Objective:To evaluate the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in patients with genotype 1 chronic hepatitis C in the real-world.Methods:This was an open-label, single-center, retrospective real-world study. A total of 103 genotype 1 chronic hepatitis C patients who were treated with EBR/GZR in Henan Provincial People′s Hospital from May 2018 to October 2019 were enrolled.And the clinical baseline characteristics of patients and the effectiveness and safety of antiviral therapy were respectively evaluated.Results:A total of 103 patients were enrolled in the study with an age of (47.6±13.9) years. Fifty-five (53.4%) patients were male and 48(46.6%) were female. One point nine percent (2/103) patients were genotype 1a hepatitis C and 98.1%(101/103) were genotype 1b hepatitis C. Seventeen genotype 1b hepatitis C patients were previously treated with interferon, and three patients co-infected with hepatitis B virus (HBV). Among the 103 cases, 35 had underlying diseases and 26 had combined medication. Ninty-eight cases completed 12-week treatment and 89 cases completed 12-week follow-up after treatment.Overall, 89 cases achieved sustained virological response. The overall incidence of adverse reactions was 20.4%(21/103), and the main adverse reactions were fatigue, insomnia and anxiety. No serious adverse event occurred. The three patients with HBV co-infection had no hepatitis B activation after treatment.Conclusion:EBR/GZR is effective and safe in the patients with genotype 1 chronic hepatitis C in China.

Since 2014, the United States and Europe has approved all oral, interferon free- regimens that combine with direct-acting antiviral agents. Hence, the sustained virological response rate of patients with chronic HCV genotype 1 infection has improved over 90%, and the treatment modalities has introduced a new era. These drugs, ombitasvir and dasabuvir, received customary authorization of Food and Drug Administration in 2015 and are the first combined direct-acting antiviral agents for treating HCV genotype 1 infection. It has superior application prospects in China because of its high-sustained virological response rate and safety profile. This article reviews the pharmacokinetics, drug interactions, efficacy and safety of this therapeutic regimen.

Objective To explore the efficacy and safety of daclatasvir (DCV ) combined with asunprevir (ASV) for chronic genotype 1b (GT1b) hepatitis C .Methods Twenty-nine GT1b hepatitis C patients who were treated with DCV combined ASV in Henan Provincial People′s Hospital from September 2017 to November 2017 were included .Hepatitis C virus (HCV ) RNA levels were tested before treatment ,1 week ,2 weeks ,3 weeks ,4 weeks ,8 weeks ,12 weeks and 24 weeks after treatment , and 12 weeks after the end of the treatment .The comorbidities ,combined use of drugs and adverse clinical events were registered .T test was used to compare the measurement data with normal distribution and M (P25,P75) was used for measurement data with non-normal distribution .Results A total of 29 patients with GT1b were included ,with 4 cirrhosis cases and 25 non cirrhotic cases .Seven patients had history of previous interferon and ribavirin combination treatment .There were 9 patients with comorbidity and 7 patients with combined medication . Finally , 25 patients completed a 24-week course of antiviral treatment ;3 patients were lost to follow-up ,and 1 patient withdrew after 16weeks of antiviral treatment because of a virus rebound .Of the 26 followed up patients ,25 achieved sustained virological response at 12-week (SVR12 ) , and one patient failed .And the HCV RNA NS5A resistance-associated variants (RAV) were detected in the patients with treatment failure .No severe adverse clinical events occurred in 26 patients .Conclusions DCV combined with ASV is effective and safe in the treatment of GT 1b chronic hepatitis C .However , the effect of RAV on therapeutic efficacy should be concerned during the treatment .

OBJECTIVETo explore the clinical features and gene mutation profiles of patients with chronic hepatitis B (CHB) and Gilbert's syndrome.

METHODSThirty-three patients with CHB and Gilbert's syndrome were enrolled in the study. Serum markers of liver function and histological features of disease-related liver injury were assessed by standard methods. Gene mutations were detected by PCR and direct DNA sequencing.Statistical analysis was carried out with the chi-square and t tests.

RESULTSSequencing of the Gilbert syndrome-associated gene, UGT 1A 1, revealed mutations in the upstream promoter phenobarbital-responsive element module (PBREM) (-3279 mutation, 23 cases), in the promoter TATA box (a TA insertion mutation, 21 cases), and in the coding region of exon 1 (a GGA-AGA Gly71Arg mutation, 18 cases); there was no statistical difference found for any of the three mutations among this patient population (x2 =1.640, P more than 0.05).

CONCLUSIONThe traditional methods of diagnosis for patients with CHB and Gilbert's syndrome remain a technical challenge in the clinic, and gene detection may represent a more favorable method for diagnosing this patient population.

Base Sequence ; Exons ; Gilbert Disease ; Glucuronosyltransferase ; Hepatitis B, Chronic ; Humans ; Mutagenesis, Insertional ; Mutation ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; TATA Box

king condition before pregnancy were associated with the development of polydactyly and syndactyly.

OBJECTIVETo explore the safety and curative effects of autologous bone marrow-derived mesenchymal stem cells (BMSCs) in the treatment of silicosis.

METHODSThe protocol was approved by the Ethics Committee of the hospital, and ten patients with silicosis who had given written consent were enrolled in this study. BMSCs isolated from 100 ml of bone marrow for each case were purified and cultured. In each case the 3rd generation of qualified BMSCs (5 × 10(7)) were intravenously administered weekly for 3 weeks. Three cases among 10 patients were treated with BMSCs modified by hepatocyte growth factor (HGF) gene. The clinical symptoms, chest films, chest CT, pulmonary functions, T cells, serum IgG and ceruloplasmin (CP) were observed in 6 or 9 months after treatment.

RESULTSNo obvious sub-effect was observed in cases treated with BMSCs, the clinical symptoms (such as cough, sputum and chest tightness) basically disappeared in 9 months after treatment. Pulmonary function tests showed that FVC increased from 71.2% ± 17.0% to 84.0% ± 10.9% (P < 0.01) and FEV1.0 increased from 67.5% ± 17.7% to 80.6% ± 14.9% (P < 0.01). The levels of serum CP and IgG significantly decreased (P < 0.01). Further, the chest films and CT in cases treated with autologous BMSCs modified by HGF gene were improved to different extent.

CONCLUSIONTreatment with autologous BMSCs modified by HGF gene exhibit a beneficial effect on silicosis.

Adult ; Bone Marrow Cells ; Female ; Hepatocyte Growth Factor ; genetics ; Humans ; Male ; Mesenchymal Stem Cell Transplantation ; methods ; Middle Aged ; Silicosis ; surgery ; Transfection ; Transplantation, Autologous ; Treatment Outcome

Objective: To investigate the influence of hepatitis B virus X gene (HBx) on apoptosis of hepatic cells mediated by Fas in HePG2 cells. Methods: HBx eukaryotic vector pcDNA3.1(+)-X was transfected into HEPG2 cells with lipofectamine, and the null vector pcDNA3.1(+) and untransfected HEPG2 were used as normal controls. The cells were collected 72 h after transfection, and the expression of HBx mRNA and protein was determined using RT-PCR and Western blot, respectively. The mRNA expression of apoptosis-related genes Bcl-2 and Bax mRNA was also determined using RT-PCR. Cytotoxicity and apoptosis were evaluated using CCK-8 and flow cytometry, respectively, after HepG2-HBx and HepG2-3.1 cells were treated with stimulatory monoclonal antibody anti-Fas CH11. The t test was used for pairwise comparison. Results: The cell line HepG2-HBx was successfully established, as confirmed by RT-PCR and Western blot, and RT-PCR results showed that HepG2-HBx cells had significantly higher expression of Bcl-2 mRNA than HepG2-3.1 and HepG2 cells (P < 0.05), but had significantly lower expression of Bax mRNA than HepG2-3.1 and HepG2 cells (P < 0.05); CCK-8 and flow cytometry showed that anti-Fas CH11 had a lower cytotoxicity to HepG2-HBx cells and allowed for a lower apoptosis rate of HepG2-HBx cells compared with HepG2-3.1 and HepG2 cells. Conclusions HBx can inhibit apoptosis of hepatic cells mediated by the Fas pathway.

OBJECTIVETo evaluate the potential role of hepatocyte growth factor (HGF) combined with bone marrow mesenchymal stem cells (BMSC) autograft for the treatment of silicosis.

METHODSBone marrow (100 ml) was aspirated from a severe silicosis patient. BMSCs isolated, purified and cultured in vitro. When BMSC came to 70% confluence at passage 3, the culture medium was added liposomes (lipo2000) and plasmid-HGF (p-HGF) and cultured for 2 d. HGF-MSCSs (5 × 10(7) cells) were resuspended in 50 ml 0.9% sodium chloride (NS) and infused Intravenous drip at 3 consecutive times (once a week). Clinical follow-up were performed before and after treatment: (1) pulmonary high-kV X-ray, chest CT examination; (2) pulmonary function test; (3) determination of serum ceruloplasmin.

RESULTSThe symptoms such as coughing, chest tightness disappeared at 12 months after treatment. Pulmonary function tests showed significant changes after treatment: forced vital capacity (FVC) increased from 64.6% to 81.0%, forced expiratory volume in one second (FEV(1.0)) increased from 68.7% to 90.1%, 1 second rate (FEV(1.0)/FVC%) reduced from 111.6% to 107.1%, the maximum mid-expiratory flow (FEF(25%∼75%) decreased from 100.2% to 94.6%, forced expiratory vital capacity 75% of the moment bit of gas flow (MEF(75%)) increased from 99.2% to 113.5%, forced expiratory vital capacity 50% of the moment bit of gas flow (MEF(50%)) increased from 125.3% to 130.2%, forced expiratory vital capacity 25% of the moment bit of gas flow (MEF(25%)) reduced from 86.9% to 71.7%; serum ceruloplasmin levels decreased from 690 mg/L to 180.6 mg/L; lung high-kV X-ray at 1st review showed that diffuse lung nodules had been absorbed and getting smaller than before treatment; chest CT showed that the distribution and number of small nodules at double lung fields decreased than before treatment.

CONCLUSIONHGF combined with BMSC transplantation may have some potential role for the treatment of silicosis patients.

Adult ; Bone Marrow Transplantation ; Female ; Follow-Up Studies ; Hepatocyte Growth Factor ; therapeutic use ; Humans ; Mesenchymal Stem Cell Transplantation ; Silicosis ; therapy ; Treatment Outcome

OBJECTIVETo summarize the experience of lymph node dissection patterns in hand-assisted laparoscopic radical gastrectomy.

METHODSOne hundred and eleven patients with gastric carcinoma between December 2010 and September 2012 were operated by hand-assisted laparoscopic system designed by us. Clinical data were analyzed retrospectively. The lymph nodes were dissected from left to right together with total tumor resection(reverse lymph nodes scavenge pattern), then digestive tract was reconstructed.

RESULTSTotal gastrectomy, distal gastrectomy and proximal gastrectomy were performed in 57, 46 and 8 cases respectively. Combined cholecystectomy and lateral segment of left liver lobe were needed in 4 and 2 patients respectively, and 1 case underwent combined splenectomy and pancreatic body and tail resection. TNM staging of patients in I(, II(, III(A, III(B, and IIII( were 16, 8, 35, 14, and 38, respectively. Histological type was poorly differentiated in 78 cases, moderate differentiation in 26 cases and good differentiation in 7 cases. The incision length was(6.8±0.3) cm, blood loss was(238.4±113.6) ml, operative time was (171.9±23.3) min, number of removed lymph node was 17.2±5.7, hospital stay was (10.1±3.7) d, postoperative complication rate was 9.0%. One case died during perioperative time.

CONCLUSIONSHand-assisted laparoscopic D2 radical gastrectomy(reverse lymph nodes scavenge pattern) can avoid the multiple conversion of open-laparoscopic operation model, and is beneficial to the standardization for surgical procedure.

Gastrectomy ; Humans ; Laparoscopy ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Staging ; Operative Time ; Postoperative Complications ; Retrospective Studies ; Stomach Neoplasms ; pathology ; surgery

OBJECTIVETo understand the characteristics of embB gene mutation of Mycobacterium tuberculosis (MTB) isolates from tuberculosis patients in Chongqing, and the value of embB306 as a molecular marker used to diagnose ethambutol (EMB)-resistant MTB strains.

METHODSDirect sequencing was used to analyze the polymorphism of embB mutation in 51 EMB-resistant MTB strains and 50 EMB-sensitive MTB strains. And diagnostic testing was used to evaluate the value of embB306 as a molecular marker of EMB -resistant MTB strains as compared with the traditional sensitivity test.

RESULTSAll 34 of 51 EMB-resistant strains (66.7%) and 3 of 51 EMB-sensitive strains (6%) had had embB306 mutation. The embB306 mutation rate in EMB-resistant strains coming from previously treated case was 87.5%, showing significantly higher than that from new cases (48.1%, P < 0.01); embB306 mutation rate was increased with the number of the resistant drugs; embB306 mutation serving as a marker to diagnose EMB-resistant MTB strains comparing with the traditional sensitivity test, had the rate of sensitivity = 66.7%, specificity = 94.0%, accuracy = 80.2% and Youden index = 60.7%.

CONCLUSIONembB306 mutation should be the main mechanism of MTB resistance to EMB in Chongqing, showing an association with the history of the treated and numbers of the resistant drugs. embB306 mutation should be a good marker to diagnose EMB-resistant MTB strains.

China ; DNA Mutational Analysis ; DNA, Bacterial ; genetics ; Genes, Bacterial ; Humans ; Mutation ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; Pentosyltransferases ; genetics ; Tuberculosis, Multidrug-Resistant ; microbiology