Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Objective To explore the short-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early carcinoma in the remnant stomach. Methods A retrospective study was conducted on 45 patients with early residual gastric cancer underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2014 to April 2024, with a total of 45 lesions. The patients were divided into an anastomotic group (n=15) and a non-anastomotic group (n=30) based on the location of tumor occurrence, and their clinical data, endoscopic diagnosis and treatment, and histopathological conditions were compared between the two groups. Results All 45 patients had lesions with redness and erosion. There were 9 cases of poor lifting of submucosal injection in the anastomotic group and 2 cases in the non-anastomotic group, respectively, and the difference was statistically significant (P<0.05). ESD surgery was performed on 13 lesions in the anastomotic group and 28 lesions in the non-anastomotic group, with surgery times of 80.00 (50.00, 100.00) min and 55.00 (43.75, 80.00) min, respectively. The difference in surgery time between the two groups was statistically significant (P=0.03). Among the 45 patients, ESD surgery achieved curative resection in 35 cases, including 11 cases in the anastomotic group and 24 cases in the non-anastomotic group, with no statistically significant difference. Conclusions Careful preoperative evaluation of early carcinoma in the remnant stomach is essential to prevent oversight. Lesions at anastomotic sites and suture lines present higher technical challenges for complete resection. ESD is safe and effective, with auxiliary traction technique available when necessary.

Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

Objective To explore the clinical value of methylation at promoter sites of urine protein kinase Y-linked(PRKY)gene in the early diagnosis of prostate cancer(PCa).Methods Urine samples were collected from 50 suspected PCa patients.After extracting DNA,the methylation levels of the PRKY gene promoter sites cg05163709,cg08045599,and cg05618150 were detected using quantitative methylation-specific PCR(qMSP).Simultaneously,the patients were divided into the benign prostatic hyperplasia(BPH)group and the PCa group.The differences in clinical indicators between the two groups were analyzed,as well as the methylation status of the PRKY gene promoter sites in the urine of the two groups of patients.The receiver operating charac-teristic(ROC)curve of PRKY promoter sites methylation was established,and the area under the curve(AUC)was calculated to analyze the diagnostic value of PRKY promoter sites methylation in PCa,and to perform com-bined diagnosis with clinical indicators.Results The methylation rates of cg05163709 and cg05618150 in urine specimens of PCa patients were significantly higher than those of BPH patients.The AUC for cg05163709 methyla-tion in diagnosing PCa was 0.762,with a sensitivity of 86.70%.It showed better performance in early screening for PCa compared to total prostate specific antigen(tPSA),percentage free prostate specific antigen(f/tPSA)and prostate specific antigen density(PSAD)index.We found that the AUC for cg05618150 methylation in conjunc-tion with PSAD in diagnosing PCa was 0.787,with a sensitivity of 86.70%.The AUC of cg05163709 methylation and PSAD in the joint diagnosis of PCa was 0.855,and the specificity could reach 95.00%.Conclusion The methylation of urine PRKY gene promoter sites cg05163709 and cg05618150 shows high sensitivity and specificity in diagnosing PCa,making them promising biomarkers for early detection of PCa.

Clarifying the applicability （indications or contraindications） of traditional Chinese medicine （TCM） dietary regimens to different syndromes is a guarantee for the rational application and safety of TCM dietary therapy. By considering evidence from ancient literature， modern research and experts' experience， the Grading System for Syndrome Suitability of Dietary Therapy in TCM （GRADE-SSD） has been constructed. According to the currently available highest-quality evidence， GRADE-SSD classified the applicability of TCM dietary therapy to various TCM syndromes into 2 categories and 4 grades： "definitely" applicable/contradicted （Grade A）， "very likely" applicable/contradicted （Grade B）， "possibly" applicable/contradicted （Grade C）， and insufficient evidence to determine （Grade D）. When applying， first， systematically search the currently available ancient books and clinical research evidence. For different types of evidence （ancient TCM books， randomized controlled trials， observational studies， and meta-analyses）， use the prescribed tools to evaluate the quality of the evidence， and then determine the applicability level of TCM syndromes of dietary therapy based on the principle of "taking the highest" quality. If there is a lack of direct evidence， GRADE-SSD supports a downgraded evaluation based on indirect evidence of "similar prescriptions". When there is a lack of ancient books and clinical research， the GRADE-SSD plan can evaluate the quality of evidence from peer consensus or expert opinions for the applicability level of TCM syndromes of dietary therapy. Based on the requirements for the safety of TCM dietary therapy， when there is both "applicable" and "contradicted" evidence， it should be considered as "contradicted" evidence. GRADE-SSD also provides an evidence certainty update plan based on new evidence in the future. The evaluation results of GRADE-SSD can provide a basis for setting inclusion/exclusion criteria in clinical trials of TCM dietary therapy and stating the applicability of each syndrome in the labels of dietary therapy products.

Objective To observe the value of nomogram obtained with multivariate logistic regression based on ultrasound for predicting residue of benign thyroid nodules after microwave ablation(MWA).Methods Totally 101 patients with 133 benign thyroid nodules who underwent ultrasound-guided MWA were retrospectively enrolled.The nodules were divided into residual group(n=21)and non-residual group(n=112)according to follow-up results of contrast-enhanced ultrasound(CEUS)1 month after MWA.The ultrasonic performances of nodules before MWA were compared between groups,and those being statistically different were included in a multivariate logistic regression model to identify the independent predictors for residue after MWA,and the model was then visualized as a nomogram.The discrimination of the nomogram for predicting residue after MWA was assessed with receiver operating characteristic curve and area under the curve(AUC),and its calibration was assessed with Hosmer-Lemeshow goodness-of-fit test.Results High ablation risk and nodules volume shown with ultrasound were both independent predictors of residue of benign thyroid nodules after MWA(both P＜0.05),indicating that benign thyroid nodules with high ablation risk(OR=17.637[2.528,123.019])and large volume(OR=1.297[1.155,1.457])had relatively higher risk of residue after MWA.AUC of the nomogram was 0.756 for predicting residue of benign thyroid nodules after MWA,while Hosmer-Lemeshow test showed good fit(P=0.401).Conclusion Benign thyroid nodules with high ablation risk and large volume shown with ultrasound had relatively high risk of residue after MWA,which could be predicted conveniently and effectively with the obtained nomogram.

Objectives:The present study evaluated the impact of ablation pain during pulmonary vein isolation(PVI)on catheter-tissue contact at different regions. Methods:Forty consecutive patients with atrial fibrillation(AF)referred to Central China Fuwai Hospital for catheter radiofrequency ablation from February to May 2023 were enrolled.The pulmonary veins on each side were divided into 8 regions.The catheter-tissue contact force(CF)and the number of ablation contact stability(>50%catheter attach time CF≥10 g)of each ablation lesion were analyzed.Pain scores during the ablation were assessed using the Faces Pain Scale-Revised and the maximum score was taken for each ablation region.Based on the pain scores,in each region,20 cases with higher pain scores were categorized into the pain group and 20 cases with lower pain scores were categorized into the normal group.The CF characteristics of each region and the relationship with ablation induced pain were analyzed. Results:A total of 3 832 lesions were recorded in 40 patients with AF,with a mean CF of(12.2±7.8)g.Among them,the CF in the pain group was significantly lower than that in the normal group([11.1±5.1]g vs.[13.4±4.8]g,P<0.05).The top region of the right pulmonary vein was the region with the largest CF(16.5±5.8)g,and the upper part of the left anterior wall(at the ridge between the left atrial appendage)was the region with the smallest CF(7.5±3.7)g.At the bottom of right pulmonary vein,right lower posterior wall,left pulmonary vein,and left posterior wall,as well as the middle region of left posterior wall,and upper region of left posterior wall,the CF was significantly smaller in the pain group than that in the normal group(all P<0.05).Of the 3 832 lesions,2 193(57.2%)were stable lesions,and the proportion of stable lesions in the pain group was significantly lower than that in the normal group(55.2%vs.59.5%,P<0.05).In the right pulmonary vein bottom,right lower posterior wall,left lower anterior wall,left pulmonary vein bottom,and left lower posterior wall,the proportion of stable lesions was significantly lower in the pain group than in the normal group(all P<0.05).In addition,the ratio of stable lesions in left pulmonary vein regions was lower than in the right(54.2%vs.60.5%,P<0.05).In the upper part of the left anterior wall(at the ridge between the left atrial appendage),only 88(39.3%)of the 224 lesions in 40 patients were stable lesions. Conclusions:Pain during ablation significantly affects the stability of the catheter to tissue.Monitoring real-time CF during PVI may have important implications for improving ablation efficacy,especially in regions with more intense pain.

Objective:To investigate the role of speckle-type POZ(pox virus and zinc finger protein) protein (SPOP) in enterovirus 71 (EV71) infection.Methods:Immunoprecipitation analysis was employed to examine the impact of SPOP on the ubiquitin level of EV71 non-structural protein 2A protease (2A pro), while the phosphorylation level of IFR3 protein was assessed through Western blot. Cells were either overexpressed or knockdown of SPOP, followed by infection with EV71. RT-qPCR was utilized to analyze the transcription level of IFN-β, and the transcription level and protein level of EV71 structural protein VP1 were determined using RT-qPCR and Western blot, respectively. Results:The inhibition of EV71 infection in RD cells was observed following transfection with HA-SPOP. Additionally, it was found that the ubiquitin level of EV71-2A pro increased in a gradient-dependent manner. Subsequent transfection with shSPOP plasmid for endogenous SPOP knockdown resulted in a dose-dependent decrease in the levels of melanoma differentiation-associated gene 5 (MDA5), mitochondrial antiviral signaling (MAVS), and p-IRF3. Conversely, transfection with HA-SPOP plasmid led to a dose-dependent increase in the levels of MDA5, MAVS, and p-IRF3. The expression of SPOP, whether high or low, had an impact on the expression of IFN-β in cells. Additionally, the levels of VP1 mRNA or protein were found to be inhibited or increased. Conclusions:SPOP plays a role in increasing the ubiquitination level of EV71-2A pro, which in turn promotes the phosphorylation level of IRF3 and secretion of IFN-β. This effect is achieved by inhibiting the cleavage of 2A pro against key molecules MAVS and MDA5 in the RLR signaling pathway, ultimately leading to the inhibition of EV71 replication.

Objective:To explore and think about the project management model of investigator-initiated trial (IIT), and the project management of industry sponsored trial (IST), we should standardize the management process of clinical research projects initiated by researchers, improve the management system of clinical research in medical institutions, improve the quality management level of clinical research, and protect the rights and interests of research participants.Methods:By taking the clinical research management of a medical and health institution in Hainan province as an example, one of the first pilot areas for the standardized management of clinical research by the National Health Commission, the difficulties in the management of clinical research initiated by researchers were sorted out, to analyze and standardize the management of clinical research project initiated by researchers.Results:Discussion Project management was the primary link and basic guarantee of standardized management of clinical research, and scientific and feasible project management was a powerful hand to carry out deep and high-quality IIT.Conclusions:It can be manifested in a Hainan provincial public medical institution that a feasible project management was the basement in carrying out the profound and high quality IIT. It is advicable to make full use of policy advantages and clinical resources to produce high-quality research results as well as build a high-level research hospital.