Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

Objective:To explore the self-care experience of arteriovenous fistula in elderly maintenance hemodialysis patients, and to provide reference for intervention and management.Methods:The descriptive phenomenological research method was used to select elderly patients as subjects who underwent hemodialysis and used arteriovenous fistula as vascular access in the blood purification center of The First Affiliated Hospital of Zhejiang University School of Medicine from November 2022 to May 2023 through objective sampling, and semi-structured in-depth interviews were conducted on them, and the data were analyzed by Colaizzi 7-step analysis method.Results:Finally, 15 interviewees were included. There were 6 males and 9 females, aged (73.53±8.59) years old. A total of 4 themes and 12 sub-themes were summarized: multiple burdens (comorbidities management burden, psychological burden, financial burden), self-care dilemmas (affected by physical decline, inadequate self-coping, inadequate counseling channels), driven by social factors (motivated by social feedback, influenced by peer behavior, promoted by extended medical services) and understanding of life philosophy (actively coping with life changes, replanning life order, appreciating life value).Conclusions:Elderly maintenance hemodialysis patients have complicated burden experience, multi-dimensional problems and needs in the process of self-care for internal arteriovenous fistula, and self-care behavior is greatly affected by social factors. Future intervention should focus on strengthening multidisciplinary collaboration, providing professional and convenient continuous nursing services, improving social support paths and giving accurate psychological intervention, so as to reduce the burden of disease management of patients, meet their self-care needs, enhance the internal motivation of self-care behavior and improve self-care ability.

Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.

This study examines inhibiting galectin 1 (Gal1) as a treatment option for hepatocellular carcinoma (HCC). Gal1 has immunosuppressive and cancer-promoting roles. Our data showed that Gal1 was highly expressed in human and mouse HCC. The levels of Gal1 positively correlated with the stages of human HCC and negatively with survival. The roles of Gal1 in HCC were studied using overexpression (OE) or silencing using Igals1 siRNA delivered by AAV9. Prior to HCC initiation induced by RAS and AKT mutations, lgals1-OE and silencing had opposite impacts on tumor load. The treatment effect of lgals1 siRNA was further demonstrated by intersecting HCC at different time points when the tumor load had already reached 9% or even 42% of the body weight. Comparing spatial transcriptomic profiles of Gal1 silenced and OE HCC, inhibiting matrix formation and recognition of foreign antigen in CD45⁺ cell-enriched areas located at tumor-margin likely contributed to the anti-HCC effects of Gal1 silencing. Within the tumors, silencing Gal1 inhibited translational initiation, elongation, and termination. Furthermore, Gal1 silencing increased immune cells as well as expanded cytotoxic T cells within the tumor, and the anti-HCC effect of lgals1 siRNA was CD8-dependent. Overall, Gal1 silencing has a promising potential for HCC treatment.

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.

Fetal STR typing of aborted tissue has long been a major problem in forensic DNA.Especially for the first trimester abortion tissue,it is difficult to isolate the embryonic components by histomorphological means,resulting in the inability to accurately obtain the STR typing of the fetus.The mixed STR typing results of mother and fetus can provide a key basis for the identification of suspects in cases of rape-induced pregnancy.In this study,next generation sequencing was used to successfully detect mixed STR typing of mother and suspected fetus or single STR typing of suspected fetus in 4 rape-induced early pregnancy abortion tissues.Combined with Y-STR and flank sequence information,it provides a more comprehensive and reliable genetic basis for the identification of suspects.

Objective:To compare the safety and efficacy of laparoscopy and laparotomy for 5-10 cm intermediate-risk gastric stromal tumor, and to evaluate whether there was evident benefits of postoperative adjuvant treatment with imatinib.Methods:A retrospective study was conducted on 72 patients with moderate risk gastric stromal tumors (5-10 cm in diameter) who received operation in Nanjing Drum Tower Hospital from January 2010 to July 2020. There were 28 cases in the laparoscopy group and 44 cases in the laparotomy group. The clinical features, pathological data, perioperative results and hospitalization costs were compared between the two groups. The survival rates of postoperative adjuvant therapy with or without imatinib were analyzed and compared.Results:There was no significant difference in clinicopathological features between the two groups ( P>0.05). The incidences of postoperative complications in the laparoscopy group and the laparotomy group were 32.1% (9/28) and 52.3% (23/44) respectively, showing no significant difference ( P=0.094). Compared with the laparotomy group, both the hospital stay (12.5±3.2 days VS 15.0±3.5 days, P=0.004) and the median postoperative hospital stay (7.5 days VS 9.0 days, P=0.006) in the laparoscopy group were significantly shorter, and the first exhaust time was significantly shorter ( P=0.003). During the median follow-up period of 58 months (13-129 months), there was no tumor-related death. Two cases died of breast cancer and heart disease in the laparotomy group, and 1 case died irrelevant to gastric stromal tumor in the laparoscopy group. Of the 72 patients, 40 received postoperative imatinib adjuvant therapy, 22 cases (50.0%) in the laparotomy group and 18 cases (64.3%) in the laparoscopy group, with no significant difference in the proportion ( χ2=1.414, P=0.234). There was significant difference in the overall survival rate between the group treated with imatinib and the group without imatinib ( P=0.015). Conclusion:Laparoscopic resection is safe and effective for intermediate-risk gastric stromal tumor of 5-10 cm. Taking imatinib adjuvant treatment does not increase overall survival rate of patients with intermediate-risk gastric stromal tumors (5-10 cm), and there is no tumor-related death, recurrence or metastasis for those who did not accept imatinib adjuvant treatment after R0 resection.

Objective:To explore the feasibility of using vascular graft interposition for lowering the complications of portal vein during pediatric liver transplantation.Methods:From June 1, 2013 to May 31, 2018, clinical data were collected for 297 children undergoing liver transplantation, including basic demographics, general preoperative status, preoperative tests, imaging findings, graft related profiles, surgical procedures and postoperative follow-ups, etc. Then the authors analyzed the effect of using interposition vessels upon lowering postoperative complications of portal vein reconstruction.Results:With a median age of 12 months, there were 153 boys (51.5%) and 144 girls (48.5%). The primary disease was mostly biliary atresia ( n=222, 74.7%). The median diameter of portal vein was 5 mm. There were 19 cases (6.4%) using vascular interposition. Among 20 cases of portal vein complications, there were portal vein stenosis ( n=17, 5.7%) and portal vein thrombosis ( n=3, 1.0%). After univariate analysis, binary Logistic regression analysis revealed that diameter of recipient's portal vein was an independent risk factor for the occurrence of portal vein complications after liver transplantation. Statistical analysis of children with portal vein diameter <4 mm ( n=90) was carried on and the results showed that there was no inter-group statistical difference ( χ2=3.061, P=0.080)on the occurrence of portal vein complications. Conclusions:Diameter of portal vein is an important factor affecting the strategic choice of portal vein reconstruction during pediatric liver transplantation and an independent risk factor for portal vein complications after liver transplantation. When the diameter of portal vein is ≤4 mm, using interposition vascular anastomosis shows no significant difference with other conventional modes.

Objective:To investigate the status of frailty and activities of daily living (ADL) in maintenance hemodialysis (MHD) patients, and to explore the effect of frailty phenotype on ADL.Methods:The patients who underwent MHD in Kidney Disease Center of the First Affiliated Hospital from March 2019 to March 2020 were enrolled in this study. The demographic and laboratorial data were collected by cross-sectional survey method. Fried frailty phenotype scale and ADL scale were used to evaluate the frailty and ADL, respectively. The differences of basic data and different frailty phenotypes between the normal function group and the function decline group were compared in terms of ADL, physical self-maintenance ability and instrumental ADL ability. Pearson correlation analysis was used to analyze the correlation between frailty and ADL, and binary logistic regression analysis was used to analyze the influencing factors of ADL.Results:A total of 676 MHD patients were included in this study, including 434 males (64.2%) and 242 females (35.8%). The age was (59.2±19.4) years old, and the median dialysis age was 59.0 (25.3, 110.0) months. There were 159 frailty patients (23.5%), 230 pre-frailty patients (34.0%), and 287 non-frailty patients (42.5%). The ADL was decreased in 163 patients (24.1%), including 131 patients (19.4%) with decreased physical self-maintenance ability and 161 patients (23.8%) with decreased instrumental ADL ability. Pearson correlation analysis showed that the frailty score was positively correlated with total ADL score ( r=0.728, P<0.001), physical self-maintenance ability score ( r=0.669, P<0.001) and instrumental ADL ability score ( r=0.729, P<0.001). Binary logistic regression analysis results showed that older age and lower physical activity, fatigue, slowed steps and lower grip strength in the frailty phenotypes were the independent influencing factors of ADL, physical self-maintenance ability and instrumental ADL ability (all P<0.05). Conclusions:The prevalence of frailty is 23.5% in MHD patients, and 24.1% of MHD patients have decreased ADL. Elder age and lower physical activity, fatigue, reduced step counts, and lower grip strength in frailty phenotypes are the independent influencing factors for poor ADL, poor physical self-maintenance ability and poor instrumental ADL ability.

Objective:To investigate the incidence of sarcopenia in maintenance hemodialysis (MHD) patients and analyze its influencing factors.Methods:Totally 441 non-hospitalized MHD patients in stable condition were selected,by bioelectrical impedance analysis (BIA) to test appendicular skeletal muscle mass(ASM), by testing grip strength of MHD patients, to assess Muscle strength, by gait speed test to measure the 4-m usual walking speed, to assess physical performance of MHD patients.Risk factors of sarcopenia were identified by Logistic regression analysis.Results:The total incidence of sarcopenia in 441 MHD patients was 16.55% (73/441) and the incidence of sarcopenia in patients over 60 years old was 28.91% (61/211).The results showed older age ( OR=0.213, 95% CI 0.099-0.458, P<0.01), Karnofsky ( OR=9.661, 95% CI 3.850-24.244, P<0.01), subjective global assessment ( OR=0.491, 95% CI 0.250-0.965, P=0.039), serum phosphorus ( OR=0.422, 95% CI 0.204-0.875, P=0.020) and body mass index ( OR=0.754, 95% CI 0.609-0.935, P=0.010) were risk factors of sacopenia. Conclusions:The incidence of sarcopenia in elder, performed less physical activity, malnutrition predisposed MHD patients was high, so to those patients we should be paid more attention and gave active interventions to reduce sarcopenia.