Deciphering the Molecular Mechanism of Escin against Neuropathic Pain: A Network Pharmacology Study.

Background: Escin is the main active component in Aesculus hippocastanum. It has been demonstrated that escin has anti-inflammatory properties. This study combined the methods of network pharmacology, molecular docking, and molecular dynamics to explore the molecular mechanism of escin against neuropathic pain (NP). Methods: The Swiss Target Prediction and the Pharm Mapper database were employed for predicting the targets of escin. Also, the candidate targets of NP were gathered via the databases including Therapeutic Targets, DisGeNet, GeneCards, DrugBank, and OMIM. Subsequently, the network of protein-protein interaction was screened for the key targets by the software Cytoscape 3.8.0. Then, the intersection of these targets was analysed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Additionally, we further investigated the ligand-target interactions by molecular docking and molecular dynamics simulations. Results: In total, 94 escin targets were predicted by network pharmacology. Among them, SRC, MMP9, PTGS2, and MAPK1 were the core candidate targets. Subsequently, the analysis of GO and KEGG enrichment revealed that escin affected NP by regulating protein kinase C, MAP kinase, TRP channels, the T-cell receptors signaling pathway, and the TNF signaling pathway. The results of molecular docking and molecular dynamics simulation confirmed that escin not only had a strong binding activity with the four core target proteins but also stably combined in 50 ns. Conclusions: Our study revealed that escin acts on the core targets SRC, MMP9, PTGS2, MAPK1, and associated enrichment pathways to alleviate neuronal inflammation and regulate the immune response, thus exerting anti-NP efficacy. This study provided innovative ideas and methods for the promising treatment of escin in relieving NP.

Analysis of Influencing Factors for Exercise Ventilation Efficiency of COPD Patients.

Dynamic pulmonary hyperinflation and abnormal air exchange are the primary causes of the exercise limitation of chronic obstructive pulmonary disease (COPD) patients. During exercise, COPD sufferers' lungs are dynamically hyperinflated. Increased inefficient ventilation reduces ventilation efficiency and causes a mismatch between ventilation volume and blood flow. The ventilatory equivalent for CO2 (VeqCO2) is a physiological parameter that can be measured using cardiopulmonary exercise testing. Therefore, the aim of this exploratory study was to perform cardiopulmonary exercise testing on people with COPD, investigate the impact of static pulmonary function on ventilation efficiency under the exercise state, and screen the predictive indicators of ventilation efficiency. Subject. The aim of this study was to look at the factors that influence the exercise ventilation efficiency of people with COPD. Method. A total of 76 people with COPD were recruited during the stable period. Age, gender, body height, body mass, and other basic information were recorded. The body mass index (BMI) was determined, and forced vital capacity (FVC), forced expiratory volume in one second (FEV1), residual volume/total lung capacity (RV/TLC), diffusing capacity of the lung for carbon monoxide (DLCO), and DLCO divided by the alveolar volume (DLCO/VA) were measured. The ventilatory equivalent for carbon dioxide (VE/VCO2) under the rest state (EqCO2rest), anaerobic threshold (EqCO2at), and maximum exercise state (EqCO2 max) were calculated to investigate the influencing factors for ventilation efficiency of people with COPD. Results. FEV1% was negatively correlated with EqCO2rest (r = -0.277, P value <0.05); FEV1/FVC % was negatively correlated with EqCO2rest and EqCO2at (r = -0.311, -0.287, P value <0.05); DLCO% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.408, -0.462, and -0.285, P value <0.05); DLCO/VA% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.390, -0.392, and -0.245, P value <0.05); RV/TLC was positively correlated with EqCO2rest and EqCO2at (r = 0.289, 0.258, P-value <0.05). The prediction equation from the multivariable regression analysis equation was Y = 40.04-0.075X (Y = EqCO2, X = DLCO/VA%). Conclusions. As the degree of ventilatory obstruction increased, the ventilation efficiency of the stable people with COPD under the exercise state showed a progressive decrease; the ventilation efficiency of the people with COPD decreased significantly under the maximum exercise state, and the ventilation capacity and diffusion capacity were the significant factors that affected the exercise ventilation efficiency. The diffusion function may predict the maximum ventilation efficiency and enable primary hospitals without exercise test equipment in developing countries to predict and screen patients at risk for current exercise based on limited information.

Efficacy And Safety Of Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler (GFF MDI) Formulated Using Co-Suspension Delivery Technology In Chinese Patients With COPD.

Background: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting ß2-agonist fixed-dose combination therapy delivered by MDI, formulated using innovative co-suspension delivery technology. The PINNACLE-4 study evaluated the efficacy and safety of GFF MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) from Asia, Europe, and the USA. This article presents the results from the China subpopulation of PINNACLE-4. Methods: In this randomized, double-blind, placebo-controlled, parallel-group Phase III study (NCT02343458), patients received GFF MDI 18/9.6 µg, glycopyrrolate (GP) MDI 18 µg, formoterol fumarate (FF) MDI 9.6 µg, or placebo MDI (all twice daily) for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second at Week 24. Secondary lung function endpoints and patient-reported outcome measures were also assessed. Safety was monitored throughout the study. Results: Overall, 466 patients from China were included in the intent-to-treat population (mean age 63.6 years, 95.7% male). Treatment with GFF MDI improved the primary endpoint compared to GP MDI, FF MDI, and placebo MDI (least squares mean differences: 98, 104, and 173 mL, respectively; all P≤0.0001). GFF MDI also improved daily total symptom scores and time to first clinically important deterioration versus monocomponents and placebo MDI, and Transition Dyspnea Index focal score versus placebo MDI. Rates of treatment-emergent adverse events were similar across the active treatment groups and slightly higher in the placebo MDI group. Conclusion: GFF MDI improved lung function and daily symptoms versus monocomponents and placebo MDI and improved dyspnea versus placebo MDI. All treatments were well tolerated with no unexpected safety findings. Efficacy and safety results were generally consistent with the global PINNACLE-4 population, supporting the use of GFF MDI in patients with COPD from China.

Efficacy of fasudil for the treatment of aneurysmal subarachnoid hemorrhage: A systematic review protocol of randomized controlled trial.

BACKGROUND: This study aims to systematically assess the efficacy and safety of fasudil for the treatment of aneurysmal subarachnoid hemorrhage (ASH). METHODS: This study will include all of randomized controlled trials on the efficacy and safety of fasudil for the treatment of ASH. Ten electronic databases of PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, Ovid, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched from inception to the May 1, 2019 without language restrictions. We will also search gray literatures to avoid missing any other potential studies. Two authors will independently perform study selection, data extraction and management, and methodologic quality assessment. The primary outcome is limbs function. The secondary outcomes comprise of muscle strength, muscle tone, quality of life, and adverse events. RESULTS: This study will provide a comprehensive literature search on the current evidence of fasudil for the treatment of ASH from primary and secondary outcomes. CONCLUSION: The results of this study will present evidence to determine whether fasudil is an effective and safety treatment for patients with ASH. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019136215.

Effect of pressure therapy for treatment of hypertrophic scar.

BACKGROUND: Pressure therapy (PST) has been reported for the treatment of hypertrophic scar (HS) effectively. However, no study has assessed its effect and safety systematically. Therefore, this study will investigate its effect and safety for patients with HS. METHODS: A comprehensive literature search will be performed from the electronic databases and grey literatures. The electronic databases include MEDILINE, EMBASE, Cochrane Library, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All of them will be searched from inception to the present without language restrictions. Any randomized controlled trials on assessing the effect and safety of PST on HS will be considered for inclusion. In addition, we will also search grey literature to avoid missing any potential studies. RevMan V.5.3 software will be utilized for statistical analysis. RESULTS: This study will provide the most recent evidence of PST on HS by evaluating primary outcomes of scar pruritus and improvement of scar; and secondary outcomes of scar blood flow, elasticity, volume, pain and burning. In addition, we will also evaluate adverse events. CONCLUSION: This study will provide up-to-date evidence of PST in patients with HS.Systematic review registration: PROSPERO CRD42019136627.

Effects of YuPingFeng granules on acute exacerbations of COPD: a randomized, placebo-controlled study.

PURPOSE: Recurrence of acute exacerbations has a major impact on patients with COPD. Therefore, effective prevention and treatment of exacerbation is crucial in the management of COPD, especially for patients with moderate to severe disease. This study evaluated the effectiveness of YuPingFeng granule administration in preventing exacerbation and improving symptom score, as well as its long-term (1 year) safety profile, in patients with COPD. PATIENTS AND METHODS: This was a randomized, double-blind, parallel, placebo-controlled study of 240 patients from eight centers in China. Participants were eligible if they had mild to severe COPD as defined by Global Initiative for Chronic Obstructive Lung Disease, had a history of at least two COPD exacerbations or one hospitalization within the previous year, and had remained clinically stable for over 4 weeks before the study. They were randomly assigned to receive 5 g of YuPingFeng or placebo, three times per day, for 1 year. The primary end point was the exacerbation rate over 1 year, and the analysis was by intention to treat. Secondary end points included symptom score, which was assessed by COPD assessment test (CAT) score and safety profiles. This trial was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn; registration number: ChiCTR-IPR-15007023). RESULTS: The YuPingFeng group had a significantly lower exacerbation rate than the placebo group (1.15 vs 1.55; risk ratio=0.677 [95% CI 0.531-0.863]; P=0.002) and a significantly reduced risk of second exacerbation (95% CI 0.326-0.772; P=0.002). After treatment, the mean change in the CAT score in the YuPingFeng group (-4.41±7.01) differed significantly from that in the placebo group (-2.49±5.31; P=0.001). YuPingFeng was well tolerated. CONCLUSION: YuPingFeng granules can be considered as a treatment option for COPD; this treatment prevents acute exacerbations of COPD and has a good safety profile.

A retrospective study of transcutaneous vagus nerve stimulation for poststroke epilepsy.

BACKGROUND: This study assessed the effect transcutaneous vagus nerve stimulation (TVNS) for poststroke epilepsy (PSE). METHODS: Fifty-two patients with PSE were included in this study. Twenty-seven patients received TVNS, 30 minutes each session, once daily, twice weekly for a total of 4 weeks; and were assigned to the treatment group. Twenty-five patients were at waiting list and were assigned to the control group. The primary outcome included weekly seizure frequency. The secondary outcomes consisted of each seizure episode, and quality of life, measured by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), as well as the adverse events. All outcomes were measured before and after 4-week treatment. RESULTS: After treatment, TVNS failed to show better outcomes in weekly seizure frequency (treatment group, P = .12; control group, P = .56), seizure episode (treatment group, P = .65; control group, P = .92), and QOLIE-31 (treatment group, P = .73; control group, P = .84) compared with these before the treatment. Furthermore, TVNS also did not elaborate the promising effect in seizure frequency (P = .81), seizure episode (P = .75), and QOLIE-31 (P = .33), compared with these in the control group. In addition, minor and acceptable adverse events were recorded in this study. CONCLUSION: The results of this study showed that TVNS may be not effective for Chinese patients PSE after 4-week treatment.

Salvianolic acid B protects from pulmonary microcirculation disturbance induced by lipopolysaccharide in rat.

The aim of the present study was to examine the effect and possible mechanism of salvianolic acid B (SalB) on pulmonary microcirculation disturbance induced by lipopolysaccharide (LPS) in rat. Male Sprague-Dawley rats were subjected to thoracotomy under continuous anesthesia and mechanical ventilation. Albumin leakage from pulmonary capillary and the numbers of leukocytes adherent to the pulmonary capillary wall were determined for 60 min by an upright microscope upon LPS (2 mg · kg(-1) · h(-1)) infusion with or without administration of SalB (5 mg · kg(-1) · h(-1)). Pulmonary tissue wet-to-dry weight ratio, tumor necrosis factor α, and interleukin 8 in plasma and bronchoalveolar lavage fluid were measured. In addition, the expressions of E-selectin, intercellular adhesion molecule 1, and myeloperoxidase in pulmonary tissue were assessed by immunohistochemistry. The expressions of aquaporin 1 (AQP-1), AQP-5, metalloproteinase 2 (MMP-2), and MMP-9 were assessed by Western blot assay. Pretreatment with SalB significantly attenuated LPS-induced pulmonary microcirculatory disturbance, including the increase in leukocyte adhesion and albumin leakage. In addition, LPS increased pulmonary tissue wet-to-dry weight ratio and tumor necrosis factor α and interleukin 8 levels in plasma and bronchoalveolar lavage fluid enhanced the expression of E-selectin, intercellular adhesion molecule 1, myeloperoxidase, MMP-2, and MMP-9, whereas it decreased the expression of AQP-1 and AQP-5 in pulmonary tissue, all of which were attenuated by SalB pretreatment. Salvianolic acid B pretreatment improves pulmonary microcirculation disturbance and lung injury on LPS exposure. More studies are required to evaluate the potential of SalB as an option for protecting lung from endotoxemia.

Tanshinone IIA improves miR-133 expression through MAPK ERK1/2 pathway in hypoxic cardiac myocytes.

Tanshinone IIA is a lipid-soluble pharmacologically active compound extracted from the rhizome of Chinese herb Salvia miltiorrhiza, a well-known traditional Chinese medicine used for the treatment of cardiovascular disorders. Previous studies have identified that tanshinone IIA inhibited overexpression of miR-1 in hypoxic neonatal cardiomyocytes. This study was designed to examine the effects of tanshinone IIA on miR-133 expression under hypoxic condition. Neonatal rat cardiomyocytes were cultured in a hypoxic environment (2% O(2)+93% N(2)+5% CO(2)) at 37°C for 24 hours. MTT, TUNEL assays, and Flow Cytometry (FCM) were performed to identify cell apoptosis. Western blot was used to examine the expression of ERK1/2 and miR-133 level was quantified by Real-time PCR. Our results showed that apoptosis was induced by hypoxia. Typical apoptotic cells were seen by TUNEL assay, and FCM showed an apoptosis rate of 13.32% in hypoxic group. Apoptosis rate in hypoxic cells was reduced significantly by tanshinone IIA. In addition, the expression level of miR-133 was increased in hypoxic cells and further upregulated by tanshinone IIA. The stress-activated protein kinase MAPK ERK1/2 was activated by hypoxia and further increased with tanshinone IIA treatment. The present study demonstrated that tanshinone IIA enhanced cell resistance to hypoxic insult by upregulating miR-133 expression through activating MAPK ERK1/2 in neonatal cardiomyocytes.