BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

Objective To systematically review the sex differences in efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) patients. Methods We conducted a computer search of Medline, The Cochrane Library, and EMbase from inception to November 2022 to identify randomized controlled trials (RCTs) assessing the efficacy of ICIs in patients with NSCLC. A meta-analysis was performed using RevMan 5.4 software. Results Finally 16 RCTs with a total of 9 653 patients were included, and the modified Jadad scale score was≥4 points. Meta-analysis results showed that in female NSCLC patients receiving immune therapy, the median overall survival (OS) [HR=0.72, 95%CI (0.61, 0.85), P<0.001] was longer than that in males [HR=0.73, 95%CI (0.69, 0.78), P<0.001]. Males [HR=0.64, 95%CI (0.58, 0.71), P<0.001] had an advantage over females [HR=0.76, 95%CI (0.57, 1.03), P=0.760] in median progression-free survival (PFS). Conclusion Females receiving ICIs have an advantage over males in terms of median OS. However, males tend to derive greater benefit from ICIs in terms of median PFS.

Objective To explore the effect of fine particulate matter (PM_2.5) in Taiyuan City on short-term pulmonary function in elderly patients with chronic obstructive pulmonary disease (COPD). Methods Among the 1 015 elderly COPD patients admitted to the respiratory departments of five general hospitals in Taiyuan City from December 2021 to December 2023 were retrospectively selected for research; medical records, air pollutant data and meteorological data were analyzed; the relationship between PM_2.5 and lung function indicators and air pollutants was analyzed; the impact of PM_2.5 on lung function and its lag effect were analyzed; the cumulative effect of PM_2.5 concentration on the risk of pulmonary ventilation dysfunction was analyzed; The influence of gender and age on the relationship between PM_2.5 and patients ' short-term pulmonary function was analyzed. Results PM_2.5, respirable particulate matter (PM₁₀), sulfur dioxide (SO₂), carbon monoxide (CO) were negatively correlated with average temperature and average humidity (P<0.05) ; Nitrogen dioxide (NO₂), ozone (O₃) were negatively correlated with average temperature (P<0.05) ; There was a positive correlation among PM_2.5, PM₁₀, SO₂, CO, NO₂, and O₃ (P<0.05) ; Elevated PM_2.5 is an independent risk factor for decreased lung function and increased air pollutants (P<0.05) ; At lag0 and lag1, PM_2.5 concentration was negatively correlated with lung function in a dose-response manner (P<0.05); daily average PM_2.5 concentration at lag0 was a dangerous effect (P<0.05). Conclusion The impact of PM_2.5 concentration on lung function has a certain time lag. An increase in PM_2.5 concentrations can lead to a decline in lung function.

Objective To systematically evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) as first-line treatment for advanced non-small cell lung cancer (NSCLC). Methods PubMed, The Cochrane Library, and EMbase databases were searched for clinical randomized controlled trials (RCTs) of ICIs as first-line treatment for NSCLC patients. The search period was from database inception to January 2023. Quality evaluation was conducted using the improved Jadad scale, and meta-analysis was performed using RevMan 5.4 software. Results Twelve RCTs were included, all of which were assessed as high-quality literature, involving a total of 7 121 patients. Meta-analysis results showed that, compared with chemotherapy, ICIs as first-line treatment for NSCLC patients significantly improved median overall survival (OS) [HR=0.72, 95%CI (0.64, 0.80), P<0.001] and median progression-free survival (PFS) [HR=0.65, 95%CI (0.53, 0.78), P<0.001], and improved objective response rate (ORR) [RR=1.52, 95%CI (1.28, 1.79), P<0.001]. Subgroup analysis showed that, compared with the ICIs monotherapy group, the ICIs combination therapy group significantly improved OS, PFS, and ORR in NSCLC patients. In terms of safety, the risk of any grade treatment-related adverse events (TRAEs) and grade 3-5 TRAEs in the ICIs group was lower than that in the chemotherapy group. The incidence of TRAEs leading to treatment discontinuation was higher in the ICIs group than in the chemotherapy group. Subgroup analysis showed that the incidence of any grade, grade 3-5, and TRAEs leading to treatment discontinuation was higher in the immune combination therapy group than in the immune monotherapy group. Conclusion ICIs as first-line treatment for NSCLC patients can significantly improve OS, PFS, and ORR compared with chemotherapy. Compared to immune monotherapy, immune combination therapy can significantly improve the efficacy in NSCLC patients, but patients have a higher risk of TRAEs.

Cough variant asthma （CVA） is a special type of asthma and the most common cause of chronic cough in China. It has a relatively high incidence， seriously affects patients' quality of life， and in some cases may even progress to typical asthma， posing an important challenge in the field of health economics. At present， first-line treatment in Western medicine mainly consists of inhaled corticosteroids combined with bronchodilators. However， there remain many problems such as poor efficacy in some patients， frequent relapse after drug withdrawal， and poor compliance， making it urgent to improve treatment strategies. In-depth research on the pathogenesis is helpful for a comprehensive understanding and prevention of CVA. The pathogenesis of CVA is complex and involves multiple pathophysiological links. While similar to typical asthma， it still presents some differences. Traditional Chinese medicine （TCM） has unique advantages in the treatment of CVA. Guided by the theory of syndrome differentiation and treatment， TCM can not only improve the clinical symptoms of CVA but also prevent recurrence. In recent years， with the continuous deepening of research on the pathogenesis of CVA and on its treatment with TCM based on syndrome differentiation， related academic achievements have been updated year by year. A review of literature in China and abroad shows that the current pathogenesis of CVA can be summarized into six aspects： airway inflammation， airway remodeling， airway hyperresponsiveness， cough hypersensitivity， genetic factors， and imbalance of intestinal flora. TCM often differentiates and treats CVA from four perspectives： cause， disease location， disease nature， and disease tendency. This paper systematically summarizes the progress in the study of CVA pathogenesis， comprehensively collates the experience and clinical research evidence on its treatment with TCM based on syndrome differentiation， and discusses the problems existing in current research. On this basis， it puts forward suggestions and prospects for future research and development of TCM in the treatment of CVA， with a view to providing a theoretical basis and therapeutic approaches for its prevention and treatment.

[摘 要] 目的：探索外周免疫功能状态与肺癌转移的关联，筛选可用于肺癌转移“正虚”评估的外周血免疫标志物。方法：回顾性分析2023年3月至2025年4月期间上海中医药大学附属市中医医院收治的肺癌患者治疗前的外周血免疫标志物，根据是否存在远处转移，将患者分为无转移组与转移组，比较两组间免疫细胞和细胞因子的表达差异。将单因素分析P < 0.05的外周血免疫指标纳入多因素二元Logistic回归模型，以识别肺癌转移的独立预测因素。结果：共纳入193例肺癌患者（无转移组101例，转移组92例），两组在性别、年龄、吸烟史、饮酒史、病理类型间的差异均无统计学意义（均P > 0.05）。单因素分析显示，无转移组与转移组间有多项免疫指标存在显著差异（均P < 0.05），包括：淋巴细胞计数，CD3+、CD4+、CD8+ T、CD19+ B细胞及CD3-CD16+56+ NK细胞绝对计数，Treg细胞、CD8+CD28+ Treg细胞、G-MDSC和CD3-CD16+CD56+dim NK细胞百分率，以及细胞因子IL-1β、IL-6和IL-10水平。将差异性指标行二元Logistic回归分析，提示外周血中Treg细胞和CD8+CD28+ Treg细胞百分率是肺癌发生远处转移的独立预测因素[OR = 1.193, 95% CI（1.047, 1.36）, P < 0.01; OR = 0.978, 95% CI（0.957, 0.999）, P < 0.05]。结论：外周血免疫功能紊乱是肺癌转移“正虚”的生物学基础，本研究以量化指标证实外周免疫功能状态与肺癌转移的相关性，为“正虚伏毒”和“肿瘤转移态”理论提供了实证。

AIM:To evaluate the efficacy,safety,and economy of camrelizumab(CAM)combined with platinum-containing chemotherapy(CT)for the first-line treatment of locally advanced/meta-static non-small cell lung cancer(NSCLC).METH-ODS:Chinese and English databases such as Pubmed,the Cochrane Library,China Knowledge Network,Wanfang Data,and other related web-sites were systematically searched.After literature screening,quality assessment,and data extraction of the literature according to the inclusion and ex-clusion criteria,two researchers conducted a rapid health technology assessment(HTA).RESULTS:A total of 7 systematic evaluations/Meta-analyses and 17 economics evaluations were included.In terms of effectiveness,compared to docetaxel che-motherapy,CAM+CT significantly prolonged the overall survival(OS),progression-free survival(PFS),and improved the objective remission rate(ORR)of mutation-negative patients with locally ad-vanced/metastatic NSCLC.Compared with CT and pembrolizumab(PEM),CAM+CT significantly pro-longed the PFS,and improved the ORR of mutation-negative patients with locally advanced/metastatic NSCLC.Subgroup analysis showed that CAM+CT significantly prolonged PFS in patients with PD-L1 ≥1％and PD-L1 ≥ 50％compared with CT.Compared with CT,CAM+CT significantly prolonged the OS and PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Compared with sintilimab(SIN),CAM+CT significantly pro-longed the PFS of mutation-negative patients with locally advanced/metastatic squamous NSCLC.Sub-group analysis showed that CAM+CT significantly prolonged OS in patients with PD-L1＜1％com-pared with CT.In terms of safety,CAM+CT was comparable in terms of the occurrence of all grades of adverse events,but the incidence of grade 3 or higher treatment-related adverse events was significantly increased compared with CT and PEM for mutation-negative locally advanced/meta-static NSCLC patients.CAM+CT was significantly in-creased the occurrence of all grades of adverse events compared with CT,but was comparable in terms of the occurrence of grade 3 or higher treat-ment-related adverse events.In terms of economy,CAM+CT has a cost-effectiveness advantage over CT for patients with mutation-negative advanced/metastatic squamous NSCLC.CAM+CT has a cost-effectiveness advantage over CT and PEM+CT;and CAM+CT does not have a cost-effectiveness ad-vantage over SIN+CT for patients with mutation-negative locally advanced/metastatic non-squa-mous NSCLC.CONCLUSION:CAM+CT has good ef-ficacy and cost-effectiveness for the first-line treat-ment of locally advanced/metastatic NSCLC,and the safety aspect is compared with CT,PEM or slightly worse.

Objective To summarize and explore the current state,hotspots,and trends in the field of surgical treatment for intracerebral hemorrhage(ICH)over the past decade through a bibliometric and visualization analysis of relevant literature.Methods Relevant Chinese and English literature on the surgical treatment of ICH,published from January 1,2014 to April 1,2024,was retrieved and screened from CNKI and Web of Science databases.Visualization analysis was conducted using CiteSpace,VOSviewer,and other software to analyze the number of published papers,authors,countries,institutions,etc.Social network analysis diagrams of authors,keyword clustering network analysis diagrams,keyword burst strength,and keyword timeline maps were also utilized.Results(1)A total of 3 456 relevant papers were included,with 2 173 in Chinese and 1 283 in English.From 2014 to 2021,the annual number of Chinese publications on ICH surgery was higher than that of English publications,but the number of Chinese publications began to decline from 2016.The number of English publications showed an overall increasing trend.(2)A total of 6 367 authors were identified from the English literature,with notable collaboration networks led by researchers such as Mocco J,Hanley DF,Ziai WC,You C,and Tang ZP.The Chinese literature included 6 522authors,with prominent collaboration networks led by Wang LK,Cai Q,Ku HB,Zhang S,and Zhu SQ.(3)Analysis of the countries involved in the English literature showed that 31 countries participated in research on ICH surgery,with China leading in the number of publications(505),followed by the United States(330)and Germany(106).The top three countries in centrality were the United States(0.32),China(0.16),and Canada(0.11).The top three institutions in English literature publications were Johns Hopkins University(51 papers),Ohio State University(39 papers),and Harvard University(38 papers).In China,Sichuan University(32 papers),Huazhong University of Science and Technology(30 papers),and Capital Medical University(27 papers)had multiple English publications;Wuhan University People's Hospital(15 papers),Affiliated Hospital of Guizhou Medical University(13 papers),and Affiliated Hospital of Yan'an University(13 papers)had multiple Chinese publications.There was close collaboration among research institutions in the English literature,whereas Chinese researchers often established research teams within their medical units with relatively less collaboration between teams.(4)Research on ICH surgery primarily focused on surgical methods,complications,and comprehensive perioperative treatment.Research hotspots included hypertensive ICH,minimally invasive surgical techniques,and perioperative management and treatment."neuroendoscopy"was the most recent emergent keyword in Chinese literature with high centrality and the strongest burst strength,while"randomized trial"had the highest burst strength in English literature.Research trends included the integration of artificial intelligence with minimally invasive techniques to optimize ICH surgery management and treatment strategies,analysis of risk factors,and evaluation of imaging value.Conclusions Over the past decade,the overall publication volume on the surgical treatment of ICH has been in a stable development phase,with research directions covering surgical techniques,diagnosis and treatment,evaluation,and management.Core research teams led by key authors were the main contributors to the publications.Future research hotspots and trends in ICH surgery may include the optimization of surgical techniques,complication management,large-scale multicenter clinical trials and integration of artificial intelligence with minimally invasive techniques.

In recent years,endovascular intervention therapy has gained popularity due to its advantages of minimal trauma and quick recovery,and become an essential method for treating cerebrovascular diseases.As a crucial surgical instrument in interventional therapy,catheters often require precise control of their tips to navigate through tortuous positions.Traditional catheters have shortages of fixed tip shapes,limited proximal torque transmission,and difficulty of manipulation,increasing the risk of complications during interventional procedures and prolonging surgical exposure time.With the rapid development of materials science and engineering,steerable catheter systems have become the spotlight of interventional physicians,making precise"bend control"possible.This article systematically explained the classification of steerable catheter systems,focusing on their application in neurointerventional therapy,and provided an outlook on the future development of steerable catheters.

Enteropathogenic Escherichia coli(EPEC),a zoonotic foodborne pathogen,can induce severe and prolonged di-arrhea,thus substantially affecting global public health safety.To understand the pathogenicity of EPEC and its potential risk to human health,this study investigated the antimicrobial resistance and genome-wide characteristics of EPEC originating from ducks.After identification of EPEC with the plate method and PCR,antimicrobial susceptibility of the isolates was examined with the microbroth dilution method.In addition,analyses of serotype,sequence type(ST),and plasmid incompatibility groups were conducted with whole-genome sequencing(WGS)and bioinformatic methods.Ten EPEC isolates were identified,including serotypes O71∶H40 and O3∶H21.All EPEC strains exhibited multiple drug resistance.The highest proportion of resistance(100％)was observed to ciprofloxacin,streptomycin,tetracycline,and polymyxin B.In contrast,the isolates showed susceptibility to cefoxitin,amikacin,and imipenem.Furthermore,all strains carried the tetracycline resistance gene tet(A)and extended-spectrum β-lactamase(ESBL)resistance genes,including blaOXA-10,blaTEM-1A,and blaTEM-1B.Various virulence genes,associated primarily with the secretory system,were de-tected in the isolates.However,no bf p genes or per ARC genes were identified,thus indicating that the EPEC isolates were atypical EPEC(aEPEC).The results demonstrated the presence of multiple antimicrobial resistance,multiple resistance and viru-lence genes,and various plasmid incompatibility groups,thus in-dicating potential pathogenicity to humans.Strengthened monitoring of duck-derived EPEC is crucial to effectively control the spread of the pathogen and safeguard public health.