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.Comparative study on the efficacy of superior rectal artery preservation versus high ligation of the inferior mesenteric artery in laparoscopic radical resection of sigmoid colon cancer
Mingye ZHENG ; Bo YANG ; Yongxiang LI
Acta Universitatis Medicinalis Anhui 2026;61(5):880-887
ObjectiveTo investigate the short-term clinical outcomes and long-term prognostic value of preserving the superior rectal artery (SRA) versus high ligation of the inferior mesenteric artery (IMA) in laparoscopic sigmoid colon cancer resection (LSCER) for sigmoid colon cancer (SCC). MethodsA retrospective comparative analysis was performed of 316 SCC patients who underwent LSCER. Patients were divided into the SRA preservation group (Group A,132 cases) and IMA high ligation group (Group B,184 cases) according to the vascular management strategy. Short-term clinical indicators and long-term follow-up outcomes were compared between the two groups. ResultsThere were no significant differences in baseline data between the two groups. The mean operation time of Group A was (190.0 ± 61.9) min, which was significantly longer than that of Group B [(165.0 ± 49.1) min, P<0.001]. However, Group A demonstrated significantly shorter time to drain removal, time to first flatus, and postoperative hospital stay (P<0.001). No significant differences were observed in intraoperative blood loss, number of lymph nodes dissected, or incidence of anastomotic leakage (AL) between the two groups. Long-term follow-up results showed that there were no significant differences in 3-year overall survival rate and 3-year disease-free survival rate between the two groups. ConclusionLaparoscopic sigmoid colon cancer resection with SRA preservation is safe and feasible for the treatment of SCC. Although the operation time is slightly prolonged, it can effectively promote short-term postoperative recovery without affecting the curative effect of tumor resection or long-term prognosis.
3.Characteristics of hearing loss among noise-exposed workers in the lithium battery manufacturing industry
Yunqiang XU ; Chunnian YOU ; Rongguang LI ; Huandi CHEN ; Yongxiang TANG ; Jijun GUO ; Huanwen TANG
China Occupational Medicine 2026;53(2):223-226
Objective To analyze the characteristics of hearing loss at different frequencies among noise-exposed workers in a lithium battery manufacturing enterprise. Methods A total of 1 954 noise-exposed workers from a large lithium battery manufacturing enterprise were selected as the study subjects using the judgmental sampling method. Pure-tone audiometry, individual noise exposure level monitoring, and workplace noise intensity measurement were conducted. Results The overall detection rate of hearing loss among the study subjects was 39.0%. The detection rates of unilateral and bilateral hearing loss were 21.0% (410/1 954) and 18.0% (352/1 954), respectively. The detection rate of hearing loss in the right ear was higher than that in the left ear (30.1% vs 26.9%, P<0.05). The detection rates of elevated hearing thresholds at high frequencies and speech frequencies were 38.8% and 1.1%, respectively. Comparisons of the detection rates of elevated hearing thresholds across different frequencies between the left and right ears showed significant differences (all P<0.01); specifically, the detection rate at 4.0 kHz in the right ear was higher than that in the left ear (P<0.01). The detection rates of elevated hearing thresholds at 2.0, 4.0, and 6.0 kHz increased with longer duration of noise exposure (all P<0.05). Except at 1.0 kHz, the detection rates of elevated hearing thresholds at 0.5, 2.0, 3.0, 4.0, and 6.0 kHz showed increasing trends with age (all P<0.05). Conclusion Hearing loss among noise-exposed workers in the lithium battery manufacturing industry is predominant in the high-frequency type, with the highest sensitivity at 4.0 kHz and greater susceptibility in the right ear. The detection rate of high frequency hearing loss increases with longer noise exposure duration and advacing age. Health surveillance should focus on workers with longer noise exposure duration and older age. Noise control measures should be strengthened.
4.Evaluation progress of the application of staplers in thoracoscopic lung surgery
Shenghui LI ; Yijiu REN ; Hang SU ; Minglei YANG ; Guofang ZHAO ; Yongxiang SONG ; Xuefei HU ; Deping ZHAO ; Qi XUE ; Chang CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):709-713
Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.
5.Correlation between SLC17A1 single nucleotide polymorphism and susceptibility to hyperuricemia in automotive manufacturing workers
Yongxiang TANG ; Yanmei RUAN ; Xiaojuan LIANG ; Yanru LI ; Guanghui DONG
China Occupational Medicine 2025;52(2):129-134
Objective To investigate the correlation of solute carrier protein 17 family member 1 (SLC17A1) gene single nucleotide polymorphisms (SNPs) and susceptibility to hyperuricemia (HUA) in automotive manufacturing workers. Methods A total of 192 Han male workers diagnosed with HUA were selected as the case group, 192 Han male workers without HUA from the same enterprises were selected as the control group. These workers were determined by the matching factor of age, total length of service, and body mass index by the 1∶1 case-control study method. Peripheral venous blood from the workers was collected for DNA extraction. Two SNPs of SLC17A1 were genotyped by MassArray system. Results The gene frequency distributions of SLC17A1 rs2096386 and rs1183201 of workers in the control group were in consistent with the Hardy-Weinberg equilibrium test (both P>0.05). The allele frequency distribution of rs2096386, and the genotype and allele frequency distribution of rs1183201 were significantly different between workers in the two groups (all P<0.05). There was no significant difference in genotype frequency distribution of rs2096386 between workers in the two groups (P>0.05). The results of conditional logistic regression analysis showed that workers with G allele at rs2096386 increased the risk of HUA [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.01-2.04], workers with T allele at rs1183201 increased the risk of HUA (OR=2.03, 95%CI =1.29-3.19), after adjusting for confounding factors such as serum creatinine, blood urea nitrogen, alanin aminotransferase and aspartate aminotransferase. While workers with TA and TA+AA genotypes at rs1183201 had a lower risk of HUA than those with TT genotype (OR=0.51, 95%CI =0.30-0.85; OR=0.50, 95%CI =0.30-0.83), workers with TA genotype at rs1183201 had a lower risk of HUA than those with TT+AA genotype (OR=0.53, 95%CI =0.32-0.88). Conclusion The polymorphisms at rs2096386 and rs1183201 of SLC17A1 gene may be correlated with HUA susceptibility among automobile manufacturing workers in Guangzhou City.
6.Erratum: Author correction to "Generation of αGal-enhanced bifunctional tumor vaccine" Acta Pharm Sin B 12 (2022) 3177-3186.
Jian HE ; Yu HUO ; Zhikun ZHANG ; Yiqun LUO ; Xiuli LIU ; Qiaoying CHEN ; Pan WU ; Wei SHI ; Tao WU ; Chao TANG ; Huixue WANG ; Lan LI ; Xiyu LIU ; Yong HUANG ; Yongxiang ZHAO ; Lu GAN ; Bing WANG ; Liping ZHONG
Acta Pharmaceutica Sinica B 2025;15(2):1207-1207
[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].
7.Targeted inhibition of macrophage STING signaling alleviates inflammatory injury and ventricular remodeling in acute myocardial infarction.
Huan YAO ; Qingman HE ; Shujun WEI ; Li XIANG ; Yuanyuan LUO ; Cong HUANG ; Weiwei LIU ; Chuan ZHENG ; Xueping LI ; Yongxiang GAO
Acta Pharmaceutica Sinica B 2025;15(8):4030-4046
Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern to activate the stimulator of interferon genes (STING) signaling in macrophages, promoting tissue inflammation. However, its role in acute myocardial infarction (AMI) remains unclear. Macrophage-specific Sting1 knockout mice were used to validate STING's pathological role in AMI. Cardiac and liver mtDNA were used to activate macrophages in co-culture systems with cardiomyocytes to assess fibrosis and hypertrophy. Panaxatriol saponin (PTS) was tested for its ability to block mtDNA-driven macrophage activation and subsequent cardiomyocyte damage. STING-PTS binding ability was analyzed. AMI rats received PTS to evaluate its effects on myocardial inflammation and ventricular remodeling. In vivo, macrophage-specific Sting1 knockout reduced myocardial inflammation and injury after AMI. In vitro, mtDNA-activated macrophages induced cardiomyocyte fibrosis and hypertrophy through STING signaling. PTS suppressed mtDNA-driven macrophage activation by directly binding STING, thereby blocking inflammatory cascades. In AMI rats, PTS treatment attenuated acute inflammation and reversed ventricular remodeling. These findings establish the mtDNA-STING axis in macrophages as a critical driver of post-AMI inflammation and identify pharmacological STING inhibition with PTS as a promising therapeutic strategy. The study bridges genetic validation with translational applications, highlighting macrophage STING as a novel target for ischemic heart disease management.
8.Effectiveness and duration of point-of-use filter in improving endoscopic final rinse water quality
Xinyue ZHANG ; Jing DING ; Dawei WU ; Shuangfeng CHEN ; Suxiang JIN ; Wenlong WANG ; Yongxiang ZHANG ; Wensen CHEN ; Weihong ZHANG ; Zhanjie LI
Chinese Journal of Infection Control 2025;24(3):323-328
Objective To study the effect and duration of point-of-use filters on the improvement of endoscopic fi-nal rinse water quality.Methods The final rinse water end at the gastroscope manual cleaning workstation in the Endoscopy Centre of the First Affiliated Hospital with Nanjing Medical University was selected to install a tap ter-minal filter;five specimens of final rinse water were collected consecutively before the installation,immediately after the installation,and 1-11 weeks after the installation.At each sampling time,the staff responsible for clea-ning and disinfecting were asked whether the flow rate of discharged water could satisfy the working demand;the final rinse water was inoculated on R2A culture medium with membrane filter method,bacterial colony forming unit(CFU)was calculated after 30℃ incubation for 5 days.Results The qualified rates of endoscopic final rinse water before point-of-use filter installation was 0,immediately after and 1-9 weeks after installation were both 100%,10 and 11 weeks after installation were 80.0%and 20.0%,respectively.The mean CFU of endoscopic final rinse wa-ter before point-of-use filter installation was 102 CFU/100 mL,immediately after and 1-9 weeks after installation were both ≤2 CFU/100 mL,10 and 11 weeks after installation were 8 and 18 CFU/100 mL,respectively.The feedback from the cleaning and disinfection staff before installation,immediately after installation,and 1-11 weeks after installation indicated that the flow rate of discharged water gradually slowed down over time,but could still meet the work requirements.Conclusion The point-of-use filter can quickly and effectively improve the quality of endoscopic final rinse water,with use duration of up to 9 weeks after installation;Its biggest advantage is that it can serve as the final barrier to all integrated measures,playing a supplementary role in case of any problems occu-rring in the front-end process,and ensuring the microbial quality of the final rinse water to the greatest extent possible.
9.Regulatory role of ITCH-TXNIP-NLRP3 signaling pathway in Alzheimer disease-like lesions in vivo and in vitro
Qiuyu XIE ; Jianfeng MA ; Qiying SHEN ; Yongxiang HE ; Xiaobing LI ; Shuo YANG ; Yuke XIANG ; Yuan QIN ; Wei WEI ; Yinghua LIU
Chinese Journal of Pathophysiology 2025;41(6):1109-1117
AIM:To investigate the modulatory role of E3 ubiquitin-protein ligase ITCH in Alzheimer disease(AD)-like pathology through the thioredoxin-interacting protein(TXNIP)-nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)signaling pathway using both in vivo and in vitro experimental models.METHODS:(1)Ten 5×FAD(AD model)mice and 10 wild-type(WT)mice at 2-,4-and 6-month-old were randomly allocated into AD and WT groups.Amyloid β-protein(Aβ)plaque burden in the brain was detected by thioflavin-S and immunofluorescence staining,with the latter method additionally applied to assess TXNIP protein expression.The protein levels of ITCH and TXNIP were determined by Western blot,while their interaction was verified by co-immunoprecipitation.(2)Mouse mi-croglia BV2 cells stimulated by lipopolysaccharide(LPS)were used to construct neuroinflammation model,and were di-vided into control(CON)group and LPS+ATP treatment group.The BV2 cells stimulated by Aβ were used to construct AD inflammation model.According to the different treatment time,they were divided into CON,and 12,24 and 48 h treatment groups.Western blot was used to evaluate the expression of ITCH,TXNIP,and NLRP3 inflammasome compo-nents(NLRP3 and caspase-1)as well as the downstream IL-1β.Adenovirus-mediated ITCH overexpression(OE-ITCH)in Aβ-stimulated BV2 cells comprised three experimental groups:negative control group,Aβ oligomer stimulation group,and OE-ITCH group,with subsequent immunoblotting of inflammatory mediators.RESULTS:The deposition of Aβ plaques in the cortex and hippocampus of 5×FAD transgenic mice exhibited an age-dependent progression(P<0.01).Compared with WT mice,the levels of TXNIP protein increased synchronously,and the levels of ubiquitin ligase ITCH was significantly down-regulated(P<0.05).Co-immunoprecipitation confirmed the interaction between ITCH and TXNIP proteins in the brain of 2-and 4-month-old 5×FAD mice,which exhibited marked attenuation by 4 months of age.In BV2 microglial models,Aβ/LPS stimulation provoked significant ITCH suppression,concurrently up-regulating TXNIP,core NLRP3 inflammasome components(NLRP3 and caspase-1),and downstream IL-1β(P<0.05).Overexpression of ITCH significantly inhibited Aβ-induced activation of TXNIP and NLRP3 and therelated inflammatory factors in BV2 cells.CONCLUSION:The results of in vitro and in vivo experiments showed that ITCH protein exerts effects against AD-like pathology by inhibiting the expression of TXNIP-NLRP3 signaling pathway.
10.Correlation between gut microbiota and blood ammonia changes before and after TIPS in patients with decompensated cirrhosis
Dong ZHANG ; Meng HU ; Yongxiang ZHOU ; Dan LI ; Yuanjun DENG ; Guangjun TIAN
Journal of Interventional Radiology 2025;34(6):590-596
Objective To explore the effect of transjugular intrahepatic portosystemic shunt(TIPS)on gut microbiota and blood ammonia level in patients with decompensated cirrhosis,and to analyze the correlation between the gut microbiota and blood ammonia level.Methods From July 2021 to December 2023,the patients with decompensated cirrhosis and portal hypertension complicated by esophagogastric variceal bleeding and/or refractory ascites,who received TIPS at Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine,were collected.The blood and stool samples were collected before and after TIPS.The changes in blood routine,prothrombin time,liver function,and blood ammonia level were determined.The change of gut microbiota was detected using 16S rRNA high-throughput sequencing,and Spearman correlation analysis was used to assess the correlation between the gut microbiota and blood ammonia level.Results In 20 patients,the post-TIPS one-month levels of AST,TBil,DBiL,PT,and blood ammonia were higher than their pre-TIPS values(P<0.05),and the albumin(Alb)level was lower than the pre-TIPS value(P<0.05).The post-TIPS 3-month levels of TBil,DBil,PT,and blood ammonia were higher than their pre-TIPS values(P<0.05).One month after TIPS,the beta diversity of the gut microbiota became significantly different from the pre-TIPS pattern(P<0.05).After TIPS,the harmful bacteria such as Veillonella,Streptococcus and Haemophilus were significantly reduced,the difference was statistically significant(P<0.05).The correlation analysis of gut microbiota and blood ammonia level showed that in T0 group Colidextribacter was positively correlated with blood ammonia level,while Roxobella was negatively correlated with blood ammonia level;and in T1 group,Colidextribacter and Streptococcus were positively correlated with blood ammonia level,while Coprococcus,Bifidobacterium and Parasutterella were negatively correlated with blood ammonia level,and the differences were statistically significant(all P<0.05).Conclusion In patients with decompensated cirrhosis after receiving TIPS,significant changes in the pattern of gut microbiota occur.Certain correlations exist between the changes of some microbiota and blood ammonia levels.Regulating the intestinal microecology may contribute to reducing blood ammonia level after TIPS.

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