Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.

Objective To investigate the mechanism by which angiotensin Ⅱ type 1 receptor autoantibody(AT1-AA)promotes phenotypic switch of vascular smooth muscle cells(VSMCs)and vascular fibrosis through abnormal expression of circadian clock protein BMAL1.Methods Twelve male SD rats(6～8 weeks old,weighing 180～220 g)were randomly divided into(n=6)a control group and an AT1-AA-positive group[established by active immunization of SD rats with AT1R extracellular loop Ⅱ peptide(AT1R-ECLⅡ)].HE and Masson stainings were used to observe structural changes and fibrosis in the thoracic aorta(n=3).Western blotting was performed to detect the expression of Collagen I,phenotypic switch-related proteins(SM22,α-SMA,OPN and MMP2)in vascular tissues and primary VSMCs(n=4),as well as the expression of BMAL1 at CT0,CT4,CT8,CT12,CT16,and CT20.Transwell and scratch assays were used to assess the proliferation and migration of VSMCs(n=3).si-RNA was employed to knock down Bmal1,followed by detection of BMAL1,Collagen I,and phenotypic conversion-related protein expression(n=3).Additionally,AT1-AA-positive AT1R-knockout(AT1R-KO)rats were constructed to measure BMAL1 expression in thoracic aortic tissues(n=4).Results The AT1-AA-positive rats had significantly thickened thoracic aortic vessel wall[(140±9)%vs(120±5)%,P<0.05],badly arranged VSMCs,obvious blue Masson staining,and up-regulated Collagen I expression(P<0.05).In the thoracic aorta of AT1-AA-positive rats and AT1-AA-treated VSMCs,the expression of contractile phenotype-related proteins(α-SMA,SM22)was decreased(P<0.05),while the expression of synthetic phenotype-related proteins(OPN,MMP2)was increased(P<0.05).AT1-AA enhanced the scratch healing ability and migration ability of VSMCs.Furthermore,both mRNA and protein levels of Bmal1 were significantly up-regulated at CT12(P<0.05),and the rhythmicity of Bmal1 was lost.Knockdown of Bmal1 partially ameliorated AT1-AA-induced phenotypic switch of VSMCs.Compared with AT1-AA-positive WT rats,AT1-AA-positive AT1R-KO rats showed significantly reduced BMAL1 expression in the thoracic aorta(1.35±0.06 vs 0.86±0.07,P<0.001).At the cellular level,AT1-AA-induced phenotypic switch and high Collagen I expression in VSMCs were partially improved in AT1R-KO VSMCs.Conclusion AT1-AA promotes VSMCs phenotypic conversion and vascular fibrosis through the AT1R-Bmal1 axis.

In the 1950s and 1960s,Japan's implementation of policies prioritizing economic develop-ment caused a lack of effective supervision over the discharge of industrial wastewater and exhaust gases,which led to the occurrence of the"Four Major Pollution Diseases",including Minamata disease,causing serious social and public health problems.To more effectively address public nuisances and pro-vide compensation to victims,the Japanese government gradually established an environmental damage compensation system with administrative relief characteristics since the 1970s.Through long-term prac-tice and system optimization,this system has evolved into a mature institutional framework with a clear division of labor and efficient collaboration.This paper systematically reviews the development process of Japan's environmental damage compensation system and deeply analyzes its legal frame-work and supporting policies,aiming to provide useful references for the construction and improve-ment of China's environmental damage compensation system.Meanwhile,through the case analysis of Minamata disease,the paper explores the specific mechanisms and effects in the compensation practices,further revealing the system's operational characteristics and implications,and providing a reference ba-sis for the construction of China's environmental governance legal system.

Background: Metals and their ions have been used to reduce bacterial infection risks. Among them, minerals containing rubidium (MCR), natural minerals containing metal ions, show potential as novel and tunable materials. Objective: This study aimed to investigate the antibacterial activity and mechanism of MCR. Methods: The inhibitory effect of MCR on bacteria was clarified using the growth curve method, turbidimetric method, and minimum inhibitory concentration method. Physiological and biochemical indices were employed to investigate the inhibitory mechanism of MCR. Results: The results revealed that MCR inhibited Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli with minimum inhibitory concentrations of 11.95, 2.60, and 2.60 mg/mL, respectively. The inhibitory activity of MCR was insignificant against Bacillus subtilis, Salmonella typhimurium, and Helicobacter pylori at 3.25 mg/mL. Mechanistic assessments showed that MCR affected bacterial conductivity, protein and nucleic acid levels, reducing sugar content, respiratory chain dehydrogenase activity, bacterial lipid peroxidation, intracellular adenosine triphosphate, and extracellular alkaline phosphatase. Conclusion: MCR has bacteriostatic activity and the mechanism primarily involves adhesion to bacteria, disrupting the integrity of their cell walls and membranes, and altering their permeability. This disruption leads to the release of intracellular molecules of various sizes, inhibiting cellular respiration and metabolism, and causing oxidative damage. These combined effects impair cellular functions, affecting cell growth and metabolism, or leading to cell death. These findings provide a theoretical reference for the development of MCR as a bacteriostatic agent.

Aim To investigate the effect of linarin on improving cognitive behavior of APP/PS1 mice,and to explore the therapeutic effect of linarin on A β deposi-tion and neuroinflammation and its correlation.Meth-ods APP/PS1 transgenic mice were randomly divid-ed into the model group,high-dose group,medium-dose group,low-dose group and positive control group.C57BL/6J mice were set as the normal group.Morris water maze was used to evaluate the learning and mem-ory abilities of mice.TUNEL staining was used to de-tect the apoptosis of neurons in the CA1 region of mice.IHC was used to detect the expression levels of Aβ42 and GFAP.Western blot was used to detect the expression levels of BACE1 and PS-1.Results Com-pared with the normal group,mice of the model group showed lower NCP,shorter target quadrant travel,less target quadrant residence time percentage(all P＜0.01),higher apoptosis rate of neurons in the CA1 re-gion(P＜0.01),significantly higher protein expres-sion levels of A β42 and GFAP(all P＜0.01),and significantly higher protein expression levels of BACE1 and PS-1(all P＜0.01).Compared with the model group,the medium-dose group,high-dose group and positive control group showed higher NCP,longer tar-get quadrant travel,more target quadrant residence time percentage(all P＜0.05),lower apoptosis rate of neurons in the CA1 region(P＜0.01),significantly lower protein expression levels of A β42 and GFAP(all P＜0.01),and significantly lower protein expression levels of BACE1 and PS-1(all P＜0.01).Conclu-sions Linarin can inhibit two key enzymes to reduce the decomposition of APP and the generation of A β42,thereby inhibiting the activation of astrocytes,allevia-ting neuroinflammation,improving the core pathologi-cal features of AD,and thus significantly improving learning and memory impairment in APP/PS1 mice.

Objective:To plot Kaplan-Meier curves using simulated survival data and compare the characteristics of different survival probability extraction methods for Kaplan-Meier curves and their performance across various scenarios.Methods:Survival datasets were simulated using R-4.4.2 with parameters including sample sizes,censoring marker,and curve numbers.GetData Graph Digitizer,IPDfromKM getpoints,SurvdigitizeR survival_digitize were evaluated.A JavaScript script was developed to extract Kaplan-Meier curve.Root Mean Square Error(RMSE)was calculated to quantify deviations between digitized and true survival probabilities.Results:The JavaScript script method demonstrated the smallest RMSE across all simulated scenarios(RMSE=1.015×10-4),significantly outperforming the other three methods(P＜0.05),with statistically significant differences observed among methods(P＜0.05).Conclusion:For vector format illustrations,JavaScript scripts enable accurate and robust reverse engineering of Kaplan-Meier curves;for bitmaps,the GetData Graph Digitizer and SurvdigitizeR survival_digitize methods yield more accurate results,and the SurvdigitizeR survival_digitize method is the most efficient.Future research should focus on integrating intelligent algorithms for enhanced robustness and precision in survival data reconstruction.

Objective:To explore the application of flipped classroom in the teaching of Laboratory Quality Management course.Methods:A total of 116 students majoring in Health Inspection and Quarantine in grade 2020 and 2021 were selected as the research subjects.Among them,58 students of grade 2020 received the traditional teaching mode as the control group,and 58 students of grade 2021 received the flipped classroom teaching mode as the experimental group.A self-designed questionnaire was conducted to investigate students'satisfaction with laboratory safety course content,and evaluate the teaching methods and effectiveness of the course.Results:The satisfaction rates of the experimental group with the teaching content on the safe use of instruments and equipment,chemical safety management and waste treatment were significantly higher than those of the control group(P＜0.05).There was no statistically significant difference in the satisfaction rate of the teaching content of safety common sense(P＞0.05).In the evaluation of teaching methods and teaching effects,the satisfaction rates of the experimental group in improving classroom participation,enhancing team assistance ability and classroom activity was higher than those of the control group(P＜0.05).Conclusion:The application of flipped classroom teaching method in teaching of Laboratory Quality Management course can enhance students'laboratory safety awareness,stimulate their learning interest and initiative,and effectively improve their learning efficiency.

Objective To evaluate the safety and efficacy of valve-in-valve transcatheter mitral valve replacement(ViV-TMVR)in patients with bioprosthetic valve degeneration who are at high surgical risk.Methods This study is a multi-center,retrospective cohort analysis of 20 consecutive patients who underwent transseptal ViV-TMVR using the Edwards SAPIEN 3 transcatheter heart valve(THV).The primary endpoints include technical success and procedural success,both defined according to the Mitral Valve Academic Research Consortium(MVARC)criteria,as well as mortality and functional change assessed based on New York Heart Association(NYHA)classification at 30-days and six months post-procedure.Clinical follow-up assessments are conducted at 30-days and six months.Results From February 2021 to October 2022,a total of 20 patients with symptoms of bioprosthetic valve degeneration were enrolled across nine sites in China.The patients had a mean age of(73.5±5.5)years,with 85.0％being females and 70.0％classified as NYHA class Ⅲ/Ⅳ.The study achieved a 100.0％technical success rate and a 90.0％procedural success rate finally.All patients remained alive during the 30-day follow-up period.However,six months post-intervention,two patients(10.0％)were re-hospitalized due to heart failure,and sadly,one of them(5.0％)died.None of the patients reported any adverse events related to ViV-TMVR during the follow-up period.Notably,there was a significant improvement in NYHA class compared to baseline(P=0.0004)at six-month follow-ups.Conclusions The transseptal ViV-TMVR technique proved to be highly successful and was associated with significant improvement in NYHA class function.These findings strongly suggest that it serves as a safe and efficient treatment alternative for high-risk patients suffering from bioprosthetic valve degeneration.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

Objective To construct a clinical-radiological nomo-gram model for severe mycoplasma pneumoniae pneumonia coinfec-tion with other pathogens(Co-SMPP)in children.Methods The clinical and radiological data of children with severe mycoplasma pneumoniae pneumonia(SMPP)who underwent nucleic acid testing or bronchoalveolar lavage(BAL)were analyzed retrospectively.The data analysis were performed by using SPSS 27.0 software.The group comparison between simple SMPP and Co-SMPP children was conducted by using t-tests,Mann-Whitney U tests,or chi-square tests.Nomogram analysis was performed by using R software and rms packages.The predictive performance of the model was evaluated by using the receiver operating characteristic(ROC)curve.Results A total of 194 SMPP children were included in the study,including 136 cases(70.1％)with simple SMPP,58 cases(29.9％)with Co-SMPP.The fibrinogen and albumin levels were lower in Co-SMPP children[(3.53±0.85)g/L,41.00(39.03,43.68)g/L]than in simple SMPP children[(3.79±0.80)g/L,42.80(41.00,44.40)g/L],with P values of 0.047 and 0.036,respec-tively.The probability of bronchial stenosis and grid shadow were higher in Co-SMPP children than in simple SMPP children,and there were significant differences between the two groups(P＜0.001,P=0.010).The odds ratio of bronchial stenosis in predicting Co-SMPP children was 14.085.The clinical-radiological nomogram model had an area under the curve(AUC)of 0.840,with sensi-tivity and specificity of 0.756 and 0.848,respectively.Conclusion The nomogram model based on clinical-radiological features can effectively predict Co-SMPP.