Effect of Jianpi Bushen Huoxue Prescription on Rat Brain Microvascular Endothelial Cells Based on HIF-1α/VEGF Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effects of Jianpi Bushen Huoxue prescription （JPBSHX） on rat brain microvascular endothelial cells （RBMECs） based on hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway， aiming to provide a theoretical basis for the treatment of ischemic stroke. MethodTwelve 8-week-old male SPF-grade SD rats were selected. Eight of them were randomly chosen and given 3.25 g·mL-1 JPBSHX solution by gavage at a dose of 10 mL·kg-1 for 5 consecutive days to prepare the medicated serum， which was then preserved for later use. The remaining four rats were given the same volume of normal saline. Follow-up operations were the same as those of the above eight rats. Normal rat serum was collected and stored for later use. RBMECs were revived， cultured， passaged， and randomly divided into five groups： normal group （20% normal rat serum+80% high glucose DMEM）， model group （hypoxia-reoxygenation injury） （20% normal rat serum+80% glucose-free DMEM）， medicated serum group （20% JPBSHX-medicated serum+80% glucose-free DMEM）， medicated serum+HIF-1α inhibitor group （20% JPBSHX-medicated serum+HIF-1α inhibitor 1 mg +80% glucose-free DMEM）， and medicated serum+VEGF inhibitor group （20% JPBSHX-medicated serum +VEGF inhibitor 1 mg+80% glucose-free DMEM）. The relative protein expression levels of Claudin-1 and Claudin-5 in RBMECs， the expression levels of HIF-1α and VEGF in RBMEC culture supernatants， the repair ability of RBMECs， and the number of nodes， microvessels， and their lengths after 72 h of culture were observed in each group. ResultAfter 24 h of reoxygenation， the scratch healing rate in the model group was significantly lower than in the normal group （P<0.01）. Compared with the result in the model group， the scratch healing rates significantly improved in the medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group （P<0.05）. However， the healing rates in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group were significantly lower than that in the medicated serum group （P<0.05）. The number of nodes， microvessels， and total length of microvessels in the model group were significantly lower than those in the normal group （P<0.01）. These indicators significantly improved in the medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group compared with those in the model group （P<0.05）， but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group compared with those in medicated serum group （P<0.05）. The relative expression levels of Claudin-1 and Claudin-5 proteins were significantly lower in the model group than in the normal group （P<0.01）. These levels were significantly higher in medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group than those in the model group （P<0.05）， but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group than those in the medicated serum group （P<0.05）. The expression levels of HIF-1α and VEGF in the RBMEC culture supernatants were significantly lower in the model group than those in the normal group （P<0.01）. These levels were significantly higher in the medicated serum group， medicated serum+HIF-1α inhibitor group， and medicated serum+VEGF inhibitor group than those in the model group （P<0.05）， but were significantly lower in the medicated serum+HIF-1α inhibitor group and medicated serum+VEGF inhibitor group than those in the medicated serum group （P<0.05）. ConclusionJPBSHX can promote the proliferation， migration， and angiogenesis， such as tubule formation， of RBMECs damaged by hypoxia-reoxygenation injury， and this effect may be achieved through the regulation of the HIF-1α/VEGF signaling pathway.

Study on Syndrome Research of Ischemic Stroke Combined with Obstructive Sleep Apnea-hypopnea Syndrome Based on Implicit Structure Method / 中国实验方剂学杂志

ObjectiveTo explore the common syndrome elements of cerebral ischemic stroke （CIS） complicated with obstructive sleep apnea-hypopnea syndrome （OSAHS）， reveal the characteristics of traditional Chinese medicine （TCM） syndromes of the disease， clarify the syndrome differentiation and syndrome types， provide evidence for clinical syndrome differentiation， and provide reference for establishing the TCM syndrome type standards of CIS complicated with OSAHS. MethodThe clinical information form of CIS complicated with OSAHS formulated by the research group was used for syndrome survey， and the four-examination information of 300 patients with CIS complicated with OSAHS was collected. The four-examination information of patients was analyzed by latent structure method and comprehensive cluster analysis， and the common syndrome elements of CIS complicated with OSAHS were extracted by combining the TCM basic theory and clinical experience. On this basis， the characteristics of TCM syndromes and the syndrome types in line with reality were summarized. ResultThe top five syndrome elements in patients with CIS and OSAHS are sleep snoring， open mouth breathing， physical obesity， night awakening and dizziness. The top five tongue and pulse manifestations are enlarged tongue， slippery pulse， slippery coating， thick and white coating and purple tongue. The disease locations are the lung， spleen， stomach， kidney， liver and brain. The nature of disease includes deficiency， depression， blood stasis， phlegm， dampness and fire. The clinical syndrome types include the syndrome of stagnation of phlegm and dampness， syndrome of phlegm-dampness blocking the mind， syndrome of spleen deficiency with dampness， syndrome of Yin deficiency leading to fire hyperactivity， syndrome of Qi depression blocking collaterals， syndrome of liver depression and blood stasis， syndrome of Qi deficiency with dampness， and syndrome of Yang deficiency induced water retention. ConclusionIn addition to the common phlegm-， dampness- and blood stasis-related syndromes in patients with CIS and OSAHS， there are also depression- and deficiency-related syndromes. The main etiology and pathogenesis is the disturbance of Qi movement. In clinical practice， attention should be paid to the specific situation of individual patients to differentiate between deficiency and excess， and the treatment should be performed by the method of soothing and reinforcing， or unblocking and clearing， or both.

Staging Sequential Treatment of Ischemic Stroke Based on Syndrome Differentiation of Deficiency and Excess in Eight Principles / 中国实验方剂学杂志

The core of diagnosing and treating diseases in traditional Chinese medicine lies in syndrome differentiation. The eight principles of syndrome differentiation serve as guidance for syndrome differentiation. As one of the eight principles of syndrome differentiation， the differentiation of deficiency and excess is the basic and critical method. Ischemic stroke is currently the leading cause harming the health of Chinese residents. Although the hypotheses about the cause of ischemic stroke have evolved from external wind to the later internal wind and to the modern theory of toxin damaging the brain collaterals， they all believe that this disease is rooted in internal deficiency and external excess. According to available studies， although stroke is characterized by complex pathogenesis and rapid progression of syndromes， the key cause evolution has a regularity， that is， from excess to deficiency. This article analyzes the historical evolution of the etiology， pathogenesis， and syndrome differentiation schemes of stroke. There are diverse schemes for the syndrome differentiation of stroke， which make it difficult to choose in clinical practice. In view of this problem， this paper puts forward a new approach of staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess according to the evolution law of the key cause of stroke. Furthermore， we conducted a randomized controlled study on 100 patients with ischemic stroke to evaluate this new approach. The results showed that the staging sequential treatment of ischemic stroke based on the differentiation of deficiency and excess demonstrated definite clinical efficacy. In addition， this article reviews the previous research results of our team and the research achievements of other teams to preliminarily explore the relationship between stroke syndromes and biomarkers， aiming to provide an objective basis for unveiling the pathogenesis of stroke. In summary， according to the key cause evolution （from excess to deficiency）， the treatment of ischemic stroke by stages based on differentiation of deficiency and excess can facilitate the rapid intervention and improve the clinical efficacy on ischemic stroke.

Screening of Clinical Efficacy Evaluation Indicators for Traditional Chinese Medicine Injections based on Mixed Method Research / 中医杂志

Currently， evidence on the efficacy and risk of traditional Chinese medicine （TCM） injections is seriously insufficient， and it is difficult to evaluate TCM injections comprehensively， truly and objectively using available efficacy evaluation indicators. Therefore， establishing a clinical efficacy evaluation system that can effectively reflect TCM injections is imperative. Core outcome set （COS） has played an important role in screening TCM efficacy evaluation indicators， however， there are still certain problems， such as large differences in efficacy indicators， non-standardization， and lack of featured and specific TCM indicators. Mixed method research （MMR） has the advantages of looking at problems from both quantitative and qualitative perspectives. It is thereby proposed to use COS and MMR integrated model to establish a clinical efficacy evaluation indicator system that not only fully considers the cha-racteristics of TCM injections， but also highlights the efficacy and advantages of TCM injections from the perspective of TCM intervention. Simultaneously， an indicator screening method using MMR to optimize COS research model is formulated， which can provide ideas for the research on efficacy evaluation indicators of TCM injections.

Efficacy and safety of a sequential treatment with clearing heat and eliminating phlegm and tonifying and activating blood circulation in treating acute ischemic stroke: study protocol for a randomized controlled trial.

OBJECTIVE: To investigate the short-term efficacy and safety outcomes following a sequential treatment with clearing heat and eliminating phlegm (CHEP) formula and tonifying Qi and activating blood circulation (TQABC) formula in patients with acute ischemic stroke (AIS) within a 72 h time window. METHODS: In this randomized, multicenter, double-blinded, placebo-controlled trial, 500 participants will be randomly assigned in a ratio of 1∶1 to the CHEP+ TQABC group or control group. In addition to guideline-based standard medical care, participants in the treatment group will receive the CHEP formula for the first 5 consecutive days followed by the TQABC formula for another 10 consecutive days, while those in the control group will receive CHEP formula placebo and TQABC formula placebo consecutively. The primary outcome measure will be the comparison of the change in the National Institutes of Health Stroke Scale score from baseline to 15 days after randomization. The secondary outcome measures will include the scores on the modified Rankin Scale, Barthel Index, Patient-Reported Outcomes, TCM symptom pattern (Zheng-hou) evaluation Scale, and the incidence of in-hospital complications. Safety assessment will include the physical examination, laboratory detection, any adverse events or serious adverse events, and the proportion of any complications during hospitalization. DISCUSSION: The results of this study will provide objective and scientific data with which to assess the efficacy and safety of a sequential treatment based on "integrating disease and symptom pattern" for patients with AIS.

Effects of local vibration and extracorporeal shock wave therapy on triceps spasticity and the walking ability of hemiplegic stroke survivors / 中华物理医学与康复杂志

Objective:To compare the effect of local vibration and extracorporeal shock wave therapy (ESWT) on triceps spasticity and the walking ability of hemiplegic stroke survivors.Methods:Sixty-nine stroke survivors with hemiplegia were randomly divided into a control group, a vibration group and an ESWT group. The control group received 60 minutes of conventional Bobath rehabilitation treatment and motor relearning from Monday to Saturday for 4 weeks. For the vibration and ESWT groups, 10 minutes of that traditional therapy were replaced by either local vibration or extracorporeal shock wave treatment every Tuesday, Wednesday and Saturday. Before and after the treatment, the three groups were evaluated using the Comprehensive Spasticity Scale (CSS) and in terms of passive joint range of motion (PROM), ankle plantar flexion angle, 10m maximum walking speed, stride frequency, and stride length.Results:After the intervention the average CSS, PROM, and ankle plantar flexion angle were significantly better for all three groups than before the treatment. At that point the ESWT group′s averages were significantly better than those of the vibration group, and the vibration group′s averages were significantly superior to those of the control group. Walking speed, stride frequency and stride length had also improved significantly in all three groups, with those in the vibration and ESWT groups significantly outperforming the control group. There was no significant difference between the vibration and ESWT groups in terms of walking ability.Conclusions:Both local vibration and extracorporeal shock wave therapy improve triceps spasticity and the walking ability of hemiplegic stroke survivors. Shock waves are more effective for improving spasticity, but there is no significant difference between the therapies in terms of improving walking ability.

Effect of Jianpi-bushen-huoxue Decoction Combining with Kinesiotherapy on Circulation in Ischemic Area of Patients with Cerebral Infarction: A Perfusion Weighted Imaging Study / 中国康复理论与实践

@#Objective To explore the effect of Jianpi-bushen-huoxue Decoction combining with kinesiotherapy on blood perfusion in the ischemic area in patients with cerebral infarction. Methods From May, 2016 to May 2017, 65 spleen-kidney-deficiency patients with cerebral infarction at convalescence were randomly divided into group A (n=22, accepting routine treatment), group B (n=22, accepting routine treatment and Jianpi-bushen-huoxue Decoction) and group C (n=21, accepting routine treatment, Jianpi-bushen-huoxue Decoction and kinesiotherapy), and were observed for 14 days. On the first day and the 14th day of treatment, they were scanned with perfusion weighted imaging, and the regional cerebral blood flows (rCBF) of region of interest were measured.Results rCBF increased after treatment in each group (t>3.572, P<0.05), and it ranked as group C, group B and group A with the rCBF from more to less after treatment (P<0.05).Conclusion Jianpi-bushen-huoxue Decoction is effective on blood flow in ischemic area of spleen-kidney-deficiency patients with cerebral infarction at convalescence, and it is even more effective when combining with kinesiotherapy.

Intracranial hematoma micro-invasive craniopuncture scavenging technique in patients with hypertensive cerebral hemorrhage: a Meta-analysis / 中国中西医结合急救杂志

Objective To evaluate the therapeutic efficacy and safety of micro-invasive craniopuncture scavenging technique (MPST) for treatment of intracranial hematoma in patients with hypertensive cerebral hemorrhage (HICH).Methods All the clinical randomized controlled trial (RCT) studies published on MPST and internal medicine conservative treatment of HICH were searched via computer screening of databases including Cochrane clinical trials database, the Chinese biomedical literature database (CBM), Chinese periodical network full-text special topic database, Chinese science and technology periodical database and electronic periodicals database of Wanfang from January 2006 to January 2017. The study group was given the MPST plus basic treatment, and the control group was given conservative treatment. The studies collected meeting the eligible criteria were sorted and analyzed by the software RevMan 5.0, the differences in therapeutic effect and mortality were compared between the two groups, and a funnel chart was plotted to analyze the potential publication bias.Results A total of 13 RCTs published studies consistent with the eligible criteria were found, including1556 patients. The Meta-analysis showed that the effective rate in the study group was significantly higher than that in the control group [odds ratio (OR) = 4.29, 95% confidence interval (95%CI) 3.33 - 5.53,P < 0.01]; the fatality rate was markedly lower than that of the control group (OR = 0.25, 95%CI 0.19 - 0.35,P < 0.01). The funnel graph showed that each study had asymmetrical scatter plot of the variable quantity of research results, indicating a publication bias being present, which might be related to the subjectivity of the researchers in publishing their results.Conclusions Using MPST to treat HICH can significantly improve the therapeutic efficiency and reduce deterioration rate. However, due to the low quality of clinical research, it is necessary to carry out rigorous andmulti-center randomized controlled studies to further confirm the results.