Exosomes derived from cardiac fibroblasts with angiotensin II stimulation provoke hypertrophy and autophagy inhibition in cardiomyocytes.

Although accumulating evidence has revealed that autophagy inhibition contributes to the development of pathological cardiac hypertrophy, the mechanisms leading to declined autophagy activity in the hypertrophic heart remain to be elucidated. Exosomes are known to be important mediators of intercellular communication, and the involvement of exosomes in cardiovascular abnormities has attracted increasing attentions. Cardiac fibroblasts (CFs) are the most abundant cell type in the heart. Here, we investigated the potential role of CFs-derived exosomes in regulating cardiomyocyte hypertrophy and autophagy. Exosomes from rat CFs treated with angiotensin II (Ang II-CFs-exosomes) were collected and characterized. Our experiments showed that these exosomes could induce hypertrophic responses and impair autophagy activity in primary neonatal rat cardiomyocytes (NRCMs). Ang II-CFs-exosomes blocked the autophagic flux of NRCMs via inhibiting the formation of autolysosomes. Moreover, the pro-hypertrophic effects and autophagy inhibition induced by Ang II-CFs-exosomes was validated in mice receiving injection of the exosomes. These findings highlight a novel role of Ang II-CFs-exosomes in suppressing cardiomyocyte autophagy, which may help to better understand the pathogenesis of cardiac hypertrophy.

Inhibition of miR-214-3p attenuates ferroptosis in myocardial infarction via regulating ME2.

Myocardial infarction (MI) contributes to an increased risk of incident heart failure and sudden death, but there is still a lack of effective treatment in clinic. Recently, growing evidence has indicated that abnormal expression of microRNAs (miRNAs) plays a crucial role in cardiovascular diseases. In this research, the involvement of miRNA-214-3p in MI was explored. A mouse model of MI was established by ligation of the left anterior descending coronary artery, and primary cultures of neonatal rat cardiomyocytes (NRCMs) were submitted to hypoxic treatment to stimulate cellular injury in vitro. Our results showed that miR-214-3p level was significantly upregulated in the infarcted region of mouse hearts and in NRCMs exposed to hypoxia, accompanying with an obvious elevation of ferroptosis. Inhibition of miR-214-3p by antagomir injection improved cardiac function, decreased infarct size, and attenuated iron accumulation and oxidant stress in myocardial tissues. MiR-214-3p could also promote ferroptosis and cellular impairments in NRCMs, while miR-214-3p inhibitor effectively protected cells from hypoxia. Furthermore, dual luciferase reporter gene assay revealed that malic enzyme 2 (ME2) is a direct target of miR-214-3p. In cardiomyocytes, overexpression of ME2 ameliorated the detrimental effects and excessive ferroptosis induced by miR-214-3p mimic, whereas ME2 depletion compromised the protective role of miR-214-3p inhibitor against hypoxic injury and ferroptosis. These findings suggest that miR-214-3p contributes to enhanced ferroptosis during MI at least partially via suppressing ME2. Inhibition of miR-214-3p may be a new approach for tackling MI.

The role of transanal drainage tube in preventing the anastomotic leakage in rectal cancer surgery without a defunctioning stoma: A meta-analysis.

BACKGROUND: Anastomotic leakage is a common and serious complication after rectal cancer surgery. The role of transanal drainage tube (TDT) in the prevention of anastomotic leakage is still controversial. The aim of this study was to evaluate the role of TDT in preventing anastomotic leakage. METHODS: Two reviewers individually searched the PubMed, Embase and Cochrane Library ranging from January 2000 to June 2022. The pooled odds ratio (ORs) and weighted mean difference (WMD) with the 95% confidence interval (95% CI) were used to assess anastomotic leakage and other parameters. RESULTS: A total of 3383 patients (1508 in the TDT group and 1875 in the cohort study group) were included in 13 studies. The study found that patients treated with TDT had a lower incidence of anastomotic leakage with or without neoadjuvant radiotherapy. Moreover, patients who received TDT had lower rates of reoperation and tended to reduce the severity of anastomotic leakage. CONCLUSIONS: For rectal cancer patients without defunctioning stoma, TDT could reduce the incidence of anastomotic leakage, decrease the reoperation rate of patients, and tend to reduce the severity of anastomotic leakage. More RCT are needed to assess the role of TDT in rectal cancer surgery.

[Distribution of non-bacterial pathogens in 1 788 children with community-acquired pneumonia]. / 1 788ä¾‹ç¤¾åŒºèŽ·å¾—æ€§è‚ºç‚Žéžç»†èŒæ€§ç— åŽŸä½“åˆ†å¸ƒç‰¹å¾åˆ†æž.

OBJECTIVES: To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children. METHODS: A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed. RESULTS: Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia. CONCLUSIONS: MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.

KI-catalyzed α-acyloxylation of acetone with carboxylic acids.

The KI-catalyzed reaction of acetone with aromatic carboxylic acids is achieved, leading to α-acyloxycarbonyl compounds in good to excellent yields under mild reaction conditions. The present method exhibits good functional-group compatibility. Notably, this reaction system is even suitable for cinnamic acid, 3-phenylpropiolic acid and 4-phenylbutanoic acid. A kinetic isotope effect (KIE) study indicates that C-H cleavage of the acetone is the rate-limiting step in the catalytic cycle.

The prevalence of nonalcoholic fatty liver disease and relationship with serum uric acid level in Uyghur population.

OBJECTIVE: To investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of serum uric acid level with NAFLD in Uygur people, Xinjiang. METHODS: A total of 2241 Uyghur persons (1214 males and 1027 females) were interviewed for physical checkups from 2011 to 2012. The clinical data of questionnaire survey, body mass index (BMI), abdominal circumference, blood pressure, blood sugar, blood lipid, and serum uric acid level were collected for analysis. RESULTS: The prevalence rates of NAFLD determined by abdominal ultrasound examination and hyperuricemia were 43.9% and 8.4%, respectively. The persons with NAFLD had significantly higher serum uric acid levels than those without NAFLD (320 ± 88 versus 254 ± 80 µ mol/L; P < 0.001). The prevalence rate of NAFLD was significantly higher in subjects with hyperuricemia than that in those without hyperuricemia (78.19% versus 40.83%; P < 0.001), and the prevalence rate increased with progressively higher serum uric acid levels (P < 0.001). Multiple regression analysis showed that hyperuricemia was associated with an increased risk of NAFLD (odds ratio (OR): 2.628, 95% confidence interval (CI): 1.608-4.294, and P < 0.001). CONCLUSION: Serum uric acid level was significantly associated with NAFLD, and the prevalence rate of NAFLD increased with progressively higher serum uric acid levels.

High serum IL-21 levels after 12 weeks of antiviral therapy predict HBeAg seroconversion in chronic hepatitis B.

BACKGROUND & AIMS: Interleukin-21 (IL-21) stimulates T cell and B cell responses and plays a role in control of chronic viral infections. The role of IL-21 in chronic hepatitis B virus (HBV) infection is not understood. METHODS: Serum IL-21 levels were measured by enzyme immunoassay in 75 HBeAg-positive chronic hepatitis B (CHB) patients undergoing telbivudine treatment. The findings were validated in 103 patients from a separate clinical trial of telbivudine. A complete response to telbivudine was defined as having both HBeAg seroconversion and serum HBV-DNA level <300 copies/ml by treatment week 52. The proportions of T-cells producing IL-21 and/or expressing programmed death 1 (PD-1) in peripheral blood mononuclear cells were assessed longitudinally during treatment by intracellular cytokine staining and flow cytometry. RESULTS: Median serum IL-21 levels at treatment week 12 were significantly higher in patients who did achieve vs. patients who did not achieve a complete response in both the initial (128.4 vs. 69.2 pg/ml, p=0.003) and the validation (142.2 vs. 89.9 pg/ml, p=0.004) trials. Serum levels of IL-21 (p=0.005) or HBV-DNA (p=0.003) levels at treatment week 12 independently predicted HBeAg seroconversion in the first year of treatment. The decrease in PD-1 expression on CD4(+) and CD8(+) T cells during the first 12 weeks on telbivudine treatment was not correlated with changes in IL-21 concentrations. CONCLUSIONS: Serum IL-21 levels may be a biomarker for HBeAg seroconversion, and may contribute to individualization of antiviral therapy in HBeAg-positive CHB. IL-21 may also have a role in immunotherapy for CHB.

[Main clinical features and prognosis of AIDS patients with the predominance of thrombocytopenia].

OBJECTIVE: To summarize the major clinical features, treatment, follow-up and outcomes of acquired immune deficiency syndrome (AIDS) patients with prominent thrombocytopenia. METHODS: The manifestations, signs, anti-virus regimens, CD4 cell count, platelet count, prognosis and outcomes of 10 AIDS patients with prominent thrombocytopenia were collected and analyzed. RESULTS: After the administration of highly active antiretroviral therapy, platelet count and CD4 significantly improved during a follow-up period up to 12 months. No opportunistic infections and HIV-related deaths occurred. CONCLUSION: The HIV/AIDS patients with prominent thrombocytopenia should start highly active antiretroviral therapy so as to effectively improve the prognosis and outcome.

[Antioxidant effects of the Uygur herb, Foeniculum Vulgare Mill, in a rat model of hepatic fibrosis].

OBJECTIVE: To evaluate therapeutic and antioxidant effects of Uygur Herb Foeniculum Vulgare Mill (FVM) in hepatic fibrosis rats. METHOD: Hepatic fibrosis model was built in rats by subcutaneous injection with 40% CCl4 olive oil mixture. At the same time the rats were given high lipoid-low protein animal feeds for 5 weeks. 94 male SD rats were randomly divided into six groups :blank control group (A-group), 8 rats were feed in normal; prevention model control group (B-group), 10 rats were given saline solution by intragastric administration during make of hepatic fibrosis model; FVM prevention group (C-group), 10 rats were given FVM by intragastric administration during make of hepatic fibrosis model; model control group (D-group), FVM treatment group (E-group); Fuzhenghuayu treatment group (F-group). 22 rats in each D, E, F-group were respectively given saline solution, FVM and Fuzhenghuayu by intragastric administration after hepatic fibrosis model were built. At the 5-th weekend, A, B, C- group rats were sacrificed. At the 6-th, 7-th, 8-th, 9-th weekend, 4-6 rats in D, E, F-group were sacrificed. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), laminin (LN) and 8 - hydroxy-2-deoxyguanosine (8-OHdG) were detected, liver tissue homogenate superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) were detected. Histopathologic changes were observed after H.E and Masson staining. The expression of alpha-smooth muscle actin(a-SMA) were detected by immunohistochemical staining. The data were analyzed by SPSS17.0 software. RESULTS: The serum levels of ALT, AST, HA, and LN in the FVM prevention group were significantly reduced compared to the prevention model control group.(P less than 0.05). Rats in FVM treatment group appeared a marked lower serum levels of ALT, AST, HA compared to the model control group (P less than 0.05), and a distinguished lower Inflammation grade and fibrosis stage (P less than 0.05) when the liver section were assayed as well; Rats in FVM treatment group and FVM prevention group had a conspicuous lower content of MDA, 8-OHdG, fibre and a-SMA expression (P less than 0.05), a significantly higher level of SOD, GSH-Px compared to those of in the model control groups. CONCLUSIONS: Foeniculum Vulgare Mill declines liver inflammation response ,and prevent the hepatic fibrosis progression,, this may be due to its effects of antioxidative results.

Effectiveness and safety of robotic gastrectomy versus laparoscopic gastrectomy for gastric cancer: a meta-analysis of 12,401 gastric cancer patients.

Advanced minimally invasive techniques, such as robotic surgeries, are applied increasingly frequently around the world and are primarily used to improve the surgical outcomes of laparoscopic gastrectomy (LG). Against that background, we conducted a meta-analysis to evaluate the feasibility, safety, and effectiveness of robotic gastrectomy (RG). Studies comparing surgical outcomes between LG and RG patients were retrieved from medical databases, including RCTs and non-RCTs. The primary outcome of this study was overall survival, which was obtained by evaluating the 3-year survival rate and the 5-year survival rate. In addition, postoperative complications, mortality, length of hospital stay, and harvested lymph nodes were also assessed. We also conducted subgroup analyses stratified by resection type, body mass index, age, depth of invasion and tumour size. Ultimately, 31 articles met the criterion for our study through an attentive check of each text, including 1 RCT and 30 non-RCTs. A total of 12,401 patients were included in the analysis, with 8127 (65.5%) undergoing LG and 4274 (34.5%) undergoing RG. Compared with LG, RG was associated with fewer postoperative complications (OR 0.81; 95% CI 0.71-0.93; P = 0.002), especially pancreas-related complications (OR 0.376; 95% CI 0.156-0.911; P = 0.030), increased harvested lymph nodes (WMD 2.03; 95% CI 0.95-3.10; P < 0.001), earlier time to first flatus (WMD - 0.105 days; 95% CI - 0.207 to - 0.003; P = 0.044), longer operation time (WMD 40.192 min, 95% CI 32.07-48.31; P < 0.001), less intraoperative blood loss (WMD - 20.09 ml; 95% CI - 26.86 to - 13.32; P < 0.001), and higher expense (WMD 19,141.68 RMB; 95% CI 11,856.07-26,427.29; P < 0.001). There was no significant difference between RG and LG regarding 3-year overall survival (OR 1.030; 95% CI 0.784-1.353; P = 0.832), 5-year overall survival (OR 0.862; 95% CI 0.721-1.031; P = 0.105), conversion rate (OR 0.857; 95% CI 0.443-1.661; P = 0.648), postoperative hospital stay (WMD - 0.368 days; 95% CI - 0.75-0.013; P = 0.059), mortality (OR 1.248; 95% CI 0.514-3.209; P = 0.592), and reoperation (OR 0.855; 95% CI 0.479-1.525; P = 0.595). Our study revealed that postoperative complications, especially pancreas-related complications, occurred less often with RG than with LG. However, long-term outcomes between the two surgical techniques need to be further examined, particularly regarding the oncological adequacy of robotic gastric cancer resections.