Insights and future prospects of traditional Chinese medicine in the treatment of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a prevalent and challenging gastrointestinal disorder. Conventional medicine often faces limitations in providing effective treatment for FD, thus indicating the need to explore alternative approaches. Traditional Chinese medicine (TCM), which is rooted in ancient Chinese traditions and has evolved over thousands of years, offers a holistic approach to well-being. TCM incorporates herbal remedies, acupuncture, and other therapies while shaping the future of complementary and alternative medicine. PURPOSE: To review the existing literature on the current status and future prospects of using TCM to treat FD. METHODS: We extensively searched the PubMed, Google Scholar, Embase, an China National Knowledge Internet databases from inception to May 31, 2023 to identify relevant literature. We also searched the reference lists of the included articles. RESULTS: Clinical evidence-based research has explored the efficacy of TCM in treating FD. Recent research has illuminated the multifaceted mechanisms through which TCM interventions affect FD. TCM is a promising alternative, as it emphasizes a holistic approach and holds potential advantages in addressing the complex nature of FD. CONCLUSIONS: The integration of TCM and Western medicine offers a comprehensive approach to understanding and managing FD by bridging traditional wisdom with modern scientific understanding. This paper highlights the practical implications of this integration, the challenges to be addressed, and the potential for international collaboration to further elucidate the efficacy of TCM. However, continued research and dialog are needed to advance the modern development of TCM and to improve the quality of life of FD patients.

Relationship among Chinese herb polysaccharide (CHP), gut microbiota, and chronic diarrhea and impact of CHP on chronic diarrhea.

Chronic diarrhea, including diarrhea-predominant irritable bowel syndrome (IBS-D), osmotic diarrhea, bile acid diarrhea, and antibiotic-associated diarrhea, is a common problem which is highly associated with disorders of the gut microbiota composition such as small intestinal bacterial overgrowth (SIBO) and so on. A growing number of studies have supported the view that Chinese herbal formula alleviates the symptoms of diarrhea by modulating the fecal microbiota. Chinese herbal polysaccharides (CHPs) are natural polymers composed of monosaccharides that are widely found in Chinese herbs and function as important active ingredients. Commensal gut microbiota has an extensive capacity to utilize CHPs and play a vital role in degrading polysaccharides into short-chain fatty acids (SCFAs). Many CHPs, as prebiotics, have an antidiarrheal role to promote the growth of beneficial bacteria and inhibit the colonization of pathogenic bacteria. This review systematically summarizes the relationship among gut microbiota, chronic diarrhea, and CHPs as well as recent progress on the impacts of CHPs on the gut microbiota and recent advances on the possible role of CHPs in chronic diarrhea.

Jian-Pi-Yin decoction attenuates lactose-induced chronic diarrhea in rats by regulating GLP-1 and reducing NHE3 ubiquitination and phosphorylation.

Objectives: Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. Design: In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. Methods: The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. Results: JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. Conclusion: JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. Innovation: In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.

Metabolomic analysis of lipid changes in Bombyx mori infected with Nosema bombycis.

The silkworm (Bombyx mori) is a model species of lepidopteran insect. Microsporidium spp. are obligate intracellular eukaryotic parasites. Infection by the microsporidian Nosema bombycis (Nb) results in an outbreak of Pébrine disease in silkworms and causes substantial losses to the sericulture industry. It has been suggested that Nb depends on nutrients from host cells for spore growth. However, little is known about changes in lipid levels after Nb infection. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was performed to analyze the effect of Nb infection on lipid metabolism in the midgut of silkworms. A total of 1601 individual lipid molecules were detected in the midgut of silkworms, of which 15 were significantly decreased after Nb challenge. Classification, chain length, and chain saturation analysis revealed that these 15 differential lipids can be classified into different lipid subclasses, of which 13 belong to glycerol phospholipid lipids and two belong to glyceride esters. The results indicated that Nb uses the host lipids to complete its own replication, and the acquisition of host lipid subclasses is selective; not all lipid subclasses are required for microsporidium growth or proliferation. Based on lipid metabolism data, phosphatidylcholine (PC) was found to be an important nutrient for Nb replication. Diet supplementation with lecithin substantially promoted the replication of Nb. Knockdown and overexpression of the key enzyme phosphatidate phosphatase (PAP) and phosphatidylcholine (Bbc) for PC synthesis also confirmed that PC is necessary for Nb replication. Our results showed that most lipids in the host midgut decreased when silkworms were infected with Nb. Reduction of or supplementation with PC may be a strategy to suppress or promote microsporidial replication.

[Systematic review and Meta-analysis of Biling Weitong Granules in treatment of stomach ache disorder].

This study aimed to evaluate the efficacy and safety of Biling Weitong Granules in the treatment of stomach ache disorder. Randomized controlled trial(RCT) of Biling Weitong Granules in the treatment of digestive diseases with stomach ache disorder as the primary symptom was retrieved from Chinese and English electronic databases and trial registration platforms from database inception to June 10, 2022. Two investigators conducted literature screening and data extraction according to the screening criteria. The Cochrane risk-of-bias tool(v 2.0) was used to assess the risk of bias in the included studies. Analyses were performed using RevMan 5.4 and R 4.2.2, with summary estimates measured using fixed or random effects models. The primary outcome indicators were the visual analogue scale(VAS) scores and stomach ache disorder symptom scores. The secondary outcome indicators were clinical recovery rate, Helicobacter pylori(Hp) eradication rate, and adverse reaction/events. Twenty-seven RCTs were included with a sample size of 2 902 cases. Meta-analysis showed that compared with conventional western medicine treatments or placebo, Biling Weitong Granules could improve VAS scores(SMD=-1.90, 95%CI[-2.18,-1.61], P<0.000 01), stomach ache disorder symptom scores(SMD=-1.26, 95%CI[-1.71,-0.82], P<0.000 01), the clinical recovery rate(RR=1.85, 95%CI[1.66, 2.08], P<0.000 01), and Hp eradication rate(RR=1.28, 95%CI[1.20, 1.37], P<0.000 01). Safety evaluation revealed that the main adverse events in the Biling Weitong Granules included nausea and vomiting, rash, diarrhea, loss of appetite, and bitter mouth, and no serious adverse events were reported. Egger's test showed no statistical significance, indicating no publication bias. The results showed that Biling Weitong Granules in the treatment of digestive system diseases with stomach ache disorder as the primary symptom could improve the VAS scores and stomach ache disorder symptom scores of patients, relieve stomach ache disorder, and improve the clinical recovery rate and Hp eradication rate, with good safety and no serious adverse reactions. However, the quality of the original studies was low with certain limitations. Future studies should use unified and standardized detection methods and evaluation criteria of outcome indicators, pay attention to the rigor of study design and implementation, and highlight the clinical safety of the medicine to provide more reliable clinical evidence support for clinical application.

[Systematic review and Meta-analysis of efficacy and safety of Fengliao Changweikang prescription in treatment of acute gastroenteritis].

This study systematically evaluated the clinical efficacy and safety of Fengliao Changweikang prescription for treating acute gastroenteritis(AGE). The databases of CNKI, Wanfang, VIP, SinoMed, Medline, Cochrane Library and two clinical trial registration platforms were retrieved from inception to August 30, 2022, to collect randomized controlled trial(RCT) on Fengliao Changweikang prescription treating AGE. Two researchers independently conducted literature screening, data extraction, and risk of bias assessment according to pre-established inclusion and exclusion criteria. RevMan 5.4.1 was used for data analysis. Finally, 18 RCTs were included, involving 3 489 patients. Meta-analysis showed that compared with conventional western medicine, Fengliao Changweikang prescription improved the relief rate of abdominal pain(RR=1.27, 95%CI[1.17, 1.38],P<0.000 01); Fengliao Changweikang prescription + conventional western medicine increased the cure rate(RR=1.43, 95%CI[1.12, 1.82], P=0.004), shortened the duration of diarrhoea(RR=-1.65, 95%CI[-2.44,-0.86], P<0.000 1), abdominal pain(RR=-1.46, 95%CI[-2.00,-0.92], P<0.000 01), vomiting(RR=-2.16, 95%CI[-2.51,-1.81], P<0.000 01) and fever(RR=-2.61, 95%CI[-4.00,-1.23], P=0.000 2), down-regulated the level of interleukin-8(IL-8)(RR=-1.07, 95%CI[-1.26,-0.88], P<0.000 01), IL-6(RR=-8.24, 95%CI[-8.99,-7.49], P<0.000 01) and hypersensitive C-reactive protein(hs-CRP)(RR=-3.04, 95%CI[-3.40,-2.69], P<0.000 01) and recurrence of AGE(RR=0.20, 95%CI[0.05, 0.90], P<0.04). In conclusion, Fengliao Changweikang prescription was safe in clinical application. It was beneficial to alleviate the clinical symptoms of diarrhea, abdominal pain, vomiting, and fever, and down-regulate the levels of some serum inflammatory factors in AGE patients. However, considering that few high-quality studies have evaluated the efficacy and safety of Fengliao Changweikang prescription in treatment of AGE, further evidence is needed in the future.

Overlapping Symptoms of Functional Gastrointestinal Disorders: Current Challenges and the Role of Traditional Chinese Medicine.

Several functional gastrointestinal disorders (FGIDs) have overlapping symptoms, and, consequently, developing treatment strategies based on symptomatology poses a challenge for the clinical management of complex FGIDs. The significant overlap in the symptoms of FGIDs caused by the shared pathophysiological mechanisms is both a challenge and an excellent target for therapeutic development, since treatment strategies focused on shared pathophysiological mechanisms can treat the associated underlying diseases rather than just alleviating the primary symptoms. Owing to its multi-targeted approach, traditional Chinese medicine (TCM) has garnered immense interest worldwide; however, the quality of the data demonstrating its effectiveness is generally weak. Additionally, the causal link between the intrinsic mechanisms of action of TCM and its clinical benefits remains obscure. Systems biology is characterized by holistic and dynamic research, which corresponds to the holistic, multi-targeted, and syndrome-based approach of TCM. Therefore, high-throughput analysis techniques can be employed to describe and comprehend the genesis and progression of diseases, as well as the impacts of TCM on the organism, which may aid in elucidating the pathogenic mechanisms of the diseases as well as the mechanism of action of TCM.

Comparing Arsenic-Containing Qinghuang Powder and Low-Intensity Chemotherapy in Elderly Patients with Acute Myeloid Leukemia.

OBJECTIVE: To compare the clinical effect of arsenic-containing Qinghuang Powder (QHP) and low-intensity chemotherapy (LIC) in treatment of elderly acute myeloid leukemia (eAML) patients. METHODS: Clinical data of 80 eAML patients treated at Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2015 to December 2020 were retrospectively analyzed. The treatment scheme was designed by real world study according to patients' preference, and patients were divided into a QHP group (35 cases) and a LIC group (45 cases). The median overall survival (mOS), 1-, 2-, and 3-year OS rates, and incidence of adverse events were compared between the two groups. RESULTS: The mOS of 80 patients was 11 months, and the 1-, 2-, and 3-year OS rates were 45.51%, 17.96%, and 11.05%, respectively. The QHP and LIC groups demonstrated no significant difference in mOS (12 months vs. 10 months), 1- (48.57% vs. 39.65%), 2- (11.43% vs. 20.04%), and 3-year OS rates (5.71% vs. 13.27%, all P>0.05). Moreover, the related factors of mOS demonstrated no significant difference in patients with age>75 years (11 months vs. 8 months), secondary AML (11 months vs. 8 months), poor genetic prognosis (9 months vs. 7 months), Eastern Cooperative Oncology Group performance status score ⩾ 3 (10 months vs. 7 months) and hematopoietic stem cell transplant comorbidity index ⩾ 4 (11 months vs. 7 months) between the QHP and LIC groups (all P>0.05). However, the incidence of myelosuppression was significantly lower in the QHP group than that in the LIC group (28.57% vs. 73.33%, P<0.01). CONCLUSIONS: QHP and LIC had similar survival rates in eAML patients, but QHP had a lower myelosuppression incidence. Hence, QHP can be an alternative for eAML patients who do not tolerate LIC.

Bacteria-targeted delivery of black phosphorus quantum dots facilitates photothermal therapy against hypoxic tumors and complementary low-dose radiotherapy.

Many approaches have been employed to relieve hypoxia in solid tumors to enhance sensitivity to radiotherapy (RT), including O2 delivery or hydrogen peroxide (H2O2) decomposition strategies. To date, however, these modalities have been restricted by poor O2 loading, rapid O2 leakage, and limited endogenous H2O2 levels. To overcome these limitations, we therefore sought to develop an effective approach for the oxygen-independent treatment of hypoxic tumors. In this study, we designed a novel black phosphorus quantum dot (BPQD)/Escherichia coli (E. coli) hybrid system (BE) capable of facilitating the photothermal therapy (PTT) of hypoxic tumors. A simple electrostatic adsorption approach was used to conjugate BPQDs to E. coli. BE is capable of reliably targeting hypoxic tumors and mediating PTT. BPQDs in BE can directly facilitate X-ray-mediated radiosensitization of tumors, thereby achieving significant RT efficacy in response to lower doses of radiation, effectively and specifically damaging hypoxic tumor tissues to suppress the growth of tumors. Our results highlight this BE system as a novel approach to tumor radiosensitization with great potential for clinical application.

Modified Gegen Qinlian decoction ameliorated ulcerative colitis by attenuating inflammation and oxidative stress and enhancing intestinal barrier function in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Modified Gegen Qinlian decoction (MGQD), which was first documented in Treatise on Febrile Disease, is recognized as a classic prescription to treat ulcerative colitis (UC). However, its protective mechanism against UC remains to be fully elucidated. AIM OF THE STUDY: To explore the impact and the potential molecular mechanism of MGQD on dextran sodium sulfate (DSS)-induced UC mice and tumor necrosis factor alpha (TNF-α)-induced Caco-2 cell monolayer model of intestinal barrier. MATERIALS AND METHODS: The chemical components of MGQD and MGQD drug containing serum (MGQD-DS) were characterized by LC-MS/MS. The therapeutic effect of MGQD on DSS-induced UC was evaluated based on body weight, disease activity index (DAI), colon length, colonic histopathological injury, inflammatory cytokines, oxidative stress response and intestinal barrier function. Cell Counting Kit (CCK)-8 assay was applied to detect the effect of MGQD-DS on the viability of Caco-2 cells. Additionally, TNF-α-induced Caco-2 cell monolayer model of intestinal barrier was established in vitro. The Caco-2 cell monolayers were administered blank serum or MGQD-DS to observe the effects of MGQD-DS on transepithelial electrical resistance (TEER), permeability of fluorescein isothiocyanate (FITC)-dextran, inflammatory cytokines, oxidative stress indicators and intestinal epithelial barrier (IEB). RESULTS: MGQD significantly improved symptoms and pathological damage in UC mice by downregulating the expression of interleukin (IL)-1ß and malondialdehyde (MDA), attenuating the loss of goblet cells and the destruction of intestinal epithelial ultrastructure, and upregulating the expression of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), zonula occludens-1 (ZO-1), Occludin, Claudin-1 and E-cadherin. In vitro, MGQD-DS significantly reduced the flux of FITC-dextran, increased the TEER, inhibited the expression of IL-21, IL-17A and MDA, and promoted the expression of IL-4, IL-10, transforming growth factor-ß (TGF-ß), SOD, CAT, GSH, Occludin and E-cadherin in TNF-α-induced Caco-2 cell monolayer model of intestinal barrier. CONCLUSION: MGQD can ameliorate DSS-induced UC mice and TNF-α-induced Caco-2 cell monolayer model of intestinal barrier, and the protective effect is related to its inhibition of inflammation, alleviation of oxidative stress, and repair of intestinal barrier damage.

[Rapid health technology assessment of four oral Chinese patent medicines in treatment of functional gastrointestinal disorders].

To provide proof of the evidence-based medicine and decision-making information for the clinical decision of functional gastrointestinal disorders(FGIDs), this study evaluated and compared the efficacy, safety, and economy of four oral Chinese patent medicines(CPMs) in the treatment of FGIDs using the method of rapid health technology assessment. The literature was systematically retrieved from CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, Cochrane Library and ClinicalTrials.gov from the establishment of the databases to May 1, 2022. Two evaluators screened out the literature, extracted data, evaluated the quality of the literature, and descriptively analyzed the results according to the prepared standard. Eventually, 16 studies were included, all of which was rando-mized controlled trial(RCT). The results showed that Renshen Jianpi Tablets, Renshen Jianpi Pills, Shenling Baizhu Granules, and Buzhong Yiqi Granules all had certain effects on the treatment of FGIDs. Renshen Jianpi Tablets treated FGIDs and persistent diarrhea. Shenling Baizhu Granules treated diarrhea with irritable bowel syndrome and FGIDs. Buzhong Yiqi Granules treated diarrhea with irritable bowel syndrome, FGIDs, and chronic diarrhea in children. Renshen Jianpi Pills treated chronic diarrhea. The four oral CPMs all have certain effects on the treatment of FGIDs and have specific advantages for specific patients. Compared with other CPMs, Renshen Jianpi Tablets have higher clinical universality. However, there are problems such as insufficient clinical research evidence, generally low quality of evidence, lack of comparative analysis among medicines, and lack of academic evaluation. More high-quality clinical research and the economic research should be carried out in the future, so as to provide more evidence for the evaluation of the four CPMs.

Research trends in the field of the gut-brain interaction: Functional dyspepsia in the spotlight - An integrated bibliometric and science mapping approach.

Objectives: This study aims to perform a bibliometric analysis of functional dyspepsia (FD), which includes visualizing bibliographic information, in order to identify prevailing study themes, topics of interest, contributing journals, countries, institutions, and authors as well as co-citation patterns. Methods: The Web of Science™ Core Collection Database was used to retrieve all peer-reviewed scientific publications related to FD research. The validated search terms were entered into the "title" and "author keywords" fields, and the results were sorted by publication year from 2006 to 2022. There were no restrictions on language. On 12 February 2023, a manual export of the complete metadata for each original publication and review article was performed. CiteSpace was used to reveal co-authorship, publication, and co-citation patterns to find prominent authors, organizations, countries, and journals in FD research as well as to identify author keywords with strong citation bursts, which could indicate an emerging research area. VOSviewer was used to build the co-occurrence indicator (co-word) to identify the main author keywords on which previous studies focused and to induce clustered scientific landscape for two consecutive periods to identify intriguing areas for future research. Results: A search of the database retrieved 2,957 documents. There was a wave-like pattern in the number of publications until 2017, after which there was a spike in publication volume. The USA, China, and Japan provided the majority of contributions. In terms of institution, Mayo Clin, Univ Newcastle, and Katholieke Univ Leuven were found to be the prolific institutions. Additionally, the results indicate that eastern Asian researchers contributed significantly to the global knowledge of literature that led other countries; however, Canada, the USA, Australia, England, and Germany were found to have the highest degree of betweenness centrality. Nicholas J. Talley, Jan Tack, Gerald Holtmann, Michael Camilleri, Ken Haruma, and Paul Moayyedi occupied the top positions based on productivity and centrality indicators. Six thematic clusters emerged (Helicobacter pylori infection; pathophysiological mechanisms of FD; extraintestinal co-morbidities and overlap syndromes associated with FD; herbal medicine in FD; diabetic gastroparesis; and dietary factors in FD). "Acupuncture," "duodenal eosinophilia," "gut microbiota," and others were among the author keywords with rising prevalence. Conclusion: In FD research, eastern Asian countries have established themselves as major contributors with the highest publishing productivity; however, research has primarily been driven by North America, Europe, and Australia, where cooperation is generally more active and highly influential scientific results are produced. Our analysis suggests that increased investments, training of human resources, improved infrastructures, and expanded collaborations are essential to improving the quality of FD research in Asia. The emerging author keyword analysis suggests that eosinophil-mast cell axis, gut microbiota, mental disorders, and acupuncture are the key areas that attract researchers' attention as future research boulevards. There is a highly skewed distribution of research output across Asia, with most focus on complementary and alternative medicine (CAM) coming from Chinese, Japanese, and South Korean centers. However, CAM remains an underexplored area of research in the context of FD, and it deserves greater research efforts in order to obtain quality scientific evidence. Furthermore, we propose that the research framework of CAM should not be limited to dysmotility; rather, it could be interpreted within a more holistic context that includes the brain-gut-microbiota axis, as well as novel concepts such as duodenitis, increased mucosal permeability, and infiltration and activation of eosinophils and mast cells, among others. Overall, we provided bibliometrics-based overviews of relevant literature to researchers from different backgrounds and healthcare professionals to provide an in-depth overview of major trends in FD research.

Modified Gegen Qinlian decoction ameliorates DSS-induced chronic colitis in mice by restoring the intestinal mucus barrier and inhibiting the activation of γδT17 cells.

BACKGROUND: Current therapeutics for ulcerative colitis (UC) have limitations. Classical Formula Gegen Qinlian decoction (GQD) is derived from Shang Han Lun and has a long history of treating gastrointestinal diseases such as diarrhea and UC. Nevertheless, the exact mechanism of it needs to be further clarified. PURPOSE: We aimed to investigate the treatment effects of modified GQD (MGQD) on dextran sodium sulfate (DSS)-induced chronic colitis in mice and conduct further exploration of its underlying mechanisms. METHODS: The protective effect of MGQD was estimated in a DSS-induced chronic colitis mouse model. Model evaluation included body weight, disease activity index (DAI) score, colon length and histopathology. Alcian Blue/Phosphoric Acid Schiff (AB/PAS) staining, transmission electron microscopy (TEM), immunofluorescence and real time‒PCR (RT-PCR) were used to assess goblet cell function. ELISA, flow cytometry and immunofluorescence were applied to estimate the immunoinflammatory status. Western blot was performed to test the protein expression levels of relevant pathways and related receptors. All experiments were conducted in duplicate. RESULTS: MGQD alleviated DSS­induced chronic colitis symptoms in mice, protected goblet cell function and restored the intestinal mucus barrier. Furthermore, MGQD efficiently suppressed the abnormal immune inflammatory response and the activate of γδT17 cells and NLRP3 inflammasome. CONCLUSION: The mechanisms by which MGQD protects against DSS-induced chronic colitis may involve restoring goblet cell function, repairing the intestinal mucus barrier, and modulating the immune inflammatory response. More importantly, MGQD inhibited NLRP3 inflammasome-associated signaling pathway activation, which consequently reduced the activation of γδT17 cells.

Chinese integrated guideline on the management of gastric precancerous conditions and lesions.

The standardized diagnosis and management of gastric precancerous conditions and lesions are important to prevent gastric cancer. This guideline, created by 5 traditional Chinese medicine and Western medicine associations, based on the current morbidity and diagnosis and treatment of gastric precancerous conditions and lesions, provides specific key points and strategies for diagnosis and treatment in the following five aspects: definition and epidemiology, diagnosis and stage, surveillance, treatment and efficacy evaluation. It is hoped that these aspects, assessed by integrating Western medicine and traditional Chinese medicine and involving multidisciplinary participation, will play a guiding role in clinical diagnosis and treatment and achieve effective secondary prevention of gastric cancer.

Chinese herbal compound prescriptions combined with Chinese medicine powder based on traditional Chinese medicine syndrome differentiation for treatment of chronic atrophic gastritis with erosion: a multi-center, randomized, positive-controlled clinical trial.

BACKGROUND: In this study, Chinese herbal compound prescriptions combined with Chinese medicine powder were evaluated for the treatment of chronic atrophic gastritis with erosion. METHODS: This multi-center, randomized, positive drug control clinical trial randomly assigned 216 patients with chronic atrophic gastritis with erosion to three groups: (1) control group: aluminum plus magnesium suspension thrice per day for 4 weeks; (2) test group 1: Chinese herbal compound prescriptions twice a day plus Sanqi (Panax notoginseng) powder twice a day for 4 weeks; (3) test group 2: Chinese herbal compound prescriptions twice a day plus Sanqi (Panax notoginseng) powder and Zhebeimu (Fritillaria thunbergii Miq.) powder twice a day for 4 weeks. The primary endpoint (improvement of gastric mucosal erosion; improvement of gastric mucosal pathology) and secondary endpoints (improvement of clinical symptoms scores; improvement of the patient-reported outcome [PRO] instrument for chronic gastrointestinal diseases) were assessed using endoscopy at week 4 following the treatment. Drug-related adverse events (AEs) and adverse drug reactions (ADRs) were also compared. RESULTS: The final analysis included 202 patients (control group, 63; test group 1, 69; test group 2, 70). At week 4, using within-group comparison, gastric mucosal erosion improved in each group following treatment with a significant difference (P < 0.05); there were no statistically significant differences in gastric mucosal erosion scores among the groups after treatment (P > 0.05); in terms of improvement of gastric mucosal erosion, the efficacy rate of the control group was 69.12%, the efficacy rate of the test group 1 was 73.24%, and the efficacy rate of the test group 2 was 69.01% and efficacy rate among the groups was not statistically significant (P > 0.05). As determined by acute inflammation, chronic inflammation, atrophy, intestinal metaplasia, and dysplasia, the pathological score (total score and the highest score) did not differ statistically among groups following treatment (P > 0.05); within the control group, the total scores of acute inflammation, chronic inflammation, atrophy, and intestinal metaplasia were significantly decreased (P < 0.05), but there was no significant improvement in dysplasia (P > 0.05); in the test group 1, chronic inflammation, atrophy, and intestinal metaplasia and dysplasia scores were significantly decreased (P < 0.05), but acute inflammation did not improve (P > 0.05); there was a significant reduction in the atrophy score in test group 2 (P < 0.05), but no improvement in the scores of acute inflammation, chronic inflammation, intestinal metaplasia, and dysplasia was observed (P > 0.05). Similarly, within the control group, the highest scores of acute inflammation, chronic inflammation, atrophy, and intestinal metaplasia were significantly decreased (P < 0.05), but there was no significant improvement in dysplasia (P > 0.05); there was a significant reduction in highest scores of atrophy, intestinal metaplasia, and dysplasia (P < 0.05) in test group 1, but the highest scores didn't not improve with acute inflammation and chronic inflammation (P > 0.05); there was a significant reduction in the highest atrophy score in test group 2 (P < 0.05), but no improvement in the highest scores of acute inflammation, chronic inflammation, intestinal metaplasia, and dysplasia was observed (P > 0.05). Compared to the control group, the main symptom scores and total symptom scores in the test groups were lower following treatment, with a statistically significant difference (P < 0.05); the analysis of covariance with center, erosion type, and group as factors was applied, and the comparison among the groups in dyspepsia, defecation, and total PRO instrument scores were statistically significant (P < 0.05). In the study period, AEs were reported in 3 (4.23%) patients in the test group 1 and 3 (4.41%) patients in the control group; ADRs were confirmed in 3 (4.23%) patients from the test group 1 and 2 (2.94%) from the control group. AEs and ADRs were not statistically significantly different among groups (AE, P = 0.2213; ADR, P = 0.2872). No serious AE or ADR was reported. CONCLUSIONS: This study has shown that both aluminum plus magnesium suspension and Chinese herbal compound prescriptions together with Panax notoginseng powder are capable of improving gastric mucosal erosion and reducing gastric mucosal pathological scores, and there were no statistically significant differences among the groups in primary endpoints, indicating that Chinese herbal therapy can achieve similar efficacy than antacids in terms of primary outcomes. The aluminum plus magnesium suspension is comparable to Chinese herbal therapy in improving atrophy and intestinal metaplasia, and is inferior to Chinese herbal therapy in improving dysplasia. In addition, the Chinese herbal therapy significantly outperforms the aluminum plus magnesium suspension in improving symptoms. Therefore, the overall clinical outcome of Chinese herbal compound prescriptions together with Panax notoginseng powder based on TCM syndrome patterns in the treatment of erosive gastritis is superior to that of antacids. Trial registration ChiCTR, ChiCTR-IPR-15005905. Registered 22 January 2015, https://www.chictr.org.cn/showproj.aspx?proj=10359.

Traditional Chinese medicine based on Tongjiang methodology combined with proton pump inhibitor (PPI) step-down in treating non-erosive reflux disease: a study protocol for a multicentered, randomized controlled clinical trial.

BACKGROUND: Non-erosive reflux disease (NERD) is characterized by typical gastroesophageal reflux symptoms, such as heartburn and regurgitation but an absence of esophageal mucosal damage during upper gastrointestinal endoscopy. Although proton pump inhibitors (PPIs) are the first line therapy, almost 50% of patients with NERD fail to respond to this treatment. Traditional Chinese medicine (TCM) can better relieve the symptoms of NERD. Therefore, a randomized controlled trial (RCT) was designed to investigate the efficiency of TCM granules based on Tongjiang (TJ) methodology combined with PPI step-down therapy for NERD patients who did not respond to PPIs alone. METHOD: This multicentered, double-blinded, RCT with two parallel groups will recruit 174 participants who will be randomized into the TCM granules combined with PPI step-down group (n = 87) and the TCM granules placebo combined with PPI step-down group (n = 87). Both groups of participants will receive 6 weeks of treatment and 4 weeks of follow-up, and all participants will be assessed for related symptoms, mental health status, and quality of life at each visit. The primary outcome measurements include visual analog scale (VAS) for heartburn and regurgitation and the major symptoms scale. The secondary outcome measurements include PPI withdrawal rate, symptom recurrence rate, minor symptoms scale, SF-36, PRO, SAS, SDS, GERD-HRQL, and TCM syndromes scales. DISCUSSION: Previous research has shown that TCM is capable to alleviate NERD symptoms. This trial will help to provide a better understanding of the synergistic efficiency of the combination of TCM and PPIs, to explore whether the dosage of PPIs can be reduced after the supplement of TCM granules and to provide a feasible plan to reduce dependencies or withdraw NERD patients from PPIs. The outcome of this trial is expected to reduce the symptom recurrence rates, lessen patients' physical and psychological burdens, and achieve good social benefits. TRIAL REGISTRATION: Clinicaltrials.gov NCT04340297. Registered on April 9, 2020.

Tong-Xie-Yao-Fang alleviates diarrhea-predominant irritable bowel syndrome in rats via the GCN2/PERK-eIF2α-ATF4 signaling pathway.

BACKGROUND: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disease. Tong-Xie-Yao-Fang (TXYF), the traditional Chinese herbal medicine prescription, is a classic and effective prescription for the treatment of IBS-D, but its mechanism of action is not fully clarified. OBJECTIVE: To evaluate the efficacy of TXYF in the treatment of IBS-D and to explore its potential mechanism of action. METHODS: Changes in the serum levels of 50 free amino acids were targeted for detection by high-performance liquid chromatography (HPLC), and the expression of glucose-regulated protein 78 (GRP78), general control nonderepressible 2 (GCN2), and endoplasmic reticulum-resident kinase (PERK) was detected by immunohistochemistry examinations in healthy volunteers and IBS-D patients. The IBS-D rat was constructed by the three-factor superposition method of neonatal maternal separation, 2,4,6-trinitrobenzene sulfonic acid enema, and chronic unpredictable stress stimulation. The treatment effect of TXYF on IBS-D rats was observed by recording the body weight, grasp force, fecal water content (FWC), and abdominal withdrawal reflex (AWR) of rats before and after treatment. The effects of GCN2/PERK-eukaryotic initiation factor-2 (eIF2α) -activating transcription Factor 4 (ATF4) pathway proteins and gene expression were analyzed by western blotting, reverse transcription-polymerase chain reaction (RT-qPCR), and immunohistochemistry evaluations. RESULTS: Compared with healthy volunteers, IBS-D patients exhibited lower levels of cysteine, γ-aminoacetic acid (GABA), homoproline, and lysine, and immunohistochemistry showed strong activation of GRP78, a marker of endoplasmic reticulum stress. Differential expression of GCN2 and PERK proteins was detected in IBS-D patients and rat colons. In the IBS-D rats, TXYF improved the body weight and grasp force, reduced the FWC, and improved the AWR score. TXYF increased the levels of p-GCN2 and GCN2 and reduced the levels of GRP78, p-PERK, PERK, p-eIF2α, and eIF2α, thereby affecting the expression of the apoptosis-related transcription factors ATF4, CHOP, Caspase-3, and Bcl-2. CONCLUSION: Our study showed that TXYF improved IBS-D by inhibiting apoptosis. The anti-apoptosis effects were potentially mediated by regulating the GCN2/PERK-eIF2a-ATF4 signaling pathway.

Paeoniflorin Ameliorates Colonic Fibrosis in Rats with Postinfectious Irritable Bowel Syndrome by Inhibiting the Leptin/LepRb Pathway.

Postinfectious irritable bowel syndrome (PI-IBS) is a highly prevalent gastrointestinal disorder associated with immune dysregulation and depression- and anxiety-like behaviors. Through traditional medicine, the active ingredient of Paeoniae Radix called paeoniflorin (PF) was previously found to prevent the symptoms of PI-IBS. However, there is limited information on the effects of PF on intestinal function and depression- and anxiety-like symptoms in PI-IBS animal models. Here, we aimed to determine the effects of PF treatment on the symptoms of PI-IBS in a rat model. The PI-IBS rat model was established via early postnatal sibling deprivation (EPSD), trinitrobenzenesulfonic acid (TNBS), and chronic unpredictable mild stress (CUMS) stimulation and then treated with different dosages of PF (10, 20, and 40 mg/kg) and leptin (1 and 10 mg/kg). The fecal water content and body weight were measured to evaluate the intestinal function, while the two-bottle test for sucrose intake, open field test (OFT), and elevated plus maze test (EMT) were performed to assess behavioral changes. The serum leptin levels were also measured using an enzyme-linked immunosorbent assay. Furthermore, the expressions of leptin and its receptor, LepRb, were detected in colonic mucosal tissues through an immunohistochemical assay. The activation of the PI3K/AKT signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) were also detected via western blotting. After the experimental period, the PI-IBS rats presented decreased body weight and increased fecal water content, which coincided with elevated leptin levels and heightened depression- and anxiety-like behaviors (e.g., low sucrose intake, less frequency in the center areas during OFT, and fewer activities in the open arms during EMT). However, the PF treatment ameliorated these observed symptoms. Furthermore, PF not only inhibited leptin/LepRb expression but also reduced the PI3K/AKT phosphorylation and BDNF expression in PI-IBS rats. Notably, cotreatment with leptin (10 mg/kg) reduced the effects of PF (20 mg/kg) on colonic fibrosis, leptin/LepRb expression, and PI3K/AKT activation. Therefore, our findings suggest that leptin is targeted by PF via the leptin/LepRb pathway, consequently ameliorating the symptoms of PI-IBS. Our study also contributes novel insights for elucidating the pharmacological action of PF on gastrointestinal disorders and may be used for the clinical treatment of PI-IBS in the future.

External therapy of traditional Chinese medicine for treating irritable bowel syndrome with diarrhea: A systematic review and meta-analysis.

Background: Irritable bowel syndrome with diarrhea (IBS-D) is a chronic functional gastrointestinal disorder that has a significant impact on quality of life, work productivity, and healthcare resources. External therapy of traditional Chinese medicine (TCM) has positive effects on IBS-D and is simple, convenient, and low-cost. This study aimed to systematically evaluate the efficacy and safety of external therapy of TCM for IBS-D. Methods: This study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals (VIP), Wan Fang, and Chinese Biomedical (CBM) databases were electronically searched to collect randomized controlled trials comparing external therapy of TCM with Western medicine for IBS-D from inception to 31 December 2021. Two authors independently screened, extracted, and assessed the selected studies. The Jadad scale and Cochrane Collaboration Risk of Bias tool were used to evaluate study quality. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). The meta-analysis was performed using the Review Manager software (version 5.3). Results: Twenty-one studies involving 1,862 subjects were included. Acupuncture and moxibustion were the most commonly used external therapies. The meta-analysis showed that based on total effective rate with moderate certainty of evidence (n = 21 studies, n = 1,862 participants, RR = 1.25, 95% CI [1.2, 1.31], I2 = 0%, P < 0.00001), clinical cure rate with low certainty of evidence (n = 17 studies, n = 1,502 participants, RR = 1.66, 95% CI [1.4, 1.96], I2 = 1%, P < 0.00001), recurrence rate with very low certainty of evidence (n = 5 studies, n = 260 participants, RR = 0.44, 95% CI [0.34, 0.58], I2 = 0%, P < 0.00001), total symptom score (MD = -4.9, 95% CI [-7.34, -2.47]), and IBS severity scoring system score (IBS-SSS) with moderate certainty of evidence (MD = -52.72, 95% CI [-63.9, -41.53]), the experimental group had significant advantages compared with the control group. The sensitivity analysis further confirmed the robustness of the primary outcomes. The improvement in quality of life associated with IBS (IBS-QOL) was superior in the experimental group compared to the control group, and the difference was statistically significant; however, the clinical heterogeneity was strong. The inverted funnel plot of the included studies indicated a potential publication bias. Conclusion: External therapy of TCM for IBS-D alleviated abdominal symptoms, improved clinical effectiveness, and reduced recurrence with great safety. However, because of the limitations of publication bias in trials, more rigorous studies with a clinical design are necessary for further verification of the outcomes. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42020222993].

Xiangsha Liujunzi Decoction improves gastrointestinal motility in functional dyspepsia with spleen deficiency syndrome by restoring mitochondrial quality control homeostasis.

BACKGROUND: Xiang Sha Liu Junzi decoction (XSLJZD) is a famous traditional Chinese medicinal prescription for the treatment of functional dyspepsia (FD) in spleen deficiency. However, its therapeutic mechanism has not been fully clarified. PURPOSE: The present study aimed to determine the role of mitochondrial quality control (MQC)-mediated gastrointestinal motility disorder in FD treated with XSLJZD by using spleen-deficient FD rats and gastrointestinal smooth muscle cells (GSMCs). METHODS: In vivo, an FD with spleen deficiency syndrome model was established by gastric perfusion with iodoacetamide solution combined with the modified multiple platform method (MMPM), followed by intragastric gavage with XSLJZD for 4 weeks. Improvement of pathological symptoms was evaluated based on food intake, water intake, grip strength, gastric histopathological changes, gastric emptying rate, small intestinal propulsion rate, and average amplitude and frequency of smooth muscle strips. The mitochondrial ultrastructure was observed by transmission electron microscopy. The colocalization of LC3 and Parkin with mitochondria was detected by immunofluorescence. The expression and localization of Drp1 proteins were detected by immunohistochemistry. In vitro, GSMCs were treated with different concentrations of XSLJZD-CS for 24 h, followed by treatment with 20 µM carbon cyanide 3-chlorophenylhydrazone (CCCP) for 4 h. Cell viability, mitochondrial membrane potential (MMP), mitochondrial reactive oxygen species (mtROS), cellular ATP generation and mitochondrial Keima (mtKeima) expression were examined. Both in vivo and in vitro, gene expression was assessed by Western blotting. All experiments were performed in duplicate. RESULTS: Disorders of the mitochondrial quality control system existed in gastric smooth muscle in FD spleen deficiency syndrome. XSLJZD administration promoted the contraction of gastric smooth muscle and restored mitochondrial function by downregulating the colocalization of LC3 or Parkin with mitochondria, reducing the ratio of LC3II/LC3I, decreasing the expression of PINK1, Parkin and Drp1 and increasing the expression of p62 to restore mitochondrial morphology and function. In vitro studies showed that the improvement in mitochondrial function by XSLJZD was related to PINK1-parkin-mediated mitochondrial quality control. CONCLUSION: We demonstrated that XSLJZD can improve gastrointestinal motility disorder in functional dyspepsia with spleen deficiency syndrome, which was related to reconstruction of the mitochondrial quality control system by restraining PINK1/Parkin-mediated mitophagy and division. This study illustrates a novel clinical significance of herbal medicine in the treatment of FD and clarifies the important role of MQC in treating gastrointestinal motility disorder.