Syndrome of liver depression and spleen deficiency is a primary TCM syndrome of response to entecavir + FuZheng HuaYu in patients with HBV-related liver fibrosis.

Objective: Although clinical studies have found that Chinese patent medicine FuZheng HuaYu tablet/capsule can promote the reversal of HBV-related liver fibrosis, not all sufferers have histopathological responses. This study aims to explore the correlation between traditional Chinese medicine (TCM) syndromes and response to entecavir + FuZheng HuaYu (ETV + FZHY) in patients with HBV-related liver fibrosis. Methods: This a multi-center cross-sectional study. According to the different treatment strategies that sufferers have ever received, a total of 437 cases were included and divided into ETV + FZHY group and ETV + placebo group. And based on the relevant efficacy determination criteria, the two groups were subdivided into efficacy responders and non-responders. Then, TCM clinical questionnaire information of these patients were collected for subsequent analysis to acquire relevant syndrome elements and TCM syndromes. Results: No matter what group was, the first three frequency of TCM pathological position in efficacy responders were as follows: Liver > Spleen > Stomach (TCM concepts). As for the ETV + FZHY group, the first three frequency of pathological nature was ranked as Qi deficiency > Dampness > Heat. Compared with the non-responders, the frequency of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation was significantly increased in the efficacy responders (P < 0.05). In terms of TCM syndromes, the frequency increase of Syndrome of liver depression and spleen deficiency (LDSD), in the efficacy responders, changed more obviously than the non-responders (Chi2 = 6.32, P = 0.0006). Conclusions: TCM syndrome elements of Spleen, Stomach, Qi deficiency, Heat, and Qi movement stagnation were closely associated with efficacy responders with HBV-related liver fibrosis in the ETV + FZHY group. Moreover, LDSD was a primary TCM syndrome in these responders.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet.

BACKGROUND: After receiving entecavir or combined with FuzhengHuayu tablet (FZHY) treatment, some sufferers with hepatitis B virus (HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen. Serum metabolomics at baseline in these patients who were effective in treatment remain unclear. AIM: To explore baseline serum metabolites characteristics in responders. METHODS: A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited. First, all subjects were divided into training set and validation set. Second, the included patients were subdivided into entecavir responders (E-R), entecavir no-responders (E-N), FZHY + entecavir responders (F-R), and FZHY + entecavir no-responders (F-N) following the pathological histological changes after 48 wk' treatments. Then, Serum samples of all subjects before treatment were tested by high performance liquid chromatography-tandem mass spectrometry (LC-MS) high-performance LC-MS. Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis. Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression. RESULTS: As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N, results showed that 4 pathways including linoleic acid metabolism, aminoacyl-tRNA biosynthesis, cyanoamino acid metabolism, alanine, aspartate and glutamate metabolism were screened out. As for the differential metabolites, these 7 intersected metabolites including hydroxypropionic acid, tyrosine, citric acid, taurochenodeoxycholic acid, benzoic acid, 2-Furoic acid, and propionic acid were selected. CONCLUSION: Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Mechanism of liver regeneration: 20-year bibliometric analyses.

Objectives: The study aims to explore the most influential countries, institutions, journals, authors, "research hotspots," and trends in the study of the mechanism of liver regeneration (MoLR) in the last 20 years using bibliometric analyses. Methods: The literature associated with the MoLR was retrieved from the Web of Science Core Collection on 11 October 2022. CiteSpace 6.1.R6 (64-bit) and VOSviewer 1.6.18 were used for bibliometric analyses. Results: A total of 18,956 authors from 2,900 institutions in 71 countries/regions published 3,563 studies in different academic journals on the MoLR. The United States was the most influential country. The University of Pittsburgh was the institution from which most articles on the MoLR were published. Cunshuan Xu published the most articles on the MoLR, and George K. Michalopoulos was the most frequently co-cited author. Hepatology was the journal in which most articles on the MoLR were published and the most frequently co-cited journal in this field. The research hotspots for the MoLR were origin and subsets of hepatocytes during LR; new factors and pathways in LR regulation; cell therapy for LR; interactions between liver cells in LR; mechanism of the proliferation of residual hepatocytes and trans-differentiation between cells; and prognosis of LR. The emerging topic was the mechanism of regeneration of a severely injured liver. Conclusion: Our bibliometric analyses provide (i) a comprehensive overview of the MoLR; (ii) important clues and ideas for scholars in this field.

Tbx5 overexpression in embryoid bodies increases TAK1 expression but does not enhance the differentiation of sinoatrial node cardiomyocytes.

Genetic studies place Tbx5 at the apex of the sinoatrial node (SAN) transcriptional program. To understand its role in SAN differentiation, clonal embryonic stem (ES) cell lines were made that conditionally overexpress Tbx5, Tbx3, Tbx18, Shox2, Islet-1, and MAP3k7/TAK1. Cardiac cells differentiated using embryoid bodies (EBs). EBs overexpressing Tbx5, Islet1, and TAK1 beat faster than cardiac cells differentiated from control ES cell lines, suggesting possible roles in SAN differentiation. Tbx5 overexpressing EBs showed increased expression of TAK1, but cardiomyocytes did not differentiate as SAN cells. EBs showed no change in the expression of the SAN transcription factors Shox2 and Islet1 and decreased expression of the SAN channel protein HCN4. EBs constitutively overexpressing TAK1 direct cardiac differentiation to the SAN fate but have reduced phosphorylation of its targets, p38 and Jnk. This opens the possibility that blocking the phosphorylation of TAK1 targets may have the same impact as forced overexpression. To test this, we treated EBs with 5z-7-Oxozeanol (OXO), an inhibitor of TAK1 phosphorylation. Like TAK1 overexpressing cardiac cells, cardiomyocytes differentiated in the presence of OXO beat faster and showed increased expression of SAN genes (Shox2, HCN4, and Islet1). This suggests that activation of the SAN transcriptional network can be accomplished by blocking the phosphorylation of TAK1.

Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B.

Background and aims: The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPARγ) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPARγ during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPARγ in patients with histological response to treatment with entecavir. Methods: Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPARγ expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPARγ was calculated using Pearson's or Spearman's correlation analysis. Results: A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPARγ in hepatic stellate cells was positively correlated with adrenic acid (r 2 = 0.451, p = 0.046). The expression of PPARγ in both groups increased after treatment, and the expression of PPARγ in the R group was restored in HSCs much more than that in the NR group (p = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (p = 0.037 and 0.014). Conclusion: Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARγ in HSCs may play a crucial role in liver fibrosis improvement.

Comparison on different traditional Chinese medicine therapies for chronic hepatitis B liver fibrosis.

Background and Aims: Although different kinds of traditional Chinese medicines could reportedly improve the efficacy of antiviral therapy on liver fibrosis caused by HBV, the problem of clinicians on how to choose the appropriate treatment strategies for the patients fails to be solved. This study aims at comparing and ranking different traditional Chinese medicine (TCM) therapies in the treatment of liver fibrosis due to chronic hepatitis B (CHB). Methods: Eight electronic databases were searched from their establishment to 17 Aug 2021. All included data and pooled odds ratio were used for network meta-analysis (NMA) and statistical analysis. The consistency was evaluated by the node-splitting analysis. The stability of results and source of heterogeneity were tested by sensitivity analysis. Different treatment strategies (regimens) in this network meta-analysis were ranked with the aid of surface under the cumulative ranking curve (SUCRA) probability value. Results: A total of 29 articles with 3,106 sufferers were recruited in this NMA. Results of SUCRA value rankings indicated that Fuzheng Huayu therapy or combined with entecavir had preferable effects in improving the clinical efficacy, recovering the level of hyaluronic acid, IV-C, ALT, ALB, and TBil, relieving the TCM symptoms including hypochondriac pain and poor appetite, regaining the width of portal vein and thickness of spleen, and lessening side effects. Apart from these, Ziyin Shugan therapy or combined with ETV could also be suitable to regain the level of laminin, PC-III, and AST, relieve fatigue and HBV-DNA conversion. Conclusion: This NMA confirmed the efficacy and safety of different treatment therapies for improving CHB liver fibrosis, including the serum biomarkers of live fibrosis and serum parameters for liver function, TCM symptoms, imaging indexes, HBV-DNA conversion rate, which offered the TCM practitioners crucial reference value on clinical medication.

Treatment of Liver Fibrosis: A 20-Year Bibliometric and Knowledge-Map Analysis.

Objectives: To analyze the research hotspots, evolution, and trends of the treatment of liver fibrosis in the recent 20 years, bibliometric and knowledge-map analysis were used. Methods: Publications associated with the treatment of liver fibrosis were retrieved from the Web of Science Core Collection on 16 April 2022. CiteSpace 5.8.R3 and VOSviewer 1.6.18 were calculated to perform bibliometric and knowledge-map analysis. Results: A total of 72,686 authors from 200 institutions in 134 countries/regions published 15,237 studies in different academic journals. United States was the most productive country, and Shanghai Jiao Tong University was the most published institution. Trauner Michael had the most published articles, whereas Scott L. Friedman was the most frequently co-cited author. Moreover, there was frequent inter-institution cooperation between countries in the years 2015 and after, but the before years showed rare inter-institution cooperation. The journal HEPATOLOGY was both the most published publication and the most frequently co-cited one in this field. Screened keywords, such as virus infection, inflammation, oxidative stress, activation of hepatic stellate cell (HSC), and hepatocellular apoptosis, could be both therapeutic targets and pathological mechanisms in terms of liver fibrosis. Furthermore, long-term suppression of hepatitis B virus replication and the activation of HSC were the latest hotspots and topics related to the treatment of liver fibrosis. Besides, the treatments of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis were also involved in the treatment of liver fibrosis, which were both emerging topics and rapidly developing hot fields. Conclusion: This bibliometric analysis conducted a full overview of the treatment of liver fibrosis, which provided important clues and ideas for scholars focusing on this field. Not only that, the field is still in a stage of rapid development and will continue to be a research hotspot in the future.

The Single-Nucleotide Polymorphism of miR-27a rs895819 and the Expression of miR-27a in Helicobacter pylori-Related Diseases and the Correlation with the Traditional Chinese Medicine Syndrome.

Aims: The study aims to explore the effects of the single-nucleotide polymorphism of miR-27a and its expression in Helicobacter pylori (H. pylori)-related diseases and the relationship between gastric pathology and traditional Chinese medicine (TCM). Methods: Subjects were classified into six histopathological groups and five TCM syndrome groups. All specimens underwent H. pylori detection through rapid urease test and methylene blue staining. Histopathological characteristics were observed by hematoxylin-eosin. The expression of miR-27a and its genotype were, respectively, detected by Quantitative Real-Time PCR and direct sequencing. Results: H. pylori promoted the malignant evolution of gastric mucosa and were involved in the formation of TCM syndrome. In H. pylori-positive patients, the frequency of miR-27a CT genotype at the rs895819 locus and its expression in the gastric cancer group were higher than those in other pathological groups. TCM syndrome had a close relationship with histopathological changes, and patients with spleen-qi deficiency syndrome had a higher risk of gastric cancer than other syndromes, regardless of H. pylori infection. Conclusion: The C allele at miR-27a rs895819 locus may be an oncogene in gastric cancer. High levels of miR-27a could play an important role in gastric malignant evolution, especially cancerization. There is a certain connection between TCM syndrome and pathological changes of the gastric mucosa to some extent, where patients with SQD syndrome had a higher risk of GC.

Functional gene polymorphisms and expression alteration of selected microRNAs and the risk of various gastric lesions in Helicobacter pylori-related gastric diseases.

Background: Helicobacter pylori (Hp) persistent infection is an important pathogenic factor for a series of chronic gastric diseases from chronic gastritis to gastric cancer. Genetic and epigenetic abnormalities of microRNAs may play a vital role in the pathological evolution of gastric mucosa in Helicobacter pylori-related gastric diseases (HPGD). This study aimed to investigate the relationship between miR-146a, miR-196a2, miR-149, miR-499 and miR-27a gene single nucleotide polymorphisms (SNPs) and their expressions with pathological changes in gastric mucosa, and to further analyze the interactions between SNPs and Hp. Methods: Subjects in this study included patients diagnosed with HPGD and healthy controls. MiR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs2292832, miR-499 rs3746444 and miR-27a rs895819 were genotyped by direct sequencing. Fluorescence quantitative PCR was used to detect microRNA expressions. Gene-gene and gene-environment interactions were evaluated by multifactor dimensionality reduction (MDR) method. Results: we found that frequency distribution of miR-196a2 rs11614913 CT genotype in gastric precancerous lesion (GPL) group and gastric cancer (GC) group was significantly higher than normal control (NOR) group [adjusted OR = 6.16, 95%CI (1.46-26.03); adjusted OR = 11.83, 95%CI (1.65-84.72), respectively]. CT genotype and C allele of miR-27a rs895819 were associated with increased risk of GC [adjusted OR = 10.14, 95%CI (2.25-45.77); adjusted OR = 3.71, 95%CI(1.46-9.44), respectively]. The MDR analysis results showed that the interaction between miR-196a2 rs11614913 and Hp was associated with the risk of GPL (p = 0.004). Meanwhile, the expression level of miR-196a2 in GC group was significantly higher than NOR, chronic inflammation (CI) and early precancerous lesion (EPL) groups among Hp-positive subjects. And expressions of miR-499 and miR-27a in GC group were both higher than EPL group. Also, miR-27a expression in GC group was higher than CI and gastric atrophy (GA) groups. Conclusion: miR-196a2 rs11614913 and miR-27a rs895819 may affect the genetic susceptibility to GPL or GC. MiR-196a2 rs11614913 and Hp have a synergistic effect in the occurrence and development of GPL. The up-regulation of miR-499, miR-196a2 and miR-27a expression caused by Hp infection may be an important mechanism of gastric carcinogenesis.

The efficacy and safety of acupuncture in nonalcoholic fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The aim of this study was to determine the efficacy and safety of acupuncture treatment (AT) or acupuncture plus conventional medicine (CM) versus CM alone using a meta-analysis of all published randomized controlled trials (RCTs) for nonalcoholic fatty liver disease (NAFLD). METHODS: Eight databases were searched independently from inception to April 30, 2020. RCTs were included if they contained reports on the use acupuncture or the use of acupuncture combined with CM and compared with the use of CM. Summary odds ratio (OR) and 95% confidence intervals (CIs) were used to calculate the overall clinical efficacy. Secondary outcomes, namely aspartate aminotransferase, alanine aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index, were calculated by mean difference with 95% CIs. RESULTS: After the final screening, 8 RCTs with 939 patients were included. This meta-analysis showed that AT was superior to CM in improving overall clinical efficacy (OR = 3.19, 95% CI: 2.06-4.92, P  < .00001). In addition, AT plus CM could significantly improve overall clinical efficacy compared to treatment with CM alone (OR = 5.11, 95% CI: 2.43-10.75, P  < .0001). Moreover, the benefits were also demonstrated in other outcomes, including alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol indexes. However, AT plus CM could not decrease body mass index levels in comparison with CM. The safety profile of Acupuncture therapy was satisfactory. Taichong, Zusanli, Fenglong, and Sanyinjiao were major acupoints on NAFLD treatment. CONCLUSION: Acupuncture may be effective and safe for treatment of NAFLD. However, due to insufficient methodological quality and sample size, further high-quality studies are needed.

Efficacy and safety of Qingre-Chushi therapies in active ulcerative colitis: A network meta-analysis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease with an increasing incidence in the world. Qingre-Chushi therapies (QC) can alleviate clinical symptoms. Therefore, a network meta-analysis was conducted to systematically evaluate the efficacy and safety of QC in the treatment of active UC patients. METHODS: 7 databases were screened and relevant randomized controlled trials were selected. The tools of Cochrane Handbook and the GRADE system were conducted to assess the quality of outcomes. Pooled risk ratio or standard mean difference was calculated with 95% credible interval for outcomes measurement using the random-effects model. The surface under the cumulative ranking curve (SUCRA) was performed to rank the treatments. The larger SUCRA scores, the more effective interventions. RESULTS: A total of 3560 articles were identified and 21 studies including 1829 participants were included for further analysis. Totally, 9 therapies regimens were compared: oral mesalazine, mesalazine enema, mesalazine suppository, oral mesalazine + mesalazine enema, oral QC, oral QC + oral mesalazine, QC enema, oral QC + QC enema, and oral mesalazine + QC enema. Based on the SUCRA plot, oral QC + oral mesalazine was the best treatment in inducing clinical response; oral QC + QC enema had the best efficacy in the improvement of Mayo scores and alleviating abdominal pain; oral mesalazine + mesalazine enema was the optimal therapy in the endoscopic improvement and reducing diarrhea; QC enema + oral mesalazine was the best option in preventing bloody stool. CONCLUSION: This study confirmed the efficacy and safety of QC in treating active UC and suggested that the combination of oral medications with topical can achieve more benefits.

Pharmacological treatments of Chinese herbal medicine for irritable bowel syndrome in adults: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Plenty of clinical studies have suggested the value of Chinese herbal medicine (CHM) for patients with irritable bowel syndrome (IBS), but their efficacy and safety have not been systematically concluded yet. This article aimed to compare and rank the therapeutic effect and safety of CHM with routine pharmacotherapies and placebo in the treatment of IBS. METHODS: Randomized controlled trials regarding CHM to treat IBS were searched in six databases from inception to Jan 31, 2020. A network meta-analysis was conducted to analyze the data of included publications. The quality assessment was assessed by Cochrane Handbook and GRADEpro software. The risk ratio was calculated for dichotomous outcomes while the standardized mean difference was used for continuous variables with 95% credible intervals. A Funnel plot was performed to evaluate publication bias. The surface under the cumulative ranking curve was conducted to rank the included interventions. Data were analyzed with STATA 15.0 and Review Manager 5.3. RESULT: 3194 records were searched, and 28 eligible trials involving 3323 patients ere identified. Compared with conventional therapies and placebo, Jianpi-Chushi therapy showed significant improvement in adequate relief and IBS symptom severity scale; Shugan-Jianpi therapy showed the best efficacy in relieving the abdominal pain and abdominal distension; Wenshen-Jianpi therapy had a better effect on avoiding adverse effects and improving stool character. CONCLUSION: This study confirmed that CHM could be beneficial for patients with IBS in relieving their clinical symptoms and should be recommended as alternative therapies. The quality of evidence in this study based on the GRADE system was "low".

A Simple Mechanochromic Mechanophore Based on Aminothiomaleimide.

Mechanochromic mechanophores have promising applications in stress sensing and damage detection. Here we report a simple mechanofluorochromic mechanophore based on aminothiomaleimide (ATM). Poly(methyl acrylate) containing this mechanophore (ATM-PMA) was synthesized by atom transfer radical polymerization (ATRP) using an ATM-derived difunctional initiator. To investigate its mechanofluorochromism, the solution of ATM-PMA was subjected to ultrasonication, and size exclusion chromatography (SEC) and fluorescence spectroscopy were employed to monitor the changes in molecular weight and fluorescence emission. The results showed that the molecular weight of ATM-PMA decreased upon ultrasonication, accompanied by a shift of fluorescence emission from bright yellow to light blue. This mechanophore of a simple functional group of ATM has great potential to be used in mechanochromic polymer materials.

Efficacy and safety of non-pharmacological interventions for irritable bowel syndrome in adults.

BACKGROUND: Although nonpharmacological interventions (NPI) for irritable bowel syndrome (IBS) have been applied clinically, their relative efficacy and safety are poorly understood. AIM: To compare and rank different NPI in the treatment of IBS. METHODS: Five electronic databases were searched from their inception to January 12, 2020. Data of included publications were analyzed using network meta-analysis (NMA). Quality of endpoints were assessed by tools of the Cochrane Handbook and the GRADEpro software. Pooled relative risk or standardized mean difference with their corresponding 95% confidence intervals were used for statistical analysis. Surface under the cumulative ranking curve (SUCRA) probability value was conducted to rank the examined interventions. Sensitivity analysis was performed to verify the robustness of results and test the source of heterogeneity. RESULTS: Forty randomized controlled trials with 4196 participants were included in this NMA. Compared with routine pharmacotherapies and placebo, acupuncture and cognitive behavioral therapy (CBT) had better efficacy in relieving IBS symptoms. Based on the SUCRA values, acupuncture ranked first in improving overall clinical efficacy and avoiding adverse effects. CBT ranked first in lowering the scores of IBS symptom severity scale, self-rating anxiety scale and self-rating depression scale. CONCLUSION: This study confirmed the efficacy and safety of NPI for improving IBS symptoms, which to some extent recommended several interventions for clinical practice.

Different Traditional Herbal Medicines for the Treatment of Gastroesophageal Reflux Disease in Adults.

BACKGROUND/AIMS: Traditional Herbal Medicines (THM) have been being used for gastroesophageal reflux disease (GERD) for a long time, but clinical evidence is still scarce. We evaluated different THM prescriptions for GERD in adults. METHODS: Data added to nine online databases from their inception to November 30, 2019, were systematically searched. All relevant randomized controlled trials (RCTs) were included and were combined with Bayesian network analysis. The Cochrane Collaboration's risk of bias tool and GRADE profiler version 3.6 were respectively employed to evaluate the quality of evidence of outcomes. RESULTS: Seventeen publications involving 1441 participants were retrieved. The results of our analysis suggested that Jianpi therapy+proton pump inhibitors (PPIs) and Ligan Hewei therapy respectively ranked first in overall clinical efficacy and efficacy under gastroscope; Ligan Hewei therapy+PPIs was the optimum intervention in the improvement of acid regurgitation and heartburn. CONCLUSION: This research indicates that Ligan Hewei therapy and Jianpi therapy, or these therapies separately combined with PPIs, should be recommended as appropriate complementary and alternative treatments based on the specific characteristics of GERD. However, additional well-designed RCTs with high methodological quality are still needed for future research.

Associations of Interleukin-1ß with H. pylori-Induced Gastric Atrophy and Syndrome of Dampness-Heat in the Spleen and Stomach in Subjects with H. pylori-Related Gastric Diseases.

H. pylori-related gastric diseases (HPGD) are a series of gastric mucosal benign and malignant lesions associated with H. pylori infection. Exploring the pathogenesis of HPGD will be of great significance to prevent and treat gastric malignancy. Traditional Chinese medicine (TCM) syndrome is the essence of TCM, reflecting the state of whole body. Potential similarities of TCM syndrome may provide a new perspective in understanding development and treatment of diseases. To seek an early warning signal for gastric malignant pathology and similarities of TCM syndrome from the viewpoint of molecular biology, we examined the relationships among H. pylori, gastric pathology, and TCM syndrome and effects of Interleukin-1ß (IL-1ß) gene polymorphisms and expression on gastric pathology and TCM syndrome in HPGD. The results indicated that detection of H. pylori with differentiation of TCM syndrome may have a predictive function to gastric pathology. H. pylori may lead to gastric atrophy via enhancing IL-1ß mRNA expression, and IL-1ß mRNA overexpression in gastric mucosa may be one of the generality characteristics for H. pylori-negative subjects with syndrome of dampness-heat in the spleen and stomach.

Interaction of Cyclooxygenase-2 with Helicobacter pylori Induces Gastric Chronic Nonresolving Inflammation and the Formation of Syndrome of Internal Block of Static Blood in Helicobacter pylori-Related Gastric Diseases.

Cyclooxygenase-2 (COX-2) is an inducible enzyme stimulated by various inflammatory factors (IFs). Chronic gastritis is a classic model of "inflammation-cancer transformation" and Helicobacter pylori-related gastric diseases (HPGD) are specific ones of this model. Traditional Chinese Medicine (TCM) syndromes could play a predictive role in gastric histopathological evolution. To search for early warning evidence about "inflammation-cancer transformation," this study is about to explore interaction of COX-2 with Helicobacter pylori (Hp) in HPGD with different TCM syndromes. All included subjects underwent endoscopy and biopsy. Hp infection was detected by rapid urease test and methylene blue staining. Histopathological characteristics and COX-2 expression in gastric mucosa (GM) were, respectively, observed by hematoxylin-eosin and Elivision™ plus. SPSS 18.0 and Stata 11.0 statistical software packages were used for statistical analysis. Results of immunohistochemical staining in this study showed COX-2 expression in Hp-positive patients was stronger than that in Hp-negative ones. Spearman' analysis indicated that degrees of both Hp infection and COX-2 expression were positively correlated with those of gastric inflammation and inflammatory activity. Compared with the relative normal group, both severe dysplasia group and gastric carcinoma group had more severe Hp infection and COX-2 expression. Compared with the nonsyndrome, syndrome of internal block of static blood (IBSB) had higher scores in semiquantitative analysis of COX-2 protein expression among TCM groups. Moreover, multivariate logistics regression analysis suggested that patients with Hp infection could increase the risk of IBSB. These results indicated that COX-2 interacting with Hp could play an important role in transforming gastric chronic nonresolving inflammation into carcinoma in subjects with HPGD, as well as inducing the formation of IBSB. HPGD together with IBSB could be an early warning evidence for GM with histopathological evolution from benign to malignant.

Efficacy of traditional Chinese Medicine for gastric precancerous lesion: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate efficacy of traditional Chinese medicine (TCM) for gastric precancerous lesion (GPL). METHOD: Literature retrieval was conducted in seven databases from their inception through Dec. 24th, 2018. The Cochrane collaboration, Review Manager (RevMan5.3) and GRADE profiler software were conducted for this meta-analysis. RESULTS: In primary outcomes, results of meta-analysis showed that TCM had superior to current routine pharmacotherapy (RP) in clinical efficacy, Helicobacter pylori (Hp) eradication rate, efficacy under endoscopy, and TCM syndrome efficacy. Meanwhile, no potential publication bias was detected by Begg's and Egger's tests. In secondary outcomes, compared with control groups, experimental groups were more positive effects on improvement of stomach distention, stomachache, and heartburn. CONCLUSION: Our findings indicated that TCM could have positive effects on GPL. However, further standardized RCTs of rigorous design should be required to obtain more forceful evidence.

TAK1/Map3k7 enhances differentiation of cardiogenic endoderm from mouse embryonic stem cells.

Specification of the primary heart field in mouse embryos requires signaling from the anterior visceral endoderm (AVE). The nature of these signals is not known. We hypothesized that the TGFß-activated kinase (TAK1/Map3k7) may act as a cardiogenic factor, based on its expression in heart-inducing endoderm and its requirement for cardiac differentiation of p19 cells. To test this, mouse embryonic stem (ES) cells overexpressing Map3k7 were isolated and differentiated as embryoid bodies (EBs). Map3k7-overexpressing EBs showed increased expression of AVE markers but interestingly, showed little effect on mesoderm formation and had no impact on overall cardiomyocyte formation. To test whether the pronounced expansion of endoderm masks an expansion of cardiac lineages, chimeric EBs were made consisting of Map3k7-overexpressing ES and wild type ES cells harboring a cardiac reporter transgene, MHCα::GFP, allowing cardiac differentiation to be assessed specifically in wild type ES cells. Wild type ES cells co-cultured with Map3k7-overexpressing cells had a 4-fold increase in expression of the cardiac reporter, supporting the hypothesis that Map3k7 increases the formation of cardiogenic endoderm. To further examine the role of Map3k7 in early lineage specification, other endodermal markers were examined. Interestingly, markers that are expressed in both the VE and later in gut development were expanded, whereas transcripts that specifically mark the early definitive (streak-derived) endoderm (DE) were not. To determine if Map3k7 is necessary for endoderm differentiation, EBs were grown in the presence of the Map3k7 specific inhibitor 5Z-7-oxozeaenol. Endoderm differentiation was dramatically decreased in these cells. Western blot analysis showed that known downstream targets of Map3k7 (Jnk, Nemo-like kinase (NLK) and p38 MAPK) were all inhibited. By contrast, transcripts for another TGFß target, Sonic Hedgehog (Shh) were markedly upregulated, as were transcripts for Gli2 (but not Gli1 and Gli3). Together these data support the hypothesis that Map3k7 governs the formation, or proliferation of cardiogenic endoderm.

Mechanochemical Degrafting of a Surface-Tethered Poly(acrylic acid) Brush Promoted Etching of Its Underlying Silicon Substrate.

The stability of surface-tethered polyelectrolyte brushes has been investigated during the past few years. We have previously reported on the degrafting of poly(acrylic acid) (PAA) polymer brushes from flat silicon substrates. Here, we present a detailed study on the effects of NaCl concentration and the grafting density and molecular weight on the stability of PAA brushes during incubation in 0.1 M ethanolamine buffer (pH 9.0) solutions. Without NaCl in the buffer solution, the PAA brushes remain intact. Adding NaCl facilitates etching of the substrate due to accelerating dissolution of the top silica layer and promoting degrafting of the PAA chains. The PAA grafting density and molecular weight play an important role in the substrate etching by affecting the penetration barrier and local concentration of the etchants. We also tested the stability of self-assembled monolayers (SAMs) made of hydrophobic alkyltrichlorosilanes anchored on silicon substrates. The results demonstrated that the SAMs were too thin to protect the substrates from etching, in contrast to thick poly(methyl methacrylate) brushes. Our findings suggest that both polymer brushes (especially polyelectrolyte brushes) and SAMs anchored to silicon substrates may undergo erosion/etching on the substrates in basic environments, which compromises their stability and therefore jeopardizes their applications in coating, biosensing, and so forth.