Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Objective:To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate(ThuFLEP)in the treatment of oversized(＞200 mL)prostate.Methods:Clinical data of 475 benign prostatic hyperplasia(BPH)patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed,all of whom were treated with thu-lium fiber laser,and the patients were divided into three groups according to the total volume of the pros-tate(TPV):group A(TPV＜100 mL),group B(100 mL≤TPV＜200 mL),and group C(TPV ≥200 mL).The age of the patients in the three groups[(69.38±7.79)years,(69.64±8.69)years,(70.32±7.44)years],International Prostate Symptom Score(IPSS)[(22.7±1.9),(22.8±2.7),(25.8±3.7)],and the maximum urinary flow rate(Qmax)[(7.9±2.7)mL/s,(9.3±4.3)mL/s,(9.9±3.3)mL/s]were not statistically significant(P＞0.05).The prostate volume in the three groups[(103.49±46.19)mL,(75.73±30.69)mL,(273.49±49.19)mL]and prostate specific antigen(PSA)[3.52(1.05,8.76)μg/L,6.78(1.61,7.45)μg/L,8.52(5.05,12.76)μg/L]were statistically significant(P＜0.05).Results:All surgeries were successfully completed.The dif-ferences in enucleation time[30.0(21.2,44.5)min,41.6(31.2,52.5)min,45.1(35.2,50.0)min]and hospitalization time[(6.06±1.21)d,(6.15±1.50)d,(7.71±1.74)d]among the three groups were not statistically significant(P＞0.05);and the differences in the postoperative in-dwelling catheter time[(4.0±1.4)d,(4.0±1.3)d,(6.6±1.1)d],operative time[61(42,89)min,82(62,105)min,115(96,142)min],enucleation efficiency[1.29(0.71,1.56)g/min,1.67(1.23,2.15)g/min,2.74(2.20,3.34)g/min],and hemoglobin drop values[12(7,19)g/L,17(11,24)g/L,27(19,35)g/L]were statistically different(P＜0.05).Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight(r=0.880,P＜0.001),and the enucleation efficiency increased with the increase of prostate volume.The differences in IPSS[(6.6±1.7),(6.2±1.4),(4.6±1.1)]and Qmax[(18.9±3.1)mL/s,(16.8±3.8)mL/s,(22.9±7.1)mL/s]were not statistically significant among the three groups(P＞0.05),and the differences in IPSS and Qmax were statistically significant compared with those before surgery.The differences were statistically significant in preoperative comparisons,but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax(P＜0.05).The patients in the three groups were followed up for 3 months,and post-operative complications were categorized into Clavien-Dindo Ⅰ(urinary retention,persistent hematu-ria),Clavien-Dindo Ⅱ(glandular remnants,urinary tract infection,blood transfusion)and Clavien-Dindo Ⅲ(urethral stenosis,contracture of the bladder neck,and reoperation for hemorrhage)based on the Clavien-Dindo Complications System score,the incidence of Clavien-Dindo in the three groups was 5.2％(13 cases),6.7％(12 cases)and 12.1％(7 cases),respectively,with statistically significant differences(P＜0.05);among them,there were statistically significant differences in urinary infection,blood transfusion and bleeding reoperation(P＜0.05),and there was no statistically significant difference in the remaining complications(P＞0.05).Conclusion:The risk of blood transfusion and re-hemostasis increases with larger prostate volume,the efficiency of enucleation increases with the increase of prostate vo-lume,and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.

Objective To explore the syndrome differentiation rules of the Yin Dan and Yang Dan method,and summarize Professor Yang Zhimin's valuable experience in the treatment of insomnia.Methods The case data of 11390 insomnia patients treated by Professor Yang Zhimin was retrospectively analyzed,and the distribution of symptoms,signs,pathogenesis and syndrome differentiation rules of insomnia patients was examined based on latent structure analysis.Result A total of 44 symptoms and signs can explain the overall situation of insomnia patients,showing the characteristics of both excess and deficiency,cold and heat.A total of 36 hidden categories(symptom clusters and pathogenesis)was composed.Symptoms and signs such as fear of wind and cold can explain the overall situation of insomnia patients with cold syndrome due to weakness of Wei Qi,symptoms and signs such as pale eyelid can explain the overall situation of insomnia patients with heat syndrome due to weakness of Ying Xve,and established diagnostic criteria for insomnia patients with cold syndrome due to weakness of Wei Qi and heat syndrome due to weakness of Ying Xve.Conclusion Based on the Yang Dan and Yin Dan method to distinguish and treat insomnia from the perspective of disharmony between Ying and Wei,it is in line with the basic understanding of the pathogenesis of insomnia in the classics of traditional Chinese medicine.The pattern differentiation rules obtained through the latent structure analysis method are helpful to summarize valuable clinical experience and provide a certain reference and basis for clinical practice.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective:To develop a staged exercise prescription for patients with Knee Osteoarthritis (KOA) based on internet information systems and evaluate its effectiveness, in order to provide a reference for exercise rehabilitation guidance for KOA patients.Methods:A systematic review of guidelines, expert consensus, systematic reviews, and evidence summaries on exercise prescriptions for osteoarthritis from January 1, 2012, to December 31, 2022, was conducted. After literature screening, semi-structured interviews, and expert consultations, a staged exercise prescription for KOA patients based on internet information systems was formulated. From April to October 2023, 90 KOA outpatients from Beijing Friendship Hospital, Capital Medical University, were selected using convenience sampling and randomly divided into the observation group and the control group, each with 45 cases. The control group received routine rehabilitation nursing, while the observation group implemented the staged exercise prescription based on the internet information system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Multidimensional Self-Efficacy for Exercise Scale (MSES) were used for evaluation before the intervention and at 4, 8, 16, and 24 weeks post-intervention. After the intervention, the Exercise Adherence Rating Scale (EARS) was used to assess exercise adherence in both groups.Results:A staged exercise prescription consisting of three phases and 27 items was successfully developed. At 8, 16, and 24 weeks after the intervention, the observation group had significantly lower scores in the pain, stiffness, and daily activity dimensions of the WOMAC compared to the control group, and the differences were statistically significant ( P<0.05). At the same time points, the observation group had significantly higher MSES scores than the control group, and the differences were statistically significant ( P<0.05). At 16 and 24 weeks post-intervention, the EARS scores of the observation group were also significantly higher than those of the control group, with statistically significant differences ( P<0.05) . Conclusions:The staged exercise prescription for KOA patients based on internet information systems is both scientifically valid and feasible. It can effectively alleviate knee joint symptoms, enhance exercise self-efficacy, and improve exercise adherence.

Objective Through organizing a proficiency evaluation activity for animal illuminance testing laboratories,to assess the accuracy of testing data from participating laboratories,and to propose suggestions for testing methods.Methods In September 2024,China National Institute for Food and Drug Control(NIFDC)organised reference laboratories to conduct on-site testing through open registration.A total of 35 laboratories participated,completed on-site testing,and submitted their reports.The samples to be tested were two adjacent guinea pig breeding rooms in the NIFDC laboratory animal facility.In order to reduce the impact of room voltage fluctuations on animal illumination,chip on board(COB)light sources powered by regulated power supply were used,and brightness was adjusted by regulating voltage output.Split-level test sample pairs were used to set animal illuminance in both rooms,and the reference laboratories conducted testing according to Laboratory animals——Environment and housing facilities(GB 14925-2023).Each reference laboratory was assigned a 3-digit random code,conducted 2 tests for each breeding room,and submitted an on-site test report,original records,and illuminance meter verification or calibration certificate.WPS Spreadsheet 12.1 was used to summarize data,Grubbs' test(α=0.01)was used to check the data and remove outliers,and SPSS 26.0 software was used for data processing and graph drawing.The median value from each reference laboratory was used as the specified value,the robust standard deviation was used as the uncertainty,the robust z-score method(both intra-laboratory and inter-laboratory z-scores)was used to evaluate the test results from each laboratory,and the factors affecting results were analyzed from aspects of personnel,equipment,and operational environment.Results Under the detection level of α=0.01,no outliers were identified.The specified values for Room 1 and Room 2 were 17.80 lx and 19.00 Ix,respectively.The results obtained from 34 laboratories were evaluated as"satisfactory",while the results from one laboratory were"unsatisfactory".Through analysis of illuminance meter calibration certificates from various laboratories,it was found that some reference laboratories had insufficient calibration points and coverage,which caused test results to fail to accurately reflect the actual illuminance of the facility.Conclusion The present study reveals that factors such as personnel,equipment,and operation environment have different impacts on animal illuminance measurements.The present study concentrates exclusively on animal illuminance in guinea pig breeding rooms,where the testing environment is relatively dim.Future research should focus on the development of more efficient methods for selecting measurement sites,with the combination of illuminance meters equipped with wireless probes and storage functions to enhance testing efficiency.

Objective To analyze the influencing factors of the success of clinical pregnancy in secondary infertility patients undergoing in vitro fertilization-embryo transfer(IVF-ET)and construct a nomogram prediction model.Methods A retrospective analysis was conducted on the clinical data of 235 patients with secondary infertility who underwent IVF-ET at Urumqi Maternal and Child Health Hospital from January 2020 to December 2023.They were divided into successful pregnancy group(n=109)and failed pregnancy group(n=1 26)based on whether clinical pregnancy was successful.The general information,ovulation induction data and embryo data of two groups of patients were compared.Multivariate Logistic regression analysis was used to screen out statistically significant indicators,and based on this,a nomogram prediction model was constructed.The receiver operating characteristic curve,calibration curve and decision analysis curve were drawn to verify the discrimination,accuracy and clinical practicability of the model.Results The results of multivariate Logistic regression analysis showed that the female's age,overweight and obesity were all risk factors for clinical pregnancy failure,while anti-Müllerian hormone(AMH)and the total amount of gonadotropins(Gn)were protective factor for clinical pregnancy outcomes.On this basis,a nomogram prediction model was successfully constructed,which has a medium degree of discrimination,good accuracy and clinical practicability.Conclusion For secondary infertility patients undergoing IVF-ET,the female's age,overweight and obesity,AMH,and the total amount of Gn have certain influences on clinical pregnancy.The clinical pregnancy outcome can be predicted through the constructed nomogram prediction model.

Insomnia is often comorbid with anxiety and/or depression.Identifying biomarkers for this comorbidity is crucial for precise diagnosis,elucidating the underlying pathological mechanisms,and developing personalized treatment strategies.Current research has preliminarily revealed a series of potential biomarkers for insomnia comorbid with anxiety and/or depression.Elevated peripheral pro-inflammatory factors(e.g.,interleukin-6),and decreased peripheral brain-derived neurotrophic factor,and monoamine neurotransmitters(e.g.,5-hydroxytryptamine)may indicate the presence of a comorbid state.However,studies focusing on this comorbidity remain relatively limited.In the future,it will be necessary to systematically explore and verify the clinical application value of potential biomarkers through measures such as expanding sample size,strengthening longitudinal design,and expanding the categories of biomarkers.This will provide a more solid theoretical foundation for the early diagnosis and personalized treatment of insomnia comorbid with anxiety and/or depression.

Objective To analyze the focus and shortcomings of provincial-level digitalization policies for Traditional Chinese Medicine(TCM),and to provide references for improving relevant policies.Methods A three-dimensional analytical framework—comprising"digitalization policy coverage-economic level-TCM development level"was constructed to quantitatively analyze provincial TCM digitalization policy documents issued over the past five years.Results A total of 750 policy items were extracted.Among them,digital applications accounted for the largest proportion(58.13%),while digital governance(26.53%)and digital infrastructure(15.33%)were relatively less emphasized.Two-dimensional analysis revealed that 48.4%of provinces had both low economic levels and low digital policy coverage,while 45.2%had both low TCM development levels and low policy coverage.Multiple linear regression result showed a positive association between digitalization policies coverage and TCM development level,with no significant correlation to economic level.Conclusion Most provincial TCM digitalization policies prioritize application while neglecting governance and infrastructure.There is a need to strengthen talent development and standard system construction,The extent of policy coverage is closely related to the level of TCM development,indicating the need to enhance top-level policy design,Provincial policies vary in focus and can be categorized into three types:industry-driven,technology-driven,and demand-driven.

Insomnia is often comorbid with anxiety and/or depression.Identifying biomarkers for this comorbidity is crucial for precise diagnosis,elucidating the underlying pathological mechanisms,and developing personalized treatment strategies.Current research has preliminarily revealed a series of potential biomarkers for insomnia comorbid with anxiety and/or depression.Elevated peripheral pro-inflammatory factors(e.g.,interleukin-6),and decreased peripheral brain-derived neurotrophic factor,and monoamine neurotransmitters(e.g.,5-hydroxytryptamine)may indicate the presence of a comorbid state.However,studies focusing on this comorbidity remain relatively limited.In the future,it will be necessary to systematically explore and verify the clinical application value of potential biomarkers through measures such as expanding sample size,strengthening longitudinal design,and expanding the categories of biomarkers.This will provide a more solid theoretical foundation for the early diagnosis and personalized treatment of insomnia comorbid with anxiety and/or depression.