1.Guizhi Fulingwan Alleviate Hepatic Fibrosis by Modulating mtDNA/NLRP3/Caspase-1/GSDMD Signaling Pathway
Yu TANG ; Xuli YANG ; Qiang YANG ; Xiaojie WANG ; Yongxiang GAO ; Xueping LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):91-99
ObjectiveTo investigate the mechanism of Guizhi Fulingwan (GFW) against hepatic fibrosis, focusing on elucidating the regulatory effect of GFW on the mitochondrial DNA (mtDNA)/NOD-like receptor protein 3 (NLRP3)/cysteinyl aspartate-specific proteinase-1 (Caspase-1)/gasdermin D (GSDMD) signaling pathway. MethodsForty-two male Sprague-Dawley (SD) rats were randomly allocated into six groups (n=7): control, model, low/medium/high-dose (0.14, 0.28, 0.56 g·kg-1·d-1) GFW (GFW-L, GFW-M, GFW-H), and Dahuang Zhechong pills (DZW, 1.8 g·kg-1·d-1). The rat model of hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride. General conditions of the rats were observed. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Liver histopathology and collagen deposition were observed through hematoxylin and eosin (HE) staining and Masson's trichrome staining. Transmission electron microscopy (TEM) was employed to observe structural alterations and damage of cellular ultrastructures including mitochondria. Mitochondrial membrane potential (MMP, ΔΨm) was detected by flow cytometry. Serum levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of mtDNA and NLRP3 in the liver tissue were quantified by Real-time polymerase chain reaction (Real-time PCR). The protein levels of key molecules in the NLRP3/Caspase-1/GSDMD signaling pathway in the liver tissue were determined by Western blot. ResultsCompared with the control group, the model group exhibited a decrease in body weight (P<0.01), an increase in liver index (P<0.01), elevations in serum ALT and AST levels (P<0.01), and typical fibrotic features such as disorganized hepatocytes, inflammatory infiltration, and increased collagen deposition in the liver tissue. TEM revealed significant karyotheca degeneration, mitochondrial swelling, endoplasmic reticulum expansion, and organelle efflux in the model group. In addition, the model group showed decreased ΔΨm (P<0.01), up-regulated mRNA levels of mtDNA and NLRP3 (P<0.01) and protein levels of NLRP3, Caspase-1, and GSDMD (P<0.01) in the liver tissue, and increased serum levels of IL-1β and IL-18 (P<0.01). Compared with that in the model group, the body weight increased in GFW-L, GFW-M, and DZW groups (P<0.05) and markedly increased in the GFW-H group (P<0.01). The liver index decreased in the GFW groups and DZW group (P<0.01). The serum ALT level declined in the GFW-L group (P<0.05), and the serum ALT and AST levels decreased in the GFW-M, GFW-H, and DZW groups (P<0.01). Histopathological damage and fibrosis were alleviated to varying degrees, and TEM revealed mitigated ultrastructural injuries including mitophagy, mitochondrial swelling, and endoplasmic reticulum expansion in the drug intervention groups. The ΔΨm increased in GFW groups without statistical significance. The mRNA level of mtDNA in the liver tissue was down-regulated in the GFW-M (P<0.05), GFW-H (P<0.01), and DZW (P<0.01) groups. The mRNA level of NLRP3 was down-regulated in GFW-M, GFW-H, and DZW groups (P<0.01). Western blot analysis showed significantly down-regulated protein level of NLRP3 in all the GFW groups and the DZW group (P<0.01). The protein level of GSDMD-N was down-regulated in GFW-H and DZW groups (P<0.01). The protein level of cleaved Caspase-1 was down-regulated in GFW-M (P<0.05), GFW-H (P<0.01), and DZW (P<0.01) groups. In addition, the serum levels of IL-1β and IL-18 declined in GFW-H and DZW groups (P<0.01). ConclusionGFW can suppress pyroptosis to ameliorate CCl4-induced hepatic fibrosis, potentially through mitigating mitochondrial damage, inhibiting inflammasome assembly and activation, and blocking pro-inflammatory cytokine release.
2.Hemolytic phenotype analysis of Staphylococcus aureus clinical isolates
Ju Gao ; Shengnan Weng ; Guiyun Leng ; Xin Li ; Jie Yao ; Qiang Zhou ; Wei Tang
Acta Universitatis Medicinalis Anhui 2025;60(7):1312-1319
Objective:
To investigate the hemolytic phenotypes of Staphylococcus aureus clinical isolates.
Methods:
The hemolytic phenotypes of 105 Staphylococcus aureus isolates were analyzed and summarized using the three-point inoculation method.Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of four hemolysin genes (hla,hlb,hlc,and hld) ; The VITEK 2 GP639 antimicrobial susceptibility card was used to detect resistance to commonly used antibiotics ; DNA gel electrophoresis was performed to determine the prevalence of the mecA,sea,tst,and pvl genes ; The microtiter plate crystal violet staining method was used to assess biofilm formation ability ; The CCK-8 assay was used to evaluate cytotoxicity against macrophages.
Results:
Seven hemo- lytic phenotypes were identified among the Staphylococcus aureus clinical isolates. Differences were found among Staphylococcus aureus clinical isolates with different hemolytic phenotypes in terms of mRNA expression levels of he- molysin genes,antibiotic resistance,virulence gene prevalence,biofilm formation ability,and cytotoxicity to mouse macrophages (P <0. 05 ) .
Conclusion
Staphylococcus aureus clinical isolates exhibit diverse hemolytic pheno- types,which should be a focus across multiple dimensions,including microbiological testing,clinical treatment, and nosocomial infection prevention and control.
3.Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.
Yuanyue ZHU ; Linhui SHEN ; Yanan HUO ; Qin WAN ; Yingfen QIN ; Ruying HU ; Lixin SHI ; Qing SU ; Xuefeng YU ; Li YAN ; Guijun QIN ; Xulei TANG ; Gang CHEN ; Yu XU ; Tiange WANG ; Zhiyun ZHAO ; Zhengnan GAO ; Guixia WANG ; Feixia SHEN ; Xuejiang GU ; Zuojie LUO ; Li CHEN ; Qiang LI ; Zhen YE ; Yinfei ZHANG ; Chao LIU ; Youmin WANG ; Shengli WU ; Tao YANG ; Huacong DENG ; Lulu CHEN ; Tianshu ZENG ; Jiajun ZHAO ; Yiming MU ; Weiqing WANG ; Guang NING ; Jieli LU ; Min XU ; Yufang BI ; Weiguo HU
Frontiers of Medicine 2025;19(1):79-89
This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans
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Mendelian Randomization Analysis
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Gallstones/complications*
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Female
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Male
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Cholecystectomy/statistics & numerical data*
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Middle Aged
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Risk Factors
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Aged
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Adult
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Neoplasms/etiology*
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Stomach Neoplasms/epidemiology*
4.Expert Consensus on the Ethical Requirements for Generative AI-Assisted Academic Writing
You-Quan BU ; Yong-Fu CAO ; Zeng-Yi CHANG ; Hong-Yu CHEN ; Xiao-Wei CHEN ; Yuan-Yuan CHEN ; Zhu-Cheng CHEN ; Rui DENG ; Jie DING ; Zhong-Kai FAN ; Guo-Quan GAO ; Xu GAO ; Lan HU ; Xiao-Qing HU ; Hong-Ti JIA ; Ying KONG ; En-Min LI ; Ling LI ; Yu-Hua LI ; Jun-Rong LIU ; Zhi-Qiang LIU ; Ya-Ping LUO ; Xue-Mei LV ; Yan-Xi PEI ; Xiao-Zhong PENG ; Qi-Qun TANG ; You WAN ; Yong WANG ; Ming-Xu WANG ; Xian WANG ; Guang-Kuan XIE ; Jun XIE ; Xiao-Hua YAN ; Mei YIN ; Zhong-Shan YU ; Chun-Yan ZHOU ; Rui-Fang ZHU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):826-832
With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.
5.Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury (version 2025)
Kai HUANG ; Lunhao BAI ; Qing BI ; Hong CHEN ; Jiwu CHEN ; Xuesong DAI ; Wenyong FEI ; Weili FU ; Zhizeng GAO ; Lin GUO ; Yinghui HUA ; Jingmin HUANG ; Suizhu HUANG ; Xuan HUANG ; Jian LI ; Qiang LI ; Shuzhen LI ; Yanlin LI ; Yunxia LI ; Zhong LI ; Ning LIU ; Yuqiang LIU ; Wei LU ; Hongbin LYU ; Haile PAN ; Xiaoyun PAN ; Chao QI ; Weiliang SHEN ; Luning SUN ; Jin TANG ; Zimin WANG ; Bide WANG ; Ru WANG ; Shaobai WANG ; Licheng WEI ; Weidong XU ; Yongsheng XU ; Jizhou YANG ; Liang YANG ; Rui YANG ; Hongbo YOU ; Tengbo YU ; Jiakuo YU ; Bing YUE ; Hua ZHANG ; Hui ZHANG ; Qingsong ZHANG ; Xintao ZHANG ; Jiajun ZHAO ; Lilian ZHAO ; Qichun ZHAO ; Song ZHAO ; Jiapeng ZHENG ; Jiang ZHENG ; Zhi ZHENG ; Jingbin ZHOU ; Jinzhong ZHAO
Chinese Journal of Trauma 2025;41(4):325-338
With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.
6.Analysis of prostate cancer screening results and exploration of screening model for elderly males in Songjiang Rural Areas of Shanghai City based on PSA preliminary screening under the community linkage mode
Daocheng FANG ; Lingfeng WU ; Lixin CHEN ; Chunhua TANG ; Yong WANG ; Hui LI ; Hui WANG ; Kui ZHANG ; Shuangquan SUN ; Qiang GAO ; Mingyuan DONG ; Chao WANG ; Yi YANG ; Zhiwei YANG ; Jing LIU ; Wendi DU ; Zhenbing SHI ; Shumei BI ; Hui WEN
Chinese Journal of Preventive Medicine 2025;59(2):230-234
This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.
7.The impact of frailty on the prognosis of chronic heart failure patients treated with cardiac resynchronization therapy defibrillator implantation
Liang GAO ; Huasheng LYU ; Baopeng TANG ; Xianhui ZHOU ; Xinchun CHENG ; Youquan SHI ; Yaodong LI ; Jianghua ZHANG ; Qiang XING ; Tuerhong ZUKELA ; Yanmei LU
Chinese Journal of Internal Medicine 2025;64(1):45-51
Objective:The aim of this study was to assess the frailty status of patients with heart failure undergoing CRT-D and then explore the predictive value of frailty for all-cause mortality and heart failure-related readmissions in these patients.Methods:We retrospectively included 374 patients with chronic heart failure who underwent CRT-D treatment at the First Affiliated Hospital of Xinjiang Medical University between June 2020 and June 2024. Based on the Tilburg Debilitation Assessment Scale, 175 patients (46.8%) were classified as frail while 199 (53.2%) were classified as non-frail. The baseline data between the two groups was compared using Cox regression analysis and Kaplan-Meier curves were used for survival analysis. P-values of <0.05 indicated statistically significant differences. Results:A total of 374 patients aged 25-93 (68±11) years were enrolled in this study, 101 (27.0%) of which were female. Among these, 175 (46.8%) were categorized as frail, and 199 (53.2%) were classified as non-frail. Over a median follow-up time of 23 (5, 45) months, 35 (9.4%) patients experienced all-cause mortality, with 30 (17.1%) deaths occurring in the frail group and 5 (2.5%) in the non-frail group; meanwhile, readmission events due to heart failure occurred in a total of 174 (46.5%) patients, including 122 (70.1%) in the frail group, and 52 (29.9%) in the non-frail group. Cox analysis showed that frailty was a significant determinant of all-cause mortality ( HR=21.25, 95% CI 3.99-113.30, P<0.001) and readmission among heart failure patients receiving CRT-D ( HR=2.52, 95% CI 1.73-3.68, P<0.001). Log-rank tests showed that the survival rate of patients in the frail group was significantly lower than that of patients in the non-frail group ( HR=7.22, 95% CI 2.80-18.60, P<0.001) and the risk of readmission events due to heart failure was significantly higher among patients in the frail group than among those in the non-frail group ( HR=2.75, 95% CI 1.98-3.81, P<0.001). Conclusions:Frailty is an independent predictor of postoperative all-cause mortality and the occurrence of heart failure-related readmissions in patients with heart failure treated receiving CRT-D.
8.Effects of Bushen Shengjing Tiaohe Qixue Prescription in Regulating Wnt/β-catenin Signaling Pathway on Diminished Ovarian Reserve Rats
Jun WANG ; Na TANG ; Chaoyang YE ; Ling LI ; Tongqing GAO ; Jiamei HUANG ; Qiang DENG ; Fengying WU ; Zhichun JIN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):100-106
Objective To investigate the effects of Bushen Shengjing Tiaohe Qixue Prescription on rats with diminished ovarian reserve(DOR)based on Wnt/β-catenin signaling pathway.Methods Totally 60 8-week-old SD female rats were randomly divided into control group,model group,estradiol valerate group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the control group,the rats in the other groups were given a single intraperitoneal injection of cyclophosphamide 75 mg/kg to replicate the DOR rat model.From the next day of modeling,the corresponding drugs was administered for medication groups by gavage for 3 weeks.The general conditions of the rats were observed,ELISA was used to detect the contents of serum follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),anti-mullerian hormone(AMH)and inhibin B(INHB),HE staining was used to observe the morphologic changes in ovarian tissue,Western blot was used to detect GSK3β,β-catenin,CyclinD1 and c-MYC protein expressions in ovarian tissues,immunohistochemical staining was used to observe β-catenin expression in ovarian tissue,RT-qPCR was used to detect Wnt1,Wnt2,Wnt4,GSK3β,β-catenin,CyclinD1 and c-MYC mRNA expression in ovarian tissue,transmission electron microscopy was used to observe ultrapathologic structure of ovarian granulosa cells.Results Compared with the control group,the rats in the model group had reduced intake of food and water,slow or even reduced body mass gain,and disturbed estrous cycle,the serum contents of FSH and LH increased(P<0.01),the contents of E2,AMH and INHB decreased(P<0.01);the number of follicles of all levels in ovarian tissue was reduced,and there was increased number of atretic follicles with disturbed arrangement of the granulosa cells;the expression of GSK3β protein in ovarian tissue increased(P<0.01),the expression of β-catenin,CyclinD1 and c-MYC protein decreased(P<0.05,P<0.01),and β-catenin positive expression decreased(P<0.01),the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue decreased(P<0.01),GSK3β mRNA expression was increased(P<0,01);organelles such as mitochondria and nuclei of ovarian granulosa cells were highly swollen and partially lysed.Compared with the model group,the rats in the administered group all had different degrees of body mass increase,partial restoration of the motility cycle,serum FSH and LH contents decreased,and serum E2,AMH and INHB contents increased(P<0.01,P<0.05);the number of follicles at all levels in ovarian tissue increased to varying degrees,and the atretic follicles were reduced;the expression of GSK3β protein in ovarian tissue decreased,β-catenin,CyclinD1 and c-MYC protein expressions increased,β-catenin positive expression increased,the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue increased,and GSK3β mRNA expression decreased,with statistical significance in estradiol valerate group and TCM high-dosage group(P<0.05,P<0.01);mitochondria,endoplasmic reticulum and other organelles of ovarian granulosa cells were mildly to moderately swollen.Conclusion Bushen Shengjing Tiaohe Qixue Prescription can improve ovarian function and regulate serum sex hormone levels in DOR model rats,and its mechanism might be related to the activation of Wnt/β-catenin signaling pathway.
9.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
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Percutaneous Coronary Intervention/methods*
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Male
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Female
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Coronary Artery Disease/drug therapy*
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Retrospective Studies
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Renal Dialysis/methods*
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Middle Aged
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Aged
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China
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Proportional Hazards Models
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Treatment Outcome
10.The efficacy and safety of nebulized inhalation of recombinant human interferon α1b in the treatment of pediatric respiratory syncytial viral associated lower respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled phase Ⅲ clinical study
Xiaohui LIU ; Baoping XU ; Yunxiao SHANG ; Han ZHANG ; Zhenkun ZHANG ; Guangyu LIN ; Ju YIN ; Aihua CUI ; Guocheng ZHANG ; Zhaoling SHI ; Liwei GAO ; Chunming JIANG ; Junmei BIAN ; Yongjian HUANG ; Rongfang ZHANG ; Xiaomei LIU ; Xiaoqing YANG ; Yu TANG ; Lili ZHONG ; Hongmei QIAO ; Chuangli HAO ; Yuqing WANG ; Qubei LI ; Ling CAO ; Yungang YANG ; Ling LU ; Rongjun LIN ; Xingzhen SUN ; Wei ZHOU ; Qiang CHEN ; Jikui DENG ; Yuejie ZHENG ; Lin ZHAO ; Tao AI ; Xiaohong LIU ; Xiaoxia LU ; Ning JIANG ; Ming LI
Chinese Journal of Applied Clinical Pediatrics 2025;40(3):180-186
Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.


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