OBJECTIVE To establish a quantitative analysis of multi-components by single-marker （QAMS） method for simultaneous determination of six flavonoids and two phenolic acids in Perilla frutescens leaves using scutellarin and rosmarinic acid as internal reference substances， and apply this method to determine the contents of eight components in 20 batches of P. frutescens leaves samples from different regions. METHODS Scutellarin served as the internal reference to calculate relative correction factors （RCFs） for scutellarin-7-O-diglucuronide， luteolin-7-O-diglucuronide， apigenin-7-O-diglucuronide， luteolin-7-O- β-D-glucuronide and apigenin-7-O-glucuronide. Rosmarinic acid was employed as the internal reference to determine the RCF for caffeic acid. The contents of the above flavonoids and phenolic acids were calculated with QAMS， and compared with the results of external standard method. RESULTS The eight analytes demonstrated excellent linearity within their respective concentration ranges （r≥0.999 0）. The mean recovery rates for spiked samples ranged from 95.60% to 102.15%， with relative standard deviations （RSDs） of 0.72% to 2.70% （n＝6）. The method exhibited good precision， repeatability， and stability （RSD＜2.50%， n＝6）. Variations in instruments， columns， column temperature， flow rate， and formic acid volume fraction had minimal impact on the RCFs （RSD＜3%， n＝3）. Comparison with the external standard method showed no significant differences in the content of each component across batches， except for caffeic acid in the ZS12 batch （absolute value of RE＜5%， n＝2）. The contents of six CARS-21） flavonoid components in P. frutescens leaves samples varied significantly across different geographic origins， while the content of total flavonoids showed no significant difference. In contrast， the contents of two phenolic acid components and total phenolic acid exhibited significant variation among samples from different regions. CONCLUSIONS The developed QAMS method can simultaneously determine the contents of six flavonoids and two phenolic acids in P. frutescens leaves. It is convenient for detection， highly accurate， and cost-effective. This method is suitable for the quality control of P. frutescens leaves， and the variation of flavonoid and phenolic acid content in samples from different regions provides a reference for the selection of optimal cultivation areas.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To investigate the predictive value of early thyroid function changes on the efficacy of patients with Graves′ disease (GD) after 131I therapy. Methods:Data of patients with GD (59 males, 214 females; age (37.4±11.4) years) who underwent single therapy of 131I in Tianjin Medical University General Hospital from November 2017 to January 2019 were retrospectively analyzed. Symptoms, signs and laboratory tests (serum free triiodothyronine (FT 3) and serum free thyroxine (FT 4)) of patients were observed to assess the efficacy of 131I treatment. Efficacy was divided into complete remission (CR), partial remission (PR), non-remission (NR) or relapse. The changes of thyroid function (ΔFT 3=FT 3 before treatment-FT 3 after treatment)/FT 3 before treatment×100%; ΔFT 4=FT 4 before treatment-FT 4 after treatment)/FT 4 before treatment×100%) 1 month after 131I therapy in each efficacy group and differences among them were compared by using independent-sample t test, χ2 test, one-way analysis of variance and the least significant difference t test. ROC curves were drawn to analyze the predictive values of early thyroid function changes on the efficacy of 131I treatment for GD. Logistic regression analyses were performed to identify the influencing factors for the efficacy of 131I therapy. Results:CR rate and total effective rate of 273 GD patients after single therapy of 131I were 67.03%(183/273) and 92.67%(253/273), respectively. After 1 month, CR rate of euthyroidism group ( n=95) was significantly higher than that of hyperthyroidism group ( n=178; 81.05%(77/95) vs 59.55%(106/178); χ2=4.60, P=0.032). ΔFT 3 and ΔFT 4 at the first month were statistically significant and decreased sequentially in the CR group ( n=183), PR group ( n=70), NR or relapse groups ( n=20; F values: 15.40, 12.54, both P<0.001). ROC curve analysis showed that patients with ΔFT 3≥73.64% and (or) ΔFT 4≥59.03% had a higher probability of achieving CR, with sensitivities of 84.3% and 86.7%, and specificities of 62.6% and 62.6%, respectively. Logistic regression analysis showed that 24 h radioactive iodine uptake (odds ratio ( OR)=1.095, 95% CI: 1.031-1.139), dose of 131I given per gram of thyroid tissue ( OR=1.562, 95% CI: 1.321-1.694), ΔFT 3 ( OR=1.354, 95% CI: 1.295-1.482), ΔFT 4 ( OR=1.498, 95% CI: 1.384-1.608) were factors affecting the outcome of patients with GD treated with 131I treatment (all P<0.05). Conclusion:Effects of 131I treatment can be predicted based on the change of the thyroid function at the first month after 131I treatment in patients with GD.

OBJECTIVE To investigate the efficacy and safety of clobazam in the additional treatment of refractory epilepsy in children， and provide reference for clinically safe and rational drug use. METHODS The literatures about additional clobazam treatment for refractory epilepsy in children were searched from PubMed， The Cochrane Library， Embase， CNKI， VIP and Wanfang database during the inception to November 2023. After literature screening and data extraction， the quality of included literature was evaluated according to quality evaluation tool for methodological evaluation indicators of non-randomized controlled trial， and then meta-analysis of single-group rate and sensitivity analysis were performed by using RevMan 5.3 software. RESULTS Finally， 18 one-arm studies were included， with a total of 1 424 children. The results showed that compared with before additional treatment， the proportion of patients with seizures-free （proportion of patients with seizure reduction of 100%） was 24%[95%CI （0.18，0.32）， P＜0.000 01] after conversion； the proportion of patients with seizure reduction ≥75% was 32%[95%CI（0.25，0.40）， P＜0.000 1] after conversion； the proportion of patients with seizure reduction ≥50% was 53%[95%CI（0.44，0.61），P＜0.000 01]； the proportion of patients with seizure reduction ＜50% or no change was 35%[95%CI（0.24，0.49），P＝0.04] after conversion； the proportion of patients with seizure increase was 9%[95%CI（0.05，0.18），P＜0.000 01] after conversion. The proportion of patients with adverse reactions was 31%[95%CI（0.23，0.40），P＜0.000 1] after conversion； the proportion of patients with discontinuation due to adverse reactions was 10%[95%CI（0.07， 0.15）， P＜0.000 01] after conversion. The common adverse drug reactions were drowsiness， fatigue and behavior change， etc. The results of the sensitivity analysis showed that the study was robust. CONCLUSIONS Clobazam is an effective additional therapy for refractory epilepsy in children， but its adverse effects should be vigilant.

Objective To evaluate the correlation and consistency between an artificial intelligence(AI)bone mineral density(BMD)measurement system based on 3D-Densenet neural network technology and quantitative computed tomography(QCT)in measuring BMD,as well as to assess its effectiveness in diagnosing osteoporosis(OP).Methods A total of 1 201 participants who underwent low dose computed tomography(LDCT)were retrospectively included.The AI BMD measurement system and QCT were utilized to measure the BMD of T12,L1,L2 vertebrae,and the average BMD.Consistency and correlation of BMD measurements between the two methods were assessed using Bland-Altman,Pearson,and Kappa analyses.With QCT results as the reference standard,the receiver operating characteristic(ROC)curve was drawn to evaluate the accuracy of AI BMD measurement system in diagnosing OP.Results The r and r2 for the average BMD measured by the two methods were 0.997 and 0.993,respectively.The Kappa value for the diagnosis of normal BMD,low bone mass,and OP using the AI BMD measurement system was 0.905.The area under the curve(AUC)for diagnosing OP using the AI BMD measurement system was 0.998,with a sensitivity of 0.888 and specificity of 0.997.Conclusion The AI BMD measurement system based on 3D-Densenet neural network technology has a high correlation and consistency with the QCT measurement result,which can accurately diagnose normal BMD,low bone mass,and OP.

Objective:Given the high incidence and mortality rate of sepsis,early identification of high-risk patients and timely intervention are crucial.However,existing mortality risk prediction models still have shortcomings in terms of operation,applicability,and evaluation on long-term prognosis.This study aims to investigate the risk factors for death in patients with sepsis,and to construct the prediction model of short-term and long-term mortality risk. Methods:Patients meeting sepsis 3.0 diagnostic criteria were selected from the Medical Information Mart for Intensive Care-IV(MIMIC-IV)database and randomly divided into a modeling group and a validation group at a ratio of 7?3.Baseline data of patients were analyzed.Univariate Cox regression analysis and full subset regression were used to determine the risk factors of death in patients with sepsis and to screen out the variables to construct the prediction model.The time-dependent area under the curve(AUC),calibration curve,and decision curve were used to evaluate the differentiation,calibration,and clinical practicability of the model. Results:A total of 14 240 patients with sepsis were included in our study.The 28-day and 1-year mortality were 21.45%(3 054 cases)and 36.50%(5 198 cases),respectively.Advanced age,female,high sepsis-related organ failure assessment(SOFA)score,high simplified acute physiology score II(SAPS II),rapid heart rate,rapid respiratory rate,septic shock,congestive heart failure,chronic obstructive pulmonary disease,liver disease,kidney disease,diabetes,malignant tumor,high white blood cell count(WBC),long prothrombin time(PT),and high serum creatinine(SCr)levels were all risk factors for sepsis death(all P<0.05).Eight variables,including PT,respiratory rate,body temperature,malignant tumor,liver disease,septic shock,SAPS II,and age were used to construct the model.The AUCs for 28-day and 1-year survival were 0.717(95%CI 0.710 to 0.724)and 0.716(95%CI 0.707 to 0.725),respectively.The calibration curve and decision curve showed that the model had good calibration degree and clinical application value. Conclusion:The short-term and long-term mortality risk prediction models of patients with sepsis based on the MIMIC-IV database have good recognition ability and certain clinical reference significance for prognostic risk assessment and intervention treatment of patients.

Objective To systematically retrieve and summarize high-quality evidence on health education for patients with temporary enterostomies to provide an evidence-based basis for clinical practice.Methods We searched UpToDate,BMJ Best Practice,AHRQ,NICE,RNAO,MEDLIVE,WCET,UOAA,NSWOCC,NHMRC,CAN,CNKI,Wanfang,VIP,CBM,PubMed,Web of Science,CINAHL,JBI,and Cochrane Collaboration databases of evidence related to health education for patients with temporary enterostomies,including clinical decisions,guidelines,expert consensuses,evidence summaries,and systematic reviews.The search time limit was from January 1,2013 to August 1,2023.2 researchers who were trained in systematic evidence-based knowledge independently conducted literature screening,quality assessment,extraction and summarization of evidence based on inclusion and exclusion criteria.Results A total of 16 articles were included,including 5 guidelines,2 clinical decisions,4 evidence summaries,2 systematic reviews,2 expert consensuses,and 1 standard.The 24 pieces of the best evidences were summarized in 7 aspects:qualification of health educators,subjects of health education,opportunity of health education,mode and evaluation index of health education,preoperative health education,postoperative health education and home follow-up management.Conclusion The best evidence of health education for patients with temporary enterostomies summarized in this study is scientific and practical,providing evidence-based basis for healthcare professionals to implement health education for patients with temporary enterostomies.

Objective:To analyze the short- and medium-term efficacy, factors influencing the efficacy, and safety of dupilumab alone or in combination for the treatment of bullous pemphigoid (BP) .Methods:A single-center retrospective cohort study was conducted. Clinical data were collected from adult BP patients, who were regularly followed up and treated with dupilumab at the Department of Dermatology, Peking University First Hospital between March 2021 and June 2022. Dupilumab was administered subcutaneously every 2 weeks at a dose of 300 mg (except for the initial dose being 600 mg). Previous medications included glucocorticoids, minocycline, immunosuppressants, etc., and their dose remained unchanged or decreased according to patient condition. The short- and medium-term response rates were evaluated at weeks 2 and 16 after the first injection of dupilumab, respectively. Multivariate logistic regression analysis was conducted to identify factors influencing the disease control rate at week 2, and odds ratios ( ORs) were calculated; a multivariate Cox regression model was employed to analyze factors influencing the disease control rate within 16 weeks of follow-up, and hazard ratios ( HRs) were calculated; multiple linear regression analysis was performed to determine factors associated with the time to pruritus relief. Results:A total of 104 BP patients were eligible, including 60 males and 44 females; they were aged 75.6 ± 12.8 years, and the disease duration ( M [ Q1, Q3]) was 4.0 (2.0, 17.0) months. According to the percentage of the lesion area to the total body surface area, the disease severity was graded, and there were 17 mild cases, 30 moderate cases, 31 severe cases, and 26 extremely severe cases; 56 patients (53.9%) were treated with dupilumab combined with oral glucocorticoids at doses of 20.0 (15.0, 30.0) mg/d. At week 2 after the start of treatment, 63 patients (60.6%) achieved disease control, and 37 (35.6%) achieved marked disease control, resulting in a short-term response rate of 96.2%. Fifty-five patients were followed up for 16 weeks, 54 (98.2%) achieved improvement, and the systemic glucocorticoid dose was reduced to 10.0 (10.0, 17.5) mg/d. Disease control was achieved in 92 of 104 patients (88.5%) within 16 weeks, with the time to disease control being 14.0 (13.0, 26.0) days and the time to pruritus relief being 12.0 (3.0, 14.0) days. Multivariate logistic regression analysis showed that the higher the baseline disease severity, the lower the disease control rate at week 2 (compared with extremely severe cases, mild cases: OR = 37.655, 95% CI: 3.664, 386.981; moderate cases: OR = 12.143, 95% CI: 2.609, 56.528; severe cases: OR = 4.014, 95% CI: 1.121, 14.369, all P < 0.05). Multivariate Cox regression analysis showed that compared with severe BP patients, mild ( HR = 2.478, 95% CI: 1.200, 5.114, P = 0.014) and moderate BP patients ( HR = 2.076, 95% CI: 1.067, 4.038, P = 0.031) were more likely to achieve disease control during the 16-week treatment and follow-up. Multiple linear regression analysis revealed that the disease duration significantly influenced the time to pruritus relief ( P = 0.006), and the longer the disease duration, the longer the time to pruritus relief. During the follow-up, 13 adverse events occurred in 11 patients (10.6%), including 6 with pulmonary infections, 2 with heart failures, 1 with scabies, 1 with viral conjunctivitis, 1 with pericardial effusion (with a high likelihood of idiopathic pericarditis), 1 with organ failure, and 1 with intracerebral hemorrhage, but none of them were clearly related to dupilumab and most of them did not affect the treatment continuation; 3 deaths were reported, including 2 due to organ failures and 1 due to lung infection, which were all unrelated to dupilumab as determined by specialists. Conclusion:Dupilumab combination therapy for BP could result in rapid disease control, relieve pruritus, and reduce systemic glucocorticoid dosage, with a good safety profile.