Sijunzi decoction enhances sensitivity of colon cancer cells to NK cell destruction by modulating P53 expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Sijunzi Decoction (SJZD), a traditional Chinese herbal remedy, is frequently employed in the treatment of various cancers, including colon cancer. Previous research suggests that SJZD plays a pivotal role in modulating the immune system and enhancing immunity against tumors. However, the precise role of SJZD in combating colon cancer and its potential molecular functions in regulating natural killer cells remain elusive. AIMS OF THE STUDY: To elucidate the potential mechanism underlying the anticolon cancer effects of SJZD in synergy with natural killer (NK) cells through both in vivo and in vitro experiments. MATERIALS AND METHODS: In vivo experiments: A subcutaneous tumor mouse model of colon cancer and in vivo NK cell depletion experiments were conducted to observe the anticolon cancer effects of SJZD. Flow cytometry assessed immune cell depletion in mouse spleens, while immunohistochemical (IHC) staining detected the expression of apoptotic genes in tumor tissues. In vitro experiments: The mechanism by which SJZD regulates the sensitization of colon cancer cells to NK cells was investigated using real-time polymerase chain reaction (RT-PCR), western blotting (WB), and co-culture experiments with NK cells. RESULTS: Sijunzi Decoction (SJZD) significantly impeded tumor growth in mice; however, NK cell depletion markedly attenuated the tumor-suppressive effect of SJZD. Immunohistochemical (IHC) results indicated that SJZD increased the expression of P53, death receptor 4 (DR4), and death receptor 5 (DR5) in tumor tissues. In vitro experiments, 24 h SJZD-pretreated colon cancer cells showed a substantial elevation in P53, DR4, and DR5 levels, and the activity of colon cancer cells significantly diminished after co-culture with NK cells. These effects of SJZD were reversed with the addition of the P53 inhibitor pifithrin-α (PFT-α), resulting in reduced inhibition of colon cancer cells by NK cells. CONCLUSION: SJZD enhances the levels of DR4 and DR5 through the modulation of P53 expression, consequently increasing the sensitivity of colon cancer cells to NK cell-mediated killing. These findings provide a theoretical foundation for the clinical application of SJZD in patients with colon cancer. In this study, we first investigated the effect of SJZD on subcutaneous tumor growth in mice with colon cancer using in vivo assays and assessed the impact of NK cells on the anticolon cancer effect of SJZD in vivo through NK cell depletion. In vitro experiments were conducted to explore the potential mechanism of action of SJZD in NK cell-mediated anticolon cancer effects.

SmEIL1 transcription factor inhibits tanshinone accumulation in response to ethylene signaling in Salvia miltiorrhiza.

Among the bioactive compounds, lipid-soluble tanshinone is present in Salvia miltiorrhiza, a medicinal plant species. While it is known that ethephon has the ability to inhibit the tanshinones biosynthesis in the S. miltiorrhiza hairy root, however the underlying regulatory mechanism remains obscure. In this study, using the transcriptome dataset of the S. miltiorrhiza hairy root induced by ethephon, an ethylene-responsive transcriptional factor EIN3-like 1 (SmEIL1) was identified. The SmEIL1 protein was found to be localized in the nuclei, and confirmed by the transient transformation observed in tobacco leaves. The overexpression of SmEIL1 was able to inhibit the tanshinones accumulation to a large degree, as well as down-regulate tanshinones biosynthetic genes including SmGGPPS1, SmHMGR1, SmHMGS1, SmCPS1, SmKSL1 and SmCYP76AH1. These are well recognized participants in the tanshinones biosynthesis pathway. Further investigation on the SmEIL1 was observed to inhibit the transcription of the CPS1 gene by the Dual-Luciferase (Dual-LUC) and yeast one-hybrid (Y1H) assays. The data in this work will be of value regarding the involvement of EILs in regulating the biosynthesis of tanshinones and lay the foundation for the metabolic engineering of bioactive ingredients in S. miltiorrhiza.

A Serum Pharmacochemistry and Network Pharmacology-based Approach to Study the Anti-depressant Effect of Chaihu-Shugan San.

AIMS: The aim of this study is to explore the anti-depressant mechanism of Chaihu- Shugan San based on serum medicinal chemistry and network pharmacology methods. BACKGROUND: Depression lacks effective treatments, with current anti-depressants ineffective in 40% of patients. Chaihu-Shugan San (CHSGS) is a well-known traditional Chinese medicine compound to treat depression. However, the chemical components and the underlying mechanisms targeting the liver and brain in the anti-depressant effects of CHSGS need to be elucidated. METHODS: The chemical components of CHSGS in most current network pharmacology studies are screened from TCMSP and TCMID databases. In this study, we investigated the mechanism and material basis of soothing the liver and relieving depression in the treatment of depression by CHSGS based on serum pharmacochemistry. The anti-depressant mechanism of CHSGS was further verified by proteomics and high-throughput data. RESULTS: Through serum medicinal chemistry, we obtained 9 bioactive substances of CHSGS. These ingredients have good human oral bioavailability and are non-toxic. Based on liver ChIPseq data, CHSGS acts on 8 targets specifically localized in the liver, such as FGA, FGB, and FGG. The main contributors to CHSGS soothing the liver qi targets are hesperetin, nobiletin, ferulic acid, naringin and albiflorin. In addition, network pharmacology analysis identified 9 blood components of CHSGS that corresponded to 63 anti-depressant targets in the brain. Among them, nobiletin has the largest number of anti-depressant targets, followed by glycyrrhizic acid, ferulic acid, albiflorin and hesperetin. We also validated the anti-depressant mechanism of CHSGS based on hippocampal proteomics. CHSGS exerts anti-depressant effects on synaptic structure and neuronal function by targeting multiple synapse related proteins. CONCLUSION: This study not only provides a theoretical basis for further expanding the clinical application of CHSGS, but also provides a series of potential lead compounds for the development of depression drugs.

Associations of 10 trace element levels in the whole blood with risk of three types of obesity in the elderly.

BACKGROUND: Currently, over 2 billion people worldwide suffer from obesity, which poses a serious health risk. More and more attention is being given to the effects of trace elements on obesity in recent years. Synergistic or antagonistic interactions among these elements can adversely or positively impact human health. However, epidemiological evidence on the relationship between trace element exposure levels and obesity has been inconclusive. METHODS: Baseline data of 994 participants from the Cohort of Elderly Health and Environment Controllable Factors were used in the present study. ICP-MS was used to measure the concentrations of 10 trace elements in the whole blood of the older population. Binary logistic regression, restricted cubic splines (RCS) models, and Bayesian kernel machine regression (BKMR) models were employed to assess single, nonlinear, and mixed relationships between 10 trace element levels and three types of obesity based on body mass index (BMI), waist circumference (WC), and body fat percentage (BFP) in the elderly. RESULTS: Based on BMI, WC and BFP, 51.8% of the included old population were defined as general overweight/obesity, 67.1% as abdominal obesity, and 36.2% as having slightly high/high BFP. After multivariable adjustment, compared with the lowest tertile, the highest tertile of blood selenium (Se) concentration was associated with an increased risk of all three types of obesity. Additionally, compared with the lowest tertile, higher tertiles of strontium (Sr) concentrations were associated with a lower risk of general overweight/obesity and having slightly high/high BFP, and the highest tertile of barium (Ba) was associated with a lower risk of having slightly high BFP, while higher tertiles of arsenic (As) concentrations were associated with an increased risk of having slightly high/high BFP, and the highest tertile of manganese (Mn) was associated with a higher risk of abdominal obesity. BKMR analyses showed a strong linear positive association between Se and three types of obesity. Higher blood levels of trace element mixture were associated with increased obesity risks in a dose-response pattern, with Se having the highest value of the posterior inclusion probability (PIP) within the mixture. CONCLUSIONS: In this study, we found higher Se levels were associated with an elevated risk of obesity and high levels of Ba, Pb and Cr were associated with a decreased risk of obesity. Studies with larger samples are needed to confirm these findings.

[Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics].

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

[Acupoint injection ameliorates Th1/Th2 imbalance through Toll-like receptor 4/activator protein-1 signal pathway and improves inflammatory response in rats with allergic rhinitis].

OBJECTIVE: To observe the effect of acupoint injection on serum T helper (Th)1/Th2 related cytokines, and the expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and activator protein-1 (AP-1) of nasal mucosa in allergic rhinitis (AR) rats, so as to explore its mechanism underlying improvement of AR. METHODS: Thirty-two SD rats were randomly divided into normal, model, non-acupoint injection and acupoint injection groups (n=8 in each group). The AR model was established by ovalbumin sensitization. In the acupoint injection group, "Yintang" (GV24+) and bilateral "Yingxiang" (LI20) were selected for injection of mixture solution of dexamethasone and lidocaine (0.05 mL/acupoint), once every 4 days for a total of 4 times. The non-acupoints, located at the midpoint between the "Houhai" and "Huantiao" (GB30) on the bilateral hips and the sites 5 cm inferior to the axillary were injected with the same dose of mixture solution as that in the acupoint injection group. The AR severity was assessed by cumulative quantification scoring methods (including the numbers of nose-catching and sneezes, and the amount of nasal secretions in 30 min). The pathological changes of nasal mucosa were observed by HE staining. The contents of immunoglobulin E (IgE), interleukin (IL)-4 and interferon (IFN)-γ in serum were detected by ELISA. The expressions of TLR4 and MyD88 in nasal mucosa was detected by immunofluorescence. The expression of AP-1 in nasal mucosa was detected by Western blot. RESULTS: Following modeling, the AR symptom score, serum IgE and IL-4 contents and expression of TLR4, MyD88 and AP-1 of nasal mucosa were significantly increased in the model group than those in the normal group (P<0.01), while the serum IFN-γ content was significantly decreased (P<0.01). Compared with the model group and non-acupoint injection group, the AR symptom score, the serum contents of IgE and IL-4 and the expressions of TLR4, MyD88 and AP-1 in nasal mucosa were significantly decreased in the acupoint injection group (P<0.01, P<0.05), while the serum IFN-γ content was significantly increased (P<0.01). H.E. staining of the nasal mucosa showed that most of the epithelium fell off, the lamina propria vessels expanded, the glands proliferated, and eosinophils and lymphocytes infiltrated in the model and non-acupoint injection groups, and those were significantly improved in the acupoint injection group. CONCLUSION: Acupoint injection can effectively improve allergic inflammation of the nose in AR rats, which may be related with its function in inhibiting the abnormal activation of TLR4/AP-1 signaling pathway and regulating the imbalance of Th1/Th2.

Compound Chinese medicine (F1) improves spleen deficiency diarrhea by protecting the intestinal mucosa and regulating the intestinal flora.

Compound Chinese medicine (F1) is a traditional prescription in Chinese medicine that is commonly used to treat spleen deficiency diarrhea (SDD). It has demonstrated remarkable effectiveness in clinical practice. However, the precise mechanism by which it exerts its antidiarrheal effect is still unclear. This study aimed at investigating the antidiarrheal efficacy and mechanism of F1 on senna-induced secretory diarrhea (SDD). Senna was utilized to induce the development of a mouse model of senna-induced secretory diarrhea (SDD) in order to observe the rate of diarrhea, diarrhea index, blood biochemistry, and histopathological changes in the small intestine. Additionally, the levels of sodium and hydrogen exchange protein 3 (NHE3) and short-chain fatty acids (SCFAs) were determined using enzyme-linked immunosorbent assay (ELISA). The impact of F1 on the senna-induced SDD mouse models was evaluated by monitoring changes in the gut microbiota through 16S rRNA (V3-V4) sequencing. The results demonstrated that F1, a traditional Chinese medicine, effectively increased the body weight of SDD mice and reduced the incidence of diarrhea and diarrhea index. Additionally, F1 restored liver and kidney function, reduced the infiltration of inflammatory cells in intestinal tissue, and promoted the growth of intestinal villi. Furthermore, F1 was found to enhance the expression of NHE3 and SCFAs. It also increased the abundance of Firmicutes and Lactobacillus species, while decreasing the abundance of Proteobacteria and Shigella.

Response mechanism of microorganisms to the inhibition of endogenous pollution release by calcium peroxide.

To further explore the response mechanism of microorganisms to the synchronous control of nitrogen and phosphorus release from sediments by CaO2, the spatiotemporal changes in the physical, chemical and biological indicators of the overlying water, interstitial water and sediments in each reactor were measured in the experiment. The experiment results showed that CaO2 could increase the ammonia monooxygenase activity, nitrite oxidase activity and Nitrospira abundance in the sediment near its dosing position, and enhanced the activities of nitrate reductase and nitrite reductase at a certain distance from the dosing position, thereby promoting nitrogen removal in sediments through the alternating process of nitrification and denitrification. At the same time, the increase of alkaline phosphatase activity and Saccharimonadales abundance in the test groups accelerated the hydrolysis of organic phosphorus, and the P immobilization in sediments was realized through the subsequent precipitation reaction of Ca2+ and PO43- under alkaline conditions. In addition, the enhanced activities of dehydrogenase and catalase ensured that CaO2 would not cause great killing effect on microorganisms when improving the hypoxic conditions and inhibiting endogenous release. As a result, the dissolved product of CaO2 such as Ca(OH)2 and H2O2 reduced the nutrients concentration and killed the algae, which kept the algae density and chlorophyll a concentration at a low level throughout the test groups. Therefore, this study systematically clarified the microbial mechanism of CaO2 synchronously controlling the release of nitrogen and phosphorus from sediments, which provided a new idea for the remediation of endogenous pollution in the water system.

Physi-chemical mechanism and control effect of CaO2 inhibiting phosphorus release from sediments under different dosing modes.

CaO2 is known as an outstanding restoration agent to control phosphorus (P) release from sediments, and its mechanism is believed to depend on chemical passivation. However, we found that the physical actions might also be involved in inhibiting endogenous P release induced by CaO2. To further explore the mechanism of CaO2 controlling P release and optimize the dosing method, a 94-day incubation experiment was conducted under different CaO2 dosing modes. The results showed that CaO2 could form a dense passivation layer near its dosing position by reducing the median diameter of sediments, thereby inhibiting P release through physical obstruction. At the same time, the increase in the specific surface area and Ca content of sediments induced by CaO2 could synchronously enhance the physical and chemical adsorption properties of sediments to P. In addition, CaO2 could significantly reduce the P concentration in sediment interstitial water and the mobile-P and BAP contents in sediments through chemical oxidation and chemical precipitation. Under the combined actions of physical obstruction, physi-chemical adsorption, chemical oxidation, and chemical precipitation, CaO2 effectively inhibited endogenous P release. Finally, the P release flux in each reactor showed that multiple coverage and shallow injection had the optimal effect on inhibiting P release, and the former is recommended for the water systems with shallow sediments, and the latter is suitable for the water systems with deep sediments. In general, this experiment proposed the physi-chemical mechanism of P immobilization mediated by CaO2, studied the formation characteristics of the passivation layer, and optimized the dosing mode, which can provide valuable reference for the research and application of CaO2 controlling P release.

Exogenously Triggered Nanozyme for Real-Time Magnetic Resonance Imaging-Guided Synergistic Cascade Tumor Therapy.

The uncontrolled treatment process and high concentration of intracellular glutathione compromise the therapeutic efficacies of chemodynamic therapy (CDT). Here, iron oxide nanocrystals embedded in N-doped carbon nanosheets (IONCNs) are designed as a near-infrared light-triggered nanozyme for synergistic cascade tumor therapy. The IONCNs can absorb and convert 980 nm light to local heat, which induces the dissolution of iron oxide for generating Fe2+/Fe3+ in a weak acid environment, apart from thermal ablation of cancer cells. The formed Fe2+ takes on the active site for the Fenton reaction. The formed Fe3+ acts as glutathione peroxidase to magnify oxidative stress, improving the antitumor performance. The IONCNs can be used to visually track the treatment process via magnetic resonance imaging. Such IONCNs demonstrate great potential as an exogenously triggered nanozyme via an integrated cascade reaction for imaging-guided synergistic cancer therapy.

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis.

ABSTRACT: Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein-protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.

Embedding the Community and Individuals in Disease Prevention.

The primary prevention of non-communicable diseases is one of the most challenging and exciting aspects of medicine and primary care this century. For cancer, it is an urgent matter in light of the increasing burden of the disease among younger people and the higher frequency of more aggressive forms of the disease for all ages. Most chronic disorders result from the influence of the environment on the expression of genes within an individual. The environment at-large encompasses lifestyle (including nutrition), and chemical/physical and social exposures. In cancer, the interaction between the (epi)genetic makeup of an individual and a multiplicity of environmental risk and protecting factors is considered key to disease onset. Thus, like for precision therapy developed for patients, personalized or precision prevention is envisioned for individuals at risk. Prevention means identifying people at higher risk and intervening to reduce the risk. It requires biological markers of risk and non-aggressive preventive actions for the individual, but it also involves acting on the environment and the community. Social scientists are considering micro (individual/family), meso (community), and macro (country population) levels of care to illustrate that problems and solutions exist on different scales. Ideally, the design of interventions in prevention should integrate all these levels. In this perspective article, using the example of breast cancer, we are discussing challenges and possible solutions for a multidisciplinary community of scientists, primary health care practitioners and citizens to develop a holistic approach of primary prevention, keeping in mind equitable access to care.

Selenium-containing polysaccharides isolated from Rosa laevigata Michx fruits exhibit excellent anti-oxidant and neuroprotective activity in vitro.

Selenium-containing polysaccharides have potential as an organic selenium dietary supplement, owing to their low toxicity, few side effects, and easy absorption attributes. In this study, we isolated two novel homogeneous selenium-containing polysaccharides from Rosa laevigata Michx fruits (Se-RLFPs). Results from primary structural analysis revealed that Se-RLFPs were α - pyranose, and were both composed of rhamnose, xylose, glucose with an average molecular weight of 24 and 16 KDa, respectively. Selenium contents in Se-RLFP-I and Se-RLFP-II were 16.49 µg/g and 21.61 µg/g, respectively. Results from analysis of antioxidant and neuroprotective activity of the polysaccharides revealed that Se-RLFPs had a radical scavenging effect. Specifically, they effectively protected SH-SY5Y cells from H2O2-induced damage by enhancing antioxidant enzyme activities (SOD), total antioxidant capacity (T-AOC) and suppressing malondialdehyde (MDA) levels. Western blots showed that the underlying mechanisms of action may be related to the Nrf2/HO-1 signaling pathway. Taken together, these results suggested that Se-RLFPs have potential as a pharmaceutical agent for treatment of neurodegenerative diseases (NDDs) or as a selenium-complementary ingredient in functional foods.

A nanoselenium-coating biomimetic cytomembrane nanoplatform for mitochondrial targeted chemotherapy- and chemodynamic therapy through manganese and doxorubicin codelivery.

The cell membrane is widely considered as a promising delivery nanocarrier due to its excellent properties. In this study, self-assembled Pseudomonas geniculate cell membranes were prepared with high yield as drug nanocarriers, and named BMMPs. BMMPs showed excellent biosafety, and could be more efficiently internalized by cancer cells than traditional red cell membrane nanocarriers, indicating that BMMPs could deliver more drug into cancer cells. Subsequently, the BMMPs were coated with nanoselenium (Se), and subsequently loaded with Mn2+ ions and doxorubicin (DOX) to fabricate a functional nanoplatform (BMMP-Mn2+/Se/DOX). Notably, in this nanoplatform, Se nanoparticles activated superoxide dismutase-1 (SOD-1) expression and subsequently up-regulated downstream H2O2 levels. Next, the released Mn2+ ions catalyzed H2O2 to highly toxic hydroxyl radicals (·OH), inducing mitochondrial damage. In addition, the BMMP-Mn2+/Se nanoplatform inhibited glutathione peroxidase 4 (GPX4) expression and further accelerated intracellular reactive oxygen species (ROS) generation. Notably, the BMMP-Mn2+/Se/DOX nanoplatform exhibited increased effectiveness in inducing cancer cell death through mitochondrial and nuclear targeting dual-mode therapeutic pathways and showed negligible toxicity to normal organs. Therefore, this nanoplatform may represent a promising drug delivery system for achieving a safe, effective, and accurate cancer therapeutic plan.

Efficacy and safety of massage therapy for autism spectrum disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: Autism spectrum disorder is a neurodevelopmental disorder with increasing incidence. At present, the global incidence of the disease is on the rise, and the cause is unknown. There is no specific treatment for this disease at present, mainly education and training. Traditional Chinese medicine treatment has a certain effect on the improvement of the symptoms of the disease. The treatment methods are mainly oral Chinese medicine and acupuncture, but children are often not easy to cooperate. As a safe and effective green therapy, massage is easy to be accepted by children. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating autism spectrum disorders: Wanfang and PubMed Database, China National Knowledge Infrastructure Database, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to March 2021. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness and safety of massage therapy for patients with autism spectrum disorders. The outcomes will include changes in autism spectrum disorder relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with autism spectrum disorders. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.

[Effect of electroacupuncture on angiopoietin-1 in spinal cord of rats with neuropathic pain].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the behavior, histomorphology and the expression of angiopoietin-1 (Angpt-1) in rats with spinal nerve injury, so as to explore its mechanism on neuropathic pain. METHODS: Forty-five male SD rats were randomly divided into sham, model and EA groups (n=15 rats in each group). Spinal nerve ligation (SNL) of the L5 lumbar vertebra was performed to establish a rat model of neuropathic pain. The rats in the EA group were given EA at "Zusanli" (ST36) and "Kunlun" (BL60) of the operation side with continuous wave at a frequency of 2 Hz and an intensity of 1.5 mA once a day, 30 minutes each time for 7 days. The sham group only exposed L5 spinal nerves without ligation. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were observed and recorded before modeling and on days 3,5,7,10,12 and 14 after modeling. L4-L6 segments of spinal cord were taken and the morphological changes of spinal dorsal horn were observed by HE staining. The changes of spinal dorsal horn nerve fiber structure were observed by silver plating staining. Angpt-1 expression was detected by Western blot and immunohistochemistry. RESULTS: Compared with the sham group, the model group had significant reductions in MWT and TWL at each time point (P<0.01); compared with the model group, the EA group had significant increases in MWT and TWL on days 10,12 and 14 after intervention (P<0.05, P<0.01). HE staining showed that in the model group, the spinal dorsal horn showed degeneration and necrosis of neurons, nuclear fixation and shrinkage, and loose surrounding tissues. The degree of tissue damage of the EA group was milder than that of the model group. The silver staining results showed the model group had obvious neuronal fibrillary tangles, while there were fewer neuronal fibrillary tangles in the EA group. Compared with the sham group, the Angpt-1 expression in the model group was significantly decreased (P<0.01), and compared with the model group, the EA group had a significant increase in the expression of Angpt-1 (P<0.01). CONCLUSION: EA can promote the recovery of nerve function in SNL rats by up-regulating Angpt-1 expression.

Effects of different levels of rapeseed cake containing high glucosinolates in steer ration on rumen fermentation, nutrient digestibility and the rumen microbial community.

This trial was conducted to study the effects of dietary rapeseed cake (RSC) containing high glucosinolates (GLS) on rumen fermentation, nutrient digestion and the rumen microbial community in steers. Eight growing steers and four rations containing RSC (GLS 226·1 µmol/g DM) at 0·00, 2·65, 5·35 and 8·00 % DM were assigned in a replicate 4 × 4 Latin square design. The results indicated that increasing RSC levels increased the ruminal concentration of thiocyanate (SCN) (P < 0·01), decreased the ruminal concentration of ammonia nitrogen (NH3-N) and the molar proportion of isovalerate (P < 0·05), did not affect the ruminal concentration of total volatile fatty acids (P > 0·05), decreased the crude protein (CP) digestibility (P < 0·05) and increased the ether extract (EE) digestibility (P < 0·01). Increasing RSC levels tended to decrease the abundances of ruminal Ruminobacter amylophilus (P = 0·055) and Ruminococcus albus (P = 0·086) but did not affect methanogens, protozoa, fungi and other bacteria (P > 0·05). Increasing RSC levels in the ration did not affect the ruminal bacterial diversity (P > 0·05), but it increased the operational taxonomic units and the bacterial richness (P < 0·05) and affected the relative abundances of some bacteria at the phylum level and genus level (P < 0·05). In conclusion, RSC decreased the ruminal concentration of NH3-N and the CP digestibility, increased the EE digestibility and partly affected the ruminal bacterial community. SCN, as the metabolite of GLS, could be a major factor affecting these indices.

Effects of massage therapy for patients with thoracic facet joint disorders: A protocol for systematic review and meta-analysis.

BACKGROUND: Thoracic facet joint disorder is a common thoracic disorder in clinic, inducing pain and discomfort at the dislocated thoracic vertebrae, radiating to pain of the neck and back. The incidence of thoracic facet joint disorder is higher than the facet disorder of the cervical and lumbar vertebrae. Therefore, an ideal strategy to relieve thoracic facet joint disorder is urgently needed. In recent years, massage therapy has been increasingly accepted by thoracic facet joint disorder patients due to its lower costs, fewer unwanted side effects and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with thoracic facet joint disorder. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness of massage therapy in treating thoracic facet joint disorder: Wanfang and PubMed Database, CNKI, CENTRAL, CINAHL and EMBASE. Each database will be searched from inception to October 2020. The entire process will include study selection, data extraction, risk of bias assessment and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness of massage therapy for patients with thoracic facet joint disorder. CONCLUSIONS: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with thoracic facet joint disorder. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/XMEJD.

Effects and safety of massage therapy for patients with metatarsal pain: A protocol for systematic review and meta-analysis.

BACKGROUND: Metatarsalgia refers to localized or generalized forefoot pain in the region of the metatarsal heads. Often this pain is plantar, beneath the metatarsal heads, and arises from either mechanical or iatrogenic causes. The treatment of metatarsalgia remains controversial. A thorough understanding of the biomechanics of the forefoot and the underlying pathology of the particular type of metatarsalgia affecting the patient is a prerequisite to selecting the proper treatment. In recent years, massage therapy has been increasingly accepted by patients due to its lower costs, fewer unwanted side effects, and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with metatarsal pain. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating metatarsal pain: Wanfang and PubMed Database, CNKI, CENTRAL, CINAHL, and EMBASE. Each database will be searched from inception to October 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULTS: This proposed study will evaluate the effectiveness and safety of massage therapy for patients with metatarsal pain. The outcomes will include changes in metatarsal pain relief and adverse effect. CONCLUSIONS: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with metatarsalgia. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/C6KFJ.

Efficacy and safety of massage therapy for chronic atrophic gastritis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic atrophic gastritis (CAG) is an established precursor of gastric carcinoma with high prevalence worldwide. It is a typical complex gastro-intestinal disease with multiple influence factors, of which exact mechanisms remain unelucidated. Therefore, an ideal strategy to relieve CAG is urgently needed. In recent years, massage therapy has been increasingly accepted by CAG patients due to its lower costs, fewer unwanted side effects and safety for clinical use. In this systematic review, we aim to evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. METHODS: We will search the following electronic databases for randomized controlled trials to evaluate the effectiveness and safety of massage therapy in treating chronic atrophic gastritis: Wanfang and Pubmed Database, China National Knowledge Infrastructure Database, Cochrane Central register of controlled trials, Cumulative Index of Nursing and Allied Health Literature, and Excerpta Medica database. Each database will be searched from inception to September 2020. The entire process will include study selection, data extraction, risk of bias assessment, and meta-analyses. RESULT: This proposed study will evaluate the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. The outcomes will include changes in CAG relief and adverse effect. CONCLUSION: This proposed systematic review will evaluate the existing evidence on the effectiveness and safety of massage therapy for patients with chronic atrophic gastritis. DISSEMINATION AND ETHICS: The results of this review will be disseminated through peer-reviewed publication. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process.