65%], respectively, and the difference was statistically significant (P<0.05). The plasma treatment multiple was 1.48 (0.29) in CMHP group, which was significantly higher than 0.87 (0.26) in cTPE group, with a statistically significant difference (P<0.001), resulting in higher TC and HDL-C reduction ratios in CMHP group than in cTPE group, with a statistically significant difference (P<0.001), while there was no significant difference in TG reduction rate between the two groups (P>0.05). At the same time, the cTPE group required 1 520.00 mL[1 462.50 mL, 2 000.00 mL] plasma input, while the CMHP group achieved zero blood input. The adverse reaction ratio was 6.52%(3/46) in CMHP group and 7.14%(1/14) in cTPE group, and the difference was not statistically significant (P>0.05). [Conclusion] Compared with cTPE, CMHP can better reduce blood lipid levels without any blood products, avoid the spread of blood infectious diseases, and have a low incidence of adverse reactions, so it has a good clinical application prospect.

Objective:At present,the doctor-patient relationship is tense.The prevalence of negative emotions,such as depression and anxiety,among healthcare workers is increasing every year.Negative attitudes of medical workers toward mental problems may aggravate the doctor-patient conflict and psychological problems of medical workers.This study aims to explore the complex network relationships between outpatient medical workers'attitudes toward mental problems,doctor-patient relationships,and their depression/anxiety levels. Methods:A total of 578 outpatient medical staff from the Second Xiangya Hospital of Central South University(167 males,411 females)completed questionnaires on their attitudes toward mental problems,doctor-patient relationships,and depression/anxiety symptoms.Network analysis was conducted separately to construct the"attitude towards mental problems-doctor-patient relationship network"and"depression-anxiety related network". Results:The edge between"M15(insulting words)"and"D8(waste time)"showed the strongest strength in the"attitude towards mental problems-doctor-patient relationship network",and"M15(insulting words)"had the highest bridge strength in the network.For the analysis of emotional variables,"P1(anhedonia)"showed the most obvious association with"D10(communication difficulties)"in the doctor-patient relationship and"M2(poor quality of life)"in the psychiatric attitudes,and"P1(anhedonia)"was the key bridge symptom in the network. Conclusion:The"insulting words"may be an intervention target for medical workers'attitudes toward mental problems.The"anhedonia"in depression is the potential symptom that needs to be treated.Intervention targeting these variables may be beneficial to improve the mental health level of medical workers and the doctor-patient relationship.

Objective:To explore the effect of pregnancy outcome of the first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer cycle on the next frozen-thawed embryo transfer cycle. Methods:A retrospective cohort study was designed by collecting data from 6658 infertile patients in Department of Reproductive Endocrinology, Women's Hospital of Zhejiang University from January 2010 to December 2019. Two groups were included, the fresh embryo-frozen embryo group ( n=4310) and the frozen embryo-frozen embryo group ( n=2348), and each group was divided into four subgroups according to the pregnancy outcome of the first transfer cycle: non-pregnancy subgroup, biochemical pregnancy subgroup, pregnancy loss subgroup, and live birth subgroup. In each group, the live birth rate (LBR) of the second transfer cycle was compared among the four subgroups. Results:In the second transfer cycle of the fresh embryo-frozen embryo group, LBR in each subgroup was 31.3% (972/3109), 33.7% (92/273), 33.3% (169/507), and 39.2% (165/421), respectively. Compared with non-pregnancy subgroup, the difference of LBR in the live birth subgroup was statistically significant [after adjustment, a P<0.001, a OR(95% CI)=1.555(1.245-1.942)]. In the second transfer cycle of the frozen embryo-frozen embryo group, LBR in each subgroup was 37.3% (655/1754), 47.0% (79/168), 45.4% (122/269), and 44.6% (70/157), respectively. Compared with non-pregnancy subgroup, the differences of LBR in biochemical pregnancy subgroup, pregnancy loss subgroup and live birth subgroup were statistically significant [after adjustment, a P=0.018, a OR(95% CI)=1.471(1.069-2.026); a P=0.014, a OR(95% CI)=1.388 (1.069-1.802); a P=0.035, a OR(95% CI)=1.452(1.026-2.054)]. Conclusion:In the fresh embryo-frozen embryo group, live birth in the first transfer cycle is associated with increased LBR in the subsequent cycles, while in the frozen embryo-frozen embryo group, biochemical pregnancy, pregnancy loss, or live birth in the first transfer cycle are associated with increased LBR in the following cycles.