1.The modulation effects of Lipopolysaccharide on miR-211/Siert1 to enhance cardiomyocytes apoptosis induced by hypoxia
Zhiwei ZHONG ; Wei ZHU ; Anjian WANG
Chinese Journal of Emergency Medicine 2016;25(4):460-464
Objective To study the effect of Sirtuin1 (Sirt1) on the pathological process through its activity of deacetylation to improve the clinical outcome of acute sepsis. After searching data base, microRNA-211 (miR-211) was found to have action potentially targeting at Sirt1.The present study aimed to find the interaction between miR-211 and Sirt1 in the pathogenesis of hypoxic injury to cardiomyocytes in the presence of lipopolysaccharide ( LPS ) . Methods Primary neonatal rat cardiomyocytes ( NRC ) isolated from neonatal SD rats and H9c2 ( cardiomyocytes after culture with 10% fetal serum of cattle and DMEM under 37 ℃ and 5% CO2 ) cell line were used in the experiments.The miR-211 expression was quantified by qRT-PCR after LPS exposure for 4 hours, and the changes in Sirt1 protein level were also detected in both NRC and H9c2 by western blot.At the same time, CCK-8 assay and TUNEL staining were also performed to measure cell proliferation and apoptosis activation when either treated with LPS alone or followed by exposure to hypoxia.Results Compared to the control group, the doses of 20μg/mL, 40μg/mL LPS treatment for 4 hours had no significant effects on H9c2 cell proliferation at 24 h, 48 h, 72 h, but it could significantly induce the cell apoptosis of neonatal rat cardiomyocytes and H9c2 cells after hypoxia, and the apoptosis rate increased all over 100% in both NRC and H9c2.At the same time, LPS treatment could significant up-regulate miR-211 expression which was closely associated with decrease in Sirt1 protein levels.Conclusions LPS enhanced cardiomyocytes injury after exposure to hypoxia which was closely associated with up-regulating miR-211 expression and in turn to suppress Sirt1 expression.
2.Laparoscopic radical cystectomy and orthotopic ileal neobladder used for treatment of invasive bladder cancer
Tiancai LIANG ; Min WANG ; Guobiao LIANG ; Yang DU ; Xin WANG ; Yuanliang WANG ; Anjian CHEN ; Zongping CHEN ; Yanan GUO ; Jiang DU ; Hao LI ; Lang YU
China Journal of Endoscopy 2017;23(1):74-79
Objective To investigate the surgical methods and experience of laparoscopic radical cystectomy and orthotopic ileal neobladder for invasive bladder cancer. Methods The clinical data of 14 patients with invasive bladder cancer underwent laparoscopic radical cystectomy and orthotopic ileal neobladder were collected retrospectively during March 2011 and October 2014. Results The 13 patients with invasive bladder cancer were successfully completed laparoscopic radical cystectomy and orthotopic ileal neobladder. 1 case was treated with laparotomy because of unsatisfactory surgery ifeld caused by excessive tumor bleeding. Twelve cases of the urethra-neobaldder anastomosis were completed through the abdominal incision, while for the other 2 cases, the anastomosis was done under the laparoscope, 2 cases were performed neovesicourethral anastomosis using single-needle running sutures through laparoscopy. The median operative time was 444 minutes, the mean intraoperative blood loss was 490 ml. Postoperative pathologic results conifrmed that 12 cases were bladder transitional cell carcinoma (1 case with partial squamous cell carcinoma) and 2 cases with bladder adenocarcinoma. No severe complication occurred except for 2 cases of urinary leakage and 1 case of urinary incontinence. Patients were followed up for 6-56 months,within which 3 patients were died of distant metastasis, 1 case was detected with intracranial metastasis, 1 case was found with urethra-vesical anastomotic stenosis while cured after urethrotomy. Ten cases were well recovered and the mean volume of the neobladder was 300 ml. Conclusions Laparoscopic radical cystectomy and orthotopic ileal neobladder have the advantage of better therapeutic effects, safety, minimal invasion and rapid recovery, which are the preferred therapeutic methods for invasive bladder cancer.
3.Analysis of clinical, gene mutation characteristics, and treatment prognosis of type 2A hereditary hemochromatosis in the Chinese population
Wei ZHANG ; Yanmeng LI ; Anjian XU ; Xiaoming WANG ; Yu WANG ; Weijia DUAN ; Xinyan ZHAO ; Hexiang XU ; Jinping JIANG ; Wei JIANG ; Jian HUANG ; Xiaojuan OU
Chinese Journal of Hepatology 2024;32(11):1013-1018
Objective:To analyze the clinical, genetic mutation characteristics, and treatment prognosis of type 2A hereditary hemochromatosis (HH) in China.Methods:Peripheral blood samples and clinical data of patients with primary iron overload were collected through the China Registry of Genetic/Metabolic Liver Disease from June 2015 to November 2023. HH-related genes were detected by Sanger sequencing. Clinical characteristics and gene mutation characteristics of HH patients carrying HJV gene mutations were analyzed.Results:Among the 37 cases with primary iron overload, ten cases (27.0%, 10/37) had detectable HJV gene mutations, which included four homozygous mutations, five compound heterozygous mutations, and one monoheterozygous mutation. p.Q6H and p.C321X (80.0%, 8/10) were the most common mutated sites. The average age of onset was 30.7±14.7 years. The age of diagnosis was 35.7±16.2 years, with male-to-female ratio of 7:3. Ferritin and transferrin saturation were (5 267±905) ng/ml, and 94.3%±1.2%, respectively. Magnetic resonance imaging showed iron overload in the liver, pancreas, and myocardium. Liver biopsy showed diffuse iron deposition within hepatocytes. All ten cases had elevated transaminases; one case (1/10, 10.0%) had liver cirrhosis; four cases (4/10, 40.0%) had heart failure and arrhythmia; five cases (5/10, 50.0%) had diabetes; six cases (6/10, 60.0%) had hypogonadism; six cases (6/10, 60.0%) had skin pigmentation; and six cases (6/10, 60.0%) had fatigue symptoms. All six cases underwent bloodletting therapy, and ferritin levels dropped to about 100 ng/ml. Two cases of oral administration of the iron chelator deferasirox did not meet the ferritin level standard, and one case died from acute heart failure following a confirmed diagnosis during hospitalization.Conclusion:The HJV gene may be one of the main pathogenic genes of HH in China. The p.Q6H and p.C321X mutations were one of the hotspot mutations. The onset age of HJV gene-related HH was between 20 and 30 years old, and their condition was severe. Therefore, early bloodletting treatment can have a favorable outcome.