International clinical practice guideline on the use of traditional Chinese medicine for ulcerative colitis by Board of Specialty Committee of Digestive System Disease of World Federation of Chinese Medicine Societies (2023).

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM-based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high-quality clinical studies on TCM for UC are essential.

Houpo paiqi mixture promotes intestinal motility in constipated rats by modulating gut microbiota and activating 5-HT-cAMP-PKA signal pathway.

AIMS: Constipation is a common functional gastrointestinal disorder, which needs more effective treatment approaches. Houpo Paiqi Mixture (HPPQM) is a type of Chinese patent medicine developed from a classical formula that has been widely applied to the treatment of intestinal motility disorder. Here we aim to assess the effectiveness of HPPQM in the treatment of constipation in rat models and its potential mechanism. METHODS AND RESULTS: UPLC-MS/MS was performed to investigate the chemical component of HPPQM. Rats were randomly divided into normal control, constipation model (CM), HPPQM (low, middle and high dose) and mosapride groups. Loperamide 8 mg/kg was given orally to induce CM. The small intestine motility, colonic contraction, rectum propulsion, and histological feature of the colon were significantly improved in HPPQM group, compared with CM group (P < 0.05). Results of 16S rRNA sequencing revealed that HPPQM treatment strikingly restructured intestinal microbiota in constipated rats by increasing the relative abundances of Bacteroides and Akkermansia and decreasing the relative abundances of Prevotella and Lactobacillus. The levels of GPR43, 5-HT, 5-HT4R, cAMP, PKA were decreased while SERT was increased in constipated rats (P < 0.05), which could be restored to normal levels by treatment with HPPQM (P < 0.05). Differences in amplitude between experimental CLSMs (with HPPQM added) and control CLSMs were discovered, starting at the concentration of 40 nL/mL (P < 0.05). It was found that GLPG0974 and GR113808 could significantly reduce this reactivity (P < 0.05). CONCLUSIONS: HPPQM manifested a curative effect in constipated rats by promoting intestinal motility. The underlying mechanisms might be related to modulating gut microbiota and activating 5-HT-cAMP-PKA signal pathway.

Management of biologics in pregnant, lactating patients with inflammatory bowel disease and the impact on neonatal vaccination: A systematic review of clinical practice guidelines and consensus statements.

WHAT IS KNOWN AND OBJECTIVE: The management of biological agents during pregnancy poses challenges as maternal and infant safety must be addressed. This study aims to compare the recommendations of existing guidelines on managing the use of biologics during pregnancy, lactation for patients with inflammatory bowel disease, and the influence on neonatal vaccination. METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database and China Biomedical Database were systematically searched from the inception date to 11 May 2022, to screen all relevant guidelines. Quality assessment was performed using the guideline methodology reporting tool AGREE II. RESULTS AND DISCUSSION: Fourteen guidelines and consensus statements with detailed recommendations were included. All guidance documents cover management comments during pregnancy, and most consider that biologics can be given safely during pregnancy but require suspension at the right time to protect the foetus. However, the roles of vedolizumab and ustekinumab are disputed. Five documents guide lactation and the use of most biologics during lactation is safe, but no guidelines recommend vedolizumab. Six papers provide recommendations for newborns' vaccination, suggesting a delay in infants' live vaccination schedule if their mothers are treated with biologics. WHAT IS NEW AND CONCLUSION: Our study concluded that future guidelines could consider incorporating newer, more robust evidence to update recommendations. The development of future guidelines needs to consider the involvement of multidisciplinary experts, adequately report on the evidence retrieval process, and provide strategies for implementation. Besides, more research is needed to explore the use of biologics during pregnancy and lactation in patients with inflammatory bowel disease.

Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study.

OBJECTIVE: To develop a gastric cancer (GC) risk prediction rule as an initial prescreening tool to identify individuals with a high risk prior to gastroscopy. DESIGN: This was a nationwide multicentre cross-sectional study. Individuals aged 40-80 years who went to hospitals for a GC screening gastroscopy were recruited. Serum pepsinogen (PG) I, PG II, gastrin-17 (G-17) and anti-Helicobacter pylori IgG antibody concentrations were tested prior to endoscopy. Eligible participants (n=14 929) were randomly assigned into the derivation and validation cohorts, with a ratio of 2:1. Risk factors for GC were identified by univariate and multivariate analyses and an optimal prediction rule was then settled. RESULTS: The novel GC risk prediction rule comprised seven variables (age, sex, PG I/II ratio, G-17 level, H. pylori infection, pickled food and fried food), with scores ranging from 0 to 25. The observed prevalence rates of GC in the derivation cohort at low-risk (≤11), medium-risk (12-16) or high-risk (17-25) group were 1.2%, 4.4% and 12.3%, respectively (p<0.001).When gastroscopy was used for individuals with medium risk and high risk, 70.8% of total GC cases and 70.3% of early GC cases were detected. While endoscopy requirements could be reduced by 66.7% according to the low-risk proportion. The prediction rule owns a good discrimination, with an area under curve of 0.76, or calibration (p<0.001). CONCLUSIONS: The developed and validated prediction rule showed good performance on identifying individuals at a higher risk in a Chinese high-risk population. Future studies are needed to validate its efficacy in a larger population.

Sini-san improves duodenal tight junction integrity in a rat model of functional dyspepsia.

BACKGROUND: Recent reports have demonstrated that impaired barrier function and local microinflammation in the duodenal mucosa contribute to the pathogeneses of functional dyspepsia (FD). Thus, restoring normal barrier integrity becomes a potential therapeutic strategy in the treatment of FD. Sini-San (SNS) is a traditional Chinese prescription that exhibits therapeutic effects in FD, but the underlying mechanisms remain not well understood. METHODS: FD rats were established by tail clamping method and the therapeutic effect of SNS was evaluated by measuring the visceral sensitivity and gastric compliance. Transepithelial electrical resistance (TEER) that reveals epithelial barrier integrity was measured by Ussing chamber. The expression of tight junction (TJ) proteins, occludin and claudin-1, in the duodenum was determined by Western blot and immunofluorescence. The amount of tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) in duodenal mucosa was detected by enzyme-linked immune sorbent assay (ELISA). The mRNA level of transient receptor potential vanilloid type 1 (TRPV1) was measured by quantitative real time-polymerase chain reaction (qPCR). RESULTS: SNS could improve gastric compliance and attenuate visceral hypersensitivity (VH) in FD rats. TEER was decreased in FD rats, but treatment with SNS restored normal level of TEER and the expression of occludin and claudin-1 in FD rats. In addition, SNS administration ameliorated FD-associated increase in the production of TNF-α, IFN-γ and the expression of TRPV1. CONCLUSIONS: The therapeutic effect of SNS on FD is at least partially through improvement of TJ integrity and attenuation of FD-associated low-grade inflammation in the duodenum. Our findings highlight the molecular basis of SNS-based treatment of FD in human patients.

Inhibitory Effects and Mechanisms of Electroacupuncture via Chronically Implanted Electrodes on Stress-Induced Gastric Hypersensitivity in Rats With Neonatal Treatment of Iodoacetamide.

BACKGROUND: Stress is considered an independent factor causing and aggravating gastrointestinal symptoms, including visceral pain. The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on stress-induced gastric hypersensitivity in rats treated with neonatal iodoacetamide mimicking human functional dyspepsia (FD). METHODS: Neonatal rats were treated with gavage of 0.2 mL of 0.1% iodoacetamide in 2% sucrose daily for six days starting on tenth day after birth. The control group was given 0.2 mL of 2% sucrose. When the rats were eight weeks old, acute restraint stress was performed on them for 90 min. EA at ST36 (ZuSanLi) was performed during the acute stress or 30 min after the stress. Adrenoceptor blocking drugs (propranolol and phentolamine) were injected intraperitoneally 30 min before acute restraint stress to explore possible sympathetic mechanisms. Visceral-motor responses to gastric distention were assessed by electromyogram (EMG). RESULTS: 1) Stress-induced gastric hypersensitivity was significantly more severe in the FD rats, compared to the control rats. It was blocked by the adrenoceptor antagonists. 2) EA inhibited stress-induced gastric hypersensitivity; the preventive effect of EA (given during stress) was more remarkable than the curative effect (given after stress). Stress resulted in a higher sympathovagal ratio and this was suppressed by EA. CONCLUSIONS: Rats treated with neonatal iodoacetamide mimicking FD are more vulnerable to stress. Stress-induced gastric hypersensitivity can be prevented or suppressed by EA at ST36 via the restoration of sympathovagal balance.

[Effect of Zhizhu Pill on Gastric Smooth Muscle Contractile Response and Protein Expression of Growth Hormone Secretagogue Receptor in Functional Dyspepsia Rats].

OBJECTIVE: To study the therapeutic mechanism of Zhizhu Pill (ZP) for treating functional dyspepsia (FD) rats. METHODS: Totally 30 ten-day-old male rats were randomly divided into the normal control group (n =10) and the model group (n = 20). The FD rat model was induced using gastric administration of 0.1% iodoacetamide (IA) combined tail clamping. The model was evaluated when rats were 8-week old. Successfully modeled rats were randomly divided into the model group (n = 10) and the ZP group (n = 10). Rats in the normal group and the model group were administered with normal saline by gastrogavage, while those in the ZP group were administered with ZP Decoction (2 mL/100 g) by gastrogavage. All medication lasted for 7 successive days. The contractile activity in in vitro longitudinal gastric muscle was recorded using Power Lab biological signal collecting system. The expression of growth hormone secretagogue receptor (GHSR) in stomach of FD rats was detected using Western blot and immunohistochemistry (IHC). RESULTS: Compared with the normal group, average frequencies of gastric contraction and changing rates of amplitude obviously decreased in the model group (P < 0.05). Results of Western blot and IHC showed that the expression of GHSR decreased in the model group (P < 0.01). Compared with the model group, average frequencies of gastric contraction and changing rates of amplitude obviously increased in the ZP group (P < 0.05). Results of Western blot and IHC showed that the expression of GHSR increased in the ZP group (P < 0.01). CONCLUSION: ZP could promote the gastric motility in FD rats induced by gastric administration of IA combined tail clamping, and its mechanism might be related to up-regulating GHSR protein level.

[Treating non-alcoholic fatty liver disease patients of Gan stagnation Pi deficiency syndrome by tiaogan lidi recipe: a randomized controlled clinical trial].

OBJECTIVE: To evaluate the efficacy and safety of tiaogan Lipi Recipe (TLR) in treating non-alcoholic fatty liver disease (NAFLD) patients of Gan stagnation Pi deficiency syndrome (GSP-DS). METHODS: A randomized, double blind, placebo-controlled clinical trial was performed. Totally 99 NAFLD patients of GSPDS were randomly allocated into two groups, 66 patients in the treatment group (treated with-TLR, one dose per day) and 33 patients in the control group (treated with placebos, one dose per day). The therapeutic course for all was 12 weeks. All patients received lifestyle interventions including moderate aerobic exercise, moderate caloric restriction, and dietary changes. Clinical symptoms, CT indices, liver functions and blood lipids were observed before and after treatment. RESULTS: After 12 weeks of treatment, the total score of clinical symptoms decreased in the two groups (P <0. 01), and it was lower in the treatment group than in the control group (P <0. 05). Liver/spleen CT ratio increased in the treatment group (P <0. 01), and it was higher in the treatment group than in the control group (P <0. 01). After treatment levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT) all decreased in the treatment group (P <0. 05, P <0. 01), while levels of ALT decreased in the control group (P <0. 05). Besides, all the 3 levels mentioned above were lower in the treatment group than in the control group (P <0. 05). Levels of total cholesterol (CHO) and triglyceride (TG) decreased in the two groups (P <0. 05), and they were lower in the treatment group (P <0. 05). Total effective rates of TCM syndrome, abdominal CT, liver functions, and blood lipids were 79. 69% (51/64 cases), 54. 69% (35/64 cases), 67. 65% (23/34 cases), and 67. 39% (31/46 cases) in the treatment group, while they were 56. 25% (18/32 cases), 25. 00% (8/32 cases), 33. 33% (6/18 cases), and 55. 56% (10/18 cases) in the control group. All were superior in the treatment group (P <0.05, P <0.01, respectively). CONCLUSION: TLR combined with lifestyle intervention could safely and effectively improve clinical symptoms of NAFLD patients of GSPDS, elevate liver/spleen CT ratios, and play a role in liver protection, anti-inflammation, and lowering blood lipids.

[Study on the mechanism of action of total saponins of Panax notoginseng in ameliorating oxidative stress and insulin resistance in rats fed with high fat diet].

OBJECTIVE: To investigate whether total saponins of Panax notoginseng (tPNS) can ameliorate oxidative stress and insulin resistance (IR) in the high fat induced nonalcoholic fatty liver disease (NAFLD) rat model and to explore the relationship between oxidative stress and IR. METHODS: Totally 50 healthy rats were randomly divided into the normal control group (NC), the model group, the high dose tPNS group (at the daily dose of 160 mg/kg), the low dose tPNS group (at the daily dose of 80 mg/kg), and the bicyclol group (at the daily dose of 100 mg/kg), 10 in each group. Rats in the NC group were fed with standard forage. Those in the rest group were fed with high fat forage. Distilled water was given by gastrogavage to those in the NC group and the model group. Corresponding medication was performed for 4 weeks. Four weeks later Lee's index and body weight were measured. All rats were sacrificed to detect the wet weight of livers. Their sera was isolated and detected to calculate liver functions (serum ALT and AST levels). Levels of fasting blood glucose (FBG) and fasting insulin (FINS) were detected. Insulin sensitive index (ISI) and insulin resistance index (IRI) were calculated. Serum levels of TNF-alpha and malondialdehyde (MDA), contents of total superoxide dismutase (T-SOD), hydroxy radical level (-OH), and total antioxidant capacity (T-AOC) were measured. Pathological changes of livers was observed by HE staining of paraffin section. RESULTS: Compared with the NC group, rats' wet liver weight and Lee's index increased in the model group (P < 0.05), and results of light microscopy showed that obvious fatty degeneration occurred in livers. Compared with the model group, rats' wet liver weight and Lee's index, as well as ALT and AST could be obviously improved by tPNS and bicyclol (P < 0.05, P < 0.01). The fatty deposition of liver cells could also be alleviated. Compared with the NC group, serum levels of-OH, MDA, and TNF-alpha significantly increased, and activities of T-SOD and T-AOC decreased in the model group (P < 0.01), also accompanied with IR. Compared with the model group, concentrations of -OH, MDA, and TNF-alpha decreased after treated by tPNS (P < 0.05, P < 0.01), activities of T-SOD and T-AOC got recovered (P < 0.05, P < 0.01), and IR got obvious improvement (P < 0.01). CONCLUSION: The anti-oxidative stress effect and IR improving effect of tPNS might play partial roles in treating NAFLD.

Exploration of Berberine Against Ulcerative Colitis via TLR4/NF-κB/HIF-1α Pathway by Bioinformatics and Experimental Validation.

Purpose: This study aimed to delineate the molecular processes underlying the therapeutic effects of berberine on UC by employing network pharmacology tactics, molecular docking, and dynamic simulations supported by empirical validations both in vivo and in vitro. Patients and Methods: We systematically screened potential targets and relevant pathways affected by berberine for UC treatment from comprehensive databases, including GeneCards, DisGeNET, and GEO. Molecular docking and simulation protocols were used to assess the interaction stability between berberine and its principal targets. The predictions were validated using both a DSS-induced UC mouse model and a lipopolysaccharide (LPS)-stimulated NCM460 cellular inflammation model. Results: Network pharmacology analysis revealed the regulatory effect of the TLR4/NF-κB/HIF-1α pathway in the ameliorative action of berberine in UC. Docking and simulation studies predicted the high-affinity interactions of berberine with pivotal targets: TLR4, NF-κB, HIF-1α, and the HIF inhibitor KC7F2. Moreover, in vivo analyses demonstrated that berberine attenuates clinical severity, as reflected by decreased disease activity index (DAI) scores, reduced weight loss, and mitigated intestinal inflammation in DSS-challenged mice. These outcomes include suppression of the proinflammatory cytokines IL-6 and TNF-α and downregulation of TLR4/NF-κB/HIF-1α mRNA and protein levels. Correspondingly, in vitro findings indicate that berberine decreases cellular inflammatory injury and suppresses TLR4/NF-κB/HIF-1α signaling, with notable effectiveness similar to that of the HIF-1α inhibitor KC7F2. Conclusion: Through network pharmacology analysis and experimental substantiation, this study confirmed that berberine enhances UC treatment outcomes by inhibiting the TLR4/NF-κB/HIF-1α axis, thereby mitigating inflammatory reactions and improving colonic pathology.

Establishment and validation of an artificial intelligence-based model for real-time detection and classification of colorectal adenoma.

Colorectal cancer (CRC) prevention requires early detection and removal of adenomas. We aimed to develop a computational model for real-time detection and classification of colorectal adenoma. Computationally constrained background based on real-time detection, we propose an improved adaptive lightweight ensemble model for real-time detection and classification of adenomas and other polyps. Firstly, we devised an adaptive lightweight network modification and effective training strategy to diminish the computational requirements for real-time detection. Secondly, by integrating the adaptive lightweight YOLOv4 with the single shot multibox detector network, we established the adaptive small object detection ensemble (ASODE) model, which enhances the precision of detecting target polyps without significantly increasing the model's memory footprint. We conducted simulated training using clinical colonoscopy images and videos to validate the method's performance, extracting features from 1148 polyps and employing a confidence threshold of 0.5 to filter out low-confidence sample predictions. Finally, compared to state-of-the-art models, our ASODE model demonstrated superior performance. In the test set, the sensitivity of images and videos reached 87.96% and 92.31%, respectively. Additionally, the ASODE model achieved an accuracy of 92.70% for adenoma detection with a false positive rate of 8.18%. Training results indicate the effectiveness of our method in classifying small polyps. Our model exhibits remarkable performance in real-time detection of colorectal adenomas, serving as a reliable tool for assisting endoscopists.

Diminished representation of vitamin-B12-producing bacteria in constipated elders with frailty.

Constipation and frailty are associated with intestinal dysbiosis. This study aims to identify intestinal microbial signatures that can differentiate between constipated elders accompanied by frailty and those without frailty. We collected stool samples from 61 participants and conducted 16S rRNA gene sequencing. Constipated patients with frailty (Constipation_F) exhibited reduced gut microbial diversities compared to constipated patients without frailty (Constipation_NF) and healthy individuals (C). From differential genera, random forest models identified 14, 8, and 5 biomarkers for distinguishing Constipation_F from Constipation_NF, Constipation_F from C, and Constipation_NF from C, respectively. Functional analysis revealed that pathways (P381-PWY and PWY-5507) related to vitamin B12 synthesis were reduced in Constipation_F, which aligns with the decreased abundances of vitamin-B12-producing Actinomyces and Akkermansia in this group. Our study unveils substantial differences in gut microbiota between constipated elders with frailty and those without, underscoring the diagnostic and therapeutic potential of genera involved in vitamin B12 synthesis.

Efficacy of modified LiuJunZi decoction on functional dyspepsia of spleen-deficiency and qi-stagnation syndrome: a randomized controlled trial.

BACKGROUND: Chinese herbal medicine (CHM) has been used in China and some other countries for the treatment of patients with functional dyspepsia (FD). However, controlled studies supporting the efficacy of such treatments in patients with FD are lacking. In this trial, we aimed to assess the efficacy and safety of modified LiuJunZi decoction in patients with FD of spleen-deficiency and qi-stagnation syndrome. METHODS: We performed a randomized, double-blind, placebo-controlled trial with patients from five centers. Patients with FD of spleen-deficiency and qi-stagnation syndrome (n = 160) were randomly assigned to groups given CHM modified LiuJunZi decoction or placebo in a 2:1 ratio. Herbal or placebo granules were dissolved in 300 ml of boiled water cooled to 70°C. Patients in both groups were administered 150 ml (50°C) twice daily. The trial included a 4-week treatment period and a 4-week follow-up period. The primary outcomes were dyspepsia symptom scores, measured by the total dyspepsia symptom scale and the single dyspepsia symptom scale at weeks 0, 1, 2, 3, 4 and 8. The secondary outcome was the change of radiopaque barium markers emptied from the stomach between week 0 and week 4 of treatment. RESULTS: Compared with patients in the placebo group, patients in the CHM group showed significant improvements according to the scores of total dyspepsia symptoms and single dyspepsia symptoms obtained from patients (P < 0.01) and investigators (P < 0.01). They also showed an improvement in the number of radiopaque barium markers emptied from the stomach (P < 0.05). CONCLUSIONS: CHM modified LiuJunZi decoction appears to offer symptomatic improvement in patients with FD of spleen-deficiency and qi-stagnation syndrome. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR): http://ChiCTR-TRC-10001074.

How Tongxie-Yaofang Regulates Intestinal Synaptic Plasticity by Activating Enteric Glial Cells and NGF/TrkA Pathway in Diarrhea-Predominant Irritable Bowel Syndrome Rats.

Purpose: Diarrhea-predominant irritable bowel syndrome (D-IBS) is a frequent functional gastrointestinal disease that affects health and quality of life owing to its high incidence and recurrence rate. Tongxie-Yaofang (TXYF) is a traditional Chinese medicine prescribed for D-IBS. However, the therapeutic mechanism of TXYF has not been fully elucidated. This study aimed to investigate the effects of TXYF on visceral hypersensitivity in stress-induced D-IBS rats and the underlying mechanisms. Methods: Electromyographic (EMG) activity of the external oblique muscles and the abdominal withdrawal reflex (AWR) score captured by Barostat were used to quantify the effect of TXYF on visceral sensitivity. Transmission electron microscopy (TEM) was used to observe the ultrastructure of the enteric nervous system (ENS). For molecular detection, the colonic expression of enteric glial cell's (EGC's) activation markers, glial fibrillary acidic protein (GFAP) and calcium-binding protein S100ß, NGF, TrkA, synaptic plasticity-related factors, synaptophysin (SYN) and postsynaptic density-95 (PSD-95), glutamate, glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR), and N-methyl-D-aspartate receptor (NMDAR) were detected by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time PCR. An ex vivo experiment was conducted to measure the EGC-induced NGF release. Results: TXYF decreased the EMG activity and AWR scores in rats with D-IBS. Under TEM, TXYF improved the dense and irregular nerve arrangement, narrowed the synaptic cleft, and decreased the number of synaptic vesicles in D-IBS rats. In addition, TXYF decreased the expression of GFAP, S100ß, SYN, and PSD-95; down-regulated the levels of NGF, TrkA, and glutamate; and reduced the mRNA expression of AMPAR1, NMDAR1, and NMDAR2B. In an ex vivo experiment, TXYF decreased NGF release in D-IBS rats, and this trend disappeared under EGC inhibition. Conclusion: TXYF alleviated visceral hypersensitivity in D-IBS rats possibly by improving synaptic plasticity through inhibiting the activity of EGCs and the NGF/TrkA signaling pathway in the colon.

Different therapies of Chinese herbal medicine for diarrhea-predominant irritable bowel syndrome: A network meta-analysis of double-blinded, placebo-controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuganjianpi Therapy (SGJP), Jianpi Therapy (JP), Shugan Therapy (SG), Jianpiwenshen Therapy (JPWS), and Shuganjianpiwenshen Therapy (SGJPWS), consisting of formulas from Chinese herbal medicine (CHM), have been tremendously applied to irritable bowel syndrome (IBS). However, it remains uncertain when exploring the preferable option among different CHM therapies for diarrhea-predominant irritable bowel syndrome (IBS-D). AIM OF THE STUDY: To compare and rank the efficacy and safety of different CHM therapies for IBS-D. MATERIALS AND METHODS: We searched randomized, double-blinded, placebo-controlled trials through mainstream databases from their inception to October 31, 2022. Eligible randomized controlled trials (RCTs) applied one of the CHM therapies as the experimental group and placebo as the control group. Two authors independently extracted data into a form and evaluated the quality of the retrieved articles by the Cochrane Risk of Bias Tool. At least one of the following outcomes was assessed: Serotonin, Neuropeptide Y (NPY), Incidence of Adverse Events (AE), and Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) with its subscales of Severity of Abdominal Pain (SAP), Frequency of Abdominal Pain (FAP), Severity of Abdominal Distension (SAD), Dissatisfaction with Bowel Habits (DBH), and Interference with Quality of Life (IQOL). A Bayesian network meta-analysis on a random-effect model was conducted using R 4.2.2 software. RESULTS: 1367 records were retrieved from databases in an initial search. Fourteen studies involving six interventions with 2248 participants were identified. Provided pairwise comparisons, the surface under the cumulative ranking curve (SUCRA) ranking, and cluster analysis, JPWS was the best option for ameliorating clinical symptoms simultaneously, which included IBS-SSS, SAP, FAP, SAD, DBH, and IQOL. As for AE, JPWS contributed to fewer adverse events than others as well. In respect of serum indicators, we noticed the dominance of SGJP in regulating both serotonin and NPY. CONCLUSIONS: JPWS and SGJP were the most prominent CHM therapies for IBS-D in terms of clinical symptoms, including abdominal pain, distension, bowel habits, and improvement of quality of life. The effect of JP and SG for IBS-D required further investigation. As a potential candidate, SGJP may well treat IBS-D by mediating dysmotility, visceral hypersensitivity, and the gut-brain axis with an increase of NPY and a reduction of serotonin. For safety, JPWS was ideal for the fewest adverse events in the treatment of IBS-D. On account of a small sample size and possible geographical publication bias, more double-blinded and placebo-controlled trials with larger samples worldwide would be necessary for strengthening current evidence.

The potential mechanism of qinghua quyu jianpi decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic and recurrent inflammation of the gastrointestinal tract. Following the idea of herbal property and compatibility, a traditional Chinese medicine (TCM) formula consists of a number of TCM herbs. Qinghua Quyu Jianpi Decoction (QQJD) has been clinically proven to be effective in treating UC, however, its therapeutic mechanism has not been fully elucidated. AIM OF STUDY: Here, we used network pharmacology analysis and ultra-performance liquid chromatography-tandem mass spectrometry to predict the mechanism of action of QQJD, and then validated our predictions through in vivo and in vitro experiments. MATERIALS AND METHODS: First, based on a number of datasets, relationship network diagrams between QQJD and UC were created. The target network for the QQJD-UC intersection genes was then built, and KEGG analysis was carried out to identify a potential pharmacological mechanism. Finally, the results of the previous prediction were validated in dextran sulfate sodium salt (DSS) induced UC mice and a cellular inflammatory model. RESULTS: Network pharmacology results suggested that QQJD may play a role in repairing intestinal mucosa by activating Wnt pathway. In vivo experiments have shown that QQJD can significantly reduce weight loss, disease activity index (DAI) score, improve colon length, and effectively repair the tissue morphology of UC mice. In addition, we also found that QQJD can activate the Wnt pathway to promote epithelial cell renewal, reduce apoptosis, and repair the mucosal barrier. To further understand how QQJD promotes cell proliferation in DSS-induced Caco-2 cells, we performed a study in vitro experiment. We were surprised to find that QQJD activated the Wnt pathway by inducing nuclear translocation of ß-catenin, accelerating the cell cycle and promoting cell proliferation in vitro. CONCLUSION: Taken together, network pharmacology and experiments showed that QQJD achieves mucosal healing and restores the colonic epithelium barrier by activating Wnt/ß-catenin signaling, regulating cell cycle progression, and promoting the proliferation of epithelial cells.

Myristicin Suppresses Gastric Cancer Growth via Targeting the EGFR/ ERK Signaling Pathway.

BACKGROUND: Myristicin is a type of natural compound showing anti-proliferative, anti-microbial, and anti-inflammatory effects. However, its role in gastric cancer treatment remains unknown. OBJECTIVE: In this study, the effect of myristicin on gastric cancer as well as its underlying mechanism was investigated. METHODS: Human gastric cancer cells were exposed to various concentrations of myristicin (0, 7.8125, 15.625, and 31.25 µM) for 48 h. Then CCK-8, fluorescence-activated cell sorting, and Hoechst staining were performed to evaluate the cell proliferation and apoptosis. The levels of proteins associated with cell cycle, apoptosis, endoplasmic reticulum (ER) stress, and EGFR/ERK signaling pathway were detected by western blot. JC-1 staining was conducted to determine the mitochondrial membrane potential. On the other hand, the effect of myristicin on gastric cancer growth and apoptosis was also determined in vivo. RESULTS: Myristicin retarded proliferation and induced ER stress and apoptosis in gastric cancer cells, with decreased expression of cyclins, increased Bax expression, activated caspases, and enhanced cytochrome C release and mitochondrial ROS. Furthermore, the EGFR/ERK signaling pathway was restrained by myristicin. In addition, EGFR over-expression abolished the inhibitory function of myristicin on proliferation, apoptosis, and ER stress. Also, myristicin inhibited the growth of gastric cancer cells as well as the EGFR/ERK signaling pathway in vivo. CONCLUSION: Myristicin exerts an anti-cancer effect on gastric cancer cells by restraining the EGFR/ ERK signaling pathway. It may have the potential to be applied as a novel drug in gastric cancer treatment.

Identification of the therapeutic effect and molecular mechanism of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) theory believes that clearing heat and promoting dampness is the main treatment method for chronic gastritis. Coptis chinensis Franch. has the effects of clearing heat, detoxifying, and anti-inflammatory; Magnolia officinalis var. biloba can be used to treat abdominal pain, cough, and asthma. Coptis chinensis Franch. and Magnolia officinalis var. biloba can regulate the balance of intestinal microbiota and inhibit inflammatory reactions. AIM: This study will verify the therapeutic effect of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis, and explore its mechanism through transcriptome sequencing. METHODS: Firstly, a rat chronic gastritis model was established, and the anal temperature and body weight changes of the rats before and after modeling were observed. Next, H&E staining, TUNEL assay and ELISA assay were performed on rat gastric mucosal tissues. Subsequently, the key fractions of Coptis chinensis Franch. and Magnolia officinalis var. biloba were obtained by high performance liquid chromatography (HPLC), and a GES-1 cell inflammation model was constructed to select the optimal monomer. Finally, the mechanism of action of Coptis chinensis Franch. and Magnolia officinalis var. biloba was explored through RNA seq. RESULTS: Compared with the control group, the rats in the administered group were in better condition, with higher anal temperature, reduced inflammatory response in gastric mucosal tissue and reduced apoptosis. The optimal fraction Coptisine was subsequently determined by HPLC and GES-1 cell model. RNA-seq analysis revealed that DEG was significantly enriched in ribosomes, NF-κB signaling pathway, etc. The key genes TPT1 and RPL37 were subsequently obtained. CONCLUSIONS: This study verified the therapeutic effects of Coptis chinensis Franch. and Magnolia officinalis var. biloba on chronic gastritis by in vivo and in vitro experiments in rats, identified Coptisine as the optimal component, and obtained two potential target genes.

Efficacy of COVID-19 vaccines in inflammatory bowel disease patients receiving anti-TNF therapy: A systematic review and meta-analysis.

Background and objectives: There are concerns about the serological responses to Coronavirus disease 2019 (COVID-19) vaccines in inflammatory bowel disease (IBD) patients, particularly those receiving anti-TNF therapy. This study aimed to systematically evaluate the efficacy of COVID-19 vaccines in IBD patients receiving anti-TNF therapy. Methods: Electronic databases were searched to identify relevant studies. We calculated pooled seroconversion rate after COVID-19 vaccination and subgroup analysis for vaccine types and different treatments were performed. Additionally, we estimated pooled rate of T cell response, neutralization response, and breakthrough infections in this population. Results: 32 studies were included in the meta-analysis. IBD patients receiving anti-TNF therapy had relatively high overall seroconversion rate after complete vaccination, with no statistical difference in antibody responses associated with different drug treatments. The pooled positivity rate of T cell response was 0.85 in IBD patients receiving anti-TNF therapy. Compared with healthy controls, the positivity of neutralization assays was significantly lower in IBD patients receiving anti-TNF therapy. The pooled rate of breakthrough infections in IBD patients receiving anti-TNF therapy was 0.04. Conclusions: COVID-19 vaccines have shown good efficacy in IBD patients receiving anti-TNF therapy. However, IBD patients receiving anti-TNF have a relatively high rate of breakthrough infections and a low level of neutralization response.

[Jinghuaweikang capsules combined with triple therapy in the treatment of Helicobacter pylori associated gastritis and duodenal ulcer and analysis of antibiotic resistance: a multicenter, randomized, controlled, clinical study].

OBJECTIVE: To explore the efficacy of Jinghuaweikang capsules plus triple therapy (LACJ) in treatment of Helicobacter pylori (H. pylori) associated gastritis or duodenal ulcer, compare it with bismuth-containing quadruple therapy (LACB) and standard triple therapy (LAC) and analyze the antibiotic sensitivity of gastric mucosal H. pylori strains from the failed patients. METHODS: A total of 565 patients with H. pylori infection were recruited from 11 hospitals from January 2010 to June 2011. There were 336 males and 229 females. They underwent gastroendoscopy examination due to upper gastrointestinal symptoms and had never received H. pylori eradication therapies. Duodenal ulcer patients were divided randomly into LACJ therapy group, LACB therapy group and LAC therapy group while gastritis patients LACJ therapy group and LACB therapy group. Group LAC received lansoprazole 30 mg + amoxicillin 1000 mg + clarithromycin 500 mg, twice a day, for 7 d (d1-7). Group LACJ: LAC therapy plus Jinghuaweikang, 3 capsules, twice a day, for 7 d (d1-7) then Jinghuaweikang, 3 capsules, twice a day, for 14 d (d8-21). Group LACB: LAC plus bismuth potassium citrate 220 mg, twice a day, for 7 d (d1-7) and then bismuth potassium citrate 220 mg, twice a day, for 14 d (d8-21). All duodenal ulcer patients received lansoprazole (30 mg, once a day) for 14 days after the first 7-day of treatment (d 8-21). At least 28 days after the end of treatment, all patients underwent (13)C urea breath test. Gastric mucosa was collected under endoscopy from the failed patients. The detection technique of gene chip was employed to detect antibiotics resistant gene from mucosa. RESULTS: The eradication rates of duodenal ulcer patients in groups LACJ, LACB and LAC were as follows: per-protocol (PP), 80.2% (77/96), 89.9% (89/99) and 72.2% (70/97) (P = 0.007), intention-to-treat (ITT), 78.6% (77/98), 88.1% (89/101) and 70.0% (70/100) (P = 0.007). No statistical differences existed between groups LACJ and LACB or LAC (all P > 0.05). But there were statistical differences between groups LACB and LAC (both P = 0.002). The eradication rates of PP and ITT of chronic gastritis patients in groups LACJ and LACB were as follows: 75.8% (97/128), 74.6% (97/130) vs 83.8% (109/130), 80.1% (109/136) (both P > 0.05). The symptomatic improvements of abdominal pain, burning and acid reflux of duodenal ulcer patients in group LACJ were higher than those in groups LACB and LAC. There were statistical differences between groups LACJ and LAC (all P < 0.05). The symptomatic improvements of bloating and belching for chronic gastritis patients in group LACJ were higher than those of group LACB. But no significant difference existed between two groups (all P > 0.05). Sixty samples of gastric mucosa were collected from the failed patients. The detection rates of antibiotic-resistant gene to clarithromycin and amoxicillin were 60.0% (36/36) and 18.3% (11/60) respectively. CONCLUSIONS: The efficacy of LACJ for the treatment of H. pylori infection patients is similar to LACB and superior to LAC. And the symptomatic improvement of patients is better than the other two regimens. The main cause of treatment failure is antibiotic resistance of H. pylori strains.