Electroacupuncture stimulation enhances the permeability of the blood-brain barrier: A systematic review and meta-analysis of preclinical evidence and possible mechanisms.

An important cellular barrier to maintain the stability of the brain's internal and external environment is the blood-brain barrier (BBB). It also prevents harmful substances from entering brain tissue through blood circulation while providing protection for the central nervous system. It should be noted, however, that the intact BBB can be a barrier to the transport of most drugs into the brain via the conventional route of administration, which can prevent them from reaching effective concentrations for the treatment of disorders affecting the central nervous system. Electroacupuncture stimulation has been shown to be effective at opening the BBB in a series of experimental studies. This study systematically analyzes the possibility and mechanism by which electroacupuncture opens the BBB. In PubMed, Web of Science, VIP Database, Wanfang Database, and the Chinese National Knowledge Infrastructure, papers have been published for nearly 22 years aimed at opening the BBB and its associated structures. A comparison of EB content between electroacupuncture and control was selected as the primary outcome. There were also results on vascular endothelial growth factor (VEGF), nerve growth factor (NGF), P-Glycoprotein (P-gp), Matrix Metalloproteinase 9 (MMP-9), and glial fibrillary acidic protein (GFAP). We utilized Review Manager software analysis to analyze correlations between studies with a view to exploring the mechanisms of similarity. Evans Blue infiltration forest plot: pooled effect size of 2.04, 95% CI: 1.21 to 2.87, P < 0.01. These results indicate that electroacupuncture significantly increases EB penetration across the BBB. Most studies have reported that GFAP, MMP-9, and VEGF were upregulated after treatment. P-gp expression decreased as well. Electroacupuncture can open the BBB, and the sparse-dense wave is currently the most effective electroacupuncture frequency for opening the BBB. VEGF plays an important role in opening the BBB. It is also important to regulate the expression of MMP-9 and GFAP and inhibit the expression of P-gp.

Acupuncture with specific mode electro-stimulation effectively and transiently opens the BBB through Shh signaling pathway.

To explore a new method that patients with brain diseases such as stroke sequelae are hindered by blood-brain barrier (BBB) in clinical treatment. Research preliminarily found that acupuncture with specific mode electro-stimulation (EA) to open BBB-assisted drug delivery may be is an effective means to improve the clinical efficacy of brain disease patients. So here we further explore the features and mechanism. Middle cerebral artery occlusion/R recovery rats were employed as the animal model. Laser Doppler monitoring cerebral blood flow decreased to 45 ±â€…10% of the baseline value as modeling criteria and TTC staining observed infarcted areas of brain tissue. The permeability of FITC-Dextran and EB in the frontal lobe of rats was observed by microscope. After that, Western blot and Immunofluorescence staining for the detection of the shh and Gli1 signal molecule, Claudin-5 Occludin ZO-1 tight junction (TJ) proteins. EA can open the BBB stably and effectively, and has the characteristics of starting to close soon after the end of EA; EA inhibits the Shh-Gli1 signaling pathway, and downregulates Occludin ZO-1 TJ proteins. These results suggest that EA is safe and reversible in opening the BBB, and its mechanism is related to the inhibition of Shh signaling pathway to down-regulate the expression of TJ proteins.

Shufeng Jiedu capsule for acute exacerbation of chronic obstructive pulmonary disease: a protocol of multicentre, randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) represents one of the leading causes of death worldwide. Published clinical trials suggest that the Chinese patent herbal medicine Shufeng Jiedu capsule (SFJD) is safe and may be effective for treating acute exacerbations of COPD (AECOPD). However, these effects have been reported with low or very low certainty evidence. This trial aims to evaluate the effectiveness and safety of SFJD for AECOPD. METHODS AND ANALYSIS: This study is designed as a multicentre, randomised, double-blind, placebo-controlled trial. Three hundred patients with moderate or severe hospitalised AECOPD will be recruited in Beijing, Shanghai and Hefei. Participants will be randomly assigned to SFJD and usual care or placebo and usual care at a ratio of 1:1. SFJD and placebo will be administered orally four capsules three times daily for 7 consecutive days followed by an 8-week follow-up period. The primary outcome will be COPD symptom severity as measured by the EXAcerbation of Chronic Pulmonary Disease Tool score. Secondary outcomes include clinical symptoms, quality of life, length of hospital stay, a total dose of antibiotics, the frequency of recurrence of AECOPD, haematological biomarkers, death and adverse events. This study will answer the question of whether SFJD was safe to use and will improve symptoms in people with AECOPD, and will therefore reduce the necessity for antibiotics, the risk and duration of admission to hospital, and the risk of recurrence. ETHICS AND DISSEMINATION: The ethics committee of the first affiliated hospital of Anhui Medical University, Beijing University of Chinese Medicine affiliated Dongzhimen hospital and fifth people's hospital of Shanghai Fudan University approved the study protocol. Informed written consent will be obtained from all the participants. The results of this trial will be disseminated at academic conferences and in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN99049821.

Natural Geranylated Sulfur-Containing Amides with Inhibitory Effect on Th17 Differentiation.

Chemical investigation of medicinal plant Glycosmis lucida Wall. ex C. C. Huang leaves led to the production of ten compounds (1-10), including two previously unreported geranylated sulfur-containing amides (1 and 2) and eight known ones (3-10). Structural characterization was carried out using comprehensive spectroscopic methods including NMR, MS and CD. The inhibitory effects of all isolates on Th17 differentiation were evaluated, of which compounds 1 and 6 significantly inhibited Th17 differentiation with IC50 values of 0.36 and 1.30 µM, respectively, while both 1 and 6 failed to bind to retinoic acid-related orphan receptor gamma t (RORγt), suggesting that their inhibition of Th17 differentiation is independent of RORγt.

Cytoreductive Surgery (CRS) Combined With Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Platinum-Sensitive Recurrence Epithelial Ovarian Cancer With HRR Mutation: A Phase III Randomized Clinical Trial.

Background: Epithelial ovarian cancer (EOC) remains the leading cause of gynecologic cancer death worldwide due to the high recurrence rate. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is an alternative modality for platinum-sensitive recurrent EOC. The latest studies demonstrate homologous recombination-related (HRR) mutation status increases the sensitivity to platinum-based chemotherapy drugs in EOC. However, the molecular analysis of recurrent EOC patient benefits from HIPEC is unknown. Thus, we aimed to evaluate the efficacy and safety of CRS combined with HIPEC for platinum-sensitive in recurrent EOC with HRR mutation. Methods: This is a phase III randomized controlled clinical trial in patients with platinum-sensitive recurrent EOC. Participants were divided into 2 groups based on the HRR mutation status and randomized to receive CRS + HIPEC. The patients then received periodic chemotherapy and follow-up. Results: The primary objective of this study was to evaluate the effect of CRS + HIPEC compared to CRS alone in patients with a platinum-sensitive recurrent EOC stratified for HRD status. We hypothesize that the addition of HIPEC to CRS improves the progression-free survival (PFS) of platinum-sensitive recurrent EOC patients with HRR mutation compared with patients without HRR mutation. Conclusion: Recurrent EOC has a poor prognosis due to implantation and metastasis in the abdominal cavity. Intraperitoneal chemotherapy reduced seeding by removing free tumor cells. HIPEC utilizes physical and biological properties to significantly increase the clearance rate of tumors. Van Driel WJ et al proposed that HIPEC using platinum-based chemotherapy improves the survival of patients with ovarian cancer. HRR mutation, as a common pathogenic mutation in ovarian cancer, has a predictive effect on the platinum sensitivity of ovarian cancer patients. Whether lobaplatin-based HIPEC will play a greater role in ovarian cancer patients with HRR mutations is currently unknown.

Alternative Splicing: A New Therapeutic Target for Ovarian Cancer.

Background: Increasing evidences have shown that abnormal alternative splicing (AS) events are closely related to the prognosis of various tumors. However, the role of AS in ovarian cancer (OV) is poorly understood. This study aims to explore the correlation between AS and the prognosis of OV and establish a prognostic model for OV. Methods: We downloaded the RNA-seq data of OV from The Cancer Genome Atlas databases and assessed cancer-specific AS through the SpliceSeq software. Then systemically investigated the overall survival (OS)-related AS and splicing factors (SFs) by bioinformatics analysis. The nomogram was established based on the clinical information, and the clinical practicability of the nomogram was verified through the calibration curve. Finally, a splicing correlation network was constructed to reveal the relationship between OS-related AS and SFs. Results: A total of 48,049 AS events were detected from 10,582 genes, of which 1523 were significantly associated with OS. The area under the curve of the final prediction model was 0.785, 0.681, and 0.781 in 1, 3, and 5 years, respectively. Moreover, the nomogram showed high calibration and discrimination in OV patients. Spearman correlation analysis was used to determine 8 SFs significantly related to survival, including major facilitator superfamily domain containing 11, synaptotagmin binding cytoplasmic RNA interacting protein, DEAH-box helicase 35, CWC15, integrator complex subunit 1, LUC7 like 2, cell cycle and apoptosis regulator 1, and heterogeneous nuclear ribonucleoprotein A2/B1. Conclusion: This study provides a prognostic model related to AS in OV, and constructs an AS-clinicopathological nomogram, which provides the possibility to predict the long-term prognosis of OV patients. We have explored the wealth of RNA splicing networks and regulation patterns related to the prognosis of OV, which provides a large number of biomarkers and potential targets for the treatment of OV. Put forward the potential possibility of interfering with the AS of OV in the comprehensive treatment of OV.

Chinese patent herbal medicine (Shufeng Jiedu capsule) for acute upper respiratory tract infections: A systematic review and meta-analysis.

BACKGROUND: Shufeng Jiedu capsule has been widely used in China for acute upper respiratory tract infections (AURTIs). The aim of this study was to evaluate its effectiveness and safety for AURTIs. METHODS: Randomized controlled trials comparing SFJD with conventional drug for patients with AURTIs were included. Eight databases were searched from their inceptions to February 2021. Data was synthesized using risk ration (RR) or mean difference (MD) with their 95% confidence interval (CI). The primary outcome was resolution time of typical symptoms. RESULTS: Twenty-five RCTs involving 3410 patients were included. SFJD in combination with conventional drug was associated with; in common cold shortening the duration of fever (MD -1.54 days, 95% CI [-2.15,-0.92], I 2 = 80%, n = 385, 3 trials) and cough (MD -1.22 days, 95% CI [-1.52, -0.93]); in herpangina, shortening the duration of fever (MD -0.68 days, 95% CI [-1.15, -0.21], I2  = 68%, n = 140, 2 trials) and blistering (MD -0.99 days, 95% CI [-1.23, -0.76], n = 386, 3 trials); in acute tonsillitis and acute pharyngitis shortening the duration of fever (MD -1.13 days, 95% CI [-1.36, -0.90], I 2 = 33%, n = 688, 7 trials) and sore throat (MD -1.13 days, 95% CI [-1.40, -0.86], I 2 = 84.1%, n = 1194, 10 trials). SFJD also improving their cure rate with a range (1-5 days). No serious adverse events were reported. CONCLUSION: Low certainty evidence suggests that SFJD appears to shorten the duration of symptoms in AURTIs, improve cure rate and seems safe for application. However, high quality placebo controlled trials are warranted to confirm its benefit.

Two new steroids with NO inhibitory effects from lansium domesticum.

Chemical investigation of Lansium domesticum has led to the isolation of two undescribed compounds, namely 17(20)E-dyscusin B (1) and 17(20)Z-dyscusin B (2), as well as three known ones (3 - 5). Structural elucidation was accomplished by the analysis of NMR, MS and IR data. Compounds 1 and 2 were a pair of Δ17(20) geometric isomers of pregnane steroids and showed the significant nitric oxide (NO) inhibitory activities.

Shufeng Jiedu capsules for treating acute exacerbations of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Chinese herbal medicine is widely used in combination with usual care for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in China. Chinese patent medicine Shufeng Jiedu (SFJD) capsules is widely used for respiratory infectious diseases. This review aims to evaluate effectiveness and safety of SFJD for AECOPD. METHODS: A systematic review of randomised controlled trials (RCTs) in patients with AECOPD, who received SFJD as a single intervention or as add-on treatment to usual care. PubMed, the Cochrane Library, EMBASE, Scopus, Web of Science and four Chinese databases were searched from inception to April 2019. Two authors screened trials, extracted data, and assessed risk of bias, independently. Meta-analysis was performed using RevMan 5.3 software. We performed subgroup analyses and sensitivity analyses according to the predefined protocol. Quality of evidence was assessed using GRADE. RESULTS: Thirteen RCTs (1036 patients, with 936 inpatients) were included, all compared SFJD in combination with usual care (including antibiotics) to usual care alone. The mean age of participants ranged from 52 to 67 years, with approximately 60% male. Due to lack of blinding and other factors, all trials were of high risk of bias. SFJD was associated with a significant reduction in treatment failure, from 20.1 to 8.3% (11 trials; 815 patients; relative risk 0.43, 95% confidence interval [CI] 0.30 to 0.62), and duration of hospital stay (2 trials; 79 patients; mean difference - 4.32 days, 95% CI - 5.89 to - 2.75 days). No significant difference in adverse events was found between SFJD and control groups. CONCLUSION: Low certainty evidence suggests SFJD may bring additional benefit in reducing treatment failure, shorten hospital stay, and improving symptoms. Further large, high quality RCTs are needed to confirm its benefit and safety. TRIAL REGISTRATION: PROSPERO CRD42019133682.