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Abstract Background At present there is no effective and accepted therapy for hepatic fibrosis. Transforming growth factor (TGF)-β1 signaling pathway contributes greatly to hepatic fibrosis. Reducing TGF-β synthesis or inhibiting components of its complex signaling pathway represent important therapeutic targets. The aim of the study was to investigate the effect of curcumin on liver fibrosis and whether curcumin attenuates the TGF-β1 signaling pathway. Methods Sprague–Dawley rat was induced liver fibrosis by carbon tetrachloride (CCl4) for six weeks together with or without curcumin, and hepatic histopathology and collagen content were employed to quantify liver necro-inflammation and fibrosis. Moreover, the mRNA and protein expression levels of TGF-β1, Smad2, phosphorylated Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF) were determined by quantitative real time-PCR, Western blot, or immunohistochemistry. Results Rats treated with curcumin improved liver necro-inflammation, and reduced liver fibrosis in association with decreased α-smooth muscle actin expression, and decreased collagen deposition. Furthermore, curcumin significantly attenuated expressions of TGFβ1, Smad2, phosphorylated Smad2, Smad3, and CTGF and induced expression of the Smad7. Conclusions Curcumin significantly attenuated the severity of CCl4-induced liver inflammation and fibrosis through inhibition of TGF-β1/Smad signalling pathway and CTGF expression. These data suggest that curcumin might be an effective antifibrotic drug in the prevention of liver disease progression.

Objective: Clinical practice guidelines can improve healthcare processes and patient outcomes; however, the quality of these guidelines varies greatly in China. The aim of this study was to construct a comprehensive instrument for the appraisal of clinical practice guidelines in China (AGREE-CHINA), and to validate its reliability as a tool for helping potential guideline users in assessing guideline quality., Methods: First, an interdisciplinary working group was established for developing the methods. They also created a checklist as a tool according to the Appraisal of Guidelines, Research and Evaluation II (AGREE II) standards, considering the particularity of Chinese clinical practice. Next, the first draft of AGREE-China was developed by vote, modification, preliminary trial, and cross-verification. To ensure the objectivity, credibility, and reproducibility of the draft assessment, all of the checklists and standards were cross-reviewed fairly widely. Finally, AGREE-CHINA and AGREE II were used to assess the Chinese guidelines published in the past five years, and the results were compared., Results: The presented AGREE-CHINA covered five main checkpoints (science and rigor, effectiveness and safety, economy, usability and feasibility, and conflicts of interest) with each point divided into several more specific checkpoints. Definitions and rationales for each main checkpoint appear in the Appendix. The quality ratings based on the total scores of AGREE-China and AGREE II were consistent ( r = 0.508, P = 0.020). Compared with AGREE II, the study showed a higher level of interrater-reliability for AGREE-CHINA overall (ICC = 0.957, P < 0.001). The mean time required for AGREE-CHINA was less than that for AGREE II; this was approximately 30 minutes for every assessment. User satisfaction was generally high., Conclusions: This paper has presented the first edition of the AGREE-CHINA appraisal tool for clinical guidelines. It is quick and easy to use; it assesses and performs well in comparison to AGREE II. This first version of AGREE-CHINA will require further development and validation., (© 2020 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Aim: To investigate whether the regulation of aquaporin 3 (AQP3) and AQP9 induced by Auphen and dibutyryl cAMP (dbcAMP) inhibits hepatic tumorigenesis., Methods: Expression of AQP3 and AQP9 was detected by Western blot, immunohistochemistry (IHC), and RT-PCR in HCC samples and paired non-cancerous liver tissue samples from 30 hepatocellular carcinoma (HCC) patients. A xenograft tumor model was used in vivo. Nine nude mice were divided into control, Auphen-treated, and dbcAMP-treated groups (n = 3 for each group). AQP3 and AQP9 protein expression after induction of xenograft tumors was detected by IHC and mRNA by RT-PCR analysis. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and histological evaluation were used to detect apoptosis of tumor cells, and the concentration of serum α-fetoprotein (AFP) was measured using RT-PCR and an ELISA kit., Results: The volumes and weights of tumors decreased significantly in the Auphen- and dbcAMP-treated mice compared with the control mice (P < 0.01). The levels of AQP3 were significantly lower in the Auphen treatment group, and levels of AQP9 were significantly higher in thedbcAMP treatment mice than in the control mice (P < 0.01). The reduction of AQP3 by Auphen and increase of AQP9 by dbcAMP in nude mice suppressed tumor growth of HCC, which resulted in reduced AFP levels in serum and tissues, and apoptosis of tumor cells in the Auphen- and dbcAMP-treated mice, when compared with control mice (P < 0.01). Compared with para-carcinoma tissues, AQP3 expression increased in tumor tissues whereas the expression of AQP9 decreased. By correlating clinicopathological and expression levels, we demonstrated that the expression of AQP3 and AQP9 was correlated with clinical progression of HCC and disease outcomes., Conclusion: AQP3 increases in HCC while AQP9 decreases. Regulation of AQP3 and AQP9 expression by Auphen and dbcAMP inhibits the development and growth of HCC.

Objective: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with pancreatic cancer, but the published studies had yielded inconsistent results.We therefore performed the present meta-analysis., Methods: A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012 was conducted to summarize associations of MTHFR polymorphisms with pancreatic cancer risk. Assessment was with odds ratios (ORs) and 95% confidence intervals (CIs). Publication bias were also calculated., Results: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were involved in this meta-analysis. Overall, C667T(TT vs. CC:OR=1.61, 95%CI=0.78-3.34; TT vs. CT:OR=1.41, 95%CI=0.88-2.25; dominant model: OR=0.68, 95%CI=0.40-1.17; recessive model: OR=0.82, 95%CI=0.52-1.30) and A1298C(CC vs. AA:OR=1.01, 95%CI=0.47-2.17; CC vs. AC:OR=0.99,95%CI=0.46-2.14; dominant model: OR=1.01, 95%CI=0.47-2.20; recessive model: OR=1.01, 95%CI=0.80-1.26) did not increase pancreatic cancer risk., Conclusion: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) were not associated with pancreatic cancer risk.

Aim: To evaluate the efficacy of 6 noninvasive liver fibrosis models and to identify the most valuable model for the prediction of liver fibrosis stage in chronic hepatitis B (CHB) patients., Methods: Seventy-eight CHB patients were consecutively enrolled in this study. Liver biopsy was performed and blood serum was obtained at admission. Histological diagnosis was made according to the METAVIR system. Significant fibrosis was defined as stage score > or = 2, severe fibrosis as stage score > or = 3. The diagnostic accuracy of 6 noninvasive liver fibrosis models, including serum aspartate aminotransferase (AST) to platelet ratio index (APRI), FIB-4, Forn's index, Fibrometer, Hepascore, and Shanghai Liver Fibrosis Group's index (SLFG), was investigated., Results: The APRI, FIB-4 and Forn's index under receiver operating characteristic curve (AUROC) for significant fibrosis were 0.71, 0.75 and 0.79, respectively, with a diagnosis accuracy of 67%, 77% and 80%, respectively, and 0.80, 0.87 and 0.86, respectively, under the AUROC for severe fibrosis. The Hepascore, SLFG, and Fibrometer were 0.80, 0.83 and 0.85, respectively under the AUROC for significant fibrosis (P < 0.01). The diagnosis accuracy of Hepascore and SLFG was 86% and 88%, respectively. The Hepascore, SLFG, and Fibrometer were 0.95, 0.93, and 0.94, respectively, under the AUROC for severe fibrosis (P < 0.01)., Conclusion: The models containing direct serum markers have a better diagnostic value than those not containing direct serum markers.

Objective: To screen highly efficient small interfering RNA (siRNA) targeting human cyclooxygenase-2 (hCOX-2) mRNA on human rheumatoid arthritis synovial fibroblasts (RASF) and to further study the impact there on prostaglandin E2 (PGE2) and cytokines, such as interleukin-1beta (IL-1beta), interleukin-6 (IL-6), timorous necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF)., Methods: 4 lines of COX-2 mRNA siRNA (1(#) - 4(#) siRNA) were designed and transfected into the fibroblasts from the synovial membrane of a patient with rheumatoid arthritis (RASF). Phorbol ester was added 4 hours later. A scrambled line (NC) group and a blank control (CTL) group were used. RT-PCR and Western blot ting were used to detect the mRNA and protein expression of COX-2 36 and 48 hours after transfection. The levels of PGE2, IL-1beta, IL-6, TNF-alpha, and VEGF were measured by ELISA., Results: RT-PCR showed that the absorbance ratios of the positively interfering groups, NC, and 1(#) - 3(#) siRNA groups, to CTL group were 0.72, 0.3, 0.25, 0.4, and 0.04 respectively. The ratios of the positively interfering groups to CTL group were 1.04, 0.52, 0.39, 0.9, and 36 h after transfection and 1.05, 0.52, 0.51, 0.9, and 0.15 respectively 48 h after transfection. The levels of PGE2, IL-1beta, IL-6, TNF-alpha, and VEGF in the culture supernatant were lower in the 4(#) siRNA group than in other groups 24, 36, and 48 h after transfection. The death rates of RASF of all trial groups were within the range of 9% - 11% and there were not statistically significant differences between the CTL group and the siRNA groups or between the 4(#) siRNA and other siRNA groups., Conclusion: 4(#) siRNA effectively inhibits the expression of COX-2 mRNA and protein the level of PGE2, IL-1beta, IL-6, TNF-alpha, and VEGF in the clear supernatant of the 4(#) group is lowest.

Objective: To study the effects of Fuzheng Huayu Decoction on plasma proteome in cirrhosis., Methods: Twenty-six male S-D rats were randomly divided into three groups, cirrhotic model group (n = 10), treated with CCl4 (CCl4/olive oil: v/v = 1:1), Fuzheng Huayu Decoction intervention group (n = 10), treated with CCl4 + Fuzheng Huayu Decoction, and normal control group (n = 6), treated with olive oil only. After 8 weeks, blood sample was collected from the vena cava inferior to undergo bi-dimensional electrophoresis (2DE) and analysis by PDQuest 7.3 software. Differential protein spots were cut, enzyme hydrolysis was conducted, and peptide fragments extracted from the mixture underwent mass spectrometry with MALDI-TOF-TOF-MS. The liver fibrogenesis was assessed by digital image analysis instrument of Masson's trichrome stained sections., Results: The fibrosis area of the Fuzheng Huayu Decoction was 9% +/- 4%, significantly smaller than that of the cirrhotic model group (12% +/- 5%, P < 0.05). Ten markedly changed protein spots were identified by MALDI-TOF-TOF-MS. Eight of the 10 proteins, including plasma glutathione peroxidase, plasma glutathione peroxidase precursor, prealbumin, haptoglobin, apolipoprotein A-IV precursor, complement C4, inter-alpha-inhibitor H4 heavy chain, and serine/threonine-protein kinase MARK1 (microtubule- affinity regulating kinase 1) were expressed very lowly in the cirrhotic model group while were expressed highly in the Fuzheng Huayu Decoction group. The expression of liver regeneration-related protein LRRG03 and vimentin increased in the cirrhotic model group, and reduced in the Fuzheng Huayu Decoction group., Conclusion: Some proteins related to oxidative stress, cell proliferation and transformation have changed in the plasma of cirrhosis induced by CCl4. Fuzheng Huayu Decoction promotes protein synthesis and plays an anti-fibrotic role by antioxidation and accommodation of cell proliferation and transformation.

Aim: To evaluate the efficacy and safety of tegaserod, 6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China., Methods: This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatment-free baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients' daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs)., Results: A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303). Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo (1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase > or = 1 CSBM/wk over wk 1-4 (47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018) and for the absolute number of > or = 3 CSBMs/wk over wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%)., Conclusion: Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile.

Aim: To determine the radiosensitizing potential of docetaxel in human hepatocellular carcinoma SMMC-7721 cells and its mechanisms., Methods: SMMC-7721 cells were incubated with docetaxel at 0.125, 0.25, and 0.5 nmoL/L for 24 h and at 0.125 and 0.25 nmol/L for 48 h before irradiation. Radiation doses were given from 0 to 10 Gy. Cell survival was measured by a standard clonogenic assay after a 9-d incubation. The reactive oxygen species (ROS) and glutathione (GSH) are detected after being given the same dose of docetaxel for the same time., Results: The sensitization enhancement ratios (SER) for SMMC-7721 cells determined at the 50% survival level were 1.15, 1.21 and 1.49 at 0.125, 0.25, and 0.5 nmol/L for pre-incubation of 24 h, respectively; the SER were 1.42, 1.67 at 0.125 and 0.25 nmol/L, for pre-incubation of 48 h, respectively. The ROS of SMMC-7721 cells increased and GSH decreased after pretreatment with the same doses of docetaxel for 24 or 48 h., Conclusion: A radiosensitizing effect of docetaxel could be demonstrated unambiguously in this cell line used. In addition, our data showed that the mechanism of radiopotentiation by docetaxel probably does not involve a G2/M block in SMMC-7721 cells, and ROS generation and GSH deletion may play a key role in the radiosensitizing effect of docetaxel.

Objective: To evaluate the antifibrotic effect of receptor-mediated sterical stability liposome (SSL) targeting hepatic stellate cells (HSCs) and containing recombinant human interferon-alpha 1b (IFNalpha-1b) on hepatic cirrhosis., Methods: The ligand, cyclo (RGD) with specific affinity to HSCs, was incorporated via PEG into the lipid bilayers of SSL. Forty male SD rats were randomly divided into 4 equal groups: liver fibrosis model group undergoing double ligation and cutting of the common bile duct (BDL group), BDL + IFN-SSL group, undergoing BDL and injection of IFN 50,000 IU per week via caudal vein for 4 times; IFN-RGD-SSL treatment group, undergoing BDL and injection of IFN-RGD-SSL (equal to 50,000 IU per week) via caudal vein for 4 times; and sham operation group used as control. The rats were killed 24 hours after the last injection. Their livers and serum samples were collected. Pathological changes of the liver were observed with HE and alpha-SMA immunohistochemical staining. Biochemical automatic analyzer was used to test the serum indices of liver function: ALT, AST, total bilirubin (TBIL), alkaline phosphatase, and gamma-glutamine (gamma-GT). Radioimmunoassay method was used to examine the s serum index of liver fibrosis: HA, procollagen III (PCIII), LN, and CIV. Colorimetry was used to examine the level of hydroxyl proline (Hyp). RT-PCR was used to detect the mRNA expression of type I collagen. Western blotting was used to examine the protein expression of alpha-SMA of HSC., Results: Compared with the control group, liver fibrosis was seen in the other 3 groups, especially in the BDL group. In comparison with the sham operation group, the levels of serum indices of liver fibrosis, liver hydroxyl proline content, and expression of type I collagen mRNA and alpha-SMA protein in liver were significantly higher in the other groups (all P < 0.05), being significantly lower in the BDL + IFN-RGD-SSL group than in the BDL + IFN-SSL group (all P < 0.05)., Conclusion: The receptor-mediated IFN-RGD-SSL displays good targeting antifibrotic effects on liver fibrosis.

Objective: To explore the Helicobacter pylori (Hp) infection status in Shanghai and its risk factors., Methods: A questionnaire survey including 60 items related to Hp was conducted among 1925 persons, 976 males (50.7%) and 949 females (49.3%), aged 37 +/- 11 (15 approximately 72), selected by cluster sampling in 12 rural and urban areas in Shanghai. Peripheral blood was collected to detect Hp IgG antibody so as to evaluate the past infection status and (14)C urea breath test (UBT) was performed so as to evaluate the present infection status. Fecal Hp antigen test was done in the subjects under 18 years of age., Results: 1822 of the 1925 subjects (94.6%) underwent the 3 tests. were followed antibody detection and (14)C UBT and response with questionnaires. The Hp infection rate was 66.4% in general, and 68.4% in the females, somehow higher than in the males (64.3%, P = 0.067). The infection rate was different in different age groups, was the lowest in the age group of 15 approximately 19 (44.4%) and the highest 70% in age group of 20 approximately 30 (70%), then somewhat lower and gradually became higher. Socio-economic status was related to Hp infection. Hp infection was related with such factors as eating raw vegetables and fruits, and never washing raw vegetables and fruits before eating. The knowledge rate about Hp infection was only 33.2% among the respondents. Only 23.8% of the respondents knew well the transmission route of Hp., Conclusion: Hp infection rate is rather high in Shanghai. Hp infection is related to socio-economic status, and family dietary and sanitary habits.