Objective To investigate the expression characteristics, prognostic value, and correlation with immune infiltration of vasoactive intestinal peptide receptor 2 (VIPR2) in esophageal adenocarcinoma (ESAD). Methods Transcriptome data of 80 ESAD and 10 normal tissues were retrieved from the TCGA database. Immune-related differential genes were identified by integrating the ImmPort database. Cox regression analysis was applied to evaluate the prognostic significance of VIPR2. GSVA and ssGSEA were employed to assess the association between VIPR2 and immune-cell infiltration. Functional enrichment was performed using GO, KEGG, and GSEA. Results VIPR2 expression was significantly downregulated in ESAD tissues (P<0.05). High VIPR2 expression was associated with prolonged overall survival (HR=0.246, P=0.047), serving as an independent prognostic factor. Fifteen immune-cell types, including CD8⁺ T cells, NK cells, and dendritic cells, showed significantly higher infiltration in the VIPR2-high group, whereas Th17-cell abundance was decreased (P<0.05). Enrichment analyses revealed that VIPR2 participated in multiple tumor-immune pathways and was positively correlated with PD-1 and CTLA-4 expression (P<0.01). Conclusion VIPR2 may serve as a potential biomarker in the prognostic assessment and could modulate the tumor-immune microenvironment in ESAD.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.

China has become the country with the highest global burden of heart failure(HF).Despite the widespread use of prognostic-improving medications today,the mortality rate of HF remains high,reaching 13.7％at one year-particularly among patients with heart failure with reduced ejection fraction(HFrEF).HF interventional device therapy(structural intervention)targets the structural factors underlying HF,including atrial pressure,ventricular remodeling,and valvular intervention.It leverages the heart's intrinsic physiological properties and pathological progression mechanisms to deliver treatments through interventions without external active forces,achieving anatomical or functional repair.This field has emerged as a rapidly growing area and plays an increasingly critical role in HF management.This article provides a comprehensive review and summary of the latest advancements in HF and cardiomyopathy interventional therapy over the past year.It covers various novel technologies and products currently in the research phase,aiming to provide an in-depth analysis of the current status and future directions of HF interventional therapy,and further advance the development of this discipline.

Objective:To evaluate the survival benefit of surgical treatment for intrahepatic cholangiocarcinoma.Methods:This study is conducted based on the hepatobiliary tumor registry database. From May 2009 to December 2022,a total of 704 patients who were initially diagnosed with intrahepatic cholangiocarcinoma and underwent liver resection were consecutively enrolled at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University. Among them,there were 380 males and 324 females,aged ( M(IQR)) 61(15) years(range:27 to 88 years). Twenty-six (3.7%) patients received neoadjuvant therapy before surgery. The overall survival(OS) and disease-free survival(DFS) rates were estimated by life table method, and Kaplan-Meier survival curves were plotted. Log-rank test was used to compare the survival difference among tumor-node-metastasis(TNM) staging or three periods. The OS and DFS differences among lymph node groups or adjuvant treatment groups were quantified as HR with 95% CI estimated using Cox proportional-hazards model with adjustment for prognostic factors. Results:Among the 704 patients,349 cases(49.6%) underwent major hepatectomy (≥3 segments),331(47.0%) had lymph node resection during surgery,and 524 cases(74.4%) achieved R0 resection. The morbidity of Clavien-Dindo grade Ⅲ or higher complications was 16.5%(116/704),with a mortality rate of 3.0%(21/704) within 30 days post-surgery. The median OS time was 27.1 months, and the OS rates at 1-,3-,5- and 10-year were 69.1%, 42.4%,34.1% and 24.5%,respectively. The median DFS time was 10.5 months,and the corresponding DFS rates were 46.0%,25.4%,21.9% and 16.9%,respectively. According to the 8 th edition of AJCC staging system, the 5-year survival rates for ⅠA,ⅠB,Ⅱ,ⅢA,ⅢB and Ⅳ were 68.4%, 43.2%, 30.3%,32.2%,14.0% and 0,respectively. The corresponding DFS rates were 55.8%, 28.1%,13.8%,21.2%,3.3% and 0,respectively. There were no statistically significant differences of OS or DFS between stage ⅠB and Ⅱ, stage ⅠB and ⅢA, or between stage Ⅱ and ⅢA(Log-rank test:all P>0.05),while there were significant differences of OS and DFS among other stages(Log-rank test:all P<0.05). Using Cox model with adjustment for prognostic factors, there were no statistically significant differences of OS and DFS between non-lymphadenectomy group or the biopsy-N0 group and dissection-N0 group(both P>0.05). However,the overall and disease-free survival of the biopsy-N1 group or dissection-N1 group were worse than those of dissection-N0 group(both P<0.05),with overall survival being better in dissection-N1 group than biopsy-N1 group( P=0.017). Overall survival in the period from 2019 to 2022 were significantly superior to that during the periods from 2009 to 2013 and 2014 to 2018(both P<0.01). Adjusting for prognostic factors, the disease-free and overall survival of the postoperative adjuvant therapy group were significantly better than those of the observation group in the period 2019 to 2022(both P<0.01). Conclusions:Surgery remains a milestone for achieving long-term survival for patients with intrahepatic cholangiocarcinoma. Regional lymph node dissection is required for patients with lymph node metastasis. Adjuvant therapy can significantly reduce tumor recurrence and prolong overall survival.

Objective To evaluate the efficacy,safety and economy of vonoprazan in the treatment of post-endoscopic submucosal dissection(ESD)ulcer by rapid health technology assessment method,and to provide reference for clinical treatment decision.Methods PubMed,Cochrane Library,Embase,ScienceDirect,CNKI,WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of vonoprazan in the treatment of post-ESD ulcer from inception to July 31,2024.Two researchers independently screened literature,extracted data,and comprehensively analyzed the results of the included literature on the basis of literature quality evaluation.Results A total of 8 studies were included,all were systematic reviews/Meta-analysis.In terms of effectiveness,compared with proton pump inhibitors(PPI),vonoprazan significantly increased the overall ulcer healing rate after ESD and more rapid reduction of ulcer area(P<0.05).The results of subgroup analysis showed that there was no significant difference in ulcer healing rate between vonoprazan and PPI treatment at 4 or 8 weeks after ESD(P>0.05).Vonoprazan significantly increased the rate of postoperative ulcer reduction in H.pylori positive patients compared with PPI(P<0.05).In terms of safety,compared with PPI,vonoprazan reduced the incidence of overall adverse events rate(P<0.05).The difference in the incidence of delayed bleeding and ulcer perforation between vonoprazan and PPIs showed no statistically significant difference.(P>0.05).Conclusion Vonoprazan demonstrated favorable efficacy and safety in the treatment of ESD ulcers,and further economic studies are warranted.

Objective:To comparatively observe optical coherence tomography (OCT) image features between traumatic macular hole (TMH) and idiopathic macular hole (IMH).Methods:A retrospective clinical study. A total of 174 patients (174 eyes) with macular hole (MH) diagnosed at Shantou International Eye Center from December 2008 to May 2024 were included in the study. Among them, there were 75 patients (75 eyes) with TMH and 99 patients (99 eyes) with IMH, and they were divided into the TMH group and the IMH group accordingly. All the affected eyes underwent best corrected visual acuity (BCVA) and OCT examinations. The BCVA was examined using a standard logarithmic visual acuity chart, and was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistical analysis. The minimum diameter and basal diameter of the MH, as well as the average, nasal, superior, inferior, and temporal center retinal thickness (CRT) around the MH were measured by OCT. The independent-sample t test was used to compare the logMAR BCVA, hole diameter, and CRT at the hole margin between the groups. Results:There were significant differences in age ( t=-15.857) and gender ratio ( χ2=28.154) between the TMH group and the IMH group ( P<0.05), while there was no significant difference in logMAR BCVA ( t=1.962, P>0.05). The minimum diameter of the hole in the TMH group was smaller than that in the IMH group, but the basal diameter was larger, with significant differences ( t=-3.322, 2.570; P<0.05). The thickness of the neuroepithelial layer at the hole margin in the TMH group was thinner than that in the IMH group, with significant differences in the superior ( t=-2.747), inferior ( t=-2.316), and nasal ( t=-2.851) regions ( P<0.05), and no significant difference in the temporal region ( t=-1.586, P>0.05). In the TMH group, the number of eyes with macular cystoid edema (CME), posterior vitreous detachment (PVD), retinal atrophy, subretinal hemorrhage, choroidal laceration, and focal neuroepithelial detachment was 36 (48.00%, 36/75), 4 (5.33%, 4/75), 4 (5.33%, 4/75), 15 (20.00%, 15/75), 8 (10.67%, 8/75), and 19 (25.33%, 19/75) eyes, respectively. In the IMH group, the number of eyes with CME and PVD was 95 (95.96%, 95/99) and 94 (94.95%, 94/99) eyes, respectively. Conclusion:Compared with IMH, TMH has a larger basal diameter, a thinner CRT at the hole margin, a lower incidence of CME and PVD, and a higher incidence of subretinal hemorrhage, focal neuroepithelial detachment, choroidal laceration, and retinal atrophy.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.

BACKGROUND:The pelvis has abundant trabecular bone content,but the ability of conventional sacroiliac percutaneous fixation to control trabecular bone is limited,leading to fixation failure.Therefore,the development of devices that can more effectively control trabecular bone tension is of significant importance.OBJECTIVE:The mechanical properties of a novel sacroiliac tension screw were investigated using biomechanical testing and numerical modeling analysis,along with an assessment of the reliability of the pull-out force numerical model.METHODS:A mechanical model was established based on the working principle of the novel sacroiliac tension screw.Numerical methods were employed to analyze its pull-out performance,validated through mechanical testing with polyurethane material to assess the reliability of the pull-out force numerical model.Using pelvic specimens,the mechanical effectiveness of the novel sacroiliac tension screw in repairing sacroiliac joint injuries was analyzed under normal standing posture,along with an evaluation of the load stiffness of different pelvic models in the standing position.RESULTS AND CONCLUSION:(1)The average error between the computed values of the numerical model and the measured values was 13.19％,indicating a certain level of validity for the numerical model.(2)The damage to the polyurethane material after the extraction of the screw was less pronounced in the novel screw group.(3)The average effective holding displacement for the novel screw was approximately(9.24±0.27)mm,significantly greater than the average displacement of(1.71±0.57)mm observed with the lag screws.However,the maximum resistance to pullout for the lag screws was significantly higher than that for the novel screws.(4)The novel screw effectively repaired sacroiliac joint injuries.(5)The stiffness after repair of sacroiliac joint injuries was equivalent when using a single novel screw compared to using two lag screws.(6)These results prove that the theoretical model for the maximum resistance to pullout of the screws established in this study has a certain level of validity and can guide the design of them with improved mechanical performance.The novel sacroiliac spiral blade screw can effectively hold trabecular bone and has practical clinical utility.

Objective To evaluate the efficacy,safety and economy of vonoprazan in the treatment of post-endoscopic submucosal dissection(ESD)ulcer by rapid health technology assessment method,and to provide reference for clinical treatment decision.Methods PubMed,Cochrane Library,Embase,ScienceDirect,CNKI,WanFang Data databases and the official website of health technology assessment(HTA)agency were electronically searched to collect HTA reports,systematic reviews/Meta-analysis and pharmacoeconomic studies of vonoprazan in the treatment of post-ESD ulcer from inception to July 31,2024.Two researchers independently screened literature,extracted data,and comprehensively analyzed the results of the included literature on the basis of literature quality evaluation.Results A total of 8 studies were included,all were systematic reviews/Meta-analysis.In terms of effectiveness,compared with proton pump inhibitors(PPI),vonoprazan significantly increased the overall ulcer healing rate after ESD and more rapid reduction of ulcer area(P<0.05).The results of subgroup analysis showed that there was no significant difference in ulcer healing rate between vonoprazan and PPI treatment at 4 or 8 weeks after ESD(P>0.05).Vonoprazan significantly increased the rate of postoperative ulcer reduction in H.pylori positive patients compared with PPI(P<0.05).In terms of safety,compared with PPI,vonoprazan reduced the incidence of overall adverse events rate(P<0.05).The difference in the incidence of delayed bleeding and ulcer perforation between vonoprazan and PPIs showed no statistically significant difference.(P>0.05).Conclusion Vonoprazan demonstrated favorable efficacy and safety in the treatment of ESD ulcers,and further economic studies are warranted.

Objective To investigate the regulatory effects and molecular mechanisms of extracellular vesicles(EVs)secreted by adri-amycin(ADR)-resistant breast cancer cells on vascular endothelial cells related to tumor microenvironment.Methods The ADR-sen-sitive breast cancer cell line(MCF-7)and its ADR-resistant counterpart(MCF-7-ADR)were established in vitro.Then,the EVs were isolated from the supernatant of cell culture using a commercial kit.The fluorescence labeling and tracking technology using PKH67 was used to validate the internalization of EVs by human umbilical vein endothelial cell(HUVEC).The effects of EVs on the proliferation,migration,and angiogenesis of HUVEC were assessed by the colony formation,scratch wound healing,and tube formation assays,re-spectively.The expression level of CD31 protein was detected by Western blot,and the levels of vascular endothelial growth factor(VEGF)in cell supernatant were determined by ELISA.The microRNA(miRNA)sequencing technology was utilized to identify the differentially expressed miRNAs in EVs secreted by ADR-resistant cells.Results Compared with the ADR-sensitive strain,the EVs secreted by the ADR-resistant strain significantly enhanced the proliferation(colony number increased by 38.7%,P=0.011),migra-tion(scratch healing rate improved by 42.3%,P=0.004),and tube formation ability(tube formation rates increased by 1.8 times and 2.3 times at 4 h and 16 h,respectively,P=0.044 and 0.010)of HUVEC.Western blot analysis showed that the expression level of CD31 in the EVs secreted by the ADR-resistant strain increased by 1.85 times compared with the ADR-sensitive strain(P=0.039).The results of ELISA showed that the expression level of VEGF increased by 2.12 times(P=0.012).The miRNA sequencing identified a differentially expressed miRNA profile.Conclusion The ADR-resistant breast cancer cells significantly enhance the proliferation,migration,and angiogenesis of vascular endothelial cells by secreting EVs rich in specific miRNA,and its mechanism may be related to the up-regulation of CD31/VEGF protein levels mediated by EVs,suggesting that the drug-resistant cells reshaping the tumor vascular microenvironment through EVs may become a new therapeutic target of chemotherapy resistance in breast cancer.