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.

Helicobacter pylori （H. pylori） infection is not only associated with gastrointestinal diseases， but also potentially links with neuropsychiatric disorders revealed by recent studies. Through a systematic review of the existing literature， this review summarizes epidemiological evidence for the association between H. pylori infection and diseases such as Parkinson′s disease （PD）， Alzheimer′s disease （AD）， multiple sclerosis （MS）， migraine， depression， and anxiety disorders， and further explores potential mechanisms by which it affects central nervous system function， including neural pathways mediated by the enteric nervous system and the vagus nerve， immune pathways mediated by inflammatory cytokines， and endocrine pathways mediated by gut microbial metabolites. Additionally， the current challenges facing H. pylori eradication therapy and the prospects for emerging adjuvant strategies such as probiotics and fecal microbiota transplantation are discussed. Finally， future research directions are outlined， emphasizing the need for prospective cohort studies based on standardized diagnostic methods and further investigation using animal models to elucidate the pathophysiological mechanisms， with the aim of providing new perspectives for the prevention， treatment， and early intervention of related neuropsychiatric disorders.

Thioredoxin-interacting protein(TXNIP) inhibitors can inhibit the apoptosis of pancreatic β cells, while dual-specificity tyrosine-phosphoryation-regulated kinase 1A (DYRK1A) inhibitors can promote the proliferation of pancreatic β cells. This study used 4-benzopyrimidine as the starting material to design and synthesize benzopyrimidine-7-azaindole scaffold derivatives targeting TXNIP/DYRK1A by linking it with variously substituted 7-azaindoles via carbon chains of different lengths. A total of 12 novel quinazoline-7-azaindole derivatives were designed and synthesized, their structures confirmed by 1H NMR and ESI-MS, and their content was determined by HPLC. Pharmacological activity assays demonstrated that all 12 compounds exhibited inhibitory effects on β-cell apoptosis, with YN-3 and YN-6 showing the strongest activity, achieving a cell survival rate exceeding 75% (compared to 43.08% in the control group). Proliferation-promoting experiments revealed that most compounds exhibited proliferative activity, with YN-1–YN-3 and YN-11 demonstrating proliferation enhancement rates greater than 125%. YN-3exhibited the strongest combined anti-apoptotic and proliferation-promoting activities and may represent a promising new chemical entity for antidiabetic drug development.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Purpose: Colorectal cancer (CRC) often spreads to the liver, necessitating surgical treatment for CRC liver metastasis (CRLM). Iron-deficiency anemia is common in CRC patients and is associated with fatigue and weakness. This study investigated the effects of iron-deficiency anemia on the outcomes of surgical resection of CRLM. Methods: This population-based, retrospective study evaluated data from adults ≥20 years old with CRLM who underwent hepatic resection. All patient data were extracted from the 2005–2018 US National (Nationwide) Inpatient Sample (NIS) database. The outcome measures were in-hospital outcomes including 30-day mortality, unfavorable discharge, and prolonged length of hospital stay (LOS), and short-term complications such as bleeding and infection. Associations between iron-deficiency anemia and outcomes were determined using logistic regression analysis. Results: Data from 7,749 patients (representing 37,923 persons in the United States after weighting) were analyzed. Multivariable analysis revealed that iron-deficiency anemia was significantly associated with an increased risk of prolonged LOS (adjusted odds ratio [aOR], 2.76; 95% confidence interval [CI], 2.30–3.30), unfavorable discharge (aOR, 2.42; 95% CI, 1.83–3.19), bleeding (aOR, 5.05; 95% CI, 2.92–8.74), sepsis (aOR, 1.60; 95% CI, 1.04–2.46), pneumonia (aOR, 2.54; 95% CI, 1.72–3.74), and acute kidney injury (aOR, 1.71; 95% CI, 1.24–2.35). Subgroup analyses revealed consistent associations between iron-deficiency anemia and prolonged LOS across age, sex, and obesity status categories. Conclusion In patients undergoing hepatic resection for CRLM, iron-deficiency anemia is an independent risk factor for prolonged LOS, unfavorable discharge, and several critical postoperative complications. These findings underscore the need for proactive anemia management to optimize surgical outcomes.

Objective To observe the effects of wheat grain moxibustion on the hippocampal ERK/CREB-BDNF/TrkB signaling pathway and neurotransmitters in rats with perimenopausal depressive disorder(PDD);To explore its mechanism in treating PDD.Methods Totally 24 female SD rats were randomly divided into sham-operation group,model group,Western medicine group and wheat grain moxibustion group,with 6 rats in each group.The PDD rat model was established by bilateral ovariectomy and chronic unpredictable mild stress.The wheat grain moxibustion group received moxibustion at the"Zhongwan","Xiawan","Qihai","Guanyuan"acupoints,with a conical moxa cone for intervention,6 cones per acupoint;the Western medicine group was given fluoxetine hydrochloride solution 1.8 mg/kg by gavage,once a day,for consecutive 21 d.Before and after modeling and after intervention,the body mass,sucrose water preference rate and immobility time in the forced swimming test of the rats were recorded;Transmission electron microscopy was used to observe the synaptic structure in hippocampal tissue;ELISA was used to detect the expressions of 5-HT,GABA and Glu in hippocampal tissue;Western blot was used to detect the expressions of ERK,p-ERK,CREB,p-CREB,BDNF and TrkB proteins in hippocampal tissue.Results Compared with the sham-operation group,the body mass and sucrose water preference rate of the model group decreased,and the immobility time in the forced swimming test was prolonged(P<0.01);the number of synaptic vesicles in hippocampus decreased,the thickness of the postsynaptic density decreased,the aggregation of transduction-related proteins decreased,the synaptic cleft increased;the contents of 5-HT and GABA in hippocampal tissue decreased,the content of Glu increased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins decreased(P<0.01).Compared with the model group,the body mass and sucrose water preference rate of the rats in Western medicine group and wheat grain moxibustion group increased,and the immobility time in the forced swimming test was shortened(P<0.01);the area of the postsynaptic density in the hippocampus increased,the synaptic cleft reduced,the contents of 5-HT and GABA in hippocampal tissue increased,the content of Glu decreased,and the expressions of p-ERK,p-CREB,BDNF and TrkB proteins increased(P<0.01).Conclusion Wheat grain moxibustion can effectively alleviate depressive-like behavior in PDD rats,and its mechanism may be related to regulating neurotransmitter expressions and mediating the ERK/CREB-BDNF/TrkB signaling pathway,thereby regulating hippocampal neuroplasticity.

Objective:Patients with metastatic urothelial carcinoma(mUC)usually receive platinum-based chemotherapy as the first-line treatment.Recently,antibody-drug conjugates(ADCs)combined with programmed death-1 antibody(PD-1 antibody)have shown promising efficacy and safety in the treatment of mUC.HER2 positivity is associated with poor prognosis,patients can benefit from anti-HER2 ADC therapy such as disitamab vedotin(RC48-ADC).This study aimed to evaluate the efficacy and safety of RC48-ADC combined with tislelizu-mab in treatment-na?ve patients with mUC.Methods:A retrospective analysis was performed on 70 mUC patients treated between July 2022 and December 2023,including 30 patients receiving RC48-ADC combined with tislelizumab(DT group)and 40 patients receiving gem-citabine plus cisplatin(GC group).Primary endpoints included objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and treatment-related adverse events(TRAEs).Results:The ORR(73.3%vs.47.5%)and DCR(86.7%vs.62.5%)were significantly higher in the DT group compared to the GC group(P<0.05).The DT group also demonstrated longer PFS(10.98 months vs.7.67 months,P<0.005)and prolonged OS(median OS:not reached vs.11.34 months).The most common TRAEs included myel-osuppression,gastrointestinal and hepatobiliary toxicities,fatigue,alopecia,and rash.No grade≥3 TRAEs or treatment-related deaths were reported.Conclusions:RC48-ADC combined with tislelizumab demonstrated superior efficacy and favorable safety in treatment-na?ve pa-tients with mUC,supporting its potential as a first-line therapeutic option.

AIM To study the chemical constituents from Pyrolae Herba and their activity against pathogenic bacteria associated with sports injuries.METHODS Silica gel and Sephadex LH-20 were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antibacterial activity was detected by filter paper method.RESULTS Twenty five compounds were isolated and identified as manuleoside H(1),5-hydroxy-3,7-dimethoxy-4,-methyl flavone(2),5-hydroxy-3,7,4'-methoxy-flavone(3),5-hydroxy-7,3',4'-trimethoxy-flavone(4),5,7-dihydroxy-3-methoxy-flavone(5),7.5,4'-trihydroxyflavone(6),ethyl vanillate(7),clovandiol(8),hydroxydihydrobovolide(9),zanthopyranone(10),eugenin(11),berchemol(12),3,7-dimethoxy-5,3',4'-trihydroxyflavone(13),2,5-dimethyl-7-hydroxychromone(14),rutalinium(15),formononetin(16),8-hydroxy-4',7-dimethoxy-isoflavones(17),isoline(18),dearabinosyl pneumonanthoside(19),3,5-dihydroxycinnamic acid(20),2,4,6-trihydroxyacetophenone(21),p-isopropyl benzoic acid(22),geraldone(23),ethylsyringin(24),4-hydroxyphenylethyl-2'-hydroxypropionate(25).Compounds 8,10,12,16 and 24 showed bacteriostatic zone on pathogenic bacteria susceptible to sports injuries.CONCLUSION All the compounds are isolated from Pyrolae Herba for the first time.Compounds 8,10,12,16 and 24 have inhibitory activity against pathogenic bacteria susceptible to sports injuries.

Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.

Objective To investigate the differences in personality traits between the patients with anx-ious depression(AND)and non-anxious depression(NAD)in order to provide the possible basis for early find of the patients with AND.Methods A total of 572 adult patients with depression visiting in the psychiatric outpatient department of the First Affiliated Hospital of Chongqing Medical University from January 2022 to December 2022 were selected to conduct the questionnaire survey.General demographic questionnaire,Self-rating Depression Scale(SDS),Generalized Anxiety Disorder Scale(GAD-7)and Minnesota Multiphasic Per-sonality Inventory(MMPI)were collected and analyzed.The patients with GAD-7 total score ≥5 points served as the AND group(n=499)and those with GAD total score＜5 points served as the NAD group(n=73).The correlation between the general demographic questionnaire,SDS and GAD-7 with MMPI was ana-lyzed.Results There were statistically significant differences in the place of residence,number of children in a family,education years,MMPI total score and high score proportions of psychopathy,athopia,hysteria,depres-sion,hypochondriasis,paranoea,schizophrenia,social introversion and hypomania dimensions between the two groups(P＜0.05).The SDS and GAD-7 scores in the AND group were higher than those in the NAD group(P＜0.05).The MMPI total score,athopia,hysteria,depression,hypochondriasis,paranoea,schizophrenia,so-cial introversion and hypomania were positively correlated with SDS and GAD-7(P＜0.05).Conclusion The patients with depression accompanied by anxiety symptom could be early identified by the MMPI testing results.