Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.

Objective To analyze the characteristics and risk factors associated with postoperative deep vein thrombosis(DVT)of the lower extremities in patients undergoing surgery for lumbar degenerative diseases.Methods A retrospective analysis was conducted on clinical data from 298 patients who were hospitalized for lumbar degenerative diseases and underwent lumbar spine surgery treatment in the First Affiliated Hospital of Nanchang University from October 1,2022 to April 15,2023.Patients were divided into DVT group(n=71)and non-DVT group(n=227)according to whether DVT of the lower limbs occurred within 1 week postoperatively.The incidence and distribution characteristics of postoperative DVT were analyzed.Univariate and binary logistic regression analyses were performed to identify risk factors for DVT,and receiver operating characteristic(ROC)curves were used to determine cut-off values for relevant risk factors.Results A total of 298 patients were included,among whom 159 were males(53.4%)and 139 were females(46.6%),with an average age of(64.5±9.8)years.DVT occurred in 71 patients,and the incidence of lower extremity DVT was 23.8%.In the DVT group,there were 49 cases(69.0%)of intermuscular vein thrombosis,and 22 cases of other types of thrombosis(7 cases of peroneal vein thrombosis,4 cases of posterior tibial vein thrombosis,3 cases of common femoral vein thrombosis,1 case of anterior tibial vein thrombosis,and 7 cases of multiple thrombosis);58 cases(81.7%)had DVT in one lower extremity,and 13 cases(18.3%)had DVT in both lower extremities.Univariate analysis results showed that age,body mass index(BMI),length of hospital stay,history of hypertension,operative time,and intraoperative blood loss were associated with the occurrence of lower extremity DVT after surgery for lumbar degenerative diseases(P<0.05).Binary logistic regression analysis results indicated that older age(OR=1.079,P<0.01),higher BMI(OR=1.130,P=0.01),history of hypertension(OR=2.992,P<0.01),and larger intraoperative blood loss(OR=1.002,P=0.03)were independent risk factors for the occurrence of lower extremity DVT.ROC curve analysis demonstrated that patients with age>58.5 years,BMI>24.01 kg/m2,history of hypertension,and intraoperative blood loss>550 ml had a significantly increased risk of postoperative lower limb DVT.Conclusions The incidence of lower extremity DVT after surgery for lumbar degenerative disease is high,and intermuscular venous thrombosis is more common.Older age,higher BMI,history of hypertension,and larger intraoperative blood loss are independent risk factors for the occurrence of lower extremity DVT after surgery.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.