Cynaroside improved depressive-like behavior in CUMS mice by suppressing microglial inflammation and ferroptosis.

Depression is a common mental health disorder, and in recent years, the incidence of various forms of depression has been on the rise. Most medications for depression are highly dependency-inducing and can lead to relapse upon discontinuation. Therefore, novel treatment modalities and therapeutic targets are urgently required. Traditional Chinese medicine (TCM) offers advantages in the treatment of depression owing to its multi-target, multi-dimensional approach that addresses the root cause of depression by regulating organ functions and balancing Yin and Yang, with minimal side effects. Cynaroside (CNS), an extract from the traditional Chinese herb honeysuckle, is a flavonoid compound with antioxidant properties. In this study, network pharmacology identified 44 potential targets of CNS associated with depression and several highly correlated inflammatory signaling pathways. CNS alleviated LPS-induced M1 polarization and the release of inflammatory factors in BV-2 cells. Transcriptomic analysis and validation revealed that CNS reduced inflammatory polarization, lipid peroxidation, and ferroptosis via the IRF1/SLC7A11/GPX4 signaling pathway. In vivo experiments showed that CNS treatment had effects similar to those of fluoxetine (FLX). It effectively ameliorated anxiety-, despair-, and anhedonia-like states in chronic unpredictable mild stress (CUMS)-induced mice and reduced microglial activation in the hippocampus. Thus, we conclude that CNS exerts its therapeutic effect on depression by inhibiting microglial cells from polarizing into the M1 phenotype and reducing inflammation and ferroptosis levels. This study provides further evidence that CNS is a potential antidepressant, offering new avenues for the treatment of depression.

Raw Pinelliae Rhizoma: examination of sedative and hypnotic effects in mice and chemical analysis.

PURPOSE: Raw "Pinelliae Rhizoma" (RPR) is widely used in Chinese clinics to treat insomnia. This study investigated its underlying sedative and hypnotic mechanisms and main active components. METHODS: A locomotor activity test was used to evaluate the sedative effects of RPR at three dosages (0.2 g/mL, 0.4 g/mL, and 0.8 g/mL) in mice. Polysomnography was used to assess its ability to improve sleep. Ultra-performance liquid chromatography/time of flight/mass spectrometry (UPLC-TOF-MS) analysis was used to identify the potential active components of RPR. RESULTS: Mice in the RPR groups were less active than mice in the vehicle group; this difference was greatest in the 0.8 g/mL RPR group. Compared with the vehicle, 0.8 g/mL RPR increased the duration of rapid eye movement (REM) sleep in the dark phase. In addition, the duration of wakefulness in the 0.8 g/mL RPR group decreased with increasing durations of nonrapid eye movement (NREM) and REM sleep. Compared with diazepam, 0.8 g/mL RPR increased REM sleep duration in both the light and dark phases and increased the number of transitions both from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 33 RPR constituents, including 15 alkaloids, were identified. CONCLUSION: The results preliminarily indicated that RPR exerts sedative and hypnotic effects in mice, mainly leading to improvements in REM sleep. These effects are possibly due to the alkaloid constituents of RPR.

A double-blind, randomized, placebo-controlled, single-center clinical trial of jiaotaiwan for the treatment of insomnia symptoms caused by disharmony of the heart and kidney.

Background: Jiaotaiwan (JTW) is a classical tranquillizing prescription in traditional Chinese medicine (TCM) for the treatment of insomnia symptoms caused by disharmony of the heart and kidney (ISDHK). This study aimed to evaluate the effectiveness and safety of JTW for treating ISDHK in a double-blind, randomized, placebo-controlled trial. Methods: From September 2018 to February 2020, 128 participants with ISDHK were included in this single-center clinical trial. All participants were equally and randomly divided into either the JTW group (2-g JTW granules, b.i.d. for 7 days) or placebo group (2-g placebo granules, b.i.d. for 7 days). Pittsburgh Sleep Quality Index (PSQI) scores were set as the primary outcome, and polysomnography (PSG), 1H-magnetic resonance spectroscopy (1H-MRS), blood tests, and Disharmony of Heart and Kidney Scoring System (DHKSS) and clinical global impression (CGI) scores were used as secondary outcomes. Laboratory tests were used to evaluate the safety of JTW. All data were collected at baseline and posttreatment. Results: A total of 106 participants completed this clinical trial. Symptom relief was more apparent in the JTW group than the placebo group (PSQI total score: 9.34 ± 3.578 vs. 10.98 ± 3.073, respectively; p = 0.006). However, no PSG changes were observed between the two groups (p > 0.05). Higher CGI and lower DHKSS scores were observed after JTW treatment. Serum melatonin was increased in patients with ISDHK after JTW treatment (JTW, 339.09 ± 256.894 vs. placebo, 219.59 ± 169.045; p = 0.004). There were significant posttreatment differences in metabolites in the left cerebellum between the two groups (myoinositol: JTW, 13.47 ± 2.094 vs. placebo, 12.48 ± 2.449; p = 0.021; choline: JTW, 3.96 ± 0.657 vs. placebo, 3.65 ± 0.562; p = 0.008). In terms of safety, JTW had no noticeable adverse effects relative to placebo. Conclusion: JTW was effective and well tolerated for the treatment of ISDHK. The development of large-scale trials with longer follow-up durations is recommended to provide further evidence. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR1800019239.

White matter alterations in heart-kidney imbalance insomnia and Jiao-Tai-Wan treatment: A diffusion-tensor imaging study.

Previous studies have reported changes in white matter microstructures in patients with insomnia. However, few neuroimaging studies have focused specifically on white matter tracts in insomnia patients after having received treatment. In this prospective study, diffusion-tensor imaging was used in two samples of heart-kidney imbalance insomnia patients who were treated with placebo or Jiao-Tai-Wan, a traditional Chinese medicine commonly used to treat heart-kidney imbalance insomnia, to assess the changes in white matter tracts. Tract-based spatial statistical analyses were first applied to compare the changes in mean diffusivity and fractional anisotropy of white matter between 75 heart-kidney imbalance insomnia patients and 41 healthy control participants. In subsequent randomized, double-blind, placebo-controlled trials, comparisons of mean diffusivity and fractional anisotropy were also performed in 24 heart-kidney imbalance insomnia patients (8 males; 16 females; 42.5 ± 10.4 years) with Jiao-Tai-Wan and 26 heart-kidney imbalance insomnia patients (11 males; 15 females; 39.7 ± 9.4 years) with a placebo, with age and sex as covariates. Fractional anisotropy values in left corticospinal tract were increased in heart-kidney imbalance insomnia patients. Heart-kidney imbalance insomnia patients showed lower mean diffusivity and fractional anisotropy values of several white matter tracts than healthy control participants, such as the bilateral anterior limb of internal capsule, bilateral superior longitudinal fasciculus and bilateral posterior corona radiata. After being treated with Jiao-Tai-Wan, heart-kidney imbalance insomnia patients showed a trend towards reduced fractional anisotropy values in the left corticospinal tract. Jiao-Tai-Wan may improve the sleep quality by reversing the structural changes of the left corticospinal tract caused by heart-kidney imbalance insomnia.

Therapeutic effects of traditional Chinese medicine (Maxingshigan-Weijing Decoction) on COVID-19: An open-label randomized controlled trial.

BACKGROUND: Wenzhou has achieved great progress in the prevention and control of the growing coronavirus disease 2019 (COVID-19) pandemic, and traditional Chinese medicine (TCM) has played an indispensable role in this fight. This study aimed to investigate the efficacy of Maxingshigan-Weijing decoction (MWD) in treating infected patients. METHODS: This study was an open-label randomized controlled trial. Inpatients with mild or moderate symptoms caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were randomly treated with routine supportive care alone or a combination of routine supportive care and MWD. The primary outcome was the rate of symptom (fever, fatigue, cough and difficulty breathing) recovery. RESULTS: Fifty-nine inpatients were enrolled, of whom 29 received routine supportive care alone (control group) and 30 received combination therapy (treatment group). The rate of symptom recovery was significantly higher in the treatment group than in the control group. The time to recovery of fever (3 vs. 7 days), fatigue (9 vs. 12 days), coughing (9 vs. 14 days) and difficulty breathing (4.5 vs. 9.5 days) was also significantly shorter in the treatment group (all p < 0.001). The syndrome score was lower after MWD treatment. However, neither group differed in the viral assay findings, hospitalization days, medication time or the rate of conversion to severe cases. CONCLUSIONS: MWD increased the rate of symptom recovery and shortened the time to recovery of clinical symptoms without deterioration to death or critical care. These findings may provide opportunities for the use of complementary medicine in treating this infection. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030759.

Individualized predictions of early isolated distal deep vein thrombosis in patients with acute ischemic stroke: a retrospective study.

BACKGROUND: Although isolated distal deep vein thrombosis (IDDVT) is a clinical complication for acute ischemic stroke (AIS) patients, very few clinicians value it and few methods can predict early IDDVT. This study aimed to establish and validate an individualized predictive nomogram for the risk of early IDDVT in AIS patients. METHODS: This study enrolled 647 consecutive AIS patients who were randomly divided into a training cohort (n = 431) and a validation cohort (n = 216). Based on logistic analyses in training cohort, a nomogram was constructed to predict early IDDVT. The nomogram was then validated using area under the receiver operating characteristic curve (AUROC) and calibration plots. RESULTS: The multivariate logistic regression analysis revealed that age, gender, lower limb paralysis, current pneumonia, atrial fibrillation and malignant tumor were independent risk factors of early IDDVT; these variables were integrated to construct the nomogram. Calibration plots revealed acceptable agreement between the predicted and actual IDDVT probabilities in both the training and validation cohorts. The nomogram had AUROC values of 0.767 (95% CI: 0.742-0.806) and 0.820 (95% CI: 0.762-0.869) in the training and validation cohorts, respectively. Additionally, in the validation cohort, the AUROC of the nomogram was higher than those of the other scores for predicting IDDVT. CONCLUSIONS: The present nomogram provides clinicians with a novel and easy-to-use tool for the prediction of the individualized risk of IDDVT in the early stages of AIS, which would be helpful to initiate imaging examination and interventions timely.

Efficacy of Traditional Chinese Medicine, Maxingshigan-Weijing in the management of COVID-19 patients with severe acute respiratory syndrome: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We aimed to test our expectation that additional administration of Traditional Chinese medicine (TCM), maxingshigan-weijing decoction, is more effective in the management of COVID-19 patients compared to those treated with routine supportive care alone. TRIAL DESIGN: This is a multicenter, open-label 2-arm (1:1 ratio) randomized controlled trial. PARTICIPANTS: Patients will be recruited from 3 hospitals in Wenzhou China: the First Affiliated Hospital of Wenzhou Medical University, the Second Affiliated Hospital of Wenzhou Medical University and Wenzhou Center Hospital. The inclusion and exclusion criteria are as follows: Inclusion criteria 1. Participants are 18-85 years of age, either male or female. 2. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3. Symptomatic. Mild (mild clinical symptoms without signs of pneumonia in chest X-ray) and Moderate (fever or respiratory symptom with signs of pneumonia in chest X-ray) . 1. Signed the informed consent before treatment. 2. Agreed not to enroll in any other clinical trials. 3. Inpatients Exclusion criteria 1. < 18 or > 85 years old. 2. Pregnancy and lactation. 3. Serious heart, liver, kidney and hematopoietic system diseases, abnormal liver or kidney function. 4. Suffering from other known virus pneumonia. 5. Allergic to Chinese herbal medicine or suffering from allergies. 6. Critical patients (respiratory failure treated by mechanical ventilation or shock or multiple organ failure). INTERVENTION AND COMPARATOR: Patients in the control group will receive routine supportive clinically care including the therapies of anti-viral, anti-bacterial and ameliorating the related symptoms, while patients in TCM group will be asked to take maxingshigan-weijing decoction (composed of 14 Chinese herbal medicines), orally 200 mL 2 times daily, for 14 consecutive days in addition to routine supportive care as mentioned above. Maxingshigan-weijing decoction consists of 10 g of Herba Ephedra (Mahuang), 10 g of Amygdalus Communis Vas (Xingren), 45 g of Gypsum Fibrosum (Shigao), 30 g of Rhizoma phragmitis (Lugen), 20 g of Peach kernel (Taoren), 20 g of Winter Melon kernel (Dongguaren), 30 g of Trichosanthes Kirilowii Maxim (Gualou), 12 g of Pericarpium Citri Reticulatae (Chenpi), 12 g of Rhizoma Pinelliae (Jiangbanxia), 12 g of caulis bambusae in taeniis (Zhuru), 30 g of semen lepidii (Tingliz), 15 g of semen lepidii (Shichangpu), 10 g of curcuma zedoary (ezhu) and 5 g of Radix Glycyrrhizae (Gancao). MAIN OUTCOMES: The primary outcome will be the number of days until the clinical symptom of fever improves in the first 14 days of treatment following randomisation. Fever will be defined as an improvement when the temperature is less than 37°C. Secondary outcomes will be TCM Syndrome Scores, the time it takes until individuals have negative test results for SARS-CoV-2 nucleic acid, the proportion of cases with chest X-ray improvements and the rate of symptom (fever, cough, malaise, shortness of breath) recovery. TCM Syndrome Scoring System is a checklist covering 4 main, 7 secondary and 13 accompanying items. The 4 main items consisting of fever, cough, malaise and shortness of breath, use a four-point scale (0, 2, 4 and 6) depending on the severity; the 7 secondary items including dysphoria, diarrhea, pharyngalgia, expectoration, muscular soreness, nasal obstruction and rhinorrhoea use 0-3-point scale; the 13 accompanying items contain chest pain, headache, aversion to cold, dizziness, nausea and vomiting, anorexia, abdominal distension, dry mouth, anxiety, spontaneous sweating, insomnia, wheezing and blood tinged sputum, and each item is rated on 0-1 scale ( 0 stands for asymptomatic, 1 stands for symptomatic ). The total scores sum up to a range from 0 to 58, with higher scores indicating more severe levels of disease. RANDOMIZATION: Minimization method will be used, balancing the two arms for pneumonia severity. Patients are randomized (1:1 ratio) to each group. Clinical researchers will get a random sequence number which is automatically generated by a random number generator (IBM Corp., Armonk, NY, USA), and sequentially number them in an opaque envelope. Researchers will open random allocation envelopes and assign participants accordingly. Eligible patients will be randomly divided into a routine supportive care group and a routine supportive care plus oral administration of traditional Chinese medicine group, with 70 patients in each group. BLINDING (MASKING): This is an open-label study. The statistical analysis will be carried out by the Professor of Statistics at Wenzhou Medical University, who is blinded to patient allocation. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The previous study reported the efficacy of TCM for COVID-19 and H1N1 influenza patients, the median survival time in the TCM group is estimated as 3 days; this time will be 1.5 times longer in the control group. Accordingly, Kaplan-Meier method and log-rank test will be used. And assuming a statistical power of 70% (one-sided type-1 error of α = 5%, ß = 30%) and a rate of withdrawal and loss to follow-up of 10%, we plan to include 140 participants in both groups ( TCM group = 70, control group = 70). TRIAL STATUS: The trial protocol is Version 2.0, October 14, 2020. Recruitment began March, 2020, and is anticipated to be completed by December 31, 2020. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000030759 . Registered on 13 March 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Jiao-Tai-Wan Ameliorates Depressive-Like Behavior through the A1R Pathway in Ovariectomized Mice after Unpredictable Chronic Stress.

OBJECTIVE: This study was aimed at observing the effect Jiao-Tai-Wan in menopausal depression. METHODS: In this paper, we used ovariectomized mice subjected to chronic unpredictable stress as a menopausal depression model. After the chronic stress, mice were administrated with JTW (3.3 and 6.6mg/kg) and imipramine (10 mg/kg) for 14 days. On the 14th day, mice were subjected to the behavior test like the forced swim test, tail suspension test, and locomotor activity or were sacrificed to assess the protein changes in different brain regions. RESULTS: The administration of JTW at doses of 3.3 and 6.6mg/kg (p.o.) significantly shortened the duration of immobility in forced swim and tail suspension tests. There was no obvious difference in locomotor activity among all the groups. The western blot analysis data indicated that treatment with JTW (3.3 and 6.6 mg/kg, p.o.) prominently increased the A1R protein and the downstream protein ERK1/2 levels in the prefrontal cortex and hippocampus. However, the administration of JTW did not influence c-Fos protein in either the prefrontal cortex or hippocampus. CONCLUSION: Our findings suggest that JTW plays a vital role in ameliorating menopausal depression symptoms in the A1R-ERK1/2 pathway in the prefrontal cortex and hippocampus.

Jiao-tai-wan for insomnia symptoms caused by the disharmony of the heart and kidney: a study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Insomnia seriously affects people's normal lives and work. However, effective treatment strategies are scarce. The purpose of this study is to explore the efficacy and safety of Jiao-tai-wan (JTW) for ameliorating insomnia symptoms caused by disharmony of the heart and kidney. DESIGN: This is a randomized, double-blind, placebo-controlled pilot clinical trial. A total of 124 participants suffering from insomnia symptoms will be randomly assigned to the JTW or placebo group in an equal ratio. The participants will be asked to take JTW or placebo granules twice a day for 1 week. All data will be gathered at baseline and at the end of the drug intervention. The primary outcome measures will be the mean change in the Pittsburgh Sleep Quality Index (PSQI) from baseline to the end of the drug intervention. Secondary outcome measures will include the altered sleep parameters in polysomnography, 1H-magnetic resonance spectroscopy (1H-MRS) evaluation, the Disharmony of Heart and Kidney Scoring System score, and blood tests, including the levels of serum adenosine and melatonin. A laboratory test will be taken before and after treatment to assess the safety of JTW. DISCUSSION: The outcomes of this study will confirm the efficacy of JTW for the treatment of insomnia symptoms and will also be used to monitor the safety of JTW. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019239. Registered on 1st November 2018.

Risk Factors of Vitamin D Deficiency in Chinese Ischemic Stroke Patients: A Cross-Sectional Study.

PURPOSE: Lower serum vitamin D has been reported to be associated with stroke. This study aimed to analyze the risk factors of vitamin deficiency in Chinese stroke patients, and further analyze its impact in different gender and their clinical variables. METHODS: 982 stroke patients were enrolled. Laboratory parameters such as serum vitamin D, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), ApoA-I/ApoB, cholesterol (CH), fibrinogen (FIB), blood glucose (Glu), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were collected and recorded. The severity of stroke was assessed by National Institute of Health Stroke Scale (NIHSS) score. Based on their serum vitamin D level, patients were divided into three groups: Vitamin D deficiency (<50 nmol/L), vitamin D insufficiency (≥50-75 nmol/L) and vitamin D sufficiency (≥75 nmol/L) and differences were compared among the three groups. Statistical analyses were done to assess the risk factors for serum vitamin D deficiency in our ischemic stroke patients. RESULTS: Gender, NIHSS, and FIB showed significant differences among the vitamin D groups (P < 0.001 ∼ P = 0.002). The female gender (OR = 2.422, P < 0.001), severity of stroke using NIHSS (OR = 1.055, P = 0.008) and FIB (OR = 1.256, P = 0.005) were risk factors of vitamin D deficiency in ischemic stroke patients. In subgroup analysis, NIHSS was significantly associated with vitamin D deficiency in the male group (OR = 1.087, P = 0.002) and higher FIB group (OR = 1.078, P = 0.001). CONCLUSIONS: The female gender, severity of stroke using NIHSS and FIB were risk factors for vitamin D deficiency in our incident stroke patients. NIHSS was more sensitive to vitamin D deficiency in male ischemic stroke patients. Besides, under higher FIB circumstance, the increasing NIHSS score was more related to the vitamin D deficiency. Levels of vitamin D in patients with ischemic stroke should be well monitored during the disease cascade.

Pinelliae Rhizoma Praeparatum Cum Alumine Extract: Sedative and Hypnotic Effects in Mice and Component Compounds.

Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) is useful for eliminating dampness and phlegm in clinical settings, targeting the main mechanisms of insomnia as defined in traditional Chinese medicine. However, little is known regarding the sedative and hypnotic effects of PRPCA. In the present study, we examined the sedative effects of PRPCA via a locomotor activity test and aimed to determine the most appropriate concentration of PRPCA for achieving these effects. The strongest sedative effects were observed at a PRPCA concentration of 0.45 g/ml. In addition, we investigated the hypnotic effects of PRPCA and its role in promoting sleep via sleep monitoring and vigilance state analysis. PRPCA increased rapid eye movement (REM) sleep and non-REM (NREM) sleep while decreasing wakefulness. In addition, PRPCA decreased the number of bouts of wakefulness (16-32 s and 32-64 s) and increased the number of bouts of NREM sleep (128-256 s). Furthermore, we identified a total of 32 component compounds via chromatography and mass spectrometry. Hence, the current work provides valuable information regarding the sedative and hypnotic effects of PRPCA and its regulatory mechanisms in promoting sleep.

Pinellia ternata (Thunb.) Makino Preparation promotes sleep by increasing REM sleep.

Pinellia ternata (Thunb.) Makino Preparation (PTP) is widely used to treat insomnia in traditional Chinese medicine; however, its specific role is not clear. In this study, PTP was prepared at three concentrations. For locomotor activity tests, mice were treated with PTP and evaluated for 14 days. For polygraph recordings, mice were treated for 14 days and recorded after treatment. The main chemical constituents in PTP were identified by Ultra performance liquid chromatography/quadrupole time spectrometry (UPLC/Q-TOF-MS). The results showed that 0.9 g/mL PTP significantly reduced locomotor activity. The effect was related to the time of treatment. PTP reduced wakefulness and increased sleep in mice. Furthermore, PTP promoted sleep by increasing the number of REM sleep episodes with a duration of 64-128s and increasing the number of transitions from NREM sleep to REM sleep and from REM sleep to wakefulness. A total of 17 compounds were identified.

The curcumin derivative WZ35 activates ROS-dependent JNK to suppress hepatocellular carcinoma metastasis.

Tumor metastasis is the leading cause of cancer death; due to the progress made in the elucidation of the mechanism of cancer cell metastasis, there is hope for patients with severe stages of cancer. Curcumin, as a novel anti-cancer drug, has been applied in cancer therapy; however, the toxicity of curcumin hinders its application. Herein, we constructed a novel derivative, WZ35, and evaluated its metastatic inhibition properties in vitro and in vivo. CCK-8 assay was performed to evaluate the tumor suppressive activity of WZ35. Cell apoptosis was detected by flow cytometry analysis. Transwell cell migration assay and RTCA were used to detect cell migration in mock and WZ35-treated cells. Western blotting was performed to analyze molecular alteration with different treatments. In this study, we found that curcumin and its derivative WZ35 could dramatically suppress proliferation, invasion, and migration of the hepatocellular HCCLM3, HepG2, and Huh7 cancer cells. Moreover, the cancer cell metastatic markers MMP-2, MMP-9, and N-cadherin were decreased, and E-cadherin was up-regulated. In addition, our data show that WZ35 promotes ROS-dependent JNK activation that is essential for WZ35-caused cell metastasis suppression. Moreover, the NAC and JNK inhibitor SP600125 could dramatically reverse WZ35-caused MMP-2, MMP-9, and N-cadherin reduction and E-cadherin up-regulation. We have also found that WZ35 exhibits powerful anti-metastasis activity of HCCLM3 in vivo. In conclusion, our data indicated that WZ35 could be a candidate for the treatment of metastatic liver cancer patients.

MiR-206 inhibits epithelial ovarian cancer cells growth and invasion via blocking c-Met/AKT/mTOR signaling pathway.

BACKGROUND: MicroRNAs play important roles in the pathogenesis of various kinds of tumors. However, there are few studies on the expression profile and function of miRNAs in epithelial ovarian cancer. In this study, we performed microRNA array to compare the expression profile of microRNA in ovarian cancer tissues with noncancerous tissues. METHODS: qRT-PCR was used to further confirm the microRNA expression levels in epithelial ovarian cancer tissues and cell lines. The function of microRNA was analyzed by overexpressing microRNA mimics followed by the analysis of cell cycle, proliferation, and metastasis. The downstream target of miR-206 was found and western blot analysis was performed to measure the activation of the downstream signaling pathway. RESULTS: In this study, we found the expression of miR-206 was significantly down-regulated in epithelial ovarian cancer tissues and epithelial ovarian cancer cell lines. In epithelial ovarian cancer patients, downregulation of miR-206 was associated with metastasis and poor prognosis. In epithelial ovarian cancer cell lines, miR-206 contributed to the cell cycle regulation, cell apoptosis, and cancer cell metastasis. MiR-206 mimics inhibited cancer cell proliferation and metastasis, and induced cell apoptosis. Moreover, our results demonstrated that miR-206 directly targeted c-Met and repressed the activation of downstream AKT/mTOR signaling pathway. CONCLUSION: Our results demonstrated that miR-206 was down-regulated in epithelial ovarian cancer tissues and cell lines. MiR-206 inhibits the development of epithelial ovarian cancer cell by directly targeting c-Met and inhibiting the c-Met/AKT/mTOR signaling pathway.

Anti-Cancer Effect of α-Solanine by Down-Regulating S100P Expression in Colorectal Cancer Cells.

BACKGROUND: α-Solanine, the most important and active component of Solanum nigrum, was found to have anti-cancer activity on multiple cancer cells. However, its effects on colorectal cancer (CRC) and associated molecular mechanisms remain to be further elucidated. OBJECTIVE: In this study, we investigated the anti-cancer effects of α-solanine against CRC cells in vitro and in vivo. MATERIALS & METHODS: Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay; cell cycle was analyzed with a Cycletest Plus DNA Reagent Kit; cell apoptosis was detected by flow cytometer; cell migration and invasive ability was determined by Transwell assays; S100P protein expression was also analyzed by western blotting; lentiviral vectors expressing shRNA targeting the S100P gene. RESULTS: We demonstrated that α-solanine inhibited CRC cell (SW480, SW620 and HT-29) growth as well as migration and invasion, induced cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Moreover, we observed that S100P expression was downregulated by α-solanine. Overexpression of S100P partially reversed the α-solanine-induced growth inhibition of CRC cells. Conversely, knockdown of S100P by lentiviral-mediated RNAi resulted in significantly promoting the α-solanine-induced growth inhibition. CONCLUSION: These findings suggest that α-solanine is a potential agent for the treatment of CRC, and the anti-tumor effect of α-solanine in the CRC cells may be mediated at least partly by the downregulation of S100P.

Controllability of flow-conservation networks.

The ultimate goal of exploring complex networks is to control them. As such, controllability of complex networks has been intensively investigated. Despite recent advances in studying the impact of a network's topology on its controllability, a comprehensive understanding of the synergistic impact of network topology and dynamics on controllability is still lacking. Here, we explore the controllability of flow-conservation networks, trying to identify the minimal number of driver nodes that can guide the network to any desirable state. We develop a method to analyze the controllability on flow-conservation networks based on exact controllability theory, transforming the original analysis on adjacency matrix to Laplacian matrix. With this framework, we systematically investigate the impact of some key factors of networks, including link density, link directionality, and link polarity, on the controllability of these networks. We also obtain the analytical equations by investigating the network's structural properties approximatively and design the efficient tools. Finally, we consider some real networks with flow dynamics, finding that their controllability is significantly different from that predicted by only considering the topology. These findings deepen our understanding of network controllability with flow-conservation dynamics and provide a general framework to incorporate real dynamics in the analysis of network controllability.

The Effects of Tai Chi Training in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

Heart Failure (HF) is associated with significantly high morbidity and mortality. We performed a meta-analysis and updated new evidences from randomized controlled trials (RCTs) to determine the effects of Tai Chi (TC) in patients with HF. Electronic literature search of Medline, PubMed, EMBASE, the Cochrane Library, China national knowledge infrastructure (CNKI), and Wan Fang Database was conducted from inception of their establishment until 2017. And we also searched Clinical Trials Registries (https://clinicaltrials.gov/ and www.controlled-trials.com) for on-going studies. A total of 11 trials with 656 patients were available for analysis. The results suggested that TC was associated with an obviously improved 6-min walk distance [6MWD, weighted mean difference (WMD) 65.29 m; 95% CI 32.55-98.04] and quality of life (Qol, WMD -11.52 points; 95% CI -16.5 to -6.98) and left ventricular ejection fraction (LVEF, WMD 9.94%; 95% CI 6.95 to 12.93). TC was shown to reduce serum B-type natriuretic peptide [BNP, standard mean difference (SMD) -1.08 pg/mL; 95% CI -1.91 to -0.26] and heart rate (HR, WMD -2.52 bpm; 95% CI -3.49 to -1.55). In summary, our meta-analysis demonstrated the clinical evidence about TC for HF is inconclusive. TC could improve 6MWD, Qol and LVEF in patients with HF and may reduce BNP and HR. However, there is a lack of evidence to support TC altering other important long-term clinical outcomes so far. Further larger and more sustainable RCTs are urgently needed to investigate the effects of TC.

Exact controllability of complex networks.

Controlling complex networks is of paramount importance in science and engineering. Despite the recent development of structural controllability theory, we continue to lack a framework to control undirected complex networks, especially given link weights. Here we introduce an exact controllability paradigm based on the maximum multiplicity to identify the minimum set of driver nodes required to achieve full control of networks with arbitrary structures and link-weight distributions. The framework reproduces the structural controllability of directed networks characterized by structural matrices. We explore the controllability of a large number of real and model networks, finding that dense networks with identical weights are difficult to be controlled. An efficient and accurate tool is offered to assess the controllability of large sparse and dense networks. The exact controllability framework enables a comprehensive understanding of the impact of network properties on controllability, a fundamental problem towards our ultimate control of complex systems.

[Meta-analysis on elemene injection combined with cisplatin chemotherapeutics in treatment of non-small cell lung cancer].

To research databases of Cochrane library, Web of Science, PubMed, FMJS, CBM, VIP, CNKI and Wanfang Data Konwledge Service Platform by computers as at July 5, 2012, which was supplemented with other search results. The findings were included into randomized controlled trials (RCTs) of elemene injection combined with cisplatin chemotherapeuties in treating small cell lung cancer (NSCLC). Data was separately collected by two researchers for literature quality evaluation, and a Meta analysis was made with RevMan 5. 2 software, in order to assess the efficacy and safety of elemene injection combined with cisplatin chemotherapeutics in treating NSCLC. Totally 11 RCTs or 844 cases were included. Meta analysis results suggested that compared with cisplatin chemotherapy alone, the combination of elemene injection and cisplatin chemotherapeutics showed a higher clinical benefit rate ( OR = 2. 03, 95% CI:1.43-2. 88, P <0. 000 1) and a better quality of life (OR = 3.23, 95% CI:2. 20-4. 74, P <0. 000 01). Besides,the combination could also reduce leucopenia (OR =0. 50, 95% CI:0. 33-0. 76, P <0. 001) , and thrombocytopenia (OR =0. 38, 95% CI:0. 16-0. 85, P <0. 02), increase CD4 (MD = 3.32, 95% C1:2. 94-3.70, P <0. 000 01), and CD4/CD8 (MD = 0. 36, 95% CI:0. 28-0. 44, P < 0. 000 01) , and relieve gastrointestinal reactions such as nausea and vomiting (OR = 0. 37, 95% CI: 0. 19-0. 71, P = 0. 003). The analysis indicates that elemene can enhance the chemotherapeutic effect on NSCLC, improve the quality of life, and reduce adverse effect of platinum-contained chemotherapeutics, thereby being worth promoting in clinic.

Efficacy and safety of Wuling capsule, a single herbal formula, in Chinese subjects with insomnia: a multicenter, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Wuling Capsule is a single herbal formula from mycelia of precious Xylaria nigripes (Kl.) Sacc and its pharmacological function have a tranquilizing effect on the central nervous system. The aim of the study to evaluate the efficacy and safety of Wuling capsule in treatment of insomnia. MATERIALS AND METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled study. The participants received either placebo (n=92) or Wuling capsule (n=94) for 4 weeks and a follow-up period for 2 weeks. RESULTS: Compared between pre-treatment and post-treatment, the global Pittsburgh sleep quality index (PSQI) scores in both Wuling capsule group and placebo group improved significantly (P<0.01). However, there was no significant difference between Wuling capsule group and placebo group (P>0.05). Scores of clinical global impressions scale (CGI-I) at each week in Wuling capsule group was similar to those in placebo group (P>0.05). Compared between pre-treatment and post-treatment, scores of the four components of world health organization on quality of life brief scale (WHOQOL-BREF) in both Wuling capsule group and placebo group improved significantly (P<0.01). However, there were no difference between the two groups (P>0.05). The rate of adverse events was 10.10% in Wuling group, and 6.73% in placebo group (P>0.05). CONCLUSIONS: Wuling capsule can improve insomnia when compared with pre-treatment for 4 weeks and be a well tolerated by all the patients at the 6 weeks of study period. However, there are no significant in the results of the variables tested when compared with placebo control. Further additional rigorous randomized clinical trials are still required.