Role of Crosstalk between Glial Cells and Immune Cells in Blood-Brain Barrier Damage and Protection after Acute Ischemic Stroke.

Blood-brain barrier (BBB) damage is the main pathological basis for acute ischemic stroke (AIS)-induced cerebral vasogenic edema and hemorrhagic transformation (HT). Glial cells, including microglia, astrocytes, and oligodendrocyte precursor cells (OPCs)/oligodendrocytes (OLs) play critical roles in BBB damage and protection. Recent evidence indicates that immune cells also have an important role in BBB damage, vasogenic edema and HT. Therefore, regulating the crosstalk between glial cells and immune cells would hold the promise to alleviate AIS-induced BBB damage. In this review, we first introduce the roles of glia cells, pericytes, and crosstalk between glial cells in the damage and protection of BBB after AIS, emphasizing the polarization, inflammatory response and crosstalk between microglia, astrocytes, and other glia cells. We then describe the role of glial cell-derived exosomes in the damage and protection of BBB after AIS. Next, we specifically discuss the crosstalk between glial cells and immune cells after AIS. Finally, we propose that glial cells could be a potential target for alleviating BBB damage after AIS and we discuss some molecular targets and potential strategies to alleviate BBB damage by regulating glial cells after AIS.

Antiferromagnetic Spin Fluctuations and Unconventional Superconductivity in Topological Superconductor Candidate YPtBi Revealed by

We report ^{195}Pt nuclear magnetic resonance (NMR) measurements on topological superconductor candidate YPtBi, which has broken inversion symmetry and topological nontrivial band structures due to the strong spin-orbit coupling. In the normal state, we find that Knight shift K is field- and temperature independent, suggesting that the contribution from the topological bands is very small at low temperatures. However, the spin-lattice relaxation rate 1/T_{1} divided by temperature (T), 1/T_{1}T, increases with decreasing T, implying the existence of antiferromagnetic spin fluctuations. In the superconducting state, no Hebel-Slichter coherence peak is seen below T_{c} and 1/T_{1} follows T^{3} variation, indicating the unconventional superconductivity. The finite spin susceptibility at zero-temperature limit and the anomalous increase of the NMR linewidth below T_{c} point to a mixed state of spin-singlet and spin-triplet (or spin-septet) pairing.

[Treatment of femoral head replacement in elderly patients with femoral neck fracture complicated with uremia].

OBJECTIVE: To investigate the treatment method and effect of artificial femoral head replacement for elderly patients with femoral neck fracture complicated with uremia. METHODS: From January 2016 to December 2020, 21 elderly patients with femoral neck fracture complicated with uremia were treated with artificial femoral head replacement. There were 3 males and 18 females, aged 65 to 83 years old with an average of (77.2±1.9) years. All patients were complicated with uremia and required long-term maintenance of hemodialysis. The age of dialysis was 2 to 11 years with an average of (6.3±1.6) years, 2 to 3 times per week. The time from injury to admission to operation was 3 to 7 days with an average of (4.0±2.1) days. The anemia and hypoproteinemia of the patients were corrected preoperatively, and the serum potassium and creatinine indexes of the patients were adjusted by hemodialysis. RESULTS: All the incisions were healed in the first stage, and there were no complications of wound infection, prosthesis loosening, dislocation and deep vein thrombosis. All patients resumed routine hemodialysis in time to maintain the stability of serum creatinine and potassium levels. All 21 patients were followed up for 5 to 23 months with an average of (16.8±2.6) months. Harris scores changed from (24.8±2.5) scores preoperatively to (87.2±3.1) scores postoperatively. CONCLUSION: Elderly patients with femoral neck fracture combined with uremia underwent artificial femoral head replacement surgery, as long as the perioperative treatment is appropriate, with active postoperative rehabilitation treatment, can obtain a good clinical effect.

Modulation of α7nAchR by Melatonin Alleviates Ischemia and Reperfusion-Compromised Integrity of Blood-Brain Barrier Through Inhibiting HMGB1-Mediated Microglia Activation and CRTC1-Mediated Neuronal Loss.

The only food and drug administration (FDA)-approved drug currently available for the treatment of acute ischemic stroke is tissue plasminogen activator (tPA), yet the therapeutic benefits of this drug are partially outweighed by the increased risk of hemorrhagic transformation (HT). Analysis of the NIH trial has shown that cigarette smoking protected tPA-treated patients from HT; however, the underlying mechanism is not clear. Nicotinic acetylcholine receptors (nAChR) has shown anti-inflammatory effect and modulation nAChR could be a strategy to reduce ischemia/reperfusion-induced blood-brain barrier (BBB) damage. Since melatonin could regulate the expression of α7nAchR and melatonin's neuroprotective effect against ischemic injury is mediated via α7nAChR modulation, here, we aim to test the hypothesis that melatonin reduces ischemia and reperfusion (I/R)-induced BBB damage through modulation of α7nACh receptor (α7nAChR). Mice were subjected to 1.5 h ischemia and 24 h reperfusion and at the onset of reperfusion, mice received intraperitoneal administration (i.p.) of either drug or saline. Mice were randomly assigned into five groups: Saline; α7nAChR agonist PNU282987; Melatonin; Melatonin+Methyllycaconitine (MLA, α7nAChR antagonist), and MLA group. BBB permeability was assessed by detecting the extravasation of Evan's blue and IgG. Our results showed that I/R significantly increased BBB permeability accompanied by occludin degradation, microglia activation, and high mobility group box 1 (HMGB1) release from the neuron. In addition, I/R significantly induced neuronal loss accompanied by the decrease of CREB-regulated transcriptional coactivator 1 (CRTC1) and p-CREB expression. Melatonin treatment significantly inhibited the above changes through modulating α7nAChR. Taken together, these results demonstrate that melatonin provides a protective effect on ischemia/reperfusion-induced BBB damage, at least in part, depending on the modulation of α7nAChR.

The quality of reporting of randomized controlled trials of HuatuoZaizao pill for stroke.

Background: HuatuoZaizao pill (HZP), a Chinese patent medicine, is often used in the treatment of stroke. However, there is still a lack of enough evidence to recommend the routine use of HZP for stroke. This study is aimed at evaluating the quality of reporting of randomized controlled trials (RCTs) on HZP for stroke. Methods: RCTs on HuatuoZaizao pill for stroke were evaluated by using Consolidated Standards of Reporting Trials (CONSORT) guidelines and CONSORT extension criteria on reporting herbal interventions (CONSORT-CHM) guidelines. Microsoft Excel 2007 and SPSS20.0 was used for statistics analyses. Results: Seventeen studies involving 1801 stroke patients were identified. CONSORT-CHM has expanded 24.3% (9/37) items in CONSORT and added a small item. The average scores of CONSORT evaluation is 14.6, while the average scores of the CONSORT-CHM evaluation is 11.6. The central items in CONSORT as eligibility criterion, sample size calculation, primary outcome, method of randomization sequence generation, allocation concealment, implementation of randomization, description of blinding, and detailed statistical methods were reported in 77%, 6%, 100%, 47%, 6%, 6%, 6%, and 94% of trials, respectively. In terms of the CONSORT-CHM, none of the articles reported in detail the dosage form, origin, formula basis and so on of HZP, and only half of studies reported the outcome indicators related to Traditional Chinese Medicine syndromes. Conclusion: The overall report quality of RCT related to HZP is low. HZP still needs to report higher quality RCTs to prove its effectiveness and safety.

Buyang Huanwu Decoction Enhances Revascularization via Akt/GSK3ß/NRF2 Pathway in Diabetic Hindlimb Ischemia.

BACKGROUND: Peripheral arterial disease (PAD) is a typical disease of atherosclerosis, most commonly influencing the lower extremities. In patients with PAD, revascularization remains a preferred treatment strategy. Buyang Huanwu decoction (BHD) is a popular Chinese herbal prescription which has showed effects of cardiovascular protection through conducting antioxidant, antiapoptotic, and anti-inflammatory effects. Here, we intend to study the effect of BHD on promoting revascularization via the Akt/GSK3ß/NRF2 pathway in diabetic hindlimb ischemia (HLI) model of mice. MATERIALS AND METHODS: All db/db mice (n = 60) were randomly divided into 6 groups by table of random number. (1) Sham group (N = 10): 7-0 suture thread passed through the underneath of the femoral artery and vein without occlusion. The remaining 5 groups were treated differently on the basis of the HLI (the femoral artery and vein from the inguinal ligament to the knee joint were transected and the vascular stump was ligated with 7-0 silk sutures) model: (2) HLI+NS group (N = 15): 0.2 ml NS was gavaged daily for 3 days before modeling and 14 days after occlusion; (3) HLI+BHD group (N = 15): 0.2 ml BHD (20 g/kg/day) was gavaged daily for 3 days before modeling and 14 days after occlusion; (4) HLI+BHD+sh-NC group (N = 8): local injection of adenovirus vector carrying the nonsense shRNA (Ad-GFP) in the hindlimbs of mice before treatment; (5) HLI+BHD+sh-NRF2 group (N = 8): knockdown of NRF2 in the hindlimbs of mice by local intramuscular injection of adenovirus vector carrying NRF2 shRNA (Ad-NRF2-shRNA) before treatment; and (6) HLI+BHD+LY294002 group (N = 4): intravenous injection of LY294002 (1.5 mg/kg) once a day for 14 days on the basis of the HLI+BHD group. Laser Doppler examination, vascular cast, and immunofluorescence staining were applied to detect the revascularization of lower limbs in mice. Western blot analysis was used to detect the expression of vascular endothelial growth factor (VEGF), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor- (TNF-) α, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase quinone-1 (NQO-1), catalase (CAT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphorylated protein kinase B (p-AKT), and phosphorylated glycogen synthase kinase-3 beta (p-GSK3ß). HE staining was used to assess the level of muscle tissue damage and inflammation in the lower extremities. Local multipoint injection of Ad-NRF2-shRNA was used to knock down NRF2, and qPCR was applied to detect the mRNA level of NRF2. The blood glucose, triglyceride, cholesterol, MDA, and SOD levels of mice were tested using corresponding kits. The SPSS 20.0 software and GraphPad Prism 6.05 were used to do all statistics. Values of P < 0.05 were considered as statistically significant. Results and Conclusions. BHD could enhance the revascularization of lower limbs in HLI mice, while BHD has no effect on blood glucose and lipid level in db/db mice (P > 0.05). BHD could elevate the protein expression of VEGF, HO-1, NQO-1, and CAT (P < 0.05) and decrease the expression of IL-1ß, IL-6, and TNF-α (P < 0.05) in HLI mice. Meanwhile, BHD could activate NRF2 and promote the phosphorylation of AKT/GSK3ß during revascularization (P < 0.05). In contrast, knockdown of NRF2 impaired the protective effects of BHD on HLI (P < 0.05). LY294002 inhibited the upregulation of NRF2 activated by BHD through inhibiting the phosphorylation of the AKT/GSK3ß pathway (P < 0.05). The present study demonstrated that BHD could promote revascularization on db/db mice with HLI through targeting antioxidation, anti-inflammation, and angiogenesis via the AKT/GSK3ß/NRF2 pathway.

Spin-triplet superconductivity in K2Cr3As3.

A spin-triplet superconductor can harbor Majorana bound states that can be used in topological quantum computing. Recently, K2Cr3As3 and its variants with critical temperature Tc as high as 8 kelvin have emerged as a new class of superconductors with ferromagnetic spin fluctuations. Here, we report a discovery in K2Cr3As3 single crystal that the spin susceptibility measured by 75As Knight shift below Tc is unchanged with the magnetic field H0 applied in the ab plane but vanishes toward zero temperature when H0 is along the c axis, which unambiguously establishes this compound as a spin-triplet superconductor described by a vector order parameter d→ parallel to the c axis. Combining with point nodal gap, we show that K2Cr3As3 is a new platform for the study of topological superconductivity and its possible technical application.

Stem Cell-Based Therapy for Experimental Ischemic Stroke: A Preclinical Systematic Review.

Stem cell transplantation offers promise in the treatment of ischemic stroke. Here we utilized systematic review, meta-analysis, and meta-regression to study the biological effect of stem cell treatments in animal models of ischemic stroke. A total of 98 eligible publications were included by searching PubMed, EMBASE, and Web of Science from inception to August 1, 2020. There are about 141 comparisons, involving 5,200 animals, that examined the effect of stem cell transplantation on neurological function and infarct volume as primary outcome measures in animal models for stroke. Stem cell-based therapy can improve both neurological function (effect size, -3.37; 95% confidence interval, -3.83 to -2.90) and infarct volume (effect size, -11.37; 95% confidence interval, -12.89 to -9.85) compared with controls. These results suggest that stem cell therapy could improve neurological function deficits and infarct volume, exerting potential neuroprotective effect for experimental ischemic stroke, but further clinical studies are still needed.

Neuroprotective Effect of Astragaloside IV on Cerebral Ischemia/Reperfusion Injury Rats Through Sirt1/Mapt Pathway.

Background: Ischemic stroke is a common disease with poor prognosis, which has become one of the leading causes of morbidity and mortality worldwide. Astragaloside IV (AS-IV) is the main bioactive ingredient of Astragali Radix (which has been used for ischemic stroke for thousands of years) and has been found to have multiple bioactivities in the nervous system. In the present study, we aimed to explore the neuroprotective effects of AS-IV in rats with cerebral ischemia/reperfusion (CIR) injury targeting the Sirt1/Mapt pathway. Methods: Sprague-Dawley rats (male, 250-280 g) were randomly divided into the Sham group, middle cerebral artery occlusion/reperfusion (MCAO/R) group, AS-IV group, MCAO/R + EX527 (SIRT1-specific inhibitor) group, and AS-IV + EX527 group. Each group was further assigned into several subgroups according to ischemic time (6 h, 1 d, 3 d, and 7 days). The CIR injury was induced in MCAO/R group, AS-IV group, MCAO/R + EX527 group, and AS-IV + EX527 group by MCAO surgery in accordance with the modified Zea Longa criteria. Modified Neurological Severity Scores (mNSS) were used to evaluate the neurological deficits; TTC (2,3,5-triphenyltetrazolium chloride) staining was used to detect cerebral infarction area; Western Blot was used to assess the protein levels of SIRT1, acetylated MAPT (ac-MAPT), phosphorylated MAPT (p-MAPT), and total MAPT (t-MAPT); Real-time Quantitative Polymerase Chain Reaction (qRT-PCR) was used in the detection of Sirt1 and Mapt transcriptions. Results: Compared with the MCAO/R group, AS-IV can significantly improve the neurological dysfunction (p < 0.05), reduce the infarction area (p < 0.05), raise the expression of SIRT1 (p < 0.05), and alleviate the abnormal hyperacetylation and hyperphosphorylation of MAPT (p < 0.05). While compared with the AS-IV group, AS-IV + EX527 group showed higher mNSS scores (p < 0.05), more severe cerebral infarction (p < 0.05), lower SIRT1 expression (p < 0.01), and higher ac-MAPT and p-MAPT levels (p < 0.05). Conclusion: AS-IV can improve the neurological deficit after CIR injury in rats and reduce the cerebral infarction area, which exerts neuroprotective effects probably through the Sirt1/Mapt pathway.

Preclinical systematic review of ginsenoside Rg1 for cognitive impairment in Alzheimer's disease.

Ginseng has been used for the treatment of aging and memory impairment for thousands of years. Several studies have found that ginsenoside Rg1, as one of the main active components of ginseng, could potentially improve cognitive function in several different animal models. A preclinical systematic review to evaluate the efficacy and mechanisms of ginsenoside Rg1 for ameliorating cognitive impairments in Alzheimer's disease is reported here. We searched six databases from their inceptions to January 2019. Thirty-two studies were selected, which included a total of 1,643 animals. According to various cognitive behavioral tests, the results of the meta-analyses showed that ginsenoside Rg1 significantly improved cognitive behavioral impairments in most Alzheimer's disease models (P < 0.05), but there were no significant effects in animals with neuronal degeneration induced by chronic stress or in SAMP8 transgenic mice. The potential mechanisms included antioxidant and anti-inflammatory effects, amelioration of Alzheimer's disease-related pathology, synapse protection, and up-regulation of nerve cells via multiple signaling pathways.

History and Development of TCM Case Report in a Real-World Setting.

OBJECTIVE: The medical record of Chinese medicine is a miniature of the theoretical system of traditional Chinese medicine (TCM), with a time-honored history in a real-world setting and a firm place in medicine. In modern times, people have emphasized the value and standardization of TCM cases. The aim of this study was to explore the historical origins and developments of TCM case records. METHODS: A chronological narrative style was used to divide the development history of TCM case records into early (1600 BC-220 AD), middle (220-1911 AD), and modern periods (1912-till now). The historical context of the origin and development of TCM case records was analyzed through the evolution of the format and content of the case recording files with the specific documents and distinctive cases. RESULTS: From the early to middle period, the development of TCM case record had experienced four periods: the budding, blossoming, maturity, and heyday. In modern times, they presented the following characteristics: A, the establishment and development of the discipline of TCM medical records; B, the standardization of the writing format of TCM medical records; C, a large number of books concentrating on recording and studying TCM medical records, especially those of prestigious veteran TCM doctors; D, the proliferation of TCM case reports published in journals; E, the establishment of TCM medical records databases and application platforms integrating computer programs and artificial intelligence; F, many reporting guidelines have been developed in order to improve the reporting quality of case report in TCM. CONCLUSIONS: The study analyzed and illustrated the characteristics of TCM case records of different dynasties in terms of writing content and format. TCM case record is a relatively young discipline in spite of its ancient origins. TCM case records still have far-reaching significance for the inheritance and development of TCM theory and clinical experience. From the wisdom of history, its positive impact has just been revalued to be validated and it will continue to develop.

Clinical and Preclinical Systematic Review of Astragalus Membranaceus for Viral Myocarditis.

Astragalus membranaceus (AM) is a traditional Chinese medicine, which possesses a variety of biological activities in the cardiovascular systems. We conducted a clinical and preclinical systematic review of 28 randomized clinical control studies with 2522 participants and 16 animal studies with 634 animals to evaluate the efficacy, safety, and possible mechanisms of AM for viral myocarditis (VM). The search strategies were performed in 7 databases from inception to January 2020. Application of the Cochrane Collaboration's tool 7-item checklist, SYRCLE's tool 10-item checklist, and Rev-Man 5.3 software to analyze the risk of bias of studies and data. The results show the score of clinical study quality ranged from 3 to 7 points with an average of 3.32, and the score of animal study quality ranged from 2 to 5 points with an average of 3. In clinical study, AM significantly reduced serum myocardial enzymes and cardiac troponin I levels and improved the clinical treatment efficiency in VM patients compared with the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions (P > 0.05). Significant increase of the survival rate and decrease of the cardiac cardiology score, cardiac enzymes, and cardiac troponin I were compared with the placebo group in animal studies (P < 0.05). The possible mechanisms of AM are largely through antivirus and antivirus receptors, anti-inflammatory, antioxidation, antiapoptotic, antifibrosis, and reducing cardiac calcium load. In conclusion, the findings suggested that AM is a cardioprotection candidate drug for VM.

Extracts or Active Components from Acorus gramineus Aiton for Cognitive Function Impairment: Preclinical Evidence and Possible Mechanisms.

Extracts or active components from Acorus gramineus Aiton (EAAGA) have been clinically used for cognition impairment more than hundreds of years and are still used in modern times in China and elsewhere worldwide. Previous studies reported that EAAGA improves cognition impairment in animal models. Here, we conducted a preclinical systematic review to assess the current evidence of EAAGA for cognition impairment. We searched 7 databases up until June 2019. Methodological quality for each included studies was accessed according to the CAMARADES 10-item checklist. The primary outcome measures were neurobehavioral function scores evaluated by the Morris water maze test, electrical Y-maze test, step-down test, radial eight-arm maze test, and step-through test. The secondary outcome measures were mechanisms of EAAGA for cognition function. Finally, 34 studies involving 1431 animals were identified. The quality score of studies range from 1 to 6, and the median was 3.32. Compared with controls, the results of the meta-analysis indicated EAAGA exerted a significant effect in decreasing the escape latency and error times and in increasing the length of time spent in the platform quadrant and the number of platform crossings representing learning ability and memory function (all P < 0.01). The possible mechanisms of EAAGA are largely through anti-inflammatory, antioxidant, antiapoptosis activities, inhibition of neurotoxicity, regulating synaptic plasticity, protecting cerebrovascular, stimulating cholinergic system, and suppressing astrocyte activation. In conclusion, EAAGA exert potential neuroprotective effects in experimental cognition impairment, and EAAGA could be a candidate for cognition impairment treatment and further clinical trials.

Clinical and Preclinical Systematic Review of Panax ginseng C. A. Mey and Its Compounds for Fatigue.

BACKGROUND: Fatigue, as a complex, multidimensional symptom, is associated with many physical illnesses. Panax ginseng C. A. Mey (PG) is an important herbal drug which has been used for benefiting Qi for thousand years. Panax ginseng C. A. Mey and its compounds (PGC) possess various pharmacological activities, including anti-fatigue. Here, we conducted a systematic review of both randomized clinical trials (RCTs) and preclinical animal studies to investigate the efficacy and safety of PGC for fatigue. METHODS: Electronic searches were performed in 7 databases from the time of each database's inception to August 2019. The methodological quality of RCTs was assessed using 7-item checklist recommended by Cochrane Collaboration or by the CAMARADES 10-item quality checklist. All the data were analyzed using Rev-Man 5.3 and Stata SE software. RESULTS: Eight eligible RCTs and 30 animal studies were identified. The risk of bias scores in RCTs ranged from 4/7 to 7/7, and of animal studies varied from 4/10 to 7/10. Meta-analyses showed that PGC was superior to placebo according to their respective fatigue scales, heart rate recovery, and clinical effect (P < 0.05). There were a similar number of adverse effects between PGC and placebo group (P > 0.05). Meta-analyses showed that PGC can significantly decrease level of blood lactate, blood urea nitrogen, creatine kinase, malondialdehyde, and lactic dehydrogenase in serum, level of malondialdehyde in liver and level of gamma-aminobutyric acid, 5-hydroxytryptamine in brain tissue, and increase swimming time, level of glutathione peroxidase, glucose, superoxide dismutase in serum, level of glycogen and activity of superoxide dismutase, glutathione peroxidase, and catalase in skeletal muscle, level of hepatic glycogen in liver and level of dopamine, acetylcholine in brain tissue, compared with control (P < 0.05). Meta-analyses showed no significant difference in animal body weight between PGC and control (P > 0.05). CONCLUSION: The present findings supported, to a certain degree, that PGC can be recommended for routine use in fatigue. The possible mechanism of PGC resists fatigue, mainly through antioxidant stress, regulating carbohydrate metabolism, delaying the accumulation of metabolites, promoting mitochondrial function, neuroprotection, antiapoptosis, and regulating neurotransmitter disorder in central nervous system.

Cerebrospinal Fluid Hypovolemia and Posterior Reversible Encephalopathy Syndrome.

Posterior reversible encephalopathy syndrome (PRES) is a reversible neuroradiological syndrome characterized by reversible vasogenic edema. The pathophysiological mechanism is still unclear, but PRES may be triggered by various etiologies. To date, only a few PRES cases linked to cerebrospinal fluid (CSF) hypovolemia were reported. The association between PRES and CSF hypovolemia needs to be explored. We presented a case of PRES with CSF hypovolemia as a result of an inadvertent dural puncture and reviewed the literature to identify the clinical characterization and pathophysiological mechanism of PRES following CSF hypovolemia. A total of 31 cases of PRES-CSF hypovolemia was included for analysis. The median age was 33 years, with a notable female predominance (87.1%). Fifteen patients (48.4%) didn't have either a history of hypertension nor an episode of hypertension. The most common cause of CSF hypovolemia was epidural or lumbar puncture (n = 21), followed by CSF shunt (n = 6). The median interval between the procedure leading to CSF hypovolemia and PRES was 4 days. Seizure, altered mental state, and headache were the most frequent presenting symptom. The parietooccipital pattern was most frequent (71.0%). Conservative management remains the mainstay of treatment with excellent outcomes. Three patients had a second episode of PRES. CSF hypovolemia is a plausible cause of PRES via a unique pathophysiologic mechanism including arterial hyperperfusion and venous dysfunction. Patients with CSF hypovolemia is more susceptible to PRES, which is potentially life-threatening. Given that CSF hypovolemia is a common complication of anesthetic, neurological, and neurosurgical procedures, PRES should be early considered for prompt diagnosis and appropriate management.

Ginsenoside-Rb1 for Ischemic Stroke: A Systematic Review and Meta-analysis of Preclinical Evidence and Possible Mechanisms.

BACKGROUND: Ischemic stroke is the most common type of stroke, while pharmacological therapy options are limited. Ginsenosides are the major bioactive compounds in Ginseng and have been found to have various pharmacological effects in the nervous system. In the present study, we sought to evaluate the effects of Ginsenoside-Rb1 (G-Rb1), an important ingredient of ginsenosides, and the probable neuroprotective mechanisms in experimental ischemic strokes. METHODS: Studies of G-Rb1 on ischemic stroke animal models were identified from 7 databases. No clinical trials were included in the analysis. The primary outcome measures were neurological function scores, infarct volume, evans blue content and/or brain water content (BWC). The second outcome measures were the possible neuroprotective mechanisms. All the data were analyzed by Rev Man 5.3. RESULT: Pooled preclinical data showed that compared with the controls, G-Rb1 could improve neurological function (Zea Longa (n = 367, P < 0.01); mNSS (n = 70, P < 0.01); Water maze test (n = 48, P < 0.01); Bederson (n = 16, P < 0.01)), infarct area (TTC (n = 211, P < 0.01); HE (n = 26, P < 0.01)), as well as blood-brain barrier function (BWC (n = 64, P < 0.01); Evans blue content (n=26, P < 0.05)). It also can increase BDNF (n = 26, P < 0.01), Gap-43 (n = 16, P < 0.01), SOD (n = 30, P < 0.01), GSH (n = 16, P < 0.01), Nissl-positive cells (n = 12, P < 0.01), Nestin-positive cells (n = 10, P < 0.05), and reduce Caspase-3 (n = 36, P < 0.01), IL-1 (n = 32, P < 0.01), TNF-α (n = 72, P < 0.01), MDA (n = 18, P < 0.01), NO (n = 44, P < 0.01), NOX (n = 32, P < 0.05), ROS (n = 6, P < 0.05), NF-κB (P < 0.05) and TUNEL-positive cells (n = 52, P < 0.01). CONCLUSION: Available findings demonstrated the preclinical evidence that G-Rb1 has a potential neuroprotective effect, largely through attenuating brain water content, promoting the bioactivities of neurogenesis, anti-apoptosis, anti-oxidative, anti-inflammatory, energy supplement and cerebral circulation.

Sanhua Decoction, a Classic Herbal Prescription, Exerts Neuroprotection Through Regulating Phosphorylated Tau Level and Promoting Adult Endogenous Neurogenesis After Cerebral Ischemia/Reperfusion Injury.

Background: Ischemia stroke is the leading cause of death and long-term disability. Sanhua Decoction (SHD), a classic Chinese herbal prescription, has been used for ischemic stroke for about thousands of years. Here, we aim to investigate the neuroprotective effects of SHD on cerebral ischemia/reperfusion (CIR) injury rat models. Methods: The male Sprague-Dawley rats (body weight, 250-280 g; age, 7-8 weeks) were randomly divided into sham group, CIR group, and SHD group and were further divided into subgroups according to different time points at 6 h, 1, 3, 7, 14, 21, and 28 d, respectively. The SHD group received intragastric administration of SHD at 10 g kg-1 d-1. The focal CIR models were induced by middle cerebral artery occlusion according to Longa's method, while sham group had the same operation without suture insertion. Neurological deficit score (NDS) was evaluated using the Longa's scale. BrdU, doublecortin (DCX), and glial fibrillary acidic protein (GFAP) were used to label proliferation, migration, and differentiation of nerve cells before being observed by immunofluorescence. The expression of reelin, total tau (t-tau), and phosphorylated tau (p-tau) were evaluated by western blot and RT-qPCR. Results: SHD can significantly improve NDS at 1, 3, 7, and 14 d (p < 0.05), increase the number of BrdU positive and BrdU/DCX positive cells in subventricular zone at 3, 7, and 14 d (p < 0.05), upregulate BrdU/GFAP positive cells in the ischemic penumbra at 28 d after CIR (p < 0.05), and reduce p-tau level at 1, 3, 7, and 14 d (p < 0.05). There was no significant difference on reelin and t-tau level between three groups at each time points after CIR. Conclusions: SHD exerts neuroprotection probably by regulating p-tau level and promoting the proliferation, migration, and differentiation of endogenous neural stem cells, accompanying with neurobehavioral recovery.

Direction and symmetry transition of the vector order parameter in topological superconductors CuxBi2Se3.

Topological superconductors have attracted wide-spreading interests for the bright application perspectives to quantum computing. Cu0.3Bi2Se3 is a rare bulk topological superconductor with an odd-parity wave function, but the details of the vector order parameter d and its pinning mechanism are still unclear. Here, we succeed in growing CuxBi2Se3 single crystals with unprecedented high doping levels. For samples with x  = 0.28, 0.36 and 0.37 with similar carrier density as evidenced by the Knight shift, the in-plane upper critical field Hc2 shows a two-fold symmetry. However, the angle at which the Hc2 becomes minimal is different by 90° among them, which indicates that the d-vector direction is different for each crystal likely due to a different local environment. The carrier density for x  = 0.46 and 0.54 increases substantially compared to x ≤ 0.37. Surprisingly, the in-plane Hc2 anisotropy disappears, indicating that the gap symmetry undergoes a transition from nematic to isotropic (possibly chiral) as carrier increases.

A Survey of Application of Complementary and Alternative Medicine in Chinese Patients with Parkinson's Disease: A Pilot Study.

OBJECTIVE: To investigate the prevalence and spectrum of complementary and alternative medicine (CAM) application and its related-factors in Parkinson's disease (PD) patients in China. METHODS: A structured questionnaire regarding the use of CAMs was administered to PD patients by face-to-face interview. Demographic and social variables, clinical characteristics and treatments, and the related factors of PD were also surveyed. RESULTS: Ninety out of 113 patients (79.6%) reported that they had received CAMs treatment, of which 48.6% (55/113) patients had received CAMs treatment for PD. The top 3 kinds of CAMs for PD were Chinese materia medica, rehabilitation exercise, and acupuncture ordinally. The source of information regarding CAMs treatment mainly came from relatives and friends (51.8%, 73 cases), followed by physicians (31.9%, 45 cases), and medias such as television, newspapers or the internet (16.3%, 28 cases). Fifty percent of CAM users reported a good therapeutic efficacy, whereas 39% patients reported that they felt neither better nor worse after the treatment, while 11% patients claimed worsening of symptoms. Multiple correspondence analyses survey found the main factors affecting the selectivity of CAMs ranked in the following order: income, education, occupation, habitation, age at onset, Hoehn and Yahr staging, PD duration, and gender. CONCLUSION: CAMs, especially Chinese materia medica, rehabilitation exercise, and acupuncture, are widely used for PD patients in China.

Astragaloside IV Exerts Cardioprotection in Animal Models of Viral Myocarditis: A Preclinical Systematic Review and Meta-Analysis.

Astragaloside IV (AS-IV), the essential active component of astragalus, possesses diverse biological activities that have beneficial effects against cardiovascular disease. Here, we conducted a preclinical systematic review of 15 studies including 577 animals to establish the efficacy and potential mechanisms of AS-IV for animal models of viral myocarditis (VM). Six databases were searched from inception to October 2018. Application of the Cochrane Collaboration's tool 10-item checklist and Rev-Man 5.3 software to analyze risk of bias of studies and data on outcome measures revealed study quality scores ranging from 2 to 5. Compared with the control group, AS-IV induced a marked decrease in mortality (P < 0.05), inflammation of myocardium and pathological score (P< 0.05) and cardiac enzymes expression (P< 0.05), and improved the function of the heart (P< 0.05). The potential mechanisms of AS-IV action were determined as anti-remodeling of myocardium (n = 1), anti-virus (n = 2), antioxidant (n = 2), anti-inflammatory (n = 6), anti-apoptosis (n = 1) and alleviation of myocardial fibrosis (n = 2). The collective results indicate that AS-IV exerts cardioprotective effects in animals with VM via multiple signaling pathways.