Ruangan Lidan decoction inhibits the growth and metastasis of liver cancer by downregulating miR-9-5p and upregulating PDK4.

A growing number of studies have suggested that traditional Chinese medicine (TCM) plays an essential role in the development and occurrence of liver cancer. However, the function of Ruangan Lidan decoction (RLD) in liver cancer are not yet adequately identified and manifested, which attracted our attention. The key genes related to liver cancer and RLD and the upstream miRNAs of PDK4 were obtained based on bioinformatics analysis, followed by verification of the targeting relationship between miR-9-5p and PDK4. Next, Huh7 cells were treated with RLD to detect cell proliferation, colony formation, migration, invasion, and apoptosis by multiple assays with gain- and loss-of-function experiments. Moreover, subcutaneous transplanted tumor model and lung metastasis model of liver cancer in nude mice were established to further verify the functional role of RLD in liver cancer growth and metastasis via miR-9-5p/PDK4 axis. Bioinformatics analysis found that PDK4 and miR-9-5p were related to liver cancer, and PDK4 may be a downstream regulator of RLD. miR-9-5p could target and inhibit PDK4. In vitro cell experiments demonstrated that RLD suppressed liver cancer cell proliferation, invasion and migration, and promoted apoptosis by inhibiting miR-9-5p expression and promoting PDK4 expression. In vivo animal experiments further confirmed that RLD inhibited liver cancer growth and metastasis via upregulation of miR-9-5p-dependent PDK4. RLD downregulated miR-9-5p and upregulated PDK4 to inhibit the proliferation, migration, invasion, and induce apoptosis, thereby suppressing the growth and metastasis of liver cancer, highlighting a potential novel target for treatment of liver cancer.

Effect of five-elements music therapy combined with Baduanjin qigong on patients with mild COVID-19.

Background: To investigate the physical and psychological effects of five-element music therapy combined with Baduanjin qigong treatment on inpatients with mild coronavirus disease 2019 (COVID-19) in Wuhan. Methods: A mixed-methods study was used. In the quantitative study, a randomized controlled trial was performed on 40 study participants divided into a control group (n = 20) and an intervention group (n = 20). The Self-rating Anxiety Scale, Self-rating Depression Scale and Pittsburgh Sleep Quality Index were compared. For qualitative analysis, it adopted purposive sampling method, 13 patients of different ages from 18 to 60 years old and different exercise behavior were selected as the participants from the intervention group. A semi-structured interview method was used to collect data, and the content analysis method was used for data analysis. An interview outline was developed to assess the psychological condition and personal functional-exercise behavior of patients. Results: In the quantitative study, the anxiety self-scores and depression self-scores of patients in intervention group were significantly lower compared with control group after treatment (p < .05). The sleep quality of intervention group was significantly improved compared with control group (p < .001). Participants in the qualitative study responded to questions posed through semi-structured interviews. The effect of intervention was good, which has been supported and recognized by patients. Conclusion: The treatment of five-element music therapy combined with Baduanjin qigong on patients with mild COVID-19 alleviated anxiety and depression, and improved sleep quality, which was beneficial to the patients' physical and psychological recovery.

Systems Pharmacology-Based Strategy to Investigate the Mechanism of Ruangan Lidan Decoction for Treatment of Hepatocellular Carcinoma.

epatocellular carcinoma (HCC) is one of the leading contributors to cancer mortality worldwide. Currently, the prevention and treatment of HCC remains a major challenge. As a traditional Chinese medicine (TCM) formula, Ruangan Lidan decoction (RGLD) has been proved to own the effect of relieving HCC symptoms. However, due to its biological effects and complex compositions, its underlying mechanism of actions (MOAs) have not been fully clarified yet. In this study, we proposed a pharmacological framework to systematically explore the MOAs of RGLD against HCC. We firstly integrated the active ingredients and potential targets of RGLD. We next highlighted 25 key targets that played vital roles in both RGLD and HCC disease via a protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Furthermore, an ingredient-target network of RGLD consisting of 216 ingredients with 306 targets was constructed, and multilevel systems pharmacology analyses indicated that RGLD could act on multiple biological processes related to the pathogenesis of HCC, such as cellular response to hypoxia and cell proliferation. Additionally, integrated pathway analysis of RGLD uncovered that RGLD might treat HCC through regulating various pathways, including MAPK signaling pathway, PI3K/Akt signaling pathway, TNF signaling pathway, and ERBB signaling pathway. Survival analysis results showed that HCC patients with low expression of VEGFA, HIF1A, CASP8, and TOP2A were related with a higher survival rate than those with high expression, indicating the potential clinical significance for HCC. Finally, molecular docking results of core ingredients and targets further proved the feasibility of RGLD in the treatment of HCC. Overall, this study indicates that RGLD may treat HCC through multiple mechanisms, which also provides a potential paradigm to investigate the MOAs of TCM prescription.

Meteorin links the bone marrow hypoxic state to hematopoietic stem/progenitor cell mobilization.

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy.

Guben Tongluo Formula Protects LPS-induced Damage in Lamina Propria B Lymphocytes Through TLR4/MyD88/NF-κB Pathway.

OBJECTIVE: The main pathological feature of immunoglobulin A nephropathy (IgAN), an autoimmune kidney disease, is the deposition of IgA immune complexes, accompanied by mesangial cell proliferation and elevated urine protein. The Guben Tongluo formula (GTF) is a traditional Chinese medicine prescription, which has predominant protective effects on IgAN. However, the therapeutic mechanism of the GTF in IgAN remains elusive. The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway. METHODS: In the present study, lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide (LPS) (0, 1, 5, 10 and 20 ng/mL). Flow cytometry was used to define positive CD86+CD19+ cells. CCK-8 assay was used to examine cell proliferation. RNAi was used to induce TLR4 silencing. qRT-PCR and Western blotting were used to determine gene expression. RESULTS: It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1 (Gd-IgA), the levels of TLR4, Cosmc, MyD88 and phosphorylated (p)-NF-κB, and the ratio of CD86+CD19+ and IgA-producing B cells. However, the TLR4 knockdown reversed the role of LPS. This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes. Furthermore, the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway. CONCLUSION: Collectively, these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.

[Therapeutic effect of Baimai Ointment on peripheral sensitization of chronic inflammatory pain in mice].

Chronic inflammatory pain is mainly manifested by peripheral sensitization. Baimai Ointment(BMO), a classical Tibetan medicine for external use, has good clinical efficacy in the treatment of chronic inflammatory pain, while its pharmacodynamics and mechanism for relieving peripheral sensitization remain unclear. This study established an animal model of chronic inflammatory pain induced by complete Freund's adjuvant to explore the mechanism of BMO in the treatment of chronic inflammatory pain by behavioral test, side effect assessment, network analysis, and experimental verification. The pharmacodynamics experiment showed that BMO increased the thresholds of mechanical pain sensitivity and thermal radiation pain sensitivity of chronic inflammatory pain mice in a dose-dependent manner, and had inhibitory effect on foot swelling, inflammatory mediator, and the expression of transient receptor potential vanilloid-1(TRPV1) and transient receptor potential A1(TRPA1). The results of body weight monitoring, pain sensitivity threshold detection in normal mice, rotarod performance test, and forced swimming test showed that BMO had no obvious toxic or side effect. The network analysis of 51 candidate active molecules selected according to the efficacy of BMO, content of main components, and ADME parameters showed that the inhibitory effect of BMO on chronic inflammatory pain was associated with the core regulatory elements of tumor necrosis factor(TNF) and T cell receptor signaling pathways. BMO down-regulated the protein levels of mitogen-activated protein kinase 14(MAPK14), MAPK1, and prostaglandin-endoperoxide synthase 2(PTGS2), and up-regulated the phosphorylation le-vel of glycogen synthase kinase 3 beta(GSK3 B) in the plantar tissue of mice. In conclusion, BMO can effectively relieve peripheral sensitization of chronic inflammatory pain without inducing tolerance and obvious toxic and side effects. The relevant mechanism may be related to the regulation of BMO on core regulatory elements of TNF and T cell receptor signaling pathways in surrounding tissues.

Genome-Wide Identification and Expansion Patterns of SULTR Gene Family in Gramineae Crops and Their Expression Profiles under Abiotic Stress in Oryza sativa.

Sulfate transporters (SULTRs), also known as H+/SO42- symporters, play a key role in sulfate transport, plant growth and stress responses. However, the evolutionary relationships and functional differentiation of SULTRs in Gramineae crops are rarely reported. Here, 111 SULTRs were retrieved from the genomes of 10 Gramineae species, including Brachypodium disachyon, Hordeum vulgare, Setaria italica, Sorghum bicolor, Zea mays, Oryza barthii, Oryza rufipogon, Oryza glabbermia and Oryza sativa (Oryza sativa ssp. indica and Oryza sativa ssp. japonica). The SULTRs were clustered into five clades based on a phylogenetic analysis. Syntheny analysis indicates that whole-genome duplication/segmental duplication and tandem duplication events were essential in the SULTRs family expansion. We further found that different clades and orthologous groups of SULTRs were under a strong purifying selective force. Expression analysis showed that rice SULTRs with high-affinity transporters are associated with the functions of sulfate uptake and transport during rice seedling development. Furthermore, using Oryza sativa ssp. indica as a model species, we found that OsiSULTR10 was significantly upregulated under salt stress, while OsiSULTR3 and OsiSULTR12 showed remarkable upregulation under high temperature, low-selenium and drought stresses. OsiSULTR3 and OsiSULTR9 were upregulated under both low-selenium and high-selenium stresses. This study illustrates the expression and evolutionary patterns of the SULTRs family in Gramineae species, which will facilitate further studies of SULTR in other Gramineae species.

Matrine Inhibitory Effect on Self-renewal and Re-sensitization of 5-FU Resistant NSCLC Stem Cells were through Let-7b dependent Downregulation of CCND1.

Matrine is one of the major alkaloids extracted from Sophora flavescens Ait of the traditional Chinese medicine, was the main chemical ingredient of compounds of Kushen injection. The Matrine is considered as a promising therapeutic agent for curing nonsmall cell lung cancer (NSCLC), used either alone or combined with chemotherapeutic agents. In the present study, we focused on the possible roles of Matrine exerted on the self-renewal ability of stem-like cells of the NSCLC group, as well as the cytotoxicity of chemotherapeutic agents, in vitro and in vivo. Here we reported that Matrine inhibits cancer stem-like cell (CSC) properties through upregulation of Let-7b and suppression of the Wnt pathway. Overexpression of Let-7b suppressed the ability of tumorsphere formation, decreased Wnt pathway activation through inhibiting its transcriptional activity in lung CSCs. Further studies revealed that Let-7b directly targeted CCND1 and decreased its expression, whereas Matrine increased Let-7b levels and followed by inactivation of the CCND1/Wnt signaling pathway and inhibition of EMT, which was characterized by loss of epithelial markers and acquisition of a mesenchymal phenotype in lung CSCs. What is more, we found that Matrine increased Let-7b level in an endoribonuclease DICER1-dependent manner. And xenografts in nude mice evidenced that Matrine increased the sensitivity of lung CSCs to 5-FU and inhibited the accumulation of CCND1 in tumor tissues induced by 5-FU. Taken together, these data illustrate the role of Let-7b in regulating lung CSCs traits and DICER1/let-7/CCND1 axis in Matrine or in combination with 5-FU intervention of lung CSCs' expansion, helping to fulfill the anti-cancer action of Matrine.

Efficacy and safety of Chuankezhi injection in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis protocol.

BACKGROUND: Chuankezhi injection (CKZ) is gaining increasing popularity for chronic obstructive pulmonary disease (COPD) treatment, yet their comparative effectiveness and safety remain unclear. Therefore, we will provide a protocol to assess the efficacy and safety of CKZ for COPD. METHODS: From now until June 2020, we will conduct a comprehensive and systematic literature search in 4 Chinese and 4 English databases, and the use of CKZ in the treatment of COPD will be included in randomized controlled trials, as well as all the treatment of stable COPD during the treatment of all CKZ. The risk assessment of the bias tool in Cochrane 5.1.0 will be combined with the quality of the trial. The 2 investigators will independently perform quality assessments and data extractions for the included studies in strict accordance with inclusion and exclusion criteria and perform the meta-analysis with Stata 15 software (version 15.0, StataCorp, College Station, TX). RESULTS: Further evidence of CKZ treatment for COPD will be provided by this study. CONCLUSION: The efficacy and safety assessment of CKZ for COPD will be supported by this protocol. PROSPERO REGISTRATION NUMBER: ROSPERO CRD 42019134133.

Danhong Injection Alleviates Postoperative Intra-abdominal Adhesion in a Rat Model.

BACKGROUND: Among all the common complications that occur after abdominal surgery, intestinal adhesion is perhaps the most unpleasant one. However, current methods to treat and prevent intestinal adhesion are limited; thus, exploring new methods to prevent and treat intestinal adhesion is greatly needed. In this study, we demonstrated that Danhong injection (DHI) may be used as a promising method to prevent and treat intra-abdominal adhesion in a rat model. MATERIALS AND METHODS: Forty-eight rats were randomly divided into six groups. Except for the sham-operated group, all rats underwent cecal abrasion to establish an adhesion model. After the operation, the rats in the DHI-treated groups received different doses of DHI via the tail vein daily, while the other group was treated with the same volume of saline solution. Seven days after the operation, all rats were sacrificed, and the degree of adhesion was evaluated by Nair's scoring system. The extent of inflammation in the adhesion tissue was detected by HE staining and the expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß). The collagen deposition was assessed by Sirius red staining and α-SMA, MMP9, t-PA, and PAI-1 levels. Oxidative stress was indicated by the level of reactive oxygen species (ROS) in adhesion tissues and by immunohistochemical labeling of Nrf2. Furthermore, rat primary peritoneal mesothelial cells (RPMCs) were treated with H2O2 and DHI, and NF-κB phosphorylation was detected to illustrate the effect of DHI on oxidative stress. RESULTS: The intra-abdominal adhesion scores were significantly decreased in the groups treated with a high dose of DHI compared with the control groups, and the degree of inflammation, fibrosis, and oxidative stress was also significantly decreased. DHI treatment significantly reduced the levels of TNF-α, TGF-ß1, and PAI and increased the expression levels of MMP9, Nrf2, and t-PA in the adhesion tissues. ROS levels and NF-κB phosphorylation were significantly reduced in DHI-treated RPMCs compared with the control RPMCs. CONCLUSION: DHI alleviates the formation of postoperative intra-abdominal adhesions by inhibiting inflammation, collagen deposition, and oxidative stress in a rat model and may serve as a promising drug to prevent intra-abdominal adhesions.

Effect of Oat and Tartary Buckwheat - Based Food on Cholesterol - Lowering and Gut Microbiota in Hypercholesterolemic Hamsters.

The nutritional components in oat and tartary buckwheat had been assessed to have cholesterollowering effects. However, The effect of oat and tartary buckwheat based-food (OF) on cholesterol-lowering and gut microbiota in hypercholesterole hamsters was still limited studied because they are usually consumed in whole gran as well as after being processed. In this study, normal diets, high fat diet (HFD) with/without OF were fed to hamsters for 30 days respectively and growth parameters, metabolic parameters, and gut microbiota were investigated, respectively. It was found that OF significantly decreased plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-cholesterol), lowered liver TC, cholesterol ester (CE), and triglycerides (TG) concentrations, and increased fecal weight and bile acids (BA) concentrations, compared with HFD (p < 0.05). Moreover, the concentrations of acetate, propionate, butyrate and total short-chain fatty acids (SCFAs) were significantly increased in hamsters fed with OF, compared with HFD (p < 0.05). OF changed the overall structure of gut microbiota. The relative abundances of Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae were decreased and the relative abundance of Eubacteriaceae was increased, compared with HFD. These results suggested that OF could reduce the concentrations of plasma lipid by inhibiting cholesterol absorption in liver and promoting excretions of fecal lipid and BA. And it also increased SCFAs and modulated the gut microbiota effectively to exert the hypocholesterolemic effects.

Modeling Analysis of Potential Target of Dolastatin 16 by Computational Virtual Screening.

Dolastatin 16 is a cyclic depsipeptide isolated from the marine invertebrates and cyanobacterium Lyngbya majuscula, however, its bioactivity has been a historical question. In this study, peptidyl-prolyl cis-trans isomerase FKBP1A (FKBP12) was predicted as a potential target of dolastatin 16 via PharmMapper as well as verified using chemical-protein interactome (CPI) and molecular docking. FKBP1A has been previously identified as a target for the natural polyketide FK506 (tacrolimus), an immune suppressor inhibiting the rejection of organ transplantation in clinical use. The comparison study via the reverse pharmacophore screening and molecular docking of dolastatin 16 and FK506 indicated the good consistency of analysis with the computational approach. As the results, the lowest binding energy of dolastatin 16-FKBP1A complex was -7.4 kcal/mol and FK506-FKBP1A complex was -8.7 kcal/mol. The ligand dolastatin 16 formed three hydrogen bonds vs. four of FK506, as well as seven hydrophobic interactions vs. six of FK506 within the active site residues. These functional residues are highly repetitive and consistent with previously reported active site of model of FK506-FKBP1A complex, and the pharmacophore model was shown feasibly matching with the molecular feature of dolastatin 16.

Arsenic trioxide-mediated suppression of miR-182-5p is associated with potent anti-oxidant effects through up-regulation of SESN2.

Arsenic trioxide (ATO) is a traditional Chinese medicine that can induce oxidative stress for treatment of cancer cells. However, ATO may generate anti-oxidative responses to compromise the cytotoxic effect, but the underlying mechanisms remain unclear. Here we found that ATO could inhibit miR-182-5p expression in patient-derived primary S1 glioblastoma (GBM) cells accompanied by up-regulation of Sestrin-2 (SESN2) mRNA, a known anti-oxidant molecule. This phenomenon was also detected in a U87MG glioma cell line, human lung adenocarcinoma H1299 cell line and A549 cell line. Pretreatment with a free radical scavenger N-acetylcysteine (NAC) reduced the oxidative stress induced by ATO. Concomitantly, ATO mediated suppression of miR-182-5p and enhancement of SESN2 expression were also compromised. The MTT assay further showed that ATO induced cytotoxicity was enhanced by transfection of miR-182-5p mimics. Overexpression of miR-182-5p mimics significantly suppressed the expression of SENS2 and a firefly luciferase reporter gene fused to 3'- untranslated region (UTR) of SESN2 mRNA. Use of ribonucleoprotein immunoprecipitation (RNP-IP), ATO mediated suppression of miR-182-5p led to the stabilization of SESN2 mRNA as a result of Argonaute-2 (AGO2) dependent gene silencing. Furthermore, high expression of miR-182-5p and low expression of SESN2 mRNA tend to be associated with longer survival of glioma or lung cancer patients using public available gene expression datasets and online tools for prediction of clinical outcomes. Taken together, current data suggest that the miR-182-5p/SENS2 pathway is involved in ATO induced anti-oxidant responses, which may be important for the design of novel strategy for cancer treatment.

Andrographolide Inhibits Inflammatory Cytokines Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB/MAPK Signaling Pathway.

Andrographolide, the main active component extracted from Andrographis paniculata (Burm.f.) Wall. ex Nees, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the molecular mechanisms of Andrographolide in modifying lipopolysaccharide- (LPS-) induced signaling pathway in RAW264.7 cells. An in vitro model of inflammation was induced by LPS in mouse RAW264.7 cells in the presence of Andrographolide. The concentration and expression levels of proinflammatory cytokines were determined by an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The nuclear level of NF-κB was measured by an electrophoretic mobility shift assay (EMSA). The expression levels of NF-κB, p38, ERK, and JNK were determined by western blot. Andrographolide dose-dependently inhibited the release and mRNA expression of TNF-α, IL-6, and IL-1ß in LPS-stimulated RAW264.7 cells. The nuclear level of p65 protein was decreased in Andrographolide treatment group. Western blot analysis showed that Andrographolide suppressed LPS-induced NF-κB activation and the phosphorylation of IkBa, ERK1/2, JNK, and p38. These results suggest that Andrographolide exerts an anti-inflammatory effect by inhibiting the activation of NF-κB/MAPK signaling pathway and the induction of proinflammatory cytokines.

Evodiamine inhibits PDGF­BB­induced proliferation of rat vascular smooth muscle cells through the suppression of cell cycle progression and oxidative stress.

Vascular smooth muscle cell (VSMC) proliferation is a key event in the development of in­stent restenosis. Evodiamine is an indole alkaloid extracted from the Chinese medicine, evodia, and has been shown to inhibit tumor cell proliferation and protect the cardiovascular system. However, whether evodiamine affects VSMC proliferation remains to be elucidated. Therefore, the present study examined the effects and the mechanisms of action of evodiamine on the proliferation of rat VSMCs. The cells were treated with evodiamine alone or in combination with platelet­derived growth factor­BB (PDGF­BB) stimulation. It was found that evodiamine inhibited PDGF­BB­induced VSMC proliferation in a dose­dependent manner, without inducing cell death. Evodiamine also retarded cell cycle progression, evidenced by the suppression of the expression of cell cycle­promoting cyclin proteins and cyclin­dependent kinases. In addition, evodiamine attenuated the PDGF­BB­induced phosphorylation of mitogen­activated protein kinases p38 and extracellular signal­regulated kinases 1/2, however, it had no effect on the phosphorylation of Akt. Evodiamine also inhibited the increase of reactive oxygen species generation and upregulated the mRNA expression levels of genes encoding antioxidant enzymes. These findings provide important insights into the mechanisms underlying the vasoprotective actions of evodiamine and suggest that it may be a useful therapeutic agent for the treatment of vascular occlusive disease.

Hyperbaric oxygen therapy in China.

Hyperbaric oxygen therapy (HBOT) is defined as a treatment in which a patient intermittently breathes 100% oxygen while the treatment chamber is pressurized to a pressure greater than sea level (1.0 atmosphere absolute, ATA). In China, for nearly 50 years, HBOT has been used as a primary or adjuvant therapy to treat a variety of diseases. This article mainly reviewed the indications and contraindications of HBOT, as well as the status of clinical and experimental HBOT research in China. At the same time, there is a brief introduction of hyperbaric oxygen preconditioning (HBO-PC) in China.

Sorafenib enhances effects of transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIM: Combination therapy of sorafenib and transarterial chemoembolization (TACE) showed benefits for hepatocellular carcinoma (HCC). This systematic review aims for evaluation of efficacy and safety between sorafenib plus TACE and TACE alone for HCC. METHODS: We systematically searched multi-databases to identify eligible studies. Studies comparing sorafenib combined with TACE and TACE alone for HCC were included. RESULTS: Nine studies with 900 patients (sorafenib + TACE = 446, TACE = 454) were finally included. Sorafenib combined with TACE significantly reduced 6-month mortality [OR 0.24, 95 % confidential interval (CI) 0.09-0.68, P = 0.007] and 1-year mortality (OR 0.35, 95 % CI 0.21-0.56, P < 0.0001), but did not decrease 2-year mortality (OR 0.58, 95 % CI 0.14-2.46, P = 0.46). Although combination therapy tend to reduce 3-month (OR 0.76, 95 % CI 0.52-1.10, P = 0.15) and 6-month progression free rate (OR 0.27, 95 % CI 0.07-1.05, P = 0.06), the changes were not significant. Additionally, objective response ratio (OR 0.39, 95 % CI 0.19-0.78, P = 0.008) and clinical benefit ratio (OR 0.27, 95 % CI 0.15-0.50, P < 0.0001) also favored for combination therapy, which, however, caused higher morbidity, especially hand-foot skin reaction (OR 53.71, 95 % CI 28.86-99.93, P < 0.00001), hematological events (OR 14.8, 95 % CI 6.07-36.07, P < 0.00001), diarrhea (OR 6.62, 95 % CI 3.82-11.45, P < 0.00001), hypertension (OR 5.03, 95 % CI 3.02-8.38, P < 0.00001), rash/desquamation (OR 5.67, 95 % CI 3.58-8.99, P < 0.00001), and fatigue (OR 2.5, 95 % CI 1.09-5.72, P = 0.03). CONCLUSION: Combination of sorafenib and TACE showed survival and clinical benefits in patients with HCC, though enhanced morbidity.

Daidzein enhances immune function in late lactation cows under heat stress.

Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P < 0.05 or P < 0.01). Moreover, 300 and 400 mg/day daidzein treatment markedly increased serum IL-2 (P < 0.01), while the levels of serum TP and ALB were not changed by any concentration of daidzein treatment (P > 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress.

[Exploration on the spectrum of disease and acupoints in post-stroke disorder treated with acupuncture and moxibustion on the basis of data mining technology].

OBJECTIVE: Data mining technology is used to analyze the spectrum of disease and acupoints in the treatment of post-stroke disorder with acupuncture and moxibustion in modern times. METHODS: The literature resources are formulated, the name of disease and acupoint are standardized, the spectrum of acupuncture for disease that post-stroke disorder belonged to and their genealogical classification are collected, the spectrum of acupoints in the treatment of post-stroke disorder are summarized. RESULTS: Totally, 652 modern clinical research papers are collected, including 9 classification systems in ICD-10 and 40 diseases; 143 nonacupoints are used and the application frequency are 737; 253 acupoints are used and the application frequency are 5395. According to application frequency, the points are divided into often used points(23 points), sometimes used points (100) and less used points (130). CONCLUSION: The lack of standardization is the common problem found in modern acupuncture literature in the treatment of post-stroke disorders and the spectrum of disease is in biased distribution. The selected acupoints are distributed in the fourteen meridians and acupoints of yang meridian are the first option. The most common used meridians are Yangming and Shaoyang.

Immobilized capillary tyrosinase microreactor for inhibitor screening in natural extracts by capillary electrophoresis.

A method for creating an immobilized capillary tyrosinase (TRS) reactor based on a layer-by-layer (LBL) assembly for inhibitor screening is described. Tyrosinase was immobilized on the surface of fused-silica capillary via ionic binding technique with cationic polyelectrolyte hexadimethrine bromide (HDB). Then, HDB solution with the same plug length as the TRS was injected again into the capillary to cover the immobilized enzyme by forming HDB-TRS-HDB sandwich-like structure. Then, the substrate of l-tyrosine was introduced into the capillary and on-line enzyme inhibition study was performed by capillary electrophoresis (CE). The enzyme activity was determined by the quantification of peak area of the product of l-DOPA. Enzyme inhibition can be read out directly from the reduced peak area of the product in comparison with a reference electropherogram obtained in the absence of any inhibitor. The immobilized enzyme could withstand 25 consecutive assays by only losing 12% activity. A known TRS inhibitor, kojic acid was employed as a model compound for the validation of the inhibitor screening method. Finally, screening 19 natural extracts of traditional Chinese drugs was demonstrated. The results indicated that inhibition activity could be straightforwardly identified with the system.