Ambroxol alleviates ventilator-induced lung injury by inhibiting c-Jun expression.

OBJECTIVE: Ventilator-induced lung injury (VILI) remains a challenge. This study was designed to investigate the effects of ambroxol on VILI and the underlying mechanisms in a rodent model. MATERIALS AND METHODS: Male Wistar rats weighing 310-380 g were divided into four groups (n=8 per group): 1) saline only, 2) ventilation plus saline, 3) ventilation plus ambroxol (2 mg/kg), and 4) ventilation plus ambroxol (50 mg/kg). Rats in groups 1 and 2 were treated (i.p.) with 2.5 ml of saline once a day for six days and last injected 1 h prior to tracheotomy. Rats in groups 3 and 4 received ambroxol on the same schedule. Rats were ventilated for 90 minutes at a tidal volume (VT) of 30 ml/kg. The expression levels of c-Jun, a component of activator protein-1 (AP-1), and gamma-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme in the synthesis of glutathione (gamma-glutamyl-cysteinyl-glycine, GSH), an endogenous antioxidant, were measured with immunohistochemical staining and in situ hybridization. Both AP-1 and GSH are involved in VILI. RESULTS: Ambroxol at 50 mg/kg inhibited ventilation-induced lung inflammation, significantly elevated the ventilation-induced down-regulation of γ-GCS mRNA and protein, and significantly decreased the ventilation-induced up-regulation of c-Jun mRNA and protein. It has been reported that reactive oxygen species (ROS) can activate AP-1, leading to the production of pro-inflammatory cytokines and lung inflammation. CONCLUSIONS: Ambroxol increases γ-GCS to promote GSH production, which in turn, inhibits ROS-dependent AP-1 activation and inflammation.

The SNORA21 expression is upregulated and acts as a novel independent indicator in human gastric cancer prognosis.

OBJECTIVE: Emerging evidence indicates that small nucleolar RNAs (snoRNAs) act crucial roles in oncogenesis. Herein, the aim of this study is to investigate the clinical value of SNORA21 expression in gastric cancer (GC). PATIENTS AND METHODS: The expression of SNORA21 was determined in 79 cases of GC tissues and adjacent normal tissues by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis. The association between SNORA21 expression and clinicopathological features was analyzed by the chi-square test. The survival curves were calculated by the Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were used to assess the prognostic value of SNORA21 expression. RESULTS: Our results first demonstrated that SNORA21 expression was significantly upregulated in human GC tissues and cells compared to their corresponding adjacent normal tissues and GES-1 cells, respectively (p<0.05). Furthermore, elevated SNORA21 expression was significantly associated with distant metastasis (p<0.05) and lymph node metastasis (p<0.05) in GC patients. Kaplan-Meier survival plots demonstrated that higher SNORA21 expression was associated with poor disease-free survival (DFS) and overall survival (OS) rate, respectively. Univariate analysis and multivariate regression analysis indicated that a higher SNORA21 was an independent risk factor for prognosis in GC patients. CONCLUSIONS: The current results indicate that SNORA21 expression may be served as a predictor of GC prognosis.

[Efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin in Asian adult patients with chronic HCV genotype 1b infection and compensated cirrhosis].

Objective: To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. Methods: An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. Results: A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. Conclusion: Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

Genetic variability of XRCC1 influences the treatment outcome of gastric cancer.

We aimed to investigate the role of XRCC1 codon 194 (Arg>Trp), 280 (Arg>His), and 399 (Arg>Gln) polymorphisms in response to chemotherapy and the overall survival of gastric cancer patients. A total of 172 patients were recruited for our study between January 2010 and March 2012. Genotyping of the three XRCC1 codons was carried out by restriction fragment length polymorphism polymerase chain reaction. By logistic regression analysis, we found that the Trp/Trp genotype of XRCC1 194 (Arg>Trp) showed a stronger association with complete or partial response to chemotherapy compared to the Arg/Arg genotype, and the adjusted odds ratio (95%CI) was 0.17 (0.05-0.58). Moreover, the Trp/Trp genotype was associated with a higher risk of death than that with the Arg/Arg genotype based on multivariate Cox proportional hazard regression analysis, and the adjusted hazard ratio (95%CI) was 4.08 (1.20-14.19). In conclusion, we found that the XRCC1 194 (Arg>Trp) polymorphism was correlated with a better response to chemotherapy and a low risk of death in patients with gastric cancer.

Impact of enteral nutrition on postoperative immune function and nutritional status.

We studied the effects of enteral nutrition (EN) support initiated 1 week before surgery on postoperative nutritional status, immune function, and inflammatory response in gastric cancer patients. A total of 200 gastric cancer patients were randomly divided into two groups: EN starting 1 week before surgery (study group) and EN starting early after surgery (control group). The two groups received EN support, following different therapeutic schedules, until the 9th day after operation. In the patients, body weight, skinfold thickness, upper-arm circumference, white blood cell count, albumin, prealbumin, C-reactive protein, peripheral immunoglobulins (IgA, IgG, and IgM), T lymphocyte subsets, interleukin-6, and tumor necrosis factor-α were measured 10 days before and after surgery and on the first day after surgery. There was no statistically significant difference in the results of recovery time of passage of gas by anus, abdominal distension, stomachache, blood glucose, hepatic and renal functions, and electrolytes between the two groups of patients (P > 0. 05). Adverse reactions occurred to both groups at 1 and 2 days after operation. Such conditions was improved after the intravenous drip rate was adjusted. The albumin and prealbumin levels of the patients in both groups decreased at 1 day after operation (P < 0. 05). The levels rose when the research was finished (P < 0. 05). The prealbumin level of the study group was higher than that of the control group at 10 days after operation (P < 0. 05). The IgG level of the study group was higher than that of the control group at 10 days after operation (P < 0. 05). The two groups of inflammatory reaction indicators of the study group were lower than those of the control group at 10 days after operation (P < 0. 05). This study indicates that appropriate preoperative EN support for gastric cancer patients can improve their postoperative nutritional status and immune function, can reduce inflammatory response, and is more conducive to the recovery of patients.