Discovery of a prominent dual-target DDR1/EGFR inhibitor aimed DDR1/EGFR-positive NSCLC.

This study aimed to develop the first dual-target small molecule inhibitor concurrently targeting Discoidin domain receptor 1 (DDR1) and Epidermal growth factor receptor (EGFR), which play a crucial interdependent roles in non-small cell lung cancer (NSCLC), demonstrating a synergistic inhibitory effect. A series of innovative dual-target inhibitors for DDR1 and EGFR were discovered. These compounds were designed and synthesized using structural optimization strategies based on the lead compound BZF02, employing 4,6-pyrimidine diamine as the core scaffold, followed by an investigation of their biological activities. Among these compounds, D06 was selected and showed micromolar enzymatic potencies against DDR1 and EGFR. Subsequently, compound D06 was observed to inhibit NSCLC cell proliferation and invasion. Demonstrating acceptable pharmacokinetic performance, compound D06 exhibited its anti-tumor activity in NSCLC PC-9/GR xenograft models without apparent toxicity or significant weight loss. These collective results showcase the successful synthesis of a potent dual-targeted inhibitor, suggesting the potential therapeutic efficacy of co-targeting DDR1 and EGFR for DDR1/EGFR-positive NSCLC.

2'-Hydroxychalcone Induces Autophagy and Apoptosis in Breast Cancer Cells via the Inhibition of the NF-κB Signaling Pathway: In Vitro and In Vivo Studies.

2'-Hydroxychalcone is a hydroxyl derivative of chalcones, which are biosynthetic precursors of flavonoids and rich in the human diet. The anticancer activity of 2'-hydroxychalcone has been reported in several cancers but remains to be investigated in breast cancer. In the current study, 2'-hydroxychalcone showed significant cytotoxicity against breast cancer cell lines MCF-7 and CMT-1211. It could inhibit breast cancer cell proliferation, migration, and invasion in vitro and suppress tumor growth and metastasis in vivo. Mechanistic investigation revealed that the NF-κB pathway was significantly inhibited by 2'-hydroxychalcone treatment accompanied by an excessive intracellular accumulation of reactive oxygen species, induction of endoplasmic reticulum stress, and activation of JNK/MAPK. In addition, 2'-hydroxychalcone elevated the autophagic levels in breast cancer cells equipped with increasing numbers of autophagy vesicles and complete autophagic flux. Finally, autophagy-dependent apoptosis was observed in 2'-hydroxychalcone-induced cell death. In conclusion, 2'-hydroxychalcone enhances the autophagic levels and induces apoptosis in breast cancer cells, which could be contributed to the inhibition of the pro-survival NF-κB signaling, indicating a promising potential for 2'-hydroxychalcone in future anticancer drug development.

An electrochemical aptasensor for detection of carbofuran using gold nanoparticles decorated hierarchical porous carbon as an effective sensing platform.

In this study, a novel electrochemical aptasensor for carbofuran (CBF) detection is prepared by gold nanoparticles decorated hierarchical porous carbon (Au@HPC). The prepared carbon materials show a three-dimensional hierarchical structure with a large specific surface area and a highly developed porous structure. Aptamers loading significantly improves when gold nanoparticles are embedded into the hierarchical porous carbon skeleton. Besides, Au@HPC modified electrode exhibits a large electroactive area and excellent electrochemical conductivity, serving as a promising platform for highly sensitive and selective electrochemical detection of CBF. The developed CBF electrochemical aptasensor shows a wide linear from 1.0 to 100000 pg/L with a detection limit of 0.5 pg/L, demonstrating an extraordinary sensitivity compared to other sensors for CBF detection. Additionally, the designed aptasensor was used to monitor the CBF in vegetable samples, with a recovery range from 98.4% to 104.8%. The results coincide with the standard test method, revealing its practicability in the food safety analysis.

A novel electrochemical aptasensor based on polyaniline and gold nanoparticles for ultrasensitive and selective detection of ascorbic acid.

Ascorbic acid (AA) is involved in many physiological activities of the body and plays an important role in maintaining and promoting human health. It is also present in many natural and artificial foods. Therefore, the development of highly sensitive and accurate AA sensors is highly desirable for human health monitoring, as well as other commercial application fields. Herein, an ultrasensitive and selective electrochemical sensor based on an aptamer was developed for the determination of AA for the first time. The aptasensor was fabricated by modifying a composite made of polyaniline (PANI) and gold nanoparticles (AuNPs) on a glassy carbon electrode. The morphologies and electrochemical properties of the resulting electrodes were characterized by various analytical methods. The results indicated relatively good electrical conduction properties of PANI for accelerated electron transfer. The modification with AuNPs provided signal amplification, suitable for applications as novel platforms for the sensitive sensing of AA. Under optimized conditions, the proposed aptasensor displayed a wide linear response toward the detection of AA from 1.0 to 1.0 × 105 ng L-1 coupled with a low detection limit of 0.10 ng L-1. The sensor also exhibited excellent selectivity and high stability, with at least 2000-fold higher sensitivity than similar previously reported methods. Importantly, the aptasensor exhibited promising properties for the determination of AA in real fruits, vegetables, and infant milk powder, thereby showing potential for food analysis.

Effect of polyphenol compounds on Helicobacter pylori eradication: a systematic review with meta-analysis.

OBJECTIVES: Polyphenol compounds are classified as organic compounds with phenolic units exhibiting a variety of biological functions. This meta-analysis aims to assess the efficacy and safety of polyphenol compounds (curcumin, cranberry, garlic, liquorice and broccoli) in eradicating Helicobacter pylori. DESIGN: Systematic review and meta-analysis. METHODS: Literature searches were conducted on PubMed, Embase, The Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal Database and Wan Fang database from inception to January 2022. All randomised controlled trials comparing polyphenol compounds with the placebo or used as an adjunct treatment are included in this meta-analysis.The treatment effect for dichotomous outcomes was assessed using risk ratio (RR), while for continuous outcomes, mean differences both with 95% CIs, were used. Subgroup analyses were carried out for different treatment schemes and polyphenol compound species. RESULTS: 12 trials were included in the meta-analysis. The total eradication rate of H.pylori in the polyphenol compounds group was higher than in the group without polyphenol compounds. Statistical significance was also observed (RR 1.19, 95% CI 1.03 to 1.38, p=0.02). The most frequent adverse effects of polyphenol compounds included diarrhoea, headache and vomiting. However, there were no differences regarding side effects between the two groups (RR 1.47, 95% CI 0.83 to 2.58, p=0.18). In subgroup analyses, the H.pylori eradication rate regimens with polyphenols therapy was superior to that of regimens without polyphenols therapy in the polyphenols versus placebo subgroup (RR 4.23, 95% CI 1.38 to 12.95, p=0.01), polyphenols plus triple therapy versus triple therapy subgroup (RR 1.11, 95% CI 1.01 to 1.22, p=0.03). CONCLUSION: Polyphenol compounds can improve H.pylori eradication rates. Polyphenol compounds plus standard triple therapy can significantly improve the eradication. However, no evidence of a higher incidence of side effects could be found. PROSPERO REGISTRATION NUMBER: CRD42022307477.

Significant Differences in Gut Microbiota Between Irritable Bowel Syndrome with Diarrhea and Healthy Controls in Southwest China.

BACKGROUND: Irritable bowel syndrome (IBS) is a heterogeneous disease, which is closely related to environmental factors and gut microbiota. OBJECTIVE: To study gut microbiota in IBS-D of Han nationality in Southwest China and explore its relationship with environmental factors. METHODS: One hundred and twenty cases of IBS-D and 63 cases of HCs were recruited; baseline data such as age, height, and weight were collected. HAMA, HAMD, IBS-SSS, IBS-QOL, and laboratory tests were performed. Feces were collected for 16S rDNA sequencing. Then, the differences of gut microbiota were analyzed and looked for biomarkers of each. FAPROTAX was used to predict the functional differences of gut microbiota. Spearman analysis was conducted between the phylum level and environmental factor. RESULTS: There were significant differences in daily life between IBS-D and HCs, especially in the spicy taste. The scores of HAMA and HAMD, urea, and transaminase in IBS-D were significantly higher than those of HCs. The richness of gut microbiota in IBS-D was significantly lower than that of HCs, as well as the beta diversity, but not diversity. The biomarkers of IBS-D were Prevotella, Clostridiales, and Roseburia, and the biomarkers of HCs were Veillonellaceae, Bacteroides coprocola, and Bifidobacteriales. The functions of gut microbiota in IBS-D were significantly different from HCs. Correlation analysis showed that multiple gut microbiota were closely related to HAMA, IBS-SSS, IBS-QOL, inflammatory indexes, and liver enzymes. CONCLUSION: There are significant differences in richness of gut microbiota, flora structure, and flora function between IBS-D and HCs in Southwest China. These differences may be closely related to environmental factors such as eating habits, living habits, and mental and psychological factors. CLINICAL TRIAL REGISTRATION: The trial was registered and approved in China Clinical Trial Registry (Registration No. ChiCTR2100045751).

A sensitive MnO2 nanosheet sensing platform based on a fluorescence aptamer sensor for the detection of zearalenone.

An aptamer sensor based on manganese dioxide (MnO2) nanosheets was developed for the detection of zearalenone (ZEN). The ZEN aptamer was modified at the 5'-end by a 6-carboxyfluorescein (6-FAM) fluorophore with self-assembly on MnO2 nanosheets. Interaction of the 6-FAM fluorophore at the 5'-end of the ZEN aptamer with the MnO2 nanosheet lowered fluorescence (FL) intensity due to fluorescence resonance energy transfer (FRET). The introduction of ZEN into the sensing system resulted in hybridization with the ZEN aptamer, forming a stable G-quadruplex/ZEN, which exhibited a low affinity for the MnO2 nanosheet surface. The distance between the 6-FAM fluorophore and MnO2 nanosheet hampered FRET, with a consequent strong FL signal. Under the optimal experimental conditions, the FL intensity of the sensing system showed a good linear correlation with ZEN concentration in the range of 1.5-10.0 ng mL-1, and a detection limit (S/N = 3) of 0.68 ng mL-1. The sensing system delivered enhanced specificity for the detection of ZEN, and can find wide application in the detection of other toxins by replacing the sequence of the recognition aptamer.

The safety of esophageal cancer surgery during COVID-19.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has drastically challenged the safety of on esophageal cancer (EC) surgery during COVID-19. The study aimed to evaluate the safety of EC surgery during the COVID-19 pandemic. METHODS: This systematic review was performed in accordance with the PRISMA-P 2015 guidelines and registered in PROSPERO (registration number: CRD42022335164). A systematic search of PubMed, Embase, Cochrane Library, Web of Science, Medline, Chinese National Knowledge Infrastructure database, Chinese Scientific Journal database, and Wan Fang database was conducted to identify potentially relevant publications from January 2020 to May 2022. All data were independently extracted by two researchers. We will apply a fixed-effect model or random effect model basis on the heterogeneity test and employ with RevMan 5.4.1 software for data synthesis. The dichotomous surgical outcomes used risk ratios or risk differences, and for continuous surgical outcomes, mean differences (MD) or standardized MD, both with 95% confidence intervals were used. The primary outcomes were postoperative complications, anastomotic leaks, and mortality. The secondary outcomes were total hospital stay, postoperative stay, preoperative waiting, operation time, blood loss, transfusion, postoperative intensive care unit (ICU) stay, number of patients needing ICU stay, and 30-day readmission. RESULTS: This study will comprehensively summarize the high-quality trials to determine the safety of EC surgery during COVID-19. CONCLUSION: Our systematic review and meta-analysis will present evidence for the safety of EC surgery during COVID-19.

Traditional Chinese Medicine Regulates Th17/Treg Balance in Treating Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), also known as chronic nonspecific inflammatory disease of the colon and rectum, is primarily characterized by mucopurulent bloody stools, diarrhea, abdominal pain, and tenesmus. Its cause is uncertain. IBD patients frequently experience a high rate of recurrence, a protracted treatment course, and a high risk of carcinogenesis. Additionally, the difficulty of treatment is significantly increased by these illness characteristics. Currently, the normal treatment for this illness can lessen symptoms to some amount and even meet clinical treatment requirements, but due to serious side effects, unfavorable reactions, and high costs, we need to develop better complementary and alternative medicines. A number of studies have found that the imbalance of T helper cell 17 (Th17)/regulatory T cells (Treg) contributes significantly to the occurrence and progression of IBD and that Th17/Treg balance restoration is frequently useful in the management of IBD. As a result, regulating the Th17/Treg balance has also emerged as a novel approach to treating IBD. Traditional Chinese medicine (TCM) has gained popularity in recent years due to its advantages of low side effects, a variety of targets, and multiple regulatory mechanisms. A number of studies have shown that TCM can successfully intervene in the Th17/Treg imbalance and restore it, and research on the prevention and treatment of IBD by TCM by restoring Th17/Treg has also shown promising results. The characteristics of the Th17/Treg balance and its role in the pathogenesis of IBD, as well as the role of TCM in regulating the Th17/Treg imbalance, are analyzed. The research results are expected to provide a theoretical basis for the clinical treatment and pathology mechanism research of IBD.

Highly sensitive electrochemical detection of myricetin in food samples based on the enhancement effect of Al-MOFs.

Microporous aluminum-based metal-organic frameworks (CAU-1) are used to develop a simple and sensitive electrochemical sensor for myricetin (MYR) based on a modified carbon paste electrode (CPE) for the first time. The morphologies and electrochemical properties of the as-synthesized CAU-1 are studied utilizing various analytical methods including scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, N2 adsorption-desorption, and electrochemical impedance spectroscopy. In terms of electrochemical oxidation of MYR, CAU-1/CPE with its large number of active micropores and rapid electron transfer demonstrates superior performance compared to the bare CPE. Under optimized conditions, the calibration curve for MYR exhibits a linear range of 1.0-10 µg L-1 and 10-1000 µg L-1 with a detection limit of 0.50 µg L-1. The developed CAU-1/CPE exhibits superior analytical characteristics, compared to previously reported electrochemical sensors for MYR detection. Furthermore, CAU-1/CPE is employed to determine MYR in Myrica bark samples, and the results are consistent with those obtained by high-performance liquid chromatography, demonstrating the excellent potential of CAU-1/CPE for the rapid analysis of MYR in complicated real samples.

Network meta-analysis on efficacy and safety of different Janus kinase inhibitors for ulcerative colitis.

WHAT IS KNOWN AND OBJECTIVE: In the absence of head-to-head comparisons, the objective of this study was to conduct a network meta-analysis (NMA) to indirectly compare the relative efficacy and safety of Janus kinase (JAK) inhibitors for ulcerative colitis (UC). METHODS: We searched PubMed, EMBASE, Web of Science and Cochrane Library from the database inception until 13 August 2021. No randomized controlled trials (RCTs) that directly compared these interventions were identified. Therefore, a fixed-effects Bayesian NMA was conducted by identifying a connected (via comparison to placebo) network of RCTs. Ranking was assessed using surface under the cumulative ranking (SUCRA) probabilities. RESULTS AND DISCUSSION: Seven RCTs including 3190 patients met the inclusion criteria. Filgotinib 100 mg was ranked highest for induction of endoscopic remission (SUCRA, 0.67) whereas peficitinib 75 mg BID was ranked highest for induction of clinical response (SUCRA, 0.72). Peficitinib 75 mg was ranked highest for induction of mucosal healing (SUCRA, 0.71), whereas peficitinib 150 mg was ranked highest for clinical remission (SUCRA, 0.74). Tofacitinib 3 mg had the highest probability of being the best treatment in terms of change from baseline in Mayo score (SUCRA, 0.78). Adverse events (AEs) and treatment discontinuations or withdrawals from the study due to AEs did not differ between JAK inhibitors and placebo groups. WHAT IS NEW AND CONCLUSION: Based on indirect comparisons, peficitinib 75 mg/75 mg BID/150 mg, tofacitinib 3 mg and filgotinib 100mg were the most efficacious JAK inhibitor interventions in patients with UC. However, head-to-head trials are warranted to inform clinical decision-making with greater confidence.

Identification of miRNAs and genes for predicting Barrett's esophagus progressing to esophageal adenocarcinoma using miRNA-mRNA integrated analysis.

Barrett's esophagus (BE) is defined as any metaplastic columnar epithelium in the distal esophagus, which predisposes to esophageal adenocarcinoma (EAC). Yet, the mechanism through which BE develops to EAC still remain unclear. Moreover, the miRNA-mRNA regulatory network in distinguishing BE from EAC still remains poorly understood. To identify differentially expressed miRNAs (DEMs) and genes (DEGs) between EAC and BE from tissue samples, gene expression microarray datasets GSE13898, GSE26886, GSE1420 and miRNA microarray datasets GSE16456, GSE20099 were downloaded from Gene Expression Omnibus (GEO) database. GEO2R was used to screen the DEMs and DEGs. Pathway and functional enrichment analysis were performed by DAVID database. The protein-protein interaction (PPI) network was constructed by STRING and been visualized by Cytoscape software. Finnal, survival analysis was performed basing TCGA database. A total of 21 DEMs were identified. The enriched functions and pathways analysis inclued Epstein-Barr virus infection, herpesvirus infection and TRP channels. GART, TNFSF11, GTSE1, NEK2, ICAM1, PSMD12, CTNNB1, CDH1, PSEN1, IL1B, CTNND1, JAG1, CDH17, ITCH, CALM1 and ITGA6 were considered as the hub-genes. Hsa-miR-143 and hsa-miR-133b were the highest connectivity target gene. JAG1 was predicted as the largest number of target miRNAs. The expression of hsa-miR-181d, hsa-miR-185, hsa-miR-15b, hsa-miR-214 and hsa-miR-496 was significantly different between normal tissue and EAC. CDH1, GART, GTSE1, NEK2 and hsa-miR-496, hsa-miR-214, hsa-miR-15b were found to be correlated with survival.

Aminoglycosides with Anti-MRSA Activity: A Concise Review.

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti- MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

Efficacy and safety of hyperbaric oxygen therapy for moderate-to-severe ulcerative colitis: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Ulcerative colitis (UC) is a type of inflammatory bowel disease, and 62% of patients with UC felt that it is difficult for them to live a normal life. Furthermore, some researches have shown that about 15% of patients with UC undergo at least one extreme clinical course in their lifetime, and 10%-30% of patients with UC oblige colectomy. Although many investigations have demonstrated that HBO2 has a beneficial impact on UC treatment, a systematic review and meta-analysis are unavailable. Therefore, a meta-analysis is essential to assess the efficacy and safety of HBO2 in treating UC. METHODS AND ANALYSIS: A systematic search plan will be performed in the following seven databases with a restriction of time from inception to September 2020 to filter the eligible studies: PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journal Database (VIP) and Chinese Biomedical Database WanFang. Other related resources will be also searched. Two independent reviewers will choose eligible researches and extract data. The risk of bias will be evaluated based on Cochrane Collaboration's Risk of Bias tool and Newcastle-Ottawa Scale. Eventually, a systematic review and meta-analysis will be performed via the Review Manager V.5.3 statistical software and STATA V.14.0 software. ETHICS AND DISSEMINATION: This study will not involve the individual patient and any ethical problems since its outcomes are based on published data. Therefore, no ethical review and approval are required. We plan to publish the study in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020210244.

Completed atrioventricular block induced by atrial septal defect occluder unfolding: A case report.

BACKGROUND: An atrial septal defect is a common condition and accounts for 25% of adult congenital heart diseases. Transcatheter occlusion is a widely used technique for the treatment of secondary aperture-type atrial septal defects (ASDs). CASE SUMMARY: A 30-year-old female patient was diagnosed with ASD by transthoracic echocardiography (TTE) 1 year ago. The electrocardiogram showed a heart rate of 88 beats per minute, normal sinus rhythm, and no change in the ST-T wave. After admission, TTE showed an atrial septal defect with a left-to-right shunt, aortic root short-axis section with an ASD diameter of 8 mm, a parasternal four-chamber section with an ASD diameter of 9 mm, and subxiphoid biatrial section with a diameter of 13 mm. Percutaneous occlusion was proposed. The intraoperative TTE scan showed that the atrial septal defect was oval in shape, was located near the root of the aorta, and had a maximum diameter of 13 mm. A 10-F sheath was placed in the right femoral vein, and a 0.035° hard guidewire was used to establish the transport track between the left pulmonary vein and the inferior vena cava. A shape-memory alloy atrial septal occluder with a waist diameter of 20 mm was placed successfully and located correctly. TTE showed that the double disk unfolded well and that the clamping of the atrial septum was smooth. Immediately after the disc was revealed, electrocardiograph monitoring showed that the ST interval of the inferior leads was prolonged, the P waves and QRS waves were separated, a junctional escape rhythm maintained the heart rate, and the blood pressure began to decrease. After removing the occluder, the elevation in the ST segment returned to normal immediately, and the sinus rhythm returned to average approximately 10 min later. After consulting the patient's family, we finally decided to withdraw from the operation. CONCLUSION: Compression of the small coronary artery, which provides an alternative blood supply to the atrioventricular nodule during the operation, leads to the emergence of a complete atrioventricular block.

Traditional Chinese medicine for irritable bowel syndrome: A protocol for meta-analysis.

BACKGROUND: Irritable bowel syndrom (IBS) is a common functional gastrointestinal disorder which is characterized as recurrent abdominal pain, abdominal discomfort, and abnormal bowel habits such as diarrhea, constipation, both or alternate appear. Although IBS is not fatal, it seriously affects the patients' daily life and work. Western drug, such as antidiarrheals, gastrointestinal antispasmodic, often cannot get satisfying curative effects. However, the therapeutic effect of Traditional Chinese medicine (TCM) on IBS is very satisfactory which was shown in a large number of randomized controlled trials. Although TCM has been widely used in clinical practice, its relative effectiveness and safety have not been confirmed. Therefore, this study will use meta-analysis to verify the efficacy and safety of different types of TCM in the treatment of IBS. METHODS: We search the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, Chinese Biomedical Literature Database, Pubmed, Embase, Web of Science, and the Cochrane library for all randomized controlled trial of TCM for the treatment of IBS from their inception to Oct 15, 2020. Two authors will independently select studies, extract data based on predesigned inclusion and exclusion criteria. Methodological quality assessment and risk of bias will be assessed using Cochrane bias risk tool. All data analysis will be conducted using Revman5.3, WinBUGS 1.4.3, and Stata14.2 software. RESULTS: This study will compare the different outcome indicators of various studies directly and indirectly, and provide a high-quality synthesis of effectiveness and safety of different TCM methods for patients with IBS. The main outcome indicators include effectiveness, remission rate (no drug symptoms), relapse rate, clinical absolute score, and relative score. Secondary outcome indicators included related adverse reactions and serum serotonin concentration. CONCLUSION: The conclusion of this systematic review will provide a high-quality evidence based on the efficacy and safety of different TCM treatment methods for IBS. REGISTRATION NUMBER: This study protocol has been funded through a protocol registry. The registry number is INPLASY2020100052.

Acupuncture combined with Tongxieyaofang for diarrhea-type irritable bowel syndrome: A protocol for meta-analysis.

BACKGROUND: As a traditional Chinese medicine external treatment method, acupuncture is characterized by simple operation, significant treatment effect and few side effects. Tong-Xie-Yao-Fang (TXYF), a Chinese patent medicine, combined with acupuncture has been widely used on treating Diarrhea Predominant Irritable Bowel Syndrome (IBS-D). However, the efficacy and safety of TXYF combined with acupuncture for the treatment of IBS-D are unclear. This study aims to investigate verify the efficacy and safety of TXYF combined with acupuncture for IBS-D. METHODS AND ANALYSIS: Randomized controlled trials of TXYF combined with acupuncture for all IBS-D will be searched in PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database from inception to October 20, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: Based on the current evidence, the potential rank of the efficacy and safety of TXYF plus acupuncture for IBS-D will be assessed. CONCLUSION: The findings of the study will provide helpful evidence for the efficacy and safety of TXYF combined with acupuncture in the treatment of IBS-D, facilitating clinical practice and further scientific studies.

Advances in Ca2+ modulation of gastrointestinal anion secretion and its dysregulation in digestive disorders (Review).

Intracellular calcium (Ca2+) is a critical cell signaling component in gastrointestinal (GI) physiology. Cytosolic calcium ([Ca2+]cyt), as a secondary messenger, controls GI epithelial fluid and ion transport, mucus and neuropeptide secretion, as well as synaptic transmission and motility. The key roles of Ca2+ signaling in other types of secretory cell (including those in the airways and salivary glands) are well known. However, its action in GI epithelial secretion and the underlying molecular mechanisms have remained to be fully elucidated. The present review focused on the role of [Ca2+]cyt in GI epithelial anion secretion. Ca2+ signaling regulates the activities of ion channels and transporters involved in GI epithelial ion and fluid transport, including Cl- channels, Ca2+-activated K+ channels, cystic fibrosis (CF) transmembrane conductance regulator and anion/HCO3 - exchangers. Previous studies by the current researchers have focused on this field over several years, providing solid evidence that Ca2+ signaling has an important role in the regulation of GI epithelial anion secretion and uncovering underlying molecular mechanisms. The present review is largely based on previous studies by the current researchers and provides an overview of the currently known molecular mechanisms of GI epithelial anion secretion with an emphasis on Ca2+-mediated ion secretion and its dysregulation in GI disorders. In addition, previous studies by the current researchers demonstrated that different regulatory mechanisms are in place for GI epithelial HCO3 - and Cl- secretion. An increased understanding of the roles of Ca2+ signaling and its targets in GI anion secretion may lead to the development of novel strategies to inhibit GI diseases, including the enhancement of fluid secretion in CF and protection of the GI mucosa in ulcer diseases.

Dietary supplements for prediabetes: A protocol for a systematic review and meta-analysis.

BACKGROUND: The number of prediabetic individuals is at a high level worldwide and they have an increased risk of developing diabetes, causing severe physical impairment and heavy financial burden. Recently, using various dietary supplements is increasingly common, and relevant trials of different diseases are increasing correspondingly. The effects of dietary supplements have been confirmed in some studies among prediabetic individuals. However, there remains no comprehensive systematic review to assess the efficacy and safety of dietary supplements intake in prediabetic individuals. METHODS: We plan to search and retrieve applicable randomized controlled trials of dietary supplements for prediabetic individuals in the following databases before June 2020: PubMed, Web of Science, EMBASE, the Cochrane Library, the Cochrane Central Register of Controlled Trials(CENTRAL), Allied and Complementary Medicine Database(AMED), Chinese Biomedical Literature database, Wan Fang database, Chinese Scientific Journal database (VIP), Chinese National Knowledge Infrastructure database(CNKI), and the ClinicalTrials.gov website. Two reviewers will separately perform study selection, data extraction, methodological quality assessment and quality of evidence assessment. Data analysis and publication bias will be conducted by Review Manager 5.3. RESULTS AND CONCLUSIONS: This evidence-based medicine systematic review will prove the efficacy and safety of multifarious dietary supplements for prediabetes. ETHICS AND DISSEMINATION: As this systematic review is based merely on already published literature, no approval of the ethics committee is required. We will disseminate this systematic review to a peer-reviewed journal. PROTOCOL REGISTRATION NUMBER: INPLASY202040057.

Mode of initiation and clinical significance of malignant rapid ventricular arrhythmias: An observational study.

The purpose of this study was to explore the modes of initiation and clinical significance of malignant rapid ventricular arrhythmias (MRVAs).The surface 12-lead electrocardiogram (ECG) or sustained electrocardiomonitor graph was analyzed in 79 patients. All patients had at least 1 MRVA after being admitted to the hospital.According to the length of coupling interval of the initial premature ventricular contraction of MRVA, the modes of initiation of MRVA were divided into the following types: those initiated by premature ventricular contraction with short coupling intervals in patients with normal Q-T interval, and for which short-long-short sequences before MRVA precipitation were not observed; those initiated following short-long-short sequences, which were divided into 2 types according to the length of Q-T interval: a normal Q-T interval and a long Q-T interval. On the basis of the different modes of onset, treatments of MRVA were different.MRVAs have different modes of onset depending on the patients' underlying condition. Prompt recognition of the mode of onset is necessary to facilitate appropriate management. These findings could have important pathophysiologic and clinical implications.