Alcoholic liver fibrosis is a critical step in the progression of alcoholic liver disease toward liver cirrhosis， yet there is currently still a lack of effective and specific anti-fibrotic therapeutic strategies. Recent studies have shown that as an iron-dependent， lipid peroxidation-driven form of regulated cell death， ferroptosis plays an important role in alcohol-related hepatocellular injury and fibrogenesis. Reactive oxygen species generated during alcohol metabolism can damage hepatocytes， impair their antioxidant defense ability， and lead to disruption of iron homeostasis and accumulation of lipid peroxides， ultimately triggering ferroptosis. Hepatocyte ferroptosis can promote fibrosis by amplifying inflammatory responses and activating hepatic stellate cells， whereas selective induction of ferroptosis in activated hepatic stellate cells may attenuate fibrosis， highlighting the “double-edged sword” effect of ferroptosis. Current interventions against ferroptosis mainly focus on applying antioxidant approaches， reducing iron burden， or blocking the amplification of lipid peroxidation， which have shown preliminary efficacy and a potential clinical value， but there are still limitations such as single-target actions and insufficient cell selectivity. In the future， nanotechnology-based delivery and other targeting strategies may help to realize multi-pathway coordination and cell-specific modulation， thereby improving the anti-fibrotic efficacy of ferroptosis-oriented therapies.

Objective To investigate the effect of gender on prognosis after transcatheter patent foramen ovale(PFO)closure in patients with cerebral infarction or transient ischemic attack.Methods A retrospective cohort study was conducted involving patients with cerebral infarction or transient ischemic attack(TIA)who underwent PFO closure at our hospital between January 2013 and December 2023.The patients were grouped by gender,and related data were collected,including age,comorbidities,Risk of Paradoxical Embolism(RoPE)score,laboratory results,findings of transthoracic/transesophageal echocardiography(TTE/TEE),and post-procedural complications,such as device-related thrombosis(DRT),recurrent stroke,bleeding,and atrial fibrillation(AF).Results A total of 112 patients were enrolled,including 59 males and 53 females,at a mean age of 42.47±12.35 years.The females had significantly higher preoperative RoPE score than the males(6.6±1.4 vs 6.0±1.5,P=0.046),and a statistical difference was observed in the distribution of infarction sites between them(Chi-square=10.25,P=0.006),indicating that the males were prone to posterior circulation infarction.Intraoperative transthoracic echocardiography revealed a greater distance from the PFO to the aortic root in the females(9.3±2.4 mm vs 7.6±2.0 mm,P<0.001).During a median follow-up of 4 years,the male group had 1 case of myocardial infarction,1 cerebral hemorrhage,1 paroxysmal AF,2 gingival bleeding episodes,and 1 skin ecchymosis.In the female group,1 case experienced pulmonary embolism,1 paroxysmal atrial fibrillation,3 gingival bleeding episodes,2 skin ecchymoses,2 recurrent cerebral infarctions,and 2 recurrent TIAs.There was no statistical difference in overall adverse events between gender(P=0.291).Although the females had higher rates of recurrent cerebral infarction and TIA,this difference lacked statistical significance(P=0.222).Multivariate Cox regression analysis indicated that after adjusting for various potential confounding factors,such as RoPE score,age,hypertension,coronary heart disease,and other factors,gender was not an independent predictor of composite endpoint events after surgery.Conclusion Gender does not significantly affect overall prognosis after PFO closure in patients with cerebral infarction or TIA.However,females showed a trend toward higher rates of recurrent cerebral infarction and TIA.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Objective:To explore the clinical application value of serum N-glycan profiles for evaluating the severity of liver tissue inflammation in patients with chronic hepatitis B (CHB).Methods:A total of 221 CHB patients who underwent liver biopsy at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2018 to December 2020 were retrospectively enrolled. The Scheuer scoring system was used to assess the histological inflammation grade of the liver tissue. Serum N-glycan levels were measured using DNA sequencer-assisted N-glycan fingerprinting (NGFP). Using the upper limit of the alanine aminotransferase (ALT) reference value (40 U/L) as a cutoff, logistic regression models were developed to construct diagnostic models under two scenarios: normal ALT or abnormal ALT. Models based on serum N-glycan levels and serum N-glycan levels combined with routine laboratory indicators, were used to non-invasively evaluation of various pathological grades of liver tissue inflammation in CHB patients. The DeLong test was used to compare the diagnostic efficacy of the models by analyzing the areas under the receiver operating characteristic curve (AUC). Glycosylation-related gene expression differences associated with varying degrees of liver inflammation were analyzed using the Gene Expression Omnibus (GEO) database.Results:In CHB patients with normal ALT level, the relative abundances of N-glycan structure peak 1 (NGA2F) and peak 2 (NGA2FB) increased with higher liver inflammation grades, while the relative abundance of peak 5 (NA2) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G A) and its enhanced version (HIS-G A Plus) for identifying significant inflammation and necrosis (≥G2, indicating the initiation of antiviral therapy) were 0.805 (95% CI 0.690-0.899) and 0.904 (95% CI 0.821-0.960), respectively. In CHB patients with ALT>40 U/L, the relative abundances of peaks 1 (NGA2F), 2 (NGA2FB), and 3 (NG1A2F) increased with higher liver inflammation grades, while the relative abundances of peaks 8 (NA3) and 11 (NA4) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G B) and its enhanced version (HIS-G B Plus) for identifying significant inflammation (≥G2) were 0.810 (95% CI 0.727-0.889) and 0.838 (95% CI 0.754-0.901), respectively. With increasing liver inflammation grades, the expression levels of four glycosyltransferase genes (CHST4, FUT8, SLC51B, and ST8SIA4) were significantly upregulated ( P<0.05). Conclusions:Serum N-glycan biomarker models can be used to assist in evaluating the severity of liver tissue inflammation in CHB patients with both normal and abnormal ALT levels.

Objective:To explore the clinical application value of serum N-glycan profiles for evaluating the severity of liver tissue inflammation in patients with chronic hepatitis B (CHB).Methods:A total of 221 CHB patients who underwent liver biopsy at Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2018 to December 2020 were retrospectively enrolled. The Scheuer scoring system was used to assess the histological inflammation grade of the liver tissue. Serum N-glycan levels were measured using DNA sequencer-assisted N-glycan fingerprinting (NGFP). Using the upper limit of the alanine aminotransferase (ALT) reference value (40 U/L) as a cutoff, logistic regression models were developed to construct diagnostic models under two scenarios: normal ALT or abnormal ALT. Models based on serum N-glycan levels and serum N-glycan levels combined with routine laboratory indicators, were used to non-invasively evaluation of various pathological grades of liver tissue inflammation in CHB patients. The DeLong test was used to compare the diagnostic efficacy of the models by analyzing the areas under the receiver operating characteristic curve (AUC). Glycosylation-related gene expression differences associated with varying degrees of liver inflammation were analyzed using the Gene Expression Omnibus (GEO) database.Results:In CHB patients with normal ALT level, the relative abundances of N-glycan structure peak 1 (NGA2F) and peak 2 (NGA2FB) increased with higher liver inflammation grades, while the relative abundance of peak 5 (NA2) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G A) and its enhanced version (HIS-G A Plus) for identifying significant inflammation and necrosis (≥G2, indicating the initiation of antiviral therapy) were 0.805 (95% CI 0.690-0.899) and 0.904 (95% CI 0.821-0.960), respectively. In CHB patients with ALT>40 U/L, the relative abundances of peaks 1 (NGA2F), 2 (NGA2FB), and 3 (NG1A2F) increased with higher liver inflammation grades, while the relative abundances of peaks 8 (NA3) and 11 (NA4) decreased ( P<0.05). The AUCs of the HIS-G model (HIS-G B) and its enhanced version (HIS-G B Plus) for identifying significant inflammation (≥G2) were 0.810 (95% CI 0.727-0.889) and 0.838 (95% CI 0.754-0.901), respectively. With increasing liver inflammation grades, the expression levels of four glycosyltransferase genes (CHST4, FUT8, SLC51B, and ST8SIA4) were significantly upregulated ( P<0.05). Conclusions:Serum N-glycan biomarker models can be used to assist in evaluating the severity of liver tissue inflammation in CHB patients with both normal and abnormal ALT levels.

Objective To observe the incidence of pericardial tamponade(PT)after left atrial appendage closure(LAAC)in patients with non-valvular atrial fibrillation(NVAF),and to explore its related factors and outcomes.Methods NVAF patients who were hospitalized and treated with LAAC in Department of Cardiology of our hospital from August 2014 to March 2023 were selected for the study.The general clinical data,preoperative transthoracic echocardiography and transesophageal echocardiography data,results of routine preoperative laboratory tests,intraoperative data and follow-up data of the patients were collected through the hospital medical record management system.The enrolled patients were classified into the non-PT group(n=8)and the PT group(n =1184)according to whether PT occurred after LAAC or not.The incidence of PT,related risk factors and outcomes were statistically analyzed.Results This study included 639 males(53.6%)and 553 females(46.4%),with an average age of 68.1±9.65 years.The CHA2 DS2-VASc score was 4.51±1.72,and the HAS-BLED score was 3.36±1.09.PT occurred in 8 cases(0.67%),among them,6 cases occurred 1 to 33 h after LAAC,and 2 cases occurred on day 19 and day 27 after LAAC.As for the results of transesophageal echocardiography(TEE)and LAA angiography,compared with the non-PT group,the PT group had the significantly larger maximum caliber of the LAA(P=0.025,P=0.015),smaller maximum depth of the LAA(P=0.028,P=0.031),and lower success rate of one-time placement of the occluder(P=0.031);The occluder compression rate of the PT group was significantly greater than that of the non-PT group(P=0.046).Multivariate analysis showed that larger maximum diameter of LAA,smaller average effective depth of LAA and larger compression rate of occluder were the main risk factors for PT.All the 8 PT patients were cured by stopping antithrombotic drugs,pericardiocentesis or surgical drainage.During a mean follow-up of 39±27 months,there were no device-related thrombosis(DRT),ischemic stroke,systemic embolism and other complications in the PT group.Conclusion The incidence of PT after LAAC is low,which is related to the large diameter of LAA,the relatively insufficient depth of the LAA and the large compression rate of the occlude.PT can be cured by stopping antithrombotic drugs and pericardiocentesis/surgical drainage.

Objective:To study the relationship between adult fluoride exposure and grip strength in rural areas of China with fluorosis, as well as the roles of basal metabolic rate (BMR) and body fat percentage (BFP) in the association between fluoride exposure and grip strength.Methods:From April to May 2017, a cluster sampling method was used to conduct a questionnaire survey, physical examination, and biological sample collection on residents aged 18 - 60 in Tongxu County, Kaifeng City, Henan Province (epidemic areas of drinking-water-borne fluorosis). A total of 1 168 subjects were included in the study, including 427 males and 741 females. The fluoride ion selective electrode method and the picric acid method were used to determine the concentrations of urine fluoride and urine creatinine, and the adjusted urine fluoride concentration (CUF) was calculated. BMR and BFP were measured by a bioelectrical impendence method, and the grip strength was measured by a Jamar grip dynamometer. The relationship between CUF, BMR, BFP and grip strength were analyzed using a generalized linear model regression. The mediation effect model was used to assess the mediating effect of BMR and BFP on the association between CUF and grip strength.Results:Female grip strength decreased by 0.28 kg ( P = 0.043) for every 1.00 mg/L increment in CUF. No similar association was found between the two in males ( P = 0.744). Regardless of gender stratification, BMR was positively correlated with grip strength ( P < 0.001). For every 1.00% increase in BFP, female grip strength decreased by 0.18 kg ( P = 0.043). The mediation effect model analysis results showed that the mediation effect ratios of BMR and BFP in the association between CUF and grip strength in female were 65.1% ( P < 0.001) and 8.4% ( P = 0.111), respectively. Conclusion:Fluoride exposure is associated with changes in female grip strength, and BMR changes play a partial mediating role in the association between fluoride exposure and female grip strength.

Deficient mismatch repair(dMMR)is currently recognized as a biomarker for predicting the efficacy of immune checkpoint inhib-itors(ICIs),and domestic and foreign guidelines recommend first-line immunotherapy for patients with solid dMMR tumors.For rectal can-cer,only 5%of patients are classified as dMMR/microsatellite instability-high(MSI-H),and most have"immune desert type"or mismatch re-pair proficient(pMMR)/microsatellite stabilization(MSS)diseases,which respond poorly to ICIs.Therefore,recently,the synergistic effect of immune drugs and neoadjuvant chemoradiotherapy has been the focus of basic and clinical research.An increasing number of clinical trials of phase Ⅱ/Ⅲ immuno-total neoadjuvant therapy(iTNT)have emerged,and the management of locally advanced rectal cancer(LARC)has begun to enter the non-operative treatment era.Furthermore,an increasing number of studies support the efficacy of neoadjuvant immun-otherapy in patients with dMMR/MSI-H LARC,which exempts such patients from surgery and chemoradiotherapy as follow-up treatment and results in a pivot in the treatment paradigm of a watch-and-wait strategy.Regarding the LARC with pMMR/MSS,the preliminary iTNT findings support ICIs as a shift from an initial posterior-line palliative scheme to a first-line selection strategy and the continuation of large-scale clinical trials.However,no definitive conclusion has been reached regarding the best iTNT application for LARC.Recent studies have shown that short-course radiotherapy and sequential neoadjuvant chemotherapy,combined with immunotherapy,can achieve good short-term outcomes.Finally,identifying other new biomarkers may facilitate the identification of patients with pMMR/MSS who are sensitive to immune drugs(especially for low rectal cancer).In the future,the treatment strategy of LARC should be combined with the stratification of clinical recurrence risk and patient willingness for organ retention to achieve stratified and accurate treatment.This article will review the re-lated research background,basic and clinical research progress and existing problems of iTNT in LARC.

Objective To compare the efficacy of MRI-transrectal ultrasound(TRUS)software fusion-guided biopsy and cognitive fusion-guided biopsy for detecting prostate cancer(PC).Methods Data of 120 patients with suspected PC(127 lesions)who underwent transperineal prostate biopsy with 2-3 times of target biopsy(TB)and 10 times of system biopsy were retrospectively analyzed.According to TB guidance methods,73 cases(78 lesions)received MRI-TRUS software fusion-guided biopsy were classified into group A,and 47 cases(49 lesions)received cognitive fusion-guided biopsy were classified into group B.The positive rate of PC,clinic significant PC(csPC)and PC in different sized lesions by TB were compared between groups,and the positive rate of PC between 2 or 3 times TB was also compared within each group.Results The positive rate of PC and csPC detected by TB was 55.13%(43/78)and 39.74%(31/78)in group A,53.06%(26/49)and 34.69%(17/49)in group B,respectively,no significant difference was found(all P＞0.05).The positive rate of PC in lesions with the maximum diameter≤10 mm detected by TB in group A was higher than that in group B(P＜0.05),but no significant difference of lesions with the maximum diameter＞10 mm and＜15 mm nor≥15 mm was found between groups(all P＞0.05).No significant difference of positive rate of PC was found between 2 and 3 times TB in group A(P＞0.05),while positive rate of PC of 3 times TB was significantly higher than that of 2 times TB in group B(P＜0.05).Conclusion MRI-TRUS software fusion-guided biopsy had positive rate of PC and csPC similar to that of cognitive fusion-guided biopsy,but was helpful for reducing times of TB and increasing detecting rate for lesions with the maximum diameter≤10 mm.

Objective To explore the influence of gender on the prognosis of patients with atrial fibrillation(AF)undergoing left atrial appendage occlusion(LAAO).Methods All non-valvular AF patients who were admitted in our hospital and underwent LAAO from August 2014 to August 2021 were enrolled and grouped according to gender.Their general information,including gender,age,comorbid underlying diseases,and results of transthoracic echocardiography and transesophageal echocardiography(TEE)were collected.The incidences of device-related thrombosis(DRT),pericardial tamponade,stroke,bleeding,hospitalization for heart failure,and cardiac death were recorded during follow-up.The influence of gender on the prognosis of these patients was analyzed.Results There were totally 673 patients with non-valvular AF were enrolled,including 366 males and 307 females,at a mean age of 68.2±9.4 years.When compared with the male patients,the female ones had a higher CHA2DS2-VASc score(P＜0.01),but smaller proportions of history of stroke,average compression ratio of occluders,and incidence of residual shunt(＜3 mm)after occlusion(P＜0.05).In 45～60 d after surgery,TEE revealed that there were 17 cases of DRT,including 8 males(2.2％)and 9 females(2.9％),though without statistical difference between the groups.Among the 17 DRT cases,1 experienced stroke,and the incidence of stroke was 5.9％in those with DRT and 0.5％without.There were 4 cases of postoperative pericardial tamponade,including 1 in the male group and 3 in the female group(no significant difference),and all of them were improved after pericardial puncture and fluid extraction.During the follow-up period of 40.2±20.5 months,no obvious differences were observed between the 2 groups in terms of stroke,bleeding,hospitalization for heart failure,and cardiogenic death.Conclusion Gender shows no significant effect on the prognosis of patients with non-valvular AF after LAAO.