Objective To investigate the regulatory mechanism of transforming growth factor-β1 (TGF-β1) in different types of mitral valvular disease (MVD) with atrial fibrillation (AF). Methods From August 2011 to August 2012, patients with moderate to severe MVD accompanied by AF who required mitral valve replacement at the Department of Cardiovascular Surgery, West China Hospital, Sichuan University, were included. Based on echocardiographic results, patients were divided into two groups: a mitral regurgitation (MR) with AF (MR-AF) group and a mitral stenosis (MS) with AF (MS-AF) group. Left atrial tissue samples were collected during surgery. Techniques such as enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, immunohistochemistry, and Western blotting were used to detect key molecules in the TGF-β1/JNK pathway. Results Sixteen patients were enrolled. There were 8 patients in the MR-AF group, including 5 males and 3 females, with an average age of (41.38±11.19) years; and 8 patients in the MS-AF group, including 6 males and 2 females, with an average age of (43.12±5.30) years. The left atrial volume load was higher in MR-AF patients, while the left atrial pressure load was higher in MS-AF patients. In MS-AF patients, the relative expression levels of MAPK9, JUN, CASP3, BAX, and BCL2 mRNA in left atrial tissues were significantly upregulated. The serum TGF-β1 protein level and the relative expression levels of p-JNK, p-c-Jun, and Caspase-3 proteins in the left atrial tissues of the MR-AF group were higher. Myocardial cell damage was more severe in the MS-AF group, and the protein expression level of Bcl-2 was higher. Conclusion Different MVD have distinct hemodynamic characteristics. The myocardium of the left atrium in MR-AF patients is more prone to apoptosis, possibly through the activation of the TGF-β1/JNK signaling pathway.

ObjectiveTaking classical herbal pair compatibility research as the entry point， this study aimed to deeply investigate the material basis and compatibility rules underlying the antidepressant effects of the traditional Chinese medicine （TCM） formula Zhizi Houpotang， and to elucidate its antidepressant mechanism， with a particular focus on its regulation of neuroinflammatory responses mediated by the NOD-like receptor protein 3 （NLRP3）/gasdermin D （GSDMD） signaling pathway and the consequent improvement of neuronal synaptic plasticity. MethodsC57BL/6J mice were randomly divided into a blank control group， a chronic unpredictable mild stress （CUMS） depression model group， a Zhizi Houpotang full-formula group （6 g·kg^-1·d^-1）， a Magnoliae Officinalis Cortex （MOC）-Aurantii Fructus Immaturus （AFI） herbal pair group （4.2 g·kg^-1·d^-1）， a Gardeniae Fructus （GF）-MOC herbal pair group （4.2 g·kg^-1·d^-1）， a GF-AFI herbal pair group （3.6 g·kg^-1·d^-1）， and a positive drug group （fluoxetine， 12 mg·kg^-1·d^-1）. Depressive-like behaviors in mice were evaluated using behavioral tests. Immunofluorescence staining was used to label and quantify the expression of the microglial marker ionized calcium-binding adaptor molecule 1 （Ibal） and the purinergic receptor P2X ligand-gated ion channel 7 （P2RX7） in the prefrontal cortex （PFC）. Enzyme-linked immunosorbent assay （ELISA） was applied to detect the levels of inflammatory cytokines interleukin-1β （IL-1β） and interleukin-18 （IL-18） in serum and PFC tissues. Western blot was employed to determine the expression of pannexin 1 （Panx1）， P2RX7， NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， Caspase-1， GSDMD， postsynaptic density protein 95 （PSD95）， and the presynaptic protein Synapsin 1 in PFC tissues. Golgi staining was used to assess dendritic spine density of neurons in the PFC. ResultsCompared with the blank control group， the depression model group exhibited significant depressive-like behaviors. In addition， the immunofluorescence areas of Ibal and P2RX7 in the PFC were significantly increased （P<0.01）， the levels of IL-1β and IL-18 in serum and the PFC were significantly elevated （P<0.01）， and the protein expression levels of Panx1， P2RX7， NLRP3， ASC， Caspase-1， and GSDMD in the PFC were significantly upregulated （P<0.01）. In contrast， the protein expression levels of PSD95 and Synapsin 1 were significantly downregulated （P<0.01）， and neuronal dendritic spine density was significantly reduced （P<0.01）. Compared with the model group， the Zhizi Houpotang full-formula group and the GF-MOC herbal pair group showed significant improvement in all the above indicators （P<0.01）. The GF-AFI herbal pair group improved all the above indicators except P2RX7， Caspase-1， GSDMD， and PSD95 （P<0.05， P<0.01）. In contrast， the MOC-AFI herbal pair group showed no statistically significant improvement in any of the above indicators compared with the model group. ConclusionZhizi Houpotang and its key herbal pair， GF-MOC， can effectively ameliorate CUMS-induced depressive-like behaviors in mice. Its core antidepressant mechanism may involve inhibition of P2RX7/Panx1 signaling， thereby blocking the NLRP3/GSDMD-mediated pyroptosis pathway and significantly reducing the release of inflammatory cytokines IL-1β and IL-18. Simultaneously， it upregulates the expression of synapse-related proteins PSD95 and Synapsin 1 and increases dendritic spine density， promoting the recovery of synaptic plasticity. These results suggest that GF plays a key role in the antidepressant effects of this formula， and that the compatibility of GF with MOC may represent the principal herbal pair combination responsible for its core therapeutic action.

ObjectiveTo investigate the characteristics of mitochondrial translational initiation factor 2 （MTIF2） gene methylation and its association with the development and progression of hepatocellular carcinoma （HCC）. MethodsMethSurv and EWAS Data Hub were used to perform the standardized analysis and the cluster analysis of MTIF2 methylation samples， including survival curve analysis， methylation signature analysis， the association of tumor signaling pathways， and a comparative analysis based on pan-cancer database. The independent-samples t test was used for comparison between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Cox proportional hazards model was used to perform the univariate and multivariate survival analyses of methylation level at the CpG site. The Kaplan-Meier method was used to investigate the survival differences between the patients with low methylation level and those with high methylation level， and the Log-likelihood ratio method was used for survival difference analysis. ResultsGlobal clustering of MTIF2 methylation showed that there was no significant difference in MTIF2 gene methylation level between different races， ethnicities， BMI levels， and ages. The Kaplan-Meier survival curve analysis showed that the patients with N-Shore hypermethylation of the MTIF2 gene had a significantly better prognosis than those with hypomethylation （hazard ratio ［HR］=0.492， P<0.001）， while there was no significant difference in survival rate between the patients with different CpG island and S-Shore methylation levels （P>0.05）. The methylation profile of the MTIF2 gene based on different ages， sexes， BMI levels， races， ethnicities， and clinical stages showed that the N-Shore and CpG island methylation levels of the MTIF2 gene decreased with the increase in age， and the Caucasian population had significantly lower N-Shore methylation levels of the MTIF2 gene than the Asian population （P<0.05）； the patients with clinical stage Ⅳ had significantly lower N-Shore and CpG island methylation levels of the MTIF2 gene than those with stage Ⅰ/Ⅱ （P<0.05）. Clinical validation showed that the patients with stage Ⅲ/Ⅳ HCC had a significantly lower methylation level of the MTIF2 gene than those with stage Ⅰ/Ⅱ HCC and the normal population （P<0.05）. ConclusionN-Shore hypomethylation of the MTIF2 gene is a risk factor for the development and progression of HCC.

Glaucoma is a group of optic nerve disorders characterized by progressive optic nerve atrophy and visual field defects, which can lead to irreversible blindness. Early diagnosis of glaucoma is essential for preventing visual loss. However, due to the absence of obvious early symptoms, the diagnosis of glaucoma remains challenging. Visual electrophysiological examinations, an objective approach for evaluating visual function, have the potential to be used in the early diagnosis of glaucoma. This review integrates the latest publications to introduce visual electrophysiological examination techniques, including electroretinography(ERG)and visual evoked potential(VEP). It also explores the mechanisms underlying these techniques and their application value in the early diagnosis of glaucoma. In addition, this review summarizes the advantages, limitations, and applicable scenarios of different visual electrophysiological techniques. Finally, the review provides an outlook on the development prospects of visual electrophysiological techniques in the early diagnosis of glaucoma. The findings of this review can assist clinicians in selecting appropriate diagnostic methods, promote the innovation and development of early visual electrophysiological diagnostic techniques for glaucoma, and contribute to reducing the risk of blindness caused by glaucoma.

OBJECTIVE:Neuromuscular exercise is a new comprehensive rehabilitation therapy in recent years,but its effect on knee osteoarthritis is still controversial.The purpose of this paper is to systematically evaluate the efficacy of neuromuscular exercise on knee osteoarthritis pain and function. METHODS:The randomized controlled trials addressing neuromuscular exercise in the treatment of knee osteoarthritis pain and function were retrieved from PubMed,Cochrane Library,Embase,EBSCO,CNKI,Web of Science,China Biomedical Database(CBM),VIP,and WanFang Database.The retrieval time ranged from database inception to October 2023.The neuromuscular training group(experimental group)was given neuromuscular training or neuromuscular training as the main intervention;the control group was a blank group or given conventional rehabilitation.Outcome indicators included the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,walking time,knee stability,and the maximum number of knee flexion in 30 seconds.The risk of bias was evaluated by the Cochrane Collaboration tool and the Physiotherapy Evidence Database.Meta-analysis was performed using RevMan 5.4 software. RESULTS:A total of 11 randomized controlled trials were included,and 628 samples were extracted.The results of Meta-analysis showed that the experimental group was superior to the control group in terms of WOMAC pain score[standardized mean difference(SMD)=0.38,95%confidence interval(CI):0.08-0.69,P=0.01],knee stability(SMD=0.57,95%CI:0.23-0.92,P=0.001),the maximum number of knee joint flexion in 30 seconds(SMD=0.35,95%CI:0.05-0.65,P=0.02),and WOMAC physical function score(SMD=-0.79,95%CI:-1.30 to-0.28,P=0.002).In both groups,walking speed was increased and walking ability was improved in patients with knee osteoarthritis,but there was no significant difference(walking time:SMD=-0.22,95%CI:-0.48-0.03,P=0.09). CONCLUSION:Neuromuscular exercise can effectively improve knee joint pain,enhance the stability of the knee joint,and promote functional recovery in patients with knee osteoarthritis.However,more high-quality randomized controlled trials are still needed to further confirm the research.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

OBJECTIVES: Ruptured abdominal aortic aneurysm (rAAA) is a life-threatening vascular emergency with extremely high in-hospital mortality. Open surgical repair (OSR) was historically the only treatment option but is associated with substantial trauma and perioperative risk. In recent years, endovascular repair (EVAR) has gained widespread use due to its minimally invasive nature and faster recovery, becoming the preferred option for anatomically suitable patients in many centers. However, controversy remains regarding the long-term survival benefits of EVAR compared with OSR and key prognostic factors affecting outcomes. This study aims to evaluate the clinical efficacy of OSR and EVAR for rAAA and identify independent predictors of postoperative survival to guide clinical decision-making. METHODS: A retrospective analysis was conducted on 83 patients diagnosed with rAAA and treated surgically in the Department of Vascular Surgery, the Second Xiangya Hospital of Central South University, between January 2013 and December 2022. Patients were divided into an OSR group and an EVAR group based on surgical approach. Baseline clinical characteristics, perioperative data, and follow-up outcomes were compared between groups. Long-term survival was analyzed, and univariate and multivariate Cox proportional hazards regression models were used to determine independent prognostic factors. RESULTS: Among the 83 patients, 32 (38.6%) underwent OSR and 51 (61.4%) received EVAR, with the proportion of EVAR steadily increasing to nearly 80% in the most recent 5 years. Patients in the EVAR group were older [(68.76±8.57) years vs (60.59±13.24) years, P=0.012], and had a lower proportion of males (76.5% vs 96.9%, P=0.013). EVAR significantly reduced operating time [(181.86±69.87) min vs (291.09±60.33) min] and hospital stay [(12.14±6.31) days vs (16.22±7.89) days (P<0.05)], but total hospitalization costs were markedly higher [(208 735.84±101 394.19) yuan vs (84 893.35±40 668.56) yuan, P<0.001]. There were no significant differences between groups in 30-day mortality (15.6% vs 15.7%), aneurysm-related mortality (9.4% vs 11.7%), overall mortality (28.1% vs 29.4%), or re-intervention rate (0 vs 5.9%) (P>0.05). The median follow-up time was 54.6 months (range, 12-144 months). Kaplan-Meier survival analysis showed comparable cumulative survival rates between OSR and EVAR (82.7% vs 76.2%, P=0.420). Cox regression identified hyperlipidemia [hazard ratio (HR)=2.32, 95% confidence interval (CI) 1.28 to 4.19, P=0.005] and elevated preoperative serum creatinine (HR=3.33, 95% CI 1.69 to 6.55, P<0.001) as significant predictors of poor prognosis. Both factors remained independently associated with mortality in the multivariate model (hyperlipidemia: HR=2.02, 95% CI 1.10 to 3.70; elevated serum creatinine: HR=2.77, 95% CI 1.40 to 5.47; P<0.05). CONCLUSIONS EVAR offeres advantages in operative and recovery times, though its long-term survival outcomes are comparable to OSR. A history of hyperlipidemia and elevated preoperative creatinine levels are independent predictors of poor prognosis. Surgical approach should be chosen based on anatomical feasibility and patient condition, with close management of lipid levels and renal function to improve outcomes.
Humans ; Aortic Aneurysm, Abdominal/mortality* ; Endovascular Procedures/methods* ; Retrospective Studies ; Male ; Female ; Prognosis ; Aged ; Aortic Rupture/mortality* ; Middle Aged ; Treatment Outcome ; Aged, 80 and over

Fractional flow reserve (FFR), an established modality for functionally assessing coronary artery disease, is increasingly applied to diagnose and manage lower extremity arterial disease. By incorporating functional parameters, FFR enhances revascularization precision by quantifying the hemodynamic impact of stenotic lesions, thereby overcoming limitations of conventional imaging. Key clinical applications in lower extremity disease include functional assessment in moderate intermittent claudication, post-vascular preparation strategy optimization, and predicting revascularization outcomes and complications. Advances in pressure wire and microcatheter systems, alongside non-invasive imaging-derived FFR techniques, are improving its feasibility and applicability. However, widespread adoption is challenged by the complex anatomy of the lower extremity arterial system, frequent severe calcification and diffuse disease, and a current lack of standardized FFR cutoff values. Promoting the standardized use of FFR is crucial for shifting the clinical management paradigm from anatomy-based repair toward functional reconstruction.
Humans ; Lower Extremity/blood supply* ; Peripheral Arterial Disease/diagnosis* ; Fractional Flow Reserve, Myocardial ; Endovascular Procedures/methods* ; Intermittent Claudication/physiopathology*

Objective: To explore the association between various components of sleep quality and the co-occurrence of non-suicidal self-injury (NSSI) behaviors and depressive symptoms among junior high school students, so as to provide evidence for targeted prevention strategies of NSSI and depression. Methods: From May to June 2024, a total of 5 008 junior high school students from 8 schools in 2 districts/counties of Chongqing were selected through a stratified cluster sampling method. The Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiological Studies Depression Scale (CES-D), and the Adolescent Non suicidal Self injury Assessment Questionnaire (ANSAQ) were used to assess sleep quality, depressive symptoms, and NSSI, respectively. Data were analyzed by using the Chi-square test, Bonferroni correction, and multivariate Logistic regression. Results: Non-NSSI group and depressive symptoms group accounted for 68.11% among junior high school students, NSSI-only group accounted for 4.71%, only depressive symptoms group accounted for 14.94%, and co-occurrence of NSSI and depressive symptoms group accounted for 12.24%. The prevalence of the co-occurrence group was higher in girls (16.39%) than in boys (7.85%) ( χ 2=84.89, P <0.01). After controlling for gender, grade, and boarding status etc., multivariate Logistic regression analysis revealed that five sleep components, including subjective sleep quality, sleep latency, sleep duration, sleep disturbances, and daytime dysfunction, were significantly and positively associated with the co-occurrence of NSSI and depressive symptoms ( OR =1.30-3.86, all P <0.05). The strength of association between these components and the co-occurrence group, in descending order, was: daytime dysfunction ( OR = 2.52), sleep disturbances ( OR =2.36), subjective sleep quality ( OR =1.76), sleep latency ( OR =1.44), and sleep duration ( OR =1.22) (all P <0.01). Conclusions The co-occurrence of NSSI and depressive symptoms is prevalent among junior high school students, with girls being more significantly affected. Sleep disturbances and daytime dysfunction may represent particularly important risk factors. Targeted and prioritized intervention strategies addressing specific sleep components should be developed and implemented to reduce the co-occurrence of NSSI and depressive symptoms in junior high school students.

Objective To compare the clinical effect between laparoscopic temporary long tunneled external ventricular drainage and traditional laparoscopic ventriculoperitoneal shunt in patients with hydrocephalus after traumatic brain injury(TBI).Methods A total of 52 patients who underwent laparoscopic temporary long tunneled external ventricular drainage(external drainage group)or traditional laparoscopic ventriculoperitoneal shunt(traditional shunt group)for hydrocephalus after TBI from October 2018 to October 2021 were retrospectively analyzed.The catheterization time,remission time of intracranial hypertension,average hospital stay,therapeutic effective rate and the incidence of complications were compared between the two groups.Results The total effective rate of the external drainage group was significantly higher than that of the traditional shunt group(92.31%vs 80.77%,P＜0.05).The external drainage group had longer catheterization time and shorter remission time of intracranial hypertension and average hospital stay than the traditional shunt group.The incidence of adverse reactions such as intracranial infection,shunt obstruction and poor healing in the traditional shunt group was significantly higher than that in the external drainage group(19.23%vs 7.69%,P＜0.05).Conclusion Laparoscopic temporary long tunneled external ventricular drainage can achieve better therapeutic effect for hydrocephalus after TBI,and it is recommended in clinical treatment.