Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation.

BACKGROUND: Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM). AIM: To explore the potential mechanism of WMP in the treatment of CIM through experimental research. METHODS: We used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed. RESULTS: WMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1ß, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid). CONCLUSION: WMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.

Effect of three Napier grass varieties on phytoextraction of Cd- and Zn-contaminated cultivated soil under mowing and their safe utilization.

The use of Napier grass to remediate heavy metal-contaminated soil is a new phytoremediation technique. The objective of this study was to evaluate the ability of Napier grass (Pennisetum purpureum Schumach.) to remediate Cd- and Zn-contaminated cultivated soil under nonmowing and mowing and the possibility of safe utilization of the stem and leaf after detoxification by liquid extraction. Three Napier grass varieties, P. purpureum cv. Mott (PM), P. purpureum cv. Red (PR), and P. purpureum cv. Guiminyin (PG), were planted in a field with 3.74 mg kg-1 Cd and 321.26 mg kg-1 Zn for 180 days. The maximum amounts of Cd and Zn removed by PG were 197.5 and 5023.9 g ha-1, respectively, almost equaling those of hyperaccumulators. Compared with nonmowing, mowing did not decrease the Cd and Zn contents in various tissues but increased the biomasses of PM, PR, and PG by 86.6%, 18.9%, and 26.1%, respectively. Compared with nonmowing, the amounts of Cd removed by PM, PR, and PG under mowing increased by 110.5%, 40.0%, and 107.9%, respectively, and that of Zn increased by 63.0%, 53.1%, and 71.6%. The dominant Cd and Zn chemical fractions in Napier grass were the pectate- and protein-integrated fractions. After liquid extraction, although the nutrient element (Ca, K, Mg, and Mn) contents in the stem and leaf were reduced significantly, the Cd and Zn contents decreased below the limit of the Chinese Hygienic Standard for Feeds, and the crude protein content was largely retained. Such detoxified stems and leaves can be safely used as feeds or as raw materials for energy production.

Acupuncture plus Chinese Herbal Medicine for Irritable Bowel Syndrome with Diarrhea: A Systematic Review and Meta-Analysis.

PURPOSE: To comprehensively evaluate the efficacy and safety of acupuncture combined with Chinese herbal medicine (CHM) in treating irritable bowel syndrome with diarrhea (IBS-D). METHODS: Relevant randomized controlled trials (RCTs) were systemically retrieved from electronic databases from inception to March 2018, including the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biological Medical Database (CBM, SinoMed), China Science and Technology Journal Database (VIP), and Wan Fang Data. Meanwhile, pooled estimates, including the 95% confidence interval (CI), were calculated for primary and secondary outcomes of IBS-D patients. Besides, quality of relevant articles was evaluated using the Cochrane Collaboration's risk of bias tool, and the Review Manager 5.3 and Stata12.0 softwares were employed for analyses. RESULTS: A total of 21 RCTs related to IBS-D were included into this meta-analysis. Specifically, the pooled results indicated that (1) acupuncture combined with CHM might result in more favorable improvements compared with the control group (relative risk [RR] 1.29; 95% CI 1.24-1.35; P =0.03); (2) the combined method could markedly enhance the clinical efficacy in the meantime of remarkably reducing the scores of abdominal pain (standardized mean difference [SMD] -0.45; 95% CI -0.72, -0.17; P = 0.002), abdominal distention/discomfort (SMD -0.36; 95% CI -0.71, -0.01; P = 0.04), diarrhea (SMD -0.97; 95% CI -1.18, -0.75; P < 0.00001), diet condition (SMD -0.73; 95% CI -0.93, -0.52; P<0.00001), physical strength (SMD -1.25; 95% CI -2.32, -0.19; P = 0.02), and sleep quality (SMD -1.02; 95% CI -1.26, -0.77; P < 0.00001) compared with those in the matched groups treated with western medicine, or western medicine combined with CHM. Additionally, a metaregression analysis was constructed according to the name of prescription, acupuncture type, treatment course and publication year, and subgroup analyses stratified based on the names of prescriptions and acupoints location were also carried out, so as to explore the potential heterogeneities; and (3) IBS-D patients treated with the combined method only developed inconspicuous adverse events; more importantly, the combined treatment had displayed promising long-term efficacy. CONCLUSIONS: Findings in this study indicate that acupuncture combined with CHM is suggestive of an effective and safe treatment approach for IBS-D patients, which may serve as a promising method to treat IBS-D in practical application. However, more large-scale, multicenter, long-term, and high-quality RCTs are required in the future, given the small size, low quality, and high risk of the studies identified in this meta-analysis.

Disaster Medicine in China: Present and Future.

Disaster can strike people in any community at any time anywhere in the world. Disasters occur with high frequency, take on multiple forms, and exert wide influence, typically causing property damage, injuries, and death. As the world's largest developing country, China incurs great costs when a disaster hits. After the Wenchuan earthquake in 2008, the Chinese government focused its attention on the construction of an emergency response system, the creation of disaster prevention and mitigation systems, and the development of a disaster medicine program. Here, we describe the current status of disaster medicine in China, focusing on the following four aspects: the Emergency Management System, Education & Training, Rescue Practices, and Research. We also discuss the future of disaster medicine in China. (Disaster Med Public Health Preparedness. 2018;12:157-165).

Preventive effect of Actinidia valvata Dunn extract on N-methyl-N'-nitro-N-nitrosoguanidine-induced gastrointestinal cancer in rats.

PURPOSE: This study was conducted to assess the preventive effect of Actinidia valvata Dunn (AVD) extract on an animal model of gastrointestinal carcinogenesis on the basis of changes in tumor incidence, cell proliferation, and apoptosis. MATERIALS AND METHODS: Seventy-five male Wistar rats were divided into five different treatment groups with 15 rats in each group. Group I was given normal feed, whereas Groups II to IV were treated with 10% sodium chloride in the first six weeks and 100 ug/mL of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in drinking water for 24 weeks. Group II was then given normal feed, whereas Group III was given AVD extract (0.24 g/kg/day) for 12 weeks. Group IV was given AVD extract from the first week to the 36th week, whereas Group V was treated with AVD extract alone for 36 weeks. All rats were sacrificed at the end of the 36-week experiment and assessed for the presence of gastrointestinal tumors. The occurrence of cancer was evaluated by histology. Bax, Bcl-2, Caspase-3, and cyclinD1 were determined by immunohistochemical staining and Western blotting. RESULTS: The incidences of gastric cancer were 0% in Group I, 73.3% in Group II, 33.3% in Group III, 26.7% in Group IV, and 0% in Group V. Bcl-2 and cyclinD1 expression was decreased in AVD extract treated groups, whereas Bax and Caspase-3 expression was increased. Comparison with group II revealed significant differences (p<0.01). CONCLUSIONS: AVD extract exhibits an obvious preventive effect on gastrointestinal carcinogenesis induced by MNNG in rats through the regulation of cell proliferation and apoptosis.

[Perioperative cardiovascular abnormality in elder patients with silent coronary heart disease].

OBJECTIVE: To explore the perioperative cardiovascular dysfunction and its relevance to age in patients with silent coronary heart disease (or silent myocardial ischemia), and explore the clinical treatment and recovery of perioperative arrhythmias. METHODS: One hundred and eighty cases were selected from selective surgery patients with silent myocardial ischemia (SMI). Among the cases, 130 patients older than 51 years old were divided into 51 - 60 year-old group, 61- 70 year-old group and 71 - 80 year-old group. Control group was set up by other 50 patients younger than 51 years old. Electrocardiogram data of 24 h before the operation, 24 h after the operation and 48 h after the operation were continuously monitored by dynamic electrocardiogram (DCG). The electrocardiogram data of ST shifting, arrhythmia incidences of different type and at different time were analyzed by professional doctors. At the same time, the treatment and recovery of perioperative arrhythmia were recorded. RESULTS: As the age increase, the magnitude and duration of ST shifting appeared upward trend compared to the control group (P < 0.05, P < 0.01). The incidence of ST elevation in 71 - 80 year-old group was higher than the control group (P < 0.05). The ST depression duration in 61 - 70 and 71 - 80 year-old group and ST elevation magnitude in 71 - 80 year-old group were higher than 51 - 60 year-old group (P < 0.05). Compared to the control group, the incidence of accelerated idioventricular rhythm (AIR) in 61 - 70 year-old group and the incidence of sinus bradycardia (SB), ventricular premature beat (VPB), ventricular tachycardia (VT) in 71 - 80 year-old group were higher (P < 0.05, P < 0.01). Compared to the 51 - 60 year-old group, the incidence of atrial fibrillation (AF) in 61 - 70 year-old group and the incidence of VP, VT, AF in 71 - 80 year-old group were higher (P < 0.05, P < 0.01). The arrhythmia incidences in 24 h after operation were higher than 48 h after operation and 24 h before operation (P < 0.01). As the age increase, the recovery incidence by removing inducement was decreased, but the recovery incidences by drug and electric-shock treatment were increased (P < 0.05). CONCLUSION: Old SMI patients have high levels of perioperative myocardial ischemia and arrhythmia, and 24 h after operation is the period of high incidence.

[Effect of Fagopyrum cymosum (Trev.) Meisn alcohol extract on defecation and isolated colon of diarrhea-IBS rats and its mechanism].

OBJECTIVE: To explore the intervention of Fagopyrum cymosum (Trev.) Meisn alcohol extract (FAE) on defecation function and motor functions of isolated colons of diarrhea-predominant irritable bowel syndrome (D-IBS) rats and to study its underlying mechanism. METHODS: The D-IBS rat model was established by neonatal pups maternal separation (NMS) combined with intracolonic infusion of acetic acid (AA). Adult IBS rats were randomly divided into the pre-intervention control group (n = 10, with no gastrogavage), the normal saline control group (n = 10, administered with normal saline by gastrogavage), the pre-treatment model group (n = 8,with no gastrogavage),the normal saline model group (n = 8, administered with normal saline by gastrogavage), the low dose FAE group (n = 8, administered with 6 g/kg FAE by gastrogavage), the high dose FAE group (n = 8, administered with 24 g/kg FAE by gastrogavage), and the Pinaverium Bromide group (n = 8, administered with 0.02 g/kg Pinaverium Bromide by gastrogavage). All medication was performed once daily for 2 weeks. The abdominal withdrawal reflex (AWR) was employed to evaluate the visceral hypersensitivity; their loose and watery stool grade was assessed by Bristol scores for stool consistency; and their fresh feces weight was calculated. In vitro effect of different concentrations of FAE and Pinaverium Bromide (0.02 µg/mL) on spontaneous contraction and spasmodic contraction induced by acetylcholine (Ach) in rats' isolated colon were observed and the influence on the intestinal calcium channel was evaluated. RESULTS: Compared with the pre-intervention control group, the pain pressure threshold and the maximum tolerance pressure decreased significantly in the pre-intervention model group (P < 0.05), and the loose and watery stool grade and fresh feces weight increased drastically (P < 0.01). Compared with the normal saline control group, the pain pressure threshold and the maximum tolerance pressure decreased significantly in the normal saline model group (P < 0.05), and the loose and watery stool grade and fresh feces weight increased markedly (P < 0.01). Compared with the normal saline model group, the pain pressure threshold of 24 g/kg FAE and Pinaverium Bromide group significantly increased (P < 0.05). The loose and watery stool grade and fresh feces weight decreased obviously in the low dose FAE group, the high dose FAE group, and the Pinaverium Bromide group (P < 0.05). FAE (30, 100, 300, 1,000, and 3,000 µg/mL) and Pinaverium Bromide could significantly inhibit spontaneous contraction of isolated intestines (P < 0.05, P < 0.01), and FAE (30, 100, and 300 x 10(-6) g/mL) could remarkably inhibit their spasmodic contraction and contractile tension induced by Ach and Ca2+ respectively (P < 0.05, P < 0.01) in a concentration-dependent manner. Pinaverium Bromide also could significantly inhibit Ach and Ca2+ induced contraction. CONCLUSION: Effective components of FAE improved the defecation function and inhibited enterospasm induced intestinal hyperactivity in IBS model rats via antagonizing calcium channel competitively and inhibiting colonic motility dose-dependently.

Cryptotanshinone has diverse effects on cell cycle events in melanoma cell lines with different metastatic capacity.

PURPOSE: Cryptotanshinone is a major active component of Salvia miltiorrhiza, which is often used as Chinese herbal medicine in cancer therapy. Here, we systematically assessed the anti-tumor effect of Cryptotanshinone on two melanoma cell lines with low/high-metastatic capacity (B16/B16BL6). METHODS: MTT and LDH assays were used to evaluate cell growth and cytotoxicity. We assessed the effect of Cryptotanshinone on cell apoptosis or proliferation by Annexin V, TUNEL or BrdU assay. Cell cycle distribution was detected by flow cytometry. The integrity of cell cycle checkpoints was determined by mutational analyses of B-RAF and N-RAS, and the expression of cell cycle-associated proteins by western blotting. RESULTS: Treatment with Cryptotanshinone had no obvious effect on cell apoptosis but significantly inhibited cell proliferation. Cryptotanshinone slightly increased the expression of p53, Chk1, and Chk2 in both B16 and B16BL6. Interestingly, Cryptotanshinone induced G1 arrest with a concomitant increase in p21 expression in B16BL6 cells. However, in B16 cells, Cryptotanshinone induced the G2/M arrest through its induction of Cdc25c. Regulation of Cyclin A1, Cyclin B1 and Cdk1/cdc2 expression might contribute to the different cell cycle patterns in B16 and B16BL6 after Cryptotanshinone treatment. CONCLUSIONS: Cryptotanshinone could have diverse effects on cell cycle events in melanoma cell lines with different metastatic capacity. This property might offer an opportunity to study underlying mechanisms for the different antitumor effects of administered Cryptotanshinone in B16 and B16BL6 cells.

Danshensu has anti-tumor activity in B16F10 melanoma by inhibiting angiogenesis and tumor cell invasion.

Danshensu, the major water-soluble component of Radix Salviae Miltiorrhizae (Danshen), is the basic chemical structure of various salvianolic acids. This study was to evaluate the anti-tumor activity of danshensu in a series of in vitro and in vivo models. The effect of danshensu on B16F10 melanoma cell and HUVEC proliferation were assessed by MTS assay, and cell invasion and migration were investigated by transwell chamber assay. The effect of danshensu on angiogenesis was evaluated by HUVEC migration assay, tube formation assay and chick chorioallantoic membrane assay. The expression of MMP-2, -9 and VEGF in B16F10 melanoma cell were detected by western blotting after danshensu treatment. The role of danshensu in tumor metastasis in vivo was evaluated by spontaneous and experimental B16F10 melanoma metastasis model. Although danshensu had no inhibitory effect on B16F10 melanoma cell and HUVEC proliferation, it significantly inhibited B16F10 melanoma cell invasion (at 0.05, 0.5, 5 microM) and migration (at 0.5, 5 microM). It also dramatically suppressed VEGF-induced endothelial migration (at 0.5, 5 microM), tube formation in vitro (at 4, 20 microM) and new vessel formation in CAM in vivo (100 microg/egg). Danshensu (at 5, 50 microM) significantly down-regulates protein expression of MMP-2, -9 and VEGF in B16F10 melanoma cell. In animal model, danshensu (20, 40 mg/kg) also possessed inhibitory effect on lung metastasis in spontaneous (46-day treatment) and experimental (23-day treatment) B16F10 melanoma metastasis model. All these results suggest that danshensu has anti-tumor activity by affecting on tumor angiogenesis and tumor invasion.