Efficacy and safety of Shenbai Granules for recurrent colorectal adenoma: A multicenter randomized controlled trial.

BACKGROUND: Colorectal adenoma is benign glandular tumor of colon, the precursor of colorectal cancer. But no pharmaceutical medication is currently available to treat and prevent adenomas. PURPOSE: To evaluate efficacy of Shenbai Granules, an herbal medicine formula, in reducing the recurrence of adenomas. STUDY DESIGN: This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted by eight hospitals in China. METHODS: Patients who had received complete polypectomy and were diagnosed with adenomas within the recent 6 months were randomly assigned (1:1) to receive either Shenbai granules or placebo twice a day for 6 months. An annual colonoscopy was performed during the 2-year follow-up period. The primary outcome was the proportion of patients with at least one adenoma detected in the modified intention-to-treat (mITT) population during follow-up for 2 years. The secondary outcomes were the proportion of patients with sessile serrated lesions and other specified polypoid lesions. The data were analyzed using logistic regression. RESULTS: Among 400 randomized patients, 336 were included in the mITT population. We found significant differences between treatment and placebo groups in the proportion of patients with at least one recurrent adenoma (42.5 % vs. 58.6 %; OR, 0.47; 95 % CI, 0.29-0.74; p = 0.001) and sessile serrated lesion (1.8 % vs. 8.3 %; OR, 0.20; 95 % CI, 0.06-0.72; p = 0.01). There was no significant difference in the proportion of patients developing polypoid lesions (70.7 % vs. 77.5 %; OR, 1.43; 95 % CI, 0.88-2.34; p = 0.15) or high-risk adenomas (9.0 % vs. 13.6 %; OR, 0.63; 95 % CI, 0.32-1.25; p = 0.18). CONCLUSION: Shenbai Granules significantly reduced the recurrence of adenomas, indicating that they could be an effective option for adenomas. Future studies should investigate its effects in larger patient populations and explore its mechanism of action to provide more comprehensive evidence for the use of Shenbai Granules in adenoma treatment.

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.

Does Chinese herbal medicine (CHM) reduce colorectal adenoma (CRA) recurrence: protocol of a registry-based, cohort study and a qualitative interview.

INTRODUCTION: Colorectal adenoma (CRA) is a precancerous lesion for colorectal cancer. Endoscopic resection is the first-line treatment for CRA. However, CRA recurrence rate is high. This proposed study aims to determine if Chinese herbal medicine (CHM) reduces CRA recurrence. METHODS AND ANALYSIS: This project encompasses an observational, registry-based, cohort study and a nested qualitative study. The cohort study aims to include 364 postpolypectomy CRA participants at Guangdong Provincial Hospital of Chinese Medicine (GPHCM), China, with a follow-up phase of up to 1 year. In addition to routine care, these participants will receive a CHM treatment prescribed by experienced Chinese medicine (CM) clinicians. The CHM treatment encompasses CHM products and CHM formulae according to CM syndromes. The primary outcome is CRA recurrence rate at 1 year after enrolment. Secondary outcomes include characteristics of recurrent CRA, incidence of colorectal polyp (except for CRA), incidence of advanced CRA, incidence of colorectal cancer, improvement of gastrointestinal symptoms commonly seen in CRA patients, faecal occult blood test result, lipid level, fasting plasma glucose level, uric acid level, carcinoembryonic antigen, carbohydrate antigen 19-9, quality of life and safety evaluations. Logistic regression analysis will be used to explore the correlation between exposure and outcome. Qualitative interviews will be conducted among approximate 30 CRA patients from the cohort study and 10 CM practitioners in Department of Gastroenterology at GPHCM. Thematic analysis will be used to analyse qualitative data. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Research Ethics Committee (HREC) of GPHCM (YF2022-320-02) and registered at Royal Melbourne Institute of Technology (RMIT) HREC. The results will be disseminated in peer-reviewed journals and international academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200065713.

Oral Chinese herbal medicine in reducing the recurrence of colorectal adenoma after polypectomy: A protocol for the systematic review and meta-analysis.

BACKGROUND: Colorectal adenoma (CRA) is a significant precancerous lesion of sporadic colorectal cancer (CRC). CRA is likely to recur after polypectomy, increasing the risk of CRC. Chinese herbal medicine (CHM) has been used to reduce CRA recurrence. This review aims to evaluate the effectiveness and safety of oral CHM in reducing CRA recurrence compared to other treatments (placebo, routine care, no treatment, and conventional medicine). METHODS: We will search for randomised controlled trials (RCTs) from nine major biomedical databases in English and Chinese from their inception to July 2023. The RCTs that investigate the effects of oral CHM in reducing CRA recurrence compared to other treatments will be involved. We will exclude trials using CHM extract or external application of CHM, cohort study and cross-section study. The Cochrane Risk of Bias Tool version 2 will be used to assess the quality of included studies. Data will be analysed using Review Manager software 5.4 and STATA. The random effect model will be used. The heterogeneity of intervention effects will be tested by Chi2 (Cochrane Q) and I2 statistics. Funnel plots will assess publication bias if more than ten studies are included. Subgroup and sensitivity analysis will be conducted when possible. DISCUSSION: This review will discuss the effectiveness and safety of oral CHM in reducing CRA recurrence. It will show the critical information for clinicians in the decision-making process and countries to develop clinical guidelines on CRA management. Systematic review registration PROSPERO CRD42023324197.

[Application of acupuncture in inhibiting intestinal peristalsis in colonoscopy].

Acupuncture regulating gastrointestinal motility has the characteristics of bidirectional benign regulation, acupoint specificity and immediacy. And its regulation is mainly achieved through the "neuro-endocrine-immune" network system. Acupuncture at Neiguan (PC 6) and Hegu (LI 4) to inhibit intestinal peristalsis may have good application value in colonoscopy.

Suppression effect and safety of acupuncture on colonic spasm during colonoscopy: a randomized controlled trial.

Background: Intestinal spasm and peristalsis during colonoscopy are common but undesirable phenomena, which can easily lead to a missed diagnosis of colorectal polyps and other diseases, and antispasmodic drugs can have adverse side effects. Previous studies find that acupuncture can regulate abnormal gastrointestinal motility. But evidence quality is low and limited at present, and high-quality studies are required. So this study sought to explore the efficacy and safety of acupuncture in inhibiting colonic spasm during endoscopy. Methods: In this prospective, single-blinded, randomized controlled trial, 54 patients experiencing intestinal spasms during colonoscopy were randomly assigned to receive either acupuncture of the bilateral Hegu (LI 4) and Neiguan (PC 6) points (n=27) or sham acupuncture (n=27). The sham points were located 1 cm above the proximal end of the true points and had no known function. The primary outcome was the latency time to colonic spasm suppression, and the secondary outcomes were the duration of colonic spasm suppression, the proportion of patients with rebound spasms within 5 minutes, and adverse events related to acupuncture-related side effects. Results: A total of 54 patients were eligible, and 27 in each group. There was no significant difference in the background characteristics of the patients in the 2 groups. The latency time to spasm suppression of the treatment group was significantly shorter than that of the sham control group (acupuncture: 32.00 s vs. sham: 82.00 s; P<0.001). However, the duration of colonic spasm suppression was similar (acupuncture: 300 s vs. sham: 268 s; P=0.142). No rebound spasms were observed in the treatment group but rebound spasms were observed in 3 patients in the sham control group (acupuncture: 0% vs. sham: 11.1%; P=0.236). No adverse events were observed in either group. Conclusions: Acupuncture of the bilateral Hegu (LI 4) and Neiguan (PC 6) points can shorten the latency time to spasm suppression, and may be used to suppress colonic spasm during colonoscopy. Trial registration: Chinese Clinical Trial Registry ChiCTR2000037796.

Anti-depressive effects of Jiao-Tai-Wan on CORT-induced depression in mice by inhibiting inflammation and microglia activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiao-Tai-Wan (JTW) is a very famous traditional Chinese medicine formula for the treatment of psychiatric disorders, especially in anxiety, insomnia and depression. However, its molecular mechanism of treatment remains indistinct. AIM OF THE STUDY: We aimed to reveal the action mechanism of JTW on anti-depression via inhibiting microglia activation and pro-inflammatory response both in vivo and in vitro. MATERIAL AND METHODS: The corticosterone (CORT)-induced depression mouse model was used to evaluate the therapeutic efficacy of JTW. Behavioral tests (open field, elevated plus maze, tail suspension and forced swim test) were conducted to evaluate the effect of JTW on depressive-like behaviors. The levels of inflammatory factors and the concentration of neurotransmitters were detected by RT-qPCR or ELISA assays. Then three hippocampal tissue samples per group (Control, CORT, and JTW group) were sent for RNA sequencing (RNA-seq). Transcriptomics data analysis was used to screen the key potential therapeutic targets and signaling pathways of JTW. Based on 8 bioactive species of JTW by our previous study using High-performance liquid chromatography (HPLC) analysis, molecular docking analyses were used to predict the interaction of JTW-derived compounds and depression targets. Finally, the results of transcriptome and molecular docking analyses were combined to verify the targets, key pathways, and efficacy of JTW treatment in vivo and vitro. RESULTS: JTW ameliorated CORT-induced depressive-like behaviors, neuronal damage and enhanced the levels of monoamine neurotransmitters in the serum of mice. JTW also inhibited CORT-induced inflammatory activation of microglia and decreased the serum levels of interleukin- 6(IL-6) and interleukin- 1ß (IL-1ß) in vivo. Transcriptomic data analysis showed there were 10 key driver analysis (KDA) genes with the strongest correlation which JTW regulated in depression mice. Molecular docking analysis displayed bioactive compound Magnoflorine had the strongest binding force to the key gene colony-stimulating factor 1 receptor (CSF1R), which is the signaling microglia dependent upon for their survival. Meanwhile, CSF1R staining showed it was consistent with inflammatory activation of microglia. Our vitro experiment also showed JTW and CSF1R inhibitor significantly reduced lipopolysaccharide (LPS)/interferon-gamma (IFNÉ£)-induced inflammatory activation response in macrophage cells. CONCLUSIONS: Our study suggests that JTW might ameliorate CORT-induced neuronal damage in depression mice by inhibiting CSF1R mediated microglia activation and pro-inflammatory response.

Establishment and Verification of Scoring System for Colorectal Adenoma Recurrence.

OBJECTIVE: The purpose of this study was to establish and verify a risk-scoring system for colorectal adenoma recurrence. METHODS: A total of 359 patients with colorectal adenoma who underwent polypectomy from October 2017 to December 2018 were included in this retrospective study. Information including taking traditional Chinese medicine, demographic characteristics, adenoma characteristics were collected. The patients will review the colonoscopy one year after surgery. The patients were divided into a modeling cohort (216 cases) and a model validation cohort (143 cases) according to the ratio of 6:4. Modeling and model verification were performed by logistic regression, ROC curve, nomogram (calibration chart) and other methods. RESULTS: After adjusting for confounding factors by logistic regression, it was found that taking Chinese medicine, the number, size, site, pathological type and morphology of adenoma were independent influencing factors for the recurrence of colorectal adenoma. The area under the ROC curve (AUC) in the model validation cohort of established risk scoring system was 0.771 (95% CI: 0.694-0.847), indicating that there was good consistency. CONCLUSION: The established risk prediction model of colorectal adenoma recurrence and its risk scoring system performed well and had high predictive value.

Establishment and Evaluation of a Time Series Model for Predicting the Seasonality of Acute Upper Gastrointestinal Bleeding.

OBJECTIVE: We aimed to establish and evaluate a time series model for predicting the seasonality of acute upper gastrointestinal bleeding (UGIB). METHODS: Patients with acute UGIB who were admitted to the Emergency Department and Gastrointestinal Endoscopy Center of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2013 to December 2019 were enrolled in the present study. The incidence trend of UGIB was analyzed by seasonal decomposition method. Then, exponential smoothing model and autoregressive integrated moving average model (ARIMA) were used to establish the model and forecast, respectively. RESULTS: Finally, the exponential smoothing model with better fitting and prediction effect was selected. The smooth R2 was 0.586, and the Ljung-Box Q (18) statistic value was 22.272 (P = 0.135). The incidence of UGIB had an obvious seasonal trend, with a peak in annual January and a seasonal factor of 140%. After that, the volatility had gradually declined, with a trough in August and a seasonal factor of 67.8%. Since then, it had gradually increased. CONCLUSION: The prediction effect of exponential smoothing model is better, which can provide prevention and treatment strategies for UGIB, and provide objective guidance for more medical staff in Emergency Department and Gastrointestinal Endoscopy Center during the peak period of UGIB.

Tiaochang Xiaoliu Decoction Granules prevent the recurrence of colorectal adenoma: a study protocol for a randomized controlled trial.

BACKGROUND: With the changes in lifestyle and diet, the incidence and mortality of colorectal cancer (CRC) is increasing in China. CRC mainly develops from colorectal adenomas (CRAs). There is a lack of chemopreventative drugs with definite efficacy for CRAs. Tiaochang Xiaoliu Decoction (TXD) was developed by Professor Yunjian Luo and has been used clinically over the last ten years for the prevention of CRA recurrence. To facilitate its clinical use, TXD was further standardized and produced as "Tiaochang Xiaoliu Decoction Granules (TXDG)". A study was designed to investigate the preventive effects of TXDG on the recurrence of CRA. METHODS: A randomized, double-blinded, controlled, and multi-center experiment is proposed to assess the effectiveness and safety of TXDG. Patients with CRAs (after complete polypectomy under colonoscopy) will be randomly divided into two groups, one will be treated with TXDG (the TXDG group) and the other will be treated with a TXDG mimetic agent (the TXDG mimetic group). The patients will be treated for 6 months and followed up for 3 years. Follow-up colonoscopy is expected to be carried out within 1 to 3 years after the baseline examinations. The primary outcome measure is adenoma detection rate within 1 to 3 years. The secondary outcome measures are the number, location, and pathology of the adenomas, and the polyp detection rate. DISCUSSION: Reliable objective evidence will be provided to evaluate the efficacy and safety of TXDG as an accessorial therapy for CRA occurrence in post-polypectomy patients. TRIAL REGISTRATION: ChiCTR2000035257.

Insights into oral bioavailability enhancement of therapeutic herbal constituents by cytochrome P450 3A inhibition.

Herbal plants typically have complex compositions and diverse mechanisms. Among them, bioactive constituents with relatively high exposure in vivo are likely to exhibit therapeutic efficacy. On the other hand, their bioavailability may be influenced by the synergistic effects of different bioactive components. Cytochrome P450 3A (CYP3A) is one of the most abundant CYP enzymes, responsible for the metabolism of 50% of approved drugs. In recent years, many therapeutic herbal constituents have been identified as CYP3A substrates. It is more evident that CYP3A inhibition derived from the herbal formula plays a critical role in improving the oral bioavailability of therapeutic constituents. CYP3A inhibition may be the mechanism of the synergism of herbal formula. In this review, we explored the multiplicity of CYP3A, summarized herbal monomers with CYP3A inhibitory effects, and evaluated herb-mediated CYP3A inhibition, thereby providing new insights into the mechanisms of CYP3A inhibition-mediated oral herb bioavailability.

Tiaochang Xiaoyan extract tablets ameliorate chronic inflammation by activating macrophage lysosomes in chronic colitis rats.

BACKGROUND: Tiaochang Xiaoyan tablet (TCXYT) is a traditional Chinese medicine prescription derived from the Xianglian pill, which is a traditional Chinese medicine for treating chronic dysentery recorded in the Taiping Huimin Heji Bureau [1078-1085]. For many years, TCXYT has been used to treat ulcerative colitis, however, its therapeutic mechanism is still unclear. In the present study, we used colonic lamina propria macrophages (LPM) and mouse-derived macrophage cell line RAW264.7 cells as the research objects, with the aim of exploring the therapeutic effects and mechanisms of TCXYT on colitis. METHODS: We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce a rat model of chronic colitis, and normal rats as the control. The disease activity index (DAI) and colonic histopathological changes of rats were used to evaluate the severity of colitis. Rats were divided into the control group; model group; high, middle-, and low-dose TCXYT group; and the hydroxychloroquine sulfate group. TCXYT was administered by gavage on the 3rd day after model replication and lasted for 7 days. The doses used for the high-, middle-, and low-dose TCXYT groups were 0.8, 0.4 and 0.2 g/kg, respectively. Enzyme-linked immunosorbent assay was used to detect the serum concentration of cytokines. Western blot was used to detect the expressions of Toll-like receptor 9 (TLR9), myeloid differentiation primary response 88 (MyD88), interleukin (IL) receptor-associated kinase (IRAK) 1, and IRAK4 in colonic LPM and RAW264.7 cells. Immunofluorescence was used to detect lysosomal activity. The chemical constituents of TCXYT were separated and identified based on Q-Orbitrap high resolution LC/MS data. RESULTS: TCXYT promoted the repair of colonic mucosal injury, attenuated inflammation, increased lysosome activity in macrophages, and decreased the DAI in rats with colitis compared with those in the model group. TCXYT decreased the serum concentrations of IL-1ß and tumor necrosis factor-α (TNF-α), increased those of IL-4 and IL-10, and decreased the TLR9, MyD88, IRAK1, and IRAK4 protein levels in LPM and RAW264.7 cells compared to the model group. CONCLUSIONS: TCXYT could ameliorate colon inflammation and CD11c+ macrophage infiltration in rats with chronic colitis. This effect may be mediated by activating lysosomes in macrophages by inhibiting the TLR9/MyD88/IRAK signaling pathway.

Clinical evaluation of traditional Chinese medicine on mild active ulcerative colitis: A multi-center, randomized, double-blind, controlled trial.

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by a relapsing-remitting course owing to recurrent intestinal inflammation. UC often has symptoms such as intermittent rectal bleeding, diarrhea, and abdominal pain. As the precise etiology of UC has not completely clarified, UC has become a public health challenge worldwide. According to an epidemiological survey, there were about 350,000 new cases of IBD in China from 2005 to 2014. By 2025, the number of IBD patients in China will reach 1.5 million. Traditional Chinese medicine (TCM) has been widely used to treat UC in China, however, it is still challenging to systematically determine the efficacy of in UC. Therefore, this trial aims to evaluate the clinical efficacy and safety of CHM in the treatment of mild active UC patients. METHODS: A multi-center, double-blinding, double-dummy, active-controlled, randomized trial will be established. A total of 240 patients in 6 centers with mild active UC (Mayo score is 3-5 points) and TCM syndrome of damp-heat stasis blocking and spleen-qi deficiency will be randomly allocated in the ratio of 1:1 to 2 groups: the experimental group and the control group. The experimental group will receive Hudi enteric-coated capsules (HEC) and enteric-coated mesalazine tablets placebo; the control group will receive enteric-coated mesalazine tablets and HEC placebo. Each group will be treated for 8 weeks. The primary therapeutic outcome: the rate of clinical efficacy and clinical remission at 8 weeks of treatment (last survey point) according to the modified Mayo score. The secondary outcomes: individual symptom score, TCM syndrome score, endoscopic response rate, mucosal healing rate, and quality of life scale score. Outcomes will be assessed at baseline and the end of the trial. Besides, intestinal mucosa, stools and blood biopsies from the mild active UC patients before and after treatment will be collected to reveal the underlying mechanisms. DISCUSSION: The results of this trial will provide compelling evidence of the efficacy and safety of HEC for treatment of mild active UC and preliminarily show the potential mechanism of how HEC acts. Finally, it will widen treatment options for patients with mild active UC.

Traditional Chinese medicine (Xiaoai Jiedu Decoction) as an adjuvant treatment for prevention new colorectal adenomatous polyp occurrence in post-polypectomy: Study protocol for a randomized controlled trial.

BACKGROUND: Colorectal Adenomatous Polyp (CAP) was one precursor of colorectal cancer (CRC) and having a high chance of developing into CRC. There was a lack of conclusive chemoprevention evidences to prevention new CAP occurrence in post-polypectomy. Xiaoai Jiedu Decoction, Chinese National Medical Professor (Zhou Zhongying)'s experience formula, has been used to treat new CAP occurrence in post-polypectomy from the 20th century in China. However, clinical research of Xiaoai Jiedu Decoction in the treatment of CAP recurrence was lack. We design this study to evaluate the efficacy and safety of Xiaoai Jiedu Decoction in the treatment of new CAP occurrence in post-polypectomy on colonoscopy. METHODS/DESIGN: A randomized, controlled, blind and multicenter trial to evaluate the efficacy and safety of Xiaoai Jiedu Decoction is proposed. CAP patients (after complete polypectomy under colonoscopy) will be randomly assigned into Xiaoai Jiedu Decoction group and Xiaoai Jiedu Decoction mimetic agent group. Patients will receive 6-course treatments and a 2-year follow-up. Follow-up colonoscopy will be anticipated to perform in 1 and 2 years after the baseline examinations. The primary outcome measure is the new CAP occurrence in 1 and 2 years. The secondary outcome measure is the occurrence of advanced adenoma in 1 and 2 years. DISCUSSION: This study will provide objective evidences to evaluate the efficacy and safety of Xiaoai Jiedu Decoction as an adjuvant treatment for new CAP occurrence in post-polypectomy. TRIAL REGISTRATION: NCT03616444.

Development of a Traditional Chinese Medicine Syndrome-Specific Scale for Ulcerative Colitis: The Large Intestine Dampness-Heat Syndrome Questionnaire.

The aim of this study was to develop and validate the large intestine dampness-heat syndrome questionnaire (LIDHSQ) for patients with ulcerative colitis (UC). The domains and items of the LIDHSQ were developed according to standard procedures, namely, construct definition, item generation, language testing, content validity, pilot study, and validation study. At first, a total of 20 items in 3 domains were generated based on literature review and expert consultation. After the item selection, the LIDHSQ contains 11 items in three domains: disease-related domain (diarrhoea, abdominal pain, bloody purulent stool, and mucus stool), heat domain (fever, dry mouth, red tongue, yellow fur, and anal burning), and dampness domain (greasy fur and defecation disorder). The Cronbach's alphas of all domains were greater than 0.6. All of the intraclass correlation coefficients were greater than 0.8. The LIDHSQ and domain scores of the patients with LIDHS were higher than those of the patients with other syndromes (P < 0.001). The area under the receiver operating characteristic curve of the LIDHSQ was 0.900, with a 95% confidence interval of 0.872-0.928. When the cut-off value of the LIDHSQ was ≥ 7, the sensitivity and specificity were 0.867 and 0.854, respectively. The LIDHSQ is valid and reliable for measuring LIDHS in UC patients with good diagnostic efficacy. We recommend the use of the LIDHSQ in Chinese UC patients.

Efficacy and indication optimization of Chinese medicine (Tiao-Chang Ke-Min granules) for diarrhea-predominant irritable bowel syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a chronic, recurring condition, prevalent in the general population. Current medication treatments usually leave patients undertreated. Nowadays, Chinese medicine (CM) is being considered as a promising treatment approach for IBS. However, due to methodological limitations, there is no strong evidence to support CM. Although IBS relapses are common, the relapse assessment has always been neglected in CM study designs. Meanwhile, in clinical practice and studies, it has been found that certain CM formulas can only benefit certain kinds of patients. Discovering what population and illness characteristics likely respond to outcomes may help improve the effectiveness of CM. The aims of this study are to evaluate the efficacy and safety of Tiao-Chang Ke-Min (TCKM) granules for IBS, especially in reducing IBS symptoms' relapse, by a high-quality randomized controlled trial and then to optimize the indication of the TCKM granules. METHODS/DESIGN: This is a parallel-group, randomized, double-blind, placebo-controlled trial embedded with outcome predictive factors. Eligible patients with diarrhea-predominant IBS will be randomized into either a TCKM granule group or a placebo group. Patients from both groups will receive health education. The treatment duration is 4 weeks and the follow-up is 12 weeks. The primary outcome is global improvement measured with adequate relief (AR). The second outcome measures include time until relief, time until first relapse, total relapse times, long-term effectiveness, individual symptoms, IBS-Symptom Severity Score (IBS-SSS), IBS-Quality of Life Questionnaire (IBS-QOL), and Hospital Anxiety and Depression Scale (HADS). Predictive factors associated with patient and illness characteristics have been widely collected. These factors will be embedded in this trial for further identification. DISCUSSION: This trial may provide high-quality evidence on the efficacy and safety of TCKM granules for IBS and a more accurate indication. Importantly, this trial will provide a new research method for improving the therapeutic effects of CM for clinicians and researchers. To address IBS relapse assessment, a series of special definitions of relapse incidents has been made for this trial. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR-IOR-17010600 . Registered on 9 February 2017.

Effects of competitive ions, humic acid, and pH on removal of ammonium and phosphorous from the synthetic industrial effluent by ion exchange resins.

The removal of the ammonium and phosphorous from the synthetic industrial effluent by the ion exchange resins was studied in this paper, aiming at the determination of the effects of competitive ions, humic acid, pH and resin amount. The kinetic experiments show that the equilibrium time for the removal of both contaminants in the absence and presence of the competing matters was 4 h. Na+ and K+ significantly reduced the ammonium removal percentage, while the existence of Mg2+, Ca2+ and humic acid also had a negative influence. Adsorption of ammonium ions in both absence and presence of Na+ and K+ observed the linear isotherm, however, it did not follow commonly used isotherms in the presence of Na+, K+, Mg2+, Ca2+ and humic acid. The phosphorous removal decreased in the presence of the competitive matters, such as Cl-, CO3(2-), SO4(2-) and humic acid. Higher pH can cause higher phosphorous removal percentage. A decrease in the solution pH was observed in the phosphorous removal experiments, possibly due to the ion exchange and the adsorption of OH-. Uptake of humic acid by the resins was observed. Finally, a series of fixed-bed experiments were performed, showing that the performance was dependent on the empty bed contact time (EBCT). Higher EBCT would cause higher bed volumes of both treated ammonium and phosphorous.