Objective To investigate the prevalence of thyroid nodules in the physical examination population in Mianyang region and analyze its association with metabolic syndrome. Methods A retrospective study was conducted on 9 978 individuals who underwent health examinations at our hospital from January 2024 to May 2025. Thyroid examinations were performed using color Doppler ultrasound to analyze the prevalence of thyroid nodules in this population. Clinical data of all subjects were collected, and logistic regression analysis was employed to assess the association between metabolic syndrome and the risk of thyroid nodule development. Results The prevalence of thyroid nodules in the physical examination population of Mianyang region was 17.98% (1 794/9 978). The logistic regression results showed that after adjusting for gender, age, BMI, occupation, consumption of non-iodized salt, staying up late, daily sleep duration, anxiety, and depression, metabolic syndrome (OR=6.593, 95% CI: 3.961-10.975) was associated with thyroid nodules (P<0.05). Conclusion The prevalence of thyroid nodules among the physical examination population in the Mianyang area is 17.98%, and metabolic syndrome remains associated with the risk of thyroid nodules after effectively controlling for confounding factors.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Da Chaihutang， first recorded in Shanghanlun by Zhang Zhongjing of the Eastern Han dynasty， is composed of eight medicinal herbs， namely Bupleuri Radix， Scutellariae Radix， Rhei Radix et Rhizoma， Aurantii Fructus Immaturus， Paeoniae Radix Alba， Pinelliae Rhizoma， Zingiberis Rhizoma Recens， and Jujubae Fructus. It features a well-defined hierarchy of sovereign， minister， assistant， and courier ingredients. The prescription is characterized by its balanced compatibility， mutually restrained cold and warm properties， and combined use of harmonizing and purging therapeutic strategies. As a renowned classical formula indicated for harmonizing Shaoyang and purging internal heat accumulation， it is the core prescription for the treatment of Shaoyang-Yangming combined disease. A comprehensive review of modern research literature on Da Chaihutang reveals that its chemical composition is notably diverse. The core pharmacologically active material bases of its constituent single herbs have been clearly identified， including saikosaponins from Bupleuri Radix， flavonoids from Scutellariae Radix， anthraquinones from Rhei Radix et Rhizoma， flavonoids and alkaloids from Aurantii Fructus Immaturus， monoterpene glycosides from Paeoniae Radix Alba， alkaloids and organic acids from Pinelliae Rhizoma， gingerols from Zingiberis Rhizoma Recens， and polysaccharides and triterpenoid acids from Jujubae Fructus. In the compound formula， a total of 163 chemical constituents have been comprehensively identified， among which flavonoids and their glycosides constitute the most abundant component category. Flavonoids and their glycosides， monoterpene glycosides， and pentacyclic triterpenoid saponins are regarded as the core pharmacologically active substances of the whole formula. In addition， 9 potential quality markers that can comprehensively characterize the overall quality and core therapeutic efficacy of the whole formula have been screened out. Modern pharmacological studies have shown that the pharmacological effects of Da Chaihutang exhibit synergistic characteristics involving multiple components， multiple targets， and multiple pathways. Its core pharmacological activities encompass the regulation of digestive system disorders， including pancreatic protection， intervention in biliary tract diseases， and protection of gastrointestinal mucosa； intervention in hepatobiliary diseases such as non-alcoholic fatty liver disease and cholestatic liver injury； and regulation of metabolic disorders such as hypoglycemic effect， improvement of insulin resistance， and regulation of lipid metabolism. Furthermore， it also possesses multiple pharmacological activities， including intervention in atherosclerosis， regulation of immune and inflammatory responses， multi-organ protection， and anti-hepatocellular carcinoma effect. In modern clinical practice， Da Chaihutang and its modified formulas are mostly used in combination with conventional Western medical regimens. They have demonstrated notable therapeutic advantages in the treatment of digestive system diseases such as cholecystitis， acute pancreatitis， cholelithiasis， and non-alcoholic fatty liver disease， but also have shown definite curative efficacy in the management of diseases affecting multiple other systems， including cardiovascular， endocrine， dermatological， reproductive， respiratory， neurological， urinary， pediatric， and immune systems. These combined applications can effectively improve the overall clinical response rate， shorten the time to symptom relief， and reduce both the disease recurrence rate and the incidence of adverse reactions. This review systematically summarized the formula compatibility， chemical constituents， pharmacological mechanisms， and modern clinical applications of Da Chaihutang and its modified formulas， to provide a theoretical basis and practical reference for the secondary development of classic formulas， the research and development of new drugs， and the precise and safe clinical application of this classical prescription.

Sepsis is a systemic inflammatory response syndrome triggered by infection. It progresses rapidly and tends to develop into multiple organ dysfunction. Tanshinone ⅡA， one of the core active ingredients of Salvia miltiorrhiza， exerts remarkable targeted protective effects against sepsis-induced multiple organ dysfunction. This paper reviews the mechanisms by which tanshinone ⅡA alleviates sepsis-induced multiple organ dysfunction. Tanshinone ⅡA can relieve sepsis-induced lung injury by inhibiting the activity of Toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor- κB， phosphatidylinositol 3-kinase/protein kinase B signaling pathways and maintaining mitochondrial homeostasis. It ameliorates sepsis- induced myocardial injury via suppressing the activation of NOD-like receptor family pyrin domain-containing 3/caspase-1 signaling pathway， downregulating the expression of inflammatory factors and regulating autophagy. It mitigates sepsis-induced renal injury by regulating oxidative stress imbalance and reducing the expression of apoptosis-related proteins. It alleviates sepsis-caused liver injury through inhibiting the release of inflammatory factors and hepatocyte apoptosis. It improves sepsis-induced intestinal barrier dysfunction by upregulating the expression of tight junction proteins and restraining inflammatory responses. Furthermore， it relieves sepsis-associated encephalopathy by activating peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A signaling pathway. Tanshinone ⅡA is expected to be a vital candidate drug for comprehensive prevention and treatment of sepsis. However， interdisciplinary research is required to break through current bottlenecks and realize the transformation from basic experiments to clinical application.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

BACKGROUND:Neurodegenerative diseases are closely related to the imbalance of mitochondrial autophagy regulation.Previous studies by the research group have shown that lycium barbarum polysaccharide has neuroprotective effects,but whether it can improve the damage of SH-SY5Y cells induced byβ-amyloid protein 1-42 by regulating mitochondrial autophagy is still unclear.OBJECTIVE:To explore the protective effect and mechanism of Lycium barbarum polysaccharide on SH-SY5Y cells induced by β-amyloid protein 1-42.METHODS:An Alzheimer's disease cell model was established by inducing SH-SY5Y cells with β-amyloid protein 1-42,and then intervening with Lycium barbarum polysaccharide.SH-SY5Y cells were divided into three groups:control group,β-amyloid protein 1-42 group(20 μmol/L β-amyloid protein 1-42 for 24 hours),and Lycium barbarum polysaccharide group(1 g/L Lycium barbarum polysaccharide was added 1 hour in advance to form a protective effect,and then 20 μmol/L β-amyloid protein 1-42 was added to intervene with Lycium barbarum polysaccharide for 24 hours).CCK8 assay was used to detect cell viability.Mitochondrial membrane potential was detected by JC-1.TUNEL staining was used to detect cell apoptosis.Immunofluorescence and western blot assay were used to detect the expression of synaptic,apoptosis,and mitophagy-related indicators.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability of the β-amyloid protein 1-42 group decreased(P＜0.05);cell apoptosis rate increased(P＜0.05);mitochondrial membrane potential decreased(P＜0.05);the expressions of pro-apoptotic proteins Bax and Caspase3 increased(P＜0.05);the expression of anti-apoptotic protein Bcl-2 decreased(P＜0.05);the expression levels of synaptic-related proteins Syn and PSD-95 decreased(P＜0.05);the expression levels of mitochondrial autophagy-related proteins Pink1,LC3A/B,Parkin,and Beclin-1 decreased(P＜0.05);and the expression of P62 increased(P＜0.05).(2)Compared with the β-amyloid protein 1-42 group,the cell viability in the Lycium barbarum polysaccharide group was increased(P＜0.05);the apoptosis rate was decreased(P＜0.05);the mitochondrial membrane potential was increased(P＜0.05);the expression levels of Bax and Caspase3 were decreased(P＜0.05);the expression of Bcl-2 was increased(P＜0.05);the expressions of Syn and PSD-95 were increased(P＜0.05);the expression levels of Pink1,LC3A/B,Parkin,and Beclin-1 were increased(P＜0.05),and the expression of P62 was decreased(P＜0.05).These findings indicate that Lycium barbarum polysaccharide may inhibit β-amyloid protein 1-42-induced damage to SH-SY5Y cells by regulating mitophagy,reduce cell apoptosis,and increase neuronal synaptic plasticity.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.