Diagnostic Potential of microRNA-122 for Stage Classification in Patients with HBV-Related Cirrhosis.

Objective: Previous studies have suggested that microRNA-122 has a relatively high diagnostic value for chronic viral hepatitis detection. In this study, we evaluated the diagnostic value of serum microRNA-122 in different stages of HBV-related cirrhosis，and serum microRNA-122 may serve as a potential biomarker for staging HBV related cirrhosis patients.. Methods: A total of 80 patients with HBV-related cirrhosis were included. Patients were characterized according to Child-Pugh score, laboratory parameters, and complications, and divided into compensated cirrhosis group and decompensated cirrhosis group. Wherein, the compensatory group for liver cirrhosis includes 21 patients, the compensatory group has 59 patients. Blood was collected from all patients, and RT-qPCR analyzed the expression levels of microRNA-122. Results: Serum microRNA-122 was decreased, while Child-Pugh score, Meld score, Prothrombin time, total bilirubin, and Direct bilirubin were higher in a decompensated group compared to the compensated group (all P < .05). For further stage classification, the mean serum microRNA-122 level was higher in stage 1 (11.3±5.1, compensated cirrhosis) compared to stage 2~5 (8.5±4.2, 4.9±1.0, 4.7±1.6, 3.5±1.1, decompensated cirrhosis, all P < .05). The expression of serum microRNA-122 independent of Child-Pugh score and complications, including ascites, varices, HCC (P > .05).However it was affected by Meld score and Prothrombin time (P < .05). Moreover, ROC analysis indicated microRNA-122 could differentiate compensated HBV-related cirrhosis (0.97 of AUC, P < .01). Furthermore, it could differentiate patients in stage 1 (compensated cirrhosis without esophageal varices) from HBV-related cirrhosis (0.91 of AUC, P < .01), with a sensitivity of 77.8% and satisfactory specificity of 88.7%. The significance of the relationship between the decrease in serum microRNA-122 levels and the stage of liver cirrhosis will be beneficial. Conclusion: Our results strongly support the diagnostic value of serum microRNA-122 as a potential biomarker of stage classification in patients with HBV-related cirrhosis, which could facilitate risk stratification and careful management. Provide new biomarkers for the diagnosis of patients with hepatitis B cirrhosis.

Influences of biochar with selenite on bacterial community in soil and Cd in peanut.

Cadmium (Cd) pollution in crops seriously affects the ecosystem and human health. Effective measures should be employed to reduce the absorption and accumulation of cadmium in crops. Currently, there are many pieces of research on the application of biochar (BC) and selenium (Se) alone to the remediation of soil Cd pollution; however, few investigations have been devoted to the application of BC and Se together to the remediation of soil Cd pollution. The peanut was taken as the target crop to explore the effects of exogenous selenium and biochar on the remediation of soil Cd pollution. The response of the soil bacterial community to two levels of Cd concentration and its relationship with soil properties and Cd availability are methodically investigated. This study sets two cadmium pollution concentrations of low Cd (5 mg/ kg) and high Cd (20 mg/kg), as well as six treatments: blank, BC, soil Se, soil Se-BC, leaf Se, and leaf Se-BC. The achieved results revealed that both Se and BC could noticeably enhance the yield of peanut seeds and reduce the Cd content in peanut seeds. Among them, Se-BC treatment on soil exhibits the most influence, which reduces the Cd content by 47.86%. Se and BC also affect the physical and chemical properties of soil and remarkably magnify the content of soil available phosphorus, organic matter, soil pH, and soil conductivity. For instance, then effect is detected in the case of applying selenium biochar to soil, leading to an increase of about 64.38%, 72.62%, 2.64%, and 61.15%, respectively, and reducing the content of soil available cadmium by 21.02%. Redundancy analysis confirms that these properties enhance the abundance of dominant bacteria Actinobacteria, Proteobacteria, and Chloroflexi. The correlation analysis also indicates that Saccharimonadales, Bacillus, Arthrobacter, and other bacteria with the function of reducing the bioavailability of cadmium in soil reveal a considerable positive correlation with the variations of physical and chemical properties. In general, exogenous Se and BC incorporate to drop the content of available Cd in the soil through direct passivation, passivation caused by soil environmental change, and passivation caused by altering the soil microbial community structure; as a result, the migration and enrichment of Cd in peanut seeds are blocked and reduced. Moreover, the mixed application of BC and soil Se exhibits the best effect.

Genes related to osmoregulation and antioxidation play important roles in the response of Trollius chinensis seedlings to saline-alkali stress.

Saline-alkali stress is one of the main abiotic stress factors affecting plant growth and development. Trollius chinensis is a perennial herbal medicinal plant with high values for garden application. However, its response and tolerance to saline-alkali stress is unclear. In this study, we mixed four salts (NaCl: Na2SO4: NaHCO3: Na2CO3) with a concentration ratio of 1:9:9:1, and applied low (40 and 80 mM) and high (120 and 160 mM) saline-alkali stress to analyze osmotic regulation substances, antioxidant systems and the gene expression of T. chinensis. Along with higher saline-alkali stress, the leaf relative water content (RWC) started to decrease only from high stress, while the malondialdehyde (MDA) content in leaves decreased continuously, and the contents of proline (Pro), soluble sugar (SS) and soluble protein (SP) increased compared with control. The activities of antioxidant enzymes and the contents of non-enzymatic antioxidants were increased positively with the accumulation of superoxide anion (O2 •-) and hydrogen peroxide (H2O2). For instance, the ascorbic acid-glutathione (AsA-GSH) cycle was enhanced in T. chinensis seedling leaves subject to saline-alkali stress. Principal Component Analysis (PCA) indicates that MDA, Pro, SS, SP, H2O2, O2 •-, and GSH are important indexes to evaluate the response and tolerance of T. chinensis to saline-alkali stress. Through RNA-Seq, a total of 474 differentially expressed genes (DEGs) were found in plant under low saline-alkaline stress (40 mM, MSA1) vs. control. Among them, 364 genes were up-regulated and 110 genes were down-regulated. DEGs were extensively enriched in carbohydrate transport, transferase activity, zeatin biosynthesis, ABC transporters, and spliceosome. The transcription factor family MYB, BZIP, WRKY, and NAC were related to its saline-alkali tolerance. In addition, some DEGs encode key enzymes in the processes of osmoregulation and antioxidation, including betaine aldehyde dehydrogenase (BADH), inositol monophosphatase (IMP), chloroperoxidase (CPO), thioredoxin (Trx), and germin-like protein (GLPs) were found. Overall, these findings provide new insights into the physiological changes and molecular mechanism of T. chinensis to saline-alkali stress and lay a foundation for application of T. chinensis in saline-alkali environment.

Advances in the Development Ubiquitin-Specific Peptidase (USP) Inhibitors.

Ubiquitylation and deubiquitylation are reversible protein post-translational modification (PTM) processes involving the regulation of protein degradation under physiological conditions. Loss of balance in this regulatory system can lead to a wide range of diseases, such as cancer and inflammation. As the main members of the deubiquitinases (DUBs) family, ubiquitin-specific peptidases (USPs) are closely related to biological processes through a variety of molecular signaling pathways, including DNA damage repair, p53 and transforming growth factor-ß (TGF-ß) pathways. Over the past decade, increasing attention has been drawn to USPs as potential targets for the development of therapeutics across diverse therapeutic areas. In this review, we summarize the crucial roles of USPs in different signaling pathways and focus on advances in the development of USP inhibitors, as well as the methods of screening and identifying USP inhibitors.

Ten-Day Quadruple Therapy Comprising Low-Dose Rabeprazole, Bismuth, Amoxicillin, and Tetracycline Is an Effective and Safe First-Line Treatment for Helicobacter pylori Infection in a Population with High Antibiotic Resistance: a Prospective, Multicenter, Randomized, Parallel-Controlled Clinical Trial in China.

The objective of this study was to investigate the efficacy and safety of 10-day bismuth quadruple therapy with amoxicillin, tetracycline, or clarithromycin and different doses of rabeprazole for first-line treatment of Helicobacter pylori infection. This multicenter, randomized, parallel-controlled clinical trial was conducted between March 2013 and August 2014. A total of 431 H. pylori-infected patients with duodenal ulcers were enrolled and randomized into four treatment groups (1:1:1:1) for 10 days, as follows: (i) a group receiving a low dose of rabeprazole of 10 mg twice a day (b.i.d.) (LR dose) plus bismuth, amoxicillin, and clarithromycin (LR-BAC); (ii) a group receiving LR plus bismuth, amoxicillin, and tetracycline (LR-BAT); (iii) a group receiving a high dose of rabeprazole of 20 mg b.i.d. (HR dose) plus bismuth, amoxicillin, and clarithromycin (HR-BAC); and (iv) a group receiving HR-BAT. Antimicrobial susceptibility was assessed by the Etest method. The primary outcome was H. pylori eradication at 4 weeks after the treatment. The per-protocol (PP) eradication rates in the LR-BAC, LR-BAT, HR-BAC, and HR-BAT groups were 94.1%, 91.9%, 94.8%, and 91.9%, respectively, while the intention-to-treat (ITT) eradication rates in those groups were 87.2%, 87.2%, 87.7%, and 86%, respectively. There was no significant difference between the four groups in PP analysis (P = 0.799) and ITT analysis (P = 0.985). The efficacies of four-treatment therapy were not affected by antibiotic resistance. The adverse events in the four treatment groups were similar; central nervous system (CNS) and gastrointestinal symptoms were the most common reported. Bismuth-containing quadruple therapy with low-dose rabeprazole, amoxicillin, and tetracycline is a good option for first-line treatment of H. pylori infection in a population with high antibiotic resistance. (This study is registered at Chinese Clinical Trials Registry [www.chictr.org.cn] under number ChiCTR1800014832.).

Endoscopic cyanoacrylate injection with or without lauromacrogol for gastric varices: A randomized pilot study.

BACKGROUND AND AIM: Current guidelines recommend injection of cyanoacrylate as first-line therapy to prevent gastric variceal rebleeding. The method still poses a risk of ectopic embolism, which possibly correlates with the volume of cyanoacrylate used. In this trial, we evaluated the short-term efficacy and safety of tissue adhesive injection combined with lauromacrogol for treating gastric varices. METHODS: Patients admitted to our hospital for variceal hemorrhage were enrolled and blindly randomized into two treatment groups: lauromacrogol group (lauromacrogol-cyanoacrylate-lauromacrogol) and lipiodol group (lipiodol-cyanoacrylate-lipiodol). Patient follow-up was 6 months. Primary outcome was rebleeds, and secondary outcomes were mortality, gastric varices eradication, and treatment-related adverse events. RESULTS: Between March 6, 2013 and October 16, 2013, 96 patients met the criteria. Two cases were lost to follow-up, and all treated cases were successful. No procedural-related adverse events were observed in either group. Cyanoacrylate volumes used in the lauromacrogol group were significantly less than those of the lipiodol group (0.9 ± 0.5 vs 2.0 ± 1.2 mL, P = 0.000). Eleven patients developed upper gastrointestinal rebleeding, which did not show significant difference between groups. On multivaritate analysis, portal venous thrombosis and fever were potential risk factors of rebleeding. Treatment failure, complications, gastric varices obturation, and survival did not differ between the two groups. CONCLUSION: Tissue adhesives combined with lauromacrogol is a safe therapeutic option for gastric varices, with comparably less cyanoacrylate volume used. Because of the small number of study patients, it cannot be proven to have better efficacy than without lauromacrogol. Multicenter studies with larger patient groups are necessary.

[Clinical study of teicoplanin in the treatment of patients with gram-positive cocci: the Chinese experience].

OBJECTIVE: To evaluate the efficacy and safety of Teicoplanin (TEC) in the treatment of Chinese patients with moderate and severe Gram positive (G(+)) coccus infections. METHODS: A prospective, multicenter, non-comparator control, open-label drug clinical trial of phase IV was conducted. RESULTS: Totally 156 cases with established and highly suspected G(+) coccus infections are enrolled. Mean age was 53.6 +/- 20.9 (9-93). The infections included: lower respiratory tract infections (66.0%), sepsis (9.0%), catheters-associated infections (5.1%), endocarditis (1.9%), leucopenia with fever (14.1%), bone-joint infections (1.3%), skin-soft tissue infections (7.7%), and other infections (10.9%). Eighty seven point eight percent of the patients suffered from severe underlying diseases, 28.2% (44/156) had immunocompromised conditions. 69.2% had received antibiotics previously (57.4% with cephalosporins and 28.7% with carbapenem, respectively). One hundred and thirty strains of G(+) cocci were isolated from 123 patients (78.8%). Among them methicillin-resistant Staphylococcus aureus (MRSA) accounted for 90.7% (49/54) and methicillin-resistant coagulase-negative Staphylococcus (MRCNS) 88.2% (30/34). The TEC susceptibility test for 105 strains showed that all of the Staphylococci and Enterococci were susceptible. In 121 strains tested for vancomycin, all of the Staphylococci but only 78.3% (18/23) of the Enterococci were susceptible. There were 18 strains of Gram negative bacilli and 1 strain of Candida A. isolated concomitantly with G(+) cocci from 17 cases. The total clinical effectiveness was 82.1% by ITT (156 cases) analysis and 85.2% by PP (135 cases) analysis, respectively. Bacteriologic eradication rate was 87.7%. Thirty three patients with negative culture result were empirically treated with TEC and had 96.8% of clinical effectiveness. The efficacy of TEC to different infections was similar. The total adverse effects, such as decrease in blood cells and transient abnormal liver functions, accounted only for 1.28%. CONCLUSIONS: Teicoplanin was a very effective antibiotic for G(+) coccus infections and safe for patients. In highly suspected infections with methicillin-resistant Staphylococci or Enterococci, TEC may be a choice for initial empirical treatment.

[Cost-effective analysis of preventive treatment on diabetes].

OBJECTIVE: To evaluate the cost-effectiveness of preventive treatment on diabetes, using metformin or acarbose among patients with impaired glucose tolerance. METHODS: Using data from diabetes prevention program (DPP) and STOP-NIDDM study, we evaluated the cost of preventing one new onset of diabetes in Shanghai, and to compare its cost with the current treatment cost. RESULTS: If metformin was used for preventive treatment as in DPP study, a total cost of 69 122.95RMB was needed for preventing one new onset of diabetes in three years period. If acarbose was used for preventive treatment as in STOP-NIDDM, then 154 116.05RMB was the cost to prevent one diabetes in 3.3 years of treatment. However, if the generic metformin was used, the total cost was only 21 666.63RMB for the 3-years treatment. Data showed that the average cost for treating diabetes per year was 9143.70RMB in Shanghai. CONCLUSION: The total cost of diabetes prevention was formidable, although generic metformin showed the trend of cost-effective. The cost of drugs took the biggest part of the total cost. To choose the cheap but effective drug for treatment might save a large part of the cost. Further clinical research concerning the prevention of complications might provide us with more information on the cost-effectiveness of preventive treatment on diabetes.