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Byline: Guobiao. Liang, Zhiqing. Li, Xu. Gao, Haifeng. Zhang, Jun. Lin, Shize. Feng, Xuezhong. Wei We report the technique and results of the endovascular treatment of jugular foramen dural arteriovenous [...]

Byline: Xu. Gao, Guobiao. Liang, Youxiang. Li, Zhongxue. Wu Background: Large and giant aneurysms still remain a therapeutic challenge both surgically and endovascularly. Objective: The authors report their clinical experience [...]

As the most common and lethal primary malignant brain cancer, glioblastoma is hard to timely diagnose and sensitive therapeutic monitoring. It is essential to develop new and effective drugs for glioblastoma multiform. Naringin belongs to citrus flavonoids and was found to display strong anti-inflammatory, antioxidant and antitumor activities. In this report, we found that naringin can specifically inhibit the kinase activity of FAK and suppress the FAKp-Try397and its downstream pathway in glioblastoma cells. Our study showed out that naringin can inhibit cell proliferation by inhibiting FAK/cyclin D1 pathway, promote cell apoptosis through influencing FAK/bads pathway, at the same time, it can also inhibit cell invasion and metastasis by inhibiting the FAK/mmps pathway. All these showed that naringin exerts the anti-tumor effects in U87 MG by inhibiting the kinase activity of FAK. [ABSTRACT FROM PUBLISHER]

Background:Smilax glabraRoxb (SGR) as a novel anti-tumor agent has been paid attention in several types of cancer cells. However, the effect of SGR on SGC7901 cells has not been investigated. Purpose: We investigate the effect and potential mechanisms of SGR on SGC7901 cells in this study. Methods: Three kinds of gastric cancer cell lines (BGC823, SGC7901 and MKN45) and one kind of human embryonic kidney cell line (HEK293) were exposed to varying concentrations of SRG. Then, we observed the effect of SRG on these cell lines and the changes on proliferation, invasion and apoptosis. Finally, we detected the signaling pathway in which SGR may involve. Results: SGR effectively suppressed the proliferation of SGC7901 cell lines by inhibiting the phosphorylation of Akt (Thr308). Moreover, we found SGR could significantly induce SGC7901 cell lines apoptosis by inhibiting Aktp-Thr308/Bad pathway and inhibit its migration and invasion partly by inhibiting Aktp-Thr308/MMPs pathway. Discussion: SGR could effectively suppress the proliferation and invasion of SGC7901 cell lines by inhibiting the phosphorylation of Akt (Thr308) and its downstream relative pathways. Conclusion: SGR could effectively suppress the phosphorylation of Akt (Thr308) and then inhibit the proliferation and invasion of SGC7901 cell and enhance its apoptosis through Akt-mediated signaling pathways. [ABSTRACT FROM PUBLISHER]

Glioblastoma multiforme (GBM) is one of the most palindromic and malignant central nervous system neoplasms, and the current treatment is not effectual for GBM. Research of specific medicine for GBM is significant. Fangchinoline possesses a wide range of pharmacological activities and attracts more attentions due to its anti-tumor effects. In this study, two WHO grade IV human GBM cell lines (U87 MG and U118 MG) were exposed to fangchinoline, and we found that fangchinoline specifically inhibits the kinase activity of Akt and markedly suppresses the phosphorylation of Thr308 and Ser473 of Akt in human GBM cells. We also observed that fangchinoline inhibits tumor cell proliferation and invasiveness and induces apoptosis through suppressing the Akt-mediated signaling cascades, including Akt/p21, Akt/Bad, and Akt/matrix metalloproteinases (MMPs). These data demonstrated that fangchinoline exerts its anti-tumor effects in human glioblastoma cells, at least partly by inhibiting the kinase activity of Akt and suppressing Akt-mediated signaling cascades. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma is the most common and lethal type of primary brain tumor. β-Elemene, a natural plant drug extracted from Curcuma wenyujin, has shown strong anti-tumor effects in various tumors with low toxicity. However, the effects of β-elemene on malignant phenotypes of human glioblastoma cells remain to be elucidated. Here we evaluated the effects of β-elemene on cell proliferation, survival, stemness, differentiation and the epithelial-to-mesenchymal transition (EMT) in vitro and in vivo, and investigated the mechanisms underlying these effects.Methods: Human primary and U87 glioblastoma cells were treated with β-elemene, cell viability was measured using a cell counting kit-8 assay, and treated cells were evaluated by flow cytometry. Western blot analysis was carried out to determine the expression levels of stemness markers, differentiation-related molecules and EMT-related effectors. Transwell assays were performed to further determine EMT of glioblastoma cells. To evaluate the effect of β-elemene on glioblastoma in vivo, we subcutaneously injected glioblastoma cells into the flank of nude mice and then intraperitoneally injected NaCl or β-elemene. The tumor xenograft volumes were measured every 3 days and the expression of stemness-, differentiation- and EMT-related effectors was determined by Western blot assays in xenografts.Results: β-Elemene inhibited proliferation, promoted apoptosis, impaired invasiveness in glioblastoma cells and suppressed the growth of animal xenografts. The expression levels of the stemness markers CD133 and ATP-binding cassette subfamily G member 2 as well as the mesenchymal markers N-cadherin and β-catenin were significantly downregulated, whereas the expression levels of the differentiation-related effectors glial fibrillary acidic protein, Notch1, and sonic hedgehog as well as the epithelial marker E-cadherin were upregulated by β-elemene in vitro and in vivo. Interestingly, the expression of vimentin was increased by β-elemene in vitro; this result was opposite that for the in vivo procedure. Inhibiting β-catenin enhanced the anti-proliferative, EMT-inhibitory and specific marker expression-regulatory effects of β-elemene.Conclusions: β-Elemene reversed malignant phenotypes of human glioblastoma cells through β-catenin-involved regulation of stemness-, differentiation- and EMT-related molecules. β-Elemene represents a potentially valuable agent for glioblastoma therapy. [ABSTRACT FROM AUTHOR]

Tim-3 acts as a negative regulatory molecule and plays a critical role in immune tolerance. The purpose of this study was to investigate the expression of Tim-3 on peripheral CD4+ and CD8+ T cells in glioma. A total of 30 newly diagnosed glioma patients and 30 healthy controls were recruited and leukocytes from peripheral blood mononuclear cells were analyzed for Tim-3 surface expression by flow cytometry. Plasma tumor necrosis factor-alpha (TNF-α) was also measured. Data showed that expression of Tim-3 was significantly increased in both CD4+ and CD8+ T cells in glioma patients than in controls ( p<0.001 and p<0.001, respectively). Patients with a higher tumor grade revealed further elevated Tim-3 expression in CD8+ T cells compared with those with a lower tumor grade. Also, the Karnofsky score of patients was negatively correlated with the percentage of Tim-3+CD8+ T cells in glioma patients ( p=0.007). In addition, an inverse correlation was observed between the plasma level of TNF-α and Tim-3+CD4+ T cells ( p=0.005) or Tim-3+CD8+ T cells ( p<0.001) in glioma patients. Our results suggested that Tim-3 may be involved in the development of glioma. [ABSTRACT FROM AUTHOR]

Background: Subarachnoid hemorrhage (SAH) is a severe cerebrovascular disorder primarily caused by the rupture of aneurysm, which results in a high mortality rate and consequently imposes a significant burden on society. The occurrence of SAH initiates an immune response that further exacerbates brain damage. The acute inflammatory reaction subsequent to SAH plays a crucial role in determining the prognosis. Th17 cells, a subset of T cells, are related to the brain injury following SAH, and it is unclear how Th17 cells are cleared in the brain. Meningeal lymphatic vessels are a newly discovered intracranial fluid transport system that has been shown to drain large molecules and immune cells to deep cervical lymph nodes. There is limited understanding of the role of the meningeal lymphatic system in SAH. The objective of this research is to explore the impact and underlying mechanism of drainage Th17 cells by meningeal lymphatics on SAH. Methods: Treatments to manipulate meningeal lymphatic function and the CCR7-CCL21 pathway were administered, including laser ablation, injection of VEGF-C geneknockout, and protein injection. Mouse behavior was assessed using the balance beam experiment and the modified Garcia scoring system. Flow cytometry, enzyme-linked immunosorbent assays (ELISA), and immunofluorescence staining were used to study the impact of meningeal lymphatic on SAH drainage. Select patients with unruptured and ruptured aneurysms in our hospital as the control group and the SAH group, with 7 cases in each group. Peripheral blood and cerebrospinal fluid (CSF) samples were assessed by ELISA and flow cytometry. Results: Mice with SAH showed substantial behavioral abnormalities and brain damage in which immune cells accumulated in the brain. Laser ablation of the meningeal lymphatic system or knockout of the CCR7 gene leads to Th17 cell aggregation in the meninges, resulting in a decreased neurological function score and increased levels of inflammatory factors. Injection of VEGF-C or CCL21 protein promotes Th17 cell drainage to lymph nodes, an increased neurological function score, and decreased levels of inflammatory factors. Clinical blood and CSF results showed that inflammatory factors in SAH group were significantly increased. The number of Th17 cells in the SAH group was significantly higher than the control group. Clinical results confirmed Th17 cells aggravated the level of neuroinflammation after SAH. Conclusion: This study shows that improving the drainage of Th17 cells by meningeal lymphatics via the CCR7-CCL21 pathway can reduce brain damage and improve behavior in the SAH mouse model. This could lead to new treatment options for SAH. [ABSTRACT FROM AUTHOR]

Aims: Deep brain stimulation (DBS) is not routinely performed in elderly patients (≥75 years old) to date because of concerns about complications and decreased benefit. This study aimed to evaluate the safety and efficacy of DBS in elderly patients with Parkinson's disease. Methods: A retrospective analysis was performed using data from 40 elderly patients from four centers who were treated with neurosurgical robot‐assisted DBS between September 2016 and December 2021. These patients were followed up for a minimum period of 2 years, with a subgroup of nine patients followed up for 5–7 years. Patient demographic characteristics, surgical information, pre‐ and postoperative motor scores, non‐motor scores, activities of daily living, and complications were retrospectively analyzed. Results: The mean surgical procedure duration was 1.65 ± 0.24 h, with a mean electrode implantation duration of 1.10 ± 0.23 h and a mean pulse generator implantation duration of 0.55 ± 0.07 h. The mean pneumocephalus volume, electrode fusion error, and Tao's DBS surgery scale were 16.23 ± 12.81 cm3, 0.81 ± 0.23 mm, and 77.63 ± 8.08, respectively. One patient developed a skin infection, and the device was removed. The Unified Parkinson's disease rating scale, Unified Parkinson's disease rating scale of Part III, tremor, rigidity, bradykinesia, axial, and Barthel index for activities of daily living (ADL‐Barthel) scores significantly improved at the 2‐year follow‐up (p < 0.05). The levodopa equivalent daily dose (LEDD) was significantly reduced at the 2‐year follow‐up (p < 0.05). However, the Montreal cognitive assessment, Hamilton depression scale, and Hamilton anxiety scale scores did not significantly change during the 2‐year follow‐up (p > 0.05). Additionally, in the subgroup with a 5‐year follow‐up, the motor symptoms, ADL‐Barthel score, and cognitive function worsened over time compared to baseline. However, there was still an improvement in motor symptoms and ADL with DBS on‐stimulation compared with the off‐stimulation state. The LEDD increased 5 years after surgery compared to that at baseline. Eleven patients had passed away during follow‐up, the mean survival time was 38.3 ± 17.3 months after surgery, and the mean age at the time of death was 81.2 (range 75–87) years. Conclusion: Robot‐assisted DBS surgery for the elderly patients with Parkinson's disease is accurate and safe. Motor symptoms and ADL significantly improve and patients can benefit from long‐term neuromodulation, which may decrease the risk of death. [ABSTRACT FROM AUTHOR]

Objective: Sex differences in outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) remain controversial. Therefore, the aim of this study was to investigate the sex differences in the prognosis of patients with aSAH. Methods: This study retrospectively analyzed the clinical data of aSAH patients admitted to the Department of Neurosurgery of General Hospital of Northern Theater Command, from April 2020 to January 2022. The modified Rankin Scale (mRS) was used to evaluate outcomes at 3-month post-discharge. Baseline characteristics, in-hospital complications and outcomes were compared after 1:1 propensity score matching (PSM). Results: A total of 665 patients were included and the majority (63.8%) were female. Female patients were significantly older than male patients (59.3 ± 10.9 years vs. 55.1 ± 10.9 years, P < 0.001). After PSM, 141 male and 141 female patients were compared. Comparing postoperative complications and mRS scores, the incidence of delayed cerebral ischemia (DCI) and hydrocephalus and mRS ≥ 2 at 3-month were significantly higher in female patients than in male patients. After adjustment, the analysis of risk factors for unfavorable prognosis at 3-month showed that age, sex, smoking, high Hunt Hess grade, high mFisher score, DCI, and hydrocephalus were independent risk factors. Conclusion: Female patients with aSAH have a worse prognosis than male patients, and this difference may be because females are more vulnerable to DCI and hydrocephalus. [ABSTRACT FROM AUTHOR]

[Display omitted] Photothermal therapy (PTT) has gained widespread attention due to its significant advantages, such as noninvasiveness and ability to perform laser localization. However, PTT usually reaches temperatures exceeding 50 °C, which causes tumor coagulation necrosis and unfavorable inflammatory reactions, ultimately decreasing its efficacy. In this study, multifunctional two-dimensional Bi 2 Se 3 nanodisks were synthesized as noninflammatory photothermal agents for glioma therapy. The Bi 2 Se 3 nanodisks showed high photothermal stability and biocompatibility and no apparent toxicology. In addition, in vitro and in vivo studies revealed that the Bi 2 Se 3 nanodisks effectively ablated gliomas at relatively low concentrations and inhibited tumor proliferation and migration. Moreover, the multienzymatic activity of the Bi 2 Se 3 nanodisks inhibited the PTT-induced inflammatory response through their high ability to scavenge reactive oxygen species. Finally, the Bi 2 Se 3 nanodisks demonstrated computed tomography capabilities for integrating diagnosis and treatment. These findings suggest that multifunctional Bi 2 Se 3 nanodisk nanozymes can enable more effective cancer therapy and noninflammatory PTT. [ABSTRACT FROM AUTHOR]

Spontaneous subarachnoid hemorrhage (SAH) accounts for approximately 5% of all cases of stroke. SAH is correlated with elevated rates of mortality and disability. Despite significant advancements in comprehending the pathogenesis and surgical management, efficacious clinical interventions remain restricted, and the prognosis is yet to be enhanced. MicroRNAs play a crucial role in various pathological processes in organisms. Revealing these regulatory processes is conducive to the development of new treatment methods. MicroRNA-124 is highly expressed in the nervous system and has significant research value for SAH. This study aims to explore the role of miR-124 in the early post-SAH period on neural function and verify whether it is involved in the pathological and physiological processes of SAH. In this study, we used methods such as comparing the expression levels of miR-124 in cerebrospinal fluid, establishing a rat SAH model, and a mouse embryonic primary neuron hemoglobin stimulation model to verify the downstream proteins of miR-124 in SAH. Through transfection techniques, we adjusted the expression of this small RNA in Vitro and in Vivo models using miR-124 inhibitor and mimic in the primary neuron hemoglobin stimulation model and rat SAH model, and observed the phenotype. Finally, by consulting the literature and verifying in Vivo and in Vitro methods, AK4 and downstream molecule ATF3 were identified as downstream targets of miR-124. [ABSTRACT FROM AUTHOR]

Activation and polarization of microglia play decisive roles in the progression of intracerebral haemorrhage (ICH), and lactate exposure correlates with microglia polarization. This study explores molecules influencing lactate production and microglia phenotype alteration following ICH. A murine model of ICH was induced by intracerebral injection of collagenase. The mice experienced autonomous neurological function recovery, haematoma resolution and rapid lactate production, along with a gradual increase in angiogenesis activity, neuronal recovery and an M1‐to‐M2 phenotype change of microglia. Galloflavin, a lactate dehydrogenase antagonist, suppressed this phenotype change and the functional recovery in mice. FOS like 2 (FOSL2) was significantly upregulated in the brain tissues from day 7 post‐ICH. Overexpression of FOSL2 induced an M1‐to‐M2 phenotype shift in microglia and accelerated lactate production in vivo and in haemoglobin‐treated microglia in vitro. Long non‐coding RNA MIR17HG impeded FOSL2‐mediated transcription activation of hypermethylated in cancer 1 (HIC1). MIR17HG overexpression induced pro‐inflammatory activation of microglia in mice, which was blocked by further HIC1 overexpression. Overall, this study demonstrates that MIR17HG maintains a pro‐inflammatory phenotype of microglia during ICH progression by negating FOSL2‐mediated transcription activation of HIC1. Specific inhibition of MIR17HG or upregulation of FOSL2 or HIC1 may favour inflammation inhibition and haematoma resolution in ICH. [ABSTRACT FROM AUTHOR]

Background: RNA methylation modifications, such as N1-methyladenosine/N6-methyladenosine /N5-methylcytosine (m1A/m6A/m5C), are the most common RNA modifications and are crucial for a number of biological processes. Nonetheless, the role of RNA methylation modifications of m1A/m6A/m5C in the pathogenesis of renal interstitial fibrosis (RIF) remains incompletely understood. Methods: Firstly, we downloaded 2 expression datasets from the GEO database, namely GSE22459 and GSE76882. In a differential analysis of these datasets between patients with and without RIF, we selected 33 methylation-related genes (MRGs). We then applied a PPI network, LASSO analysis, SVM-RFE algorithm, and RF algorithm to identify key MRGs. Results: We eventually obtained five candidate MRGs (WTAP, ALKBH5, YTHDF2, RBMX, and ELAVL1) to forecast the risk of RIF. We created a nomogram model derived from five key MRGs, which revealed that the nomogram model may be advantageous to patients. Based on the selected five significant MRGs, patients with RIF were classified into two MRG patterns using consensus clustering, and the correlation between the five MRGs, the two MRG patterns, and the genetic pattern with immune cell infiltration was shown. Moreover, we conducted GO and KEGG analyses on 768 DEGs between MRG clusters A and B to look into their different involvement in RIF. To measure the MRG patterns, a PCA algorithm was developed to determine MRG scores for each sample. The MRG scores of the patients in cluster B were higher than those in cluster A. Conclusions: Ultimately, we concluded that cluster A in the two MRG patterns identified on these five key m1A/m6A/m5C regulators may be associated with RIF. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a neurological condition with high mortality and poor prognosis, and there are currently no effective therapeutic drugs available. Poly (ADP-ribose) polymerase 1 (PARP-1) dependent cell death pathway-parthanatos is closely associated with stroke. We investigated improvements in neurological function, oxidative stress, blood-brain barrier and parthanatos-related protein expression in rats with SAH after intraperitoneal administration of PARP-1 inhibitor (AG14361). Our study found that the expression of parthanatos-related proteins was significantly increased after SAH. Immunofluorescence staining showed increased expression of apoptosis-inducing factor (AIF) in the nucleus after SAH. Administration of PARP-1 inhibitor significantly reduced malondialdehyde (MDA) level and the expression of parthanatos-related proteins. Immunofluorescence staining showed that PARP-1 inhibitor reduced the expression of 8-hydroxy-2' -deoxyguanosine (8-OHdG) and thus reduced oxidative stress. Moreover, PARP-1 inhibitor could inhibit inflammation-associated proteins level and neuronal apoptosis, protect the blood-brain barrier and significantly improve neurological function after SAH. These results suggest that PARP-1 inhibitor can significantly improve SAH, and the underlying mechanism may be through inhibiting parthanatos pathway. [ABSTRACT FROM AUTHOR]

• Serum APOE level of TLE patients is significantly higher than that of healthy people. • Serum APOE level is associated with cognitive dysfunction in TLE patients. • The cognitive function of APOE ε 4 allele carriers in TLE patients is poor. To investigate the effect of serum apolipoprotein E (APOE) levels on cognitive function in patients with temporal lobe epilepsy (TLE). Clinical data were collected from 190 subjects including 110 TLE patients and 80 healthy people. Cognitive function was assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R) scale. Serum levels of APOE were measured using ELISA kits. Genotyping of APOE in peripheral blood was detected by microarray hybridization. Patients with TLE had significantly lower ACE-R total score, memory and verbal fluency scores compared to the healthy group. Serum levels of APOE were significantly higher in TLE patients than in the healthy subjects. Serum APOE levels were significantly negatively correlated with ACE-R total score, memory and verbal fluency scores. The cognitive function score of TLE with APOE ε 4 allele was lower than that of TLE without APOE ε 4 allele. Our study showed that serum APOE levels were higher in TLE patients than in the healthy population. And serum APOE levels were associated with cognitive dysfunction in TLE patients. APOE ε 4 allele carriers have poor cognitive function in TLE patients. [ABSTRACT FROM AUTHOR]

To explore the feasibility of using a modified power-on programming method in deep brain stimulation (DBS) for Parkinson disease (PD). We conducted a retrospective cohort study including 151 PD patients with bilateral robot-assisted DBS surgery from July 2017 to June 2020. Ninety-seven patients were adopted to the modified power-on programming method (Group I) and 54 patients were adopted to the traditional power-on programming method (Group II). In one-year follow-up, power-on programming duration, stimulation parameters, scores of Unified PD Rating Scale (UPDRS) and UPDRS-III of the 2 groups were recorded and compared. There were no significant differences in the postoperative UPDRS, UPDRS-III improvement rate, and stimulation parameters between the 2 groups. The duration of power-on programming of Group I (1.7 ± 1.1 hours) was significantly less than that of Group II (3.5 ± 1.8 hours, P < 0.0001). The modified power-on programming method can achieve a similar clinical effect to the traditional method, with the advantage of more efficiency. [ABSTRACT FROM AUTHOR]

We investigated the safety and efficacy of the Numen coil compared with the Axium coil in the treatment of intracranial aneurysms. Because CATCH (Coil Application Trial in China) is a prospective randomized controlled open-label noninferiority trial conducted in 10 centers across China, patients who fulfilled the inclusion and exclusion criteria were randomized 1:1 to either a test group (Numen) or a control group (Axium). The primary outcome was based on successful aneurysm occlusion at 6 months follow-up, whereas secondary outcomes included technical success, the recanalization and retreatment rates, and the rate of serious adverse events (SAEs) at 6 months and 12 months follow-up. Between August 2017 and December 2019, 350 patients presenting with 350 aneurysms were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 91.18% for the test group compared with 91.85% in the control group, with a difference of –0.68% (P = 0.8419), and the overall mortality during the 30-day follow-up period was 1.19% and 1.81% in the test and control group, respectively, showing no significant difference between the 2 groups (P = 0.6837), whereas the SAE incidence during the 12-month follow-up period was 12.50% and 17.47% in the test and control groups, respectively, which was not statistically significant (P = 0.2222). This trial showed that the Numen coil was noninferior to the Axium coil in terms of intracranial aneurysm embolization and can be considered as a safe and effective coil for treating patients with intracranial aneurysm in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To explore the efficacy of 5-ARIs in PCA (Prostate Cancer).Methods: Searching through the major medical databases such as PubMed, Science Citation Index, EMBASE, Medline, Web of Science, Cochrane Library for all published studies in English until 2018. The following search terms were used: "Finasteride", "dutasteride", "5α reductase inhibitors", "5-ARIs", "prostate cancer", "prostate neoplasm" and the additional related studies were manually searched. Newcastle-Ottawa Scale (NOS) assessed the qualities of studies, and the outcome measures were observed by RR or OR with 95% CIs.Results: We included 9 eligible studies for analyses from 2011 to 2017. We found that 5-ARIs group may have fewer progression (OR = 0.48 95%CI: 0.37-0.61 P < 0.00001, I2=4% p = 0.39) and lower pathological progression (OR = 0.46; 95%CI: 0.29-0.73; p = 0.001, I2=0% p = 0.45), compared with control groups. However, the OS did not show significant difference between two groups (OR=1.10; 95%CI:0.90-1.35; P = 0.35, I2 = 93% P < .00001 ).Conclusion: The use of 5-ARIs could prevent progression in PCA patients both clinical and pathological. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) triggers a cascade of events that lead to early brain injury (EBI), which contributes to poor outcomes and appears within 3 days after SAH initiation. EBI involves multiple process including neuronal death, blood-brain barrier (BBB) injury and inflammation response. Microglia are cluster of immune cells originating in the brain which respond to SAH by changing their states and releasing inflammatory molecules through various signaling pathways. M0, M1, M2 are three states of microglia represent resting state, promoting inflammation state, and anti-inflammation state respectively, which can be modulated by pharmacological strategies. After identified potential active ingredients and targets of Sanhua Decoction (SHD) for SAH, we selected aloe-emodin (AE) as a potential ingredient modulating microglia activation states. Molecular mechanisms, targets and pathways of SHD were reveal by network pharmacology technique. The effects of AE on SAH were evaluated in vivo by assessing neurological deficits, neuronal apoptosis and BBB integrity in a mouse SAH model. Furthermore, BV-2 cells were used to examine the effects of AE on microglial polarization. The influence of AE on microglia transformation was measured by Iba-1, TNF-α, CD68, Arg-1 and CD206 staining. The signal pathways of neuronal apoptosis and microglia polarization was measured by Western blot. Network pharmacology identified potential active ingredients and targets of SHD for SAH. And AE is one of the active ingredients. We also confirmed that AE via NF-κB and PKA/CREB pathway inhibited the microglia activation and promoted transformation from M1 phenotype to M2 at EBI stage after SAH. AE, as one ingredient of SHD, can alleviate the inflammatory response and protecting neurons from SAH-induced injury. AE has potential value for treating SAH-induced nerve injury and is expected to be applied in clinical practice. [Display omitted] • Network pharmacology identified potential ingredients and targets of Sanhua Decoction for SAH. • Aloe-emodin is chosen as a candidate ingredient for SAH-induced brain injury. • AE protected against early brain injury and reduced neurological deficits and blood-brain barrier disruption after SAH. [ABSTRACT FROM AUTHOR]

Carvedilol, the third generation of vasodilators; serves as the blocker of non-selective beta-adrenergic receptor and alpha1 adrenergic receptor. It could protect the cardiovascular system of patients receiving dialysis treatment. However, current clinical trials discussing the therapeutic benefit of carvedilol on patients receiving dialysis treatment remain inconsistent. Consequently, we decided to perform a meta-analysis to evaluate the clinical efficacy of carvedilol on patients receiving dialysis treatment. A search was conducted using EMBASE, Pubmed, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure (CNKI), and VIP information database up to February 2020. We research publications (include English and Chinese language) that discuss the effects of carvedilol on cardiovascular events, all-cause mortality, hospitalizations or left ventricular ejection fraction (LVEF) in dialysis population. Our analysis included 4 randomized control trials and 2 observational studies. We discussed the therapeutical effects of carvedilol on all-cause mortality, cardiovascular events, hospitalizations, and LVEF of patients receiving dialysis treatment. Totally, this analysis reported 2998 hemodialysis (HD) patients. We found a significant association between carvedilol and reduced incidence of all-cause mortality, cardiovascular events and hospitalizations in HD patients. In addition, carvedilol significantly improves LVEF (n = 241; WMD = 6.95; 95% CI, 0.54 to 13.36; I2 = 90%) in HD population. Our systematic review and meta-analysis demonstrates that carvedilol is associated with a reduced incidence of cardiovascular events, all-cause mortality and hospitalizations in patients on HD. Besides; carvedilol significantly improves LVEF in HD population. Nevertheless, high-quality and well-powered evidence is still needed, so as to further confirm the impacts of carvedilol on HD patients. [ABSTRACT FROM AUTHOR]