BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Objective:This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer. Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods:Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals). The clinicopathological data, the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed. To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results:A total of 224 patients with advanced breast cancer were enrolled in this study, with a median age of 52 years (26-77 years), 55.4%(124/224) was postmenopausal. Luminal type were 83 cases, TNBC were 97 cases, and human epidermal growth factor receptor 2 (HER's-2) overexpression were 44. At the analysis, 224 patients who received the gemcitabine-based regimens were evaluated, included 5 complete reponse (CR), 77 partial response (PR), 112 stable disease (SD) and 27 progressive disease (PD). The objective response rate (ORR) was 36.6%(82/224). Seventy patients had serious adverse diseases, including leukopenia (9), neutrophilia (49), thrombocytopenia (15), and elevated transaminase (2). The median follow-up time was 41 months (26~61 months), and the median PFS was 5.6 months. The reasons of termination treatment were listed: disease progression were 90 patients; personal reasons were 51 patients; adverse drug reactions were 18 patients; completed treatment were 65 patients. It was found that progression-free survival (PFS) was significantly longer in patients receiving >6 cycles than that in patients with ≤6 cycles (8.2 months vs 5.4 months, HR=2.474, 95% CI: 1.730-3.538, P＜0.001). Conclusions:Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world. The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory′s experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

Objective:To investigated the safety and efficacy of donor-derived CD19+ or sequential CD19+ CD22+ chimeric antigen receptor T-cell (CAR-T) therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The data of 22 patients with B-ALL who relapsed after allo-HSCT and who underwent donor-derived CAR-T therapy at the Zhujiang Hospital of Southern Medical University and the 920th Hospital of Joint Logistics Support Force of the People’s Liberation Army of China from September 2015 to December 2022 were retrospectively analyzed. The primary endpoint was overall survival (OS), and the secondary endpoints were event-free survival (EFS), complete remission (CR) rate, and Grade 3-4 adverse events.Results:A total of 81.82% ( n=18) of the 22 patients achieved minimal residual disease-negative CR after CAR-T infusion. The median follow-up time was 1037 (95% CI 546–1509) days, and the median OS and EFS were 287 (95% CI 132-441) days and 212 (95% CI 120-303) days, respectively. The 6-month OS and EFS rates were 67.90% (95% CI 48.30%-84.50%) and 58.70% (95% CI 37.92%-79.48%), respectively, and the 1-year OS and EFS rates were 41.10% (95% CI 19.15%-63.05%) and 34.30% (95% CI 13.92%-54.68%), respectively. Grade 1-2 cytokine release syndrome occurred in 36.36% ( n=8) of the patients, and grade 3-4 occurred in 13.64% of the patients ( n=3). Grade 2 and 4 graft-versus-host disease occurred in two patients. Conclusion:Donor-derived CAR-T therapy is safe and effective in patients with relapsed B-ALL after allo-HSCT.

Objective:To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes.Methods:A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results:Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ2=15.00, P<0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR=4.58,95% CI 1.96-10.70, P<0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR=0.90, 95% CI 0.57-1.41, P=0.517). Multivariate analysis further confirmed SNHL ( OR=11.58, 95% CI 2.10-63.93, P=0.005) and preterm birth ( OR=4.98, 95% CI 1.06-23.41, P=0.042) as independent risk factors for poor hearing outcomes. Conclusions:SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

A retrospective analysis was made on the clinical data and gene mutation characteristics of 2 children admitted to the Children′s Hospital of Zhejiang University School of Medicine for epilepsy without periventricular nodules caused by the ARF1 gene mutation from August 2023 to February 2024, and relevant literature was reviewed.Both patients presented with seizures and psychomotor retardation, and 1 of them was diagnosed with West syndrome.Whole exome sequencing confirmed that the 2 patients carried a missense mutation in the ARF1 gene (c.55C>A, p.R19S).Brain magnetic resonance imaging (MRI) of 2 patients revealed no obvious abnormalities.A summary analysis of 5 cases of ARF1 gene mutations reported in three foreign literatures showed that patients with ARF1 gene mutations usually presented with seizures, developmental delay, hypotonia, mental retardation, and motor stereotypies.MRI showed periventricular nodular heterotopia, corpus callosum dysplasia, subcortical white matter abnormalities, and delayed myelination.This study found for the first time that ARF1-related disorders can occur without significant brain structural malformations, indicating that there are inconsistencies in neuroimaging findings, adding valuable phenotypic information to this gene.The differences in imaging findings may be the result of genetic background or variation in ARF1-interacting proteins, or may be caused by altered regulatory mechanisms of protein activity.

Clinical trials are an important method for evaluating the safety and efficacy of in vitro diagnostic reagents, and are a key basis for product registration review and approval. In order to strengthen the management of clinical trials of in vitro diagnostic reagents, the National Medical Products Administration and relevant departments have formulated a series of regulations at the regulatory level, and require applicants and clinical trial institutions to establish a quality management system for clinical trials of in vitro diagnostic reagents. Medical laboratory is the main department and implementer of in vitro diagnostic reagent clinical trials in medical institutions. In recent years, with the rapid development of the in vitro diagnostic industry, the clinical trial projects of in vitro diagnostic reagents conducted by medical laboratory have been increasing day by day. However, there are currently few discussions on the clinical trial of in vitro diagnostic reagents from the perspective of researchers. Therefore, this article summarizes the characteristics of clinical trials of in vitro diagnostic reagents, analyzes the problems and difficulties in conducting clinical trials of in vitro diagnostic reagents in current medical laboratories, and introduces the laboratory′s experience in management; to provide reference for medical testing laboratories that have not yet conducted or have already conducted clinical trials of in vitro diagnostic reagents, in order to improve the quality and efficiency of clinical trials.

Background::Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women.Methods::Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension.Results::Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women ( Pfor trend <0.001). Compared with non-stressed participants, female participants with the highest stress themselves were at a greater risk of hypertension, with adjusted odds ratio (OR) of 1.31 (95% confidence interval [CI]: 1.25-1.37); and compared with participants whose husbands had no stress, those whose husbands had the highest stress level were at a higher risk of hypertension with adjusted OR of 1.24 (95% CI: 1.20-1.29). Moreover, compared with non-stressed status for both couples, only-wife-stressed, only-husband-stressed, and both-stressed couples were found to be significantly associated with increased risks of wives’ hypertension, with adjusted ORs of 1.28 (95% CI: 1.25-1.31), 1.19 (95% CI: 1.17-1.21), and 1.28 (95% CI: 1.26-1.31), respectively. Conclusion::Moderate to severe stress in both spouses might be associated with female hypertension prevalence, which highlights the importance of paying attention to the psychological stresses of couples within the family.