BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective:To investigate the effects of tumor burden score (TBS) and post-radiotherapy alpha-fetoprotein (AFP) stabilization time on the prognosis of hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT).Methods:Clinical data of 40 eligible HCC patients complicated with PVTT admitted to the Affiliated Tumor Hospital of Xinjiang Medical University from July 2018 to March 2022 were retrospectively analyzed. The objective response rate (ORR), overall survival (OS), progression-free survival (PFS), AFP response, and post-radiotherapy AFP stabilization time in the entire group were observed. Diagnostic thresholds were determined by the receiver operating characteristic (ROC) curve. Survival analysis was conducted by Kaplan-Meier method, and the differences of survival rate were assessed by log-rank test. Multivariate analysis was performed by Cox proportional risk model.Results:The optimal cut-off value for TBS was 4.27 [area under the ROC curve (AUC)=0.752, P=0.018]. The ORR in the entire group was 35.7%, with a median OS and PFS of 8 and 5 months, respectively. The median AFP stabilization time was 6 months. Univariate analysis showed that a total of 9 factors were associated with OS, including gender, maximum tumor diameter, TBS, China liver cancer staging, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, gamma-glutamyl transferase (GGT), radiation dose, AFP stabilization time, and tumor response. Multivariate analysis showed that TBS>4.27 ( HR=0.195, 95% CI=0.060-0.638, P=0.007), China liver cancer stage Ⅲb staging ( HR=0.328, 95% CI=0.144-0.745, P=0.008), and AFP stabilization time ≤6 months ( HR=10.282, 95% CI=2.304-45.883, P=0.002) were the independent risk factors for OS in HCC patients complicated with PVTT. Conclusion:HCC patients complicated with PVTT who have low TBS and AFP stabilization time after radiotherapy may obtain longer OS, and the combination of TBS and AFP is expected to become a new risk assessment model.

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

AIM: To analyze the clinical characteristics of anticoagulant rat poisoning and vitamin K

This study aims to optimize the teaching design of Nutritional Counseling and Education, a core course for registered dietitians in China, to strengthen the cultivation of practical nutrition counseling and education abilities of nutritional professionals in China, and to provide reference for other colleges and universities intending to offer the same type of courses. This study thoroughly examined the course design of Nutrition Counseling and Education in four universities in the United States, and compared it with the course design in Shanghai Jiao Tong University School of Medicine. A profound comparison revealed that our course design was basically in line with that of the United States in terms of knowledge and ability cultivation objectives as well as the contents, teaching modes, and performance evaluation methods of theoretical and practical courses. However, there were slight deficiencies in our course design in terms of the integration of theoretical and practical courses, as well as the diversity and depth of practical courses. Our course design can be optimized by developing online teaching resources, drafting practical guidance manuals, increasing the number of practice bases, and enriching the modality and content of practical courses.

Objective:To understand the status quo of the job preparedness among newly recruited nurses and analyze its influencing factors.Methods:Totally 355 newly recruited nurses who joined 5 Class Ⅲ Grade A hospitals nationwide between September 2021 and September 2022 were selected by convenience sampling and investigated by general information surveys, the Work Readiness Scale for Graduate Nurses and the Transition Shock of Newly Graduated Nurses Scale. Logistic regression was employed to analyze the influencing factors of the job preparedness among these newly recruited nurses.Results:A total of 355 questionnaires were distributed, and 350 valid responses were received, with a valid response rate of 98.6%. The overall score for the job preparedness of the newly recruited nurses was (271.05±49.97), with a standardized total score of (73.26±13.57). 208 individuals (59.4%) scored high (standardized total score ≥70), while 142 individuals (40.6%) scored low (standardized total score<70). Logistic regression analysis revealed that the department of employment, part-time job experience, harmonious relationships with classmates during schooling, and the level of transition shock were influencing factors for the job preparedness of the newly recruited nurses ( P<0.05) . Conclusions:The job preparedness of newly recruited nurses is influenced by various factors. Nursing educators and managers should adopt targeted educational and management strategies based on the nurses' different experiences, interpersonal relationships, department of employment, and level of transition shock to enhance their job preparedness.

ObjectiveTo investigate the moderating effect of psychological resilience in relation to depressive symptoms and suicidal risk among adolescents. MethodsThe research is a descriptive survey. A total of 71 137 adolescents were selected from 163 schools in Deyang by stratified cluster sampling. Their psychological resilience， depressive symptoms and suicide risks were measured oneline by using 10-item Connor-davidson Resilience Scale （CD-RICS-10）， Patients’ Health Questionnaire Depression Scale-9 item （PHQ-9） and Suicidal Behaviors Questionnaire-Revised （SBQ-R）. The moderating effect of psychological resilience in relation to depressive symptoms and suicidal risk was examined by multivariate stratified regression analysis. Results① The score of CD-RISC-10 was negatively related to PHQ-9 score and SBQ-R score （r=-0.305， -0.268， P<0.01）. ② Psychological resilience significantly moderated the relationship between depressive symptoms and suicidal risk （β=-0.100， t=-31.716， P<0.01）. ③ In both male and female adolescents， resilience played a significant role in depressive symptoms and suicide risk （β=-0.086， -0.084， t=-17.502， -18.839， P<0.01）. ConclusionPsychological resilience could significantly alleviate the impact of high-level depressive symptoms on suicidal risk among adolescents， and this effects both male and female adolescents.

Objective    To investigate the effectiveness and safety of totally endoscopic transmitral myectomy (TETM) for hypertrophic obstructive cardiomyopathy (HOCM), comparing with traditional sternotomy modified Morrow procedure (SMMP). Methods    Thirty-eight patients with HOCM who needed surgical intervention were selected from our hospital in 2019, including 14 males and 24 females, with an average age of 56 (44-68) years. According to the operation method, they were divided into a TETM group (n=18) and a SMMP group (n=20). Appropriate patients  were screened by propensity matching scores. Finally, the clinical data of two matched groups were compared and

Objective:To explore the early surgical outcomes of Thoracoscopic Transmitral Myectomy(TTM) on patients with hypertrophic obstructive cardiomyopathy(HOCM).Methods:Preoperative echocardiography and cardiac magnetic resonance were used to evaluate the patient's hypertrophy extent, mitral valve morphology and function. Myocardial resection was performed via the trans-mitral approach under total thoracoscopy, and the surgical methods and early results were analyzed.Results:From April 2019 to October 2019, a total of 15 cases of TTM were performed by a single surgeon in our ward. Preoperative imaging evaluation revealed that 6 patients(40.0%) had predominantly hypertrophic basal septum while another 9 patients(60.0%) had concomitant midventricular septal hypertrophy. Two(13.3%) patients were interrogated ruptured posterior mitral chord by preoperative echocardiogram. After myocardial resection, the mitral valve was treated as follows: 11 patients(73.3%) underwent anterior leaflet enlargement, and 3(20.0%) were directly reattached to mitral valve annulus, and 1(6.7%) underwent bioprosthetic mitral replacement. There was no case of perioperative death, ventricular septal perforation, residual left ventricular outflow tract obstruction and complete atrioventricular block. Median aortic crossclamp time, cardiopulmonary bypass time, postoperative ventilator use time, ICU stay time, and postoperative hospital stay were 129.0min(116.0, 147.0), 184.0 min(158.0, 227.0), 22.0 h(9.0, 26.0), 3 days(2, 7) and 9 days(7, 14) respectively. No patient lost to follow up, the median follow-up time was 4 months(2, 5). One patient(6.7%) underwent mitral angioplasty three months after surgery due to a tear in the A3 area; the ventricular septal thickness and left ventricular outflow tract pressure decreased significantly(preoperative vs follow-up), and were(19.3±3.3)mm vs. (8.9±4.4) mm( P=0.001), (90.8±23.2)mmHg vs. (8.9±4.4) mmHg(1 mmHg = 0.133kPa)( P<0.001) respectively; no residual SAM was observed during follow-up. Patients with moderate-to severe mitral regurgitation were decreased from 12(80.0%) before surgery to 1(6.7%) during follow up( P<0.001). Conclusion:TTM is a safe and effective procedure for HOCM patients with appropriate surgical indications, providing better exposure to septum from basal to apical area, eliminating left ventricular outflow tract obstruction and SAM-related mitral regurgitation. The anterior mitral valve leaflet should be carefully treated during surgery to reduce the occurrence of residual mitral regurgitation resulted in inappropriate selection of patch size and suturing technique.

Monitoring neuronal activity in vivo is critical to understanding the physiological or pathological functions of the brain. Two-photon Ca imaging in vivo using a cranial window and specific neuronal labeling enables real-time, in situ, and long-term imaging of the living brain. Here, we constructed a recombinant rabies virus containing the Ca indicator GCaMP6s along with the fluorescent protein DsRed2 as a baseline reference to ensure GCaMP6s signal reliability. This functional tracer was applied to retrogradely label specific V1-thalamus circuits and detect spontaneous Ca activity in the dendrites of V1 corticothalamic neurons by in vivo two-photon Ca imaging. Notably, we were able to record single-spine spontaneous Ca activity in specific circuits. Distinct spontaneous Ca dynamics in dendrites of V1 corticothalamic neurons were found for different V1-thalamus circuits. Our method can be applied to monitor Ca dynamics in specific input circuits in vivo, and contribute to functional studies of defined neural circuits and the dissection of functional circuit connections.