This study aimed to explore the mechanism of Zhongfeng Xingnao Decoction(ZFXN) in intervening microcirculatory di-sorders in cerebral hemorrhage by network pharmacology and molecular docking techniques. The information on the components of ZFXN was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and the predicted targets of chemical components were obtained from PubChem and SwissTargetPrediction. The relevant targets of cerebral hemorrhage and microcirculatory disorders were collected from the GeneCards database, and the common targets of the components and diseases were analyzed by the Database for Annotation, Visualization, and Integrated Discovery(DAVID) for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. Visualization of the correlation network was carried out using Cytoscape software to further screen important chemical components for molecular docking prediction with disease targets. The animal experiment validation was performed using modified neurological severity score(mNSS), enzyme-linked immunosorbent assay(ELISA), quantitative real-time polymerase chain reaction(qRT-PCR), immunofluorescence, and Western blot to detect the effects of ZFXN intervention in mice with cerebral hemorrhage. The results showed that there were 31 chemical components and 856 targets in the four drugs contained in ZFXN, 173 targets for microcirculatory disorders in cerebral hemorrhage, and 57 common targets for diseases and components. The enrichment analysis showed that common targets were mainly involved in biological processes, such as cell proliferation and apoptosis, and signaling pathways, such as tumor pathway, viral infection, phosphoinositide-3-kinase/protein kinase B(PI3K/AKT) signaling pathway, and mitogen-activated protein kinase(MAPK) signaling pathway. Molecular docking results revealed that the common components β-sitosterol of Rhei Radix et Rhizoma, Notoginseng Radix et Rhizoma, and Ginseng Radix et Rhizoma Rubra showed good docking with proto-oncogene tyrosine-protein kinase(SRC), signal transducer and activator of transcription 3(STAT3), phosphoinositide-3-kinase catalytic alpha polypeptide gene(PIK3CA), recombinant protein tyrosine phosphatase non receptor type 11(PTPN11), AKT1, epidermal growth factor receptor(EGFR), calcium adhesion-associated protein beta 1(CTNNB1), vascular endothelial growth factor A(VEGFA), and tumor protein p53(TP53). Moreover, sennoside E of Rhei Radix et Rhizoma showed good docking with MAPK1. The results revealed that the ZFXN relieved the neural injury in mice with cerebral hemorrhage, decreased the expression of S100 calcium-binding protein B(S100β), neuron specific enolase(NSE), matrix metalloproteinase 9(MMP9), tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), SRC, EGFR, CTNNB1, VEGFA, TP53, glial fibrillary acidic protein(GFAP), and leukocyte differentiation antigen 86(CD86), and increased the expression of p-PI3K, p-AKT, and zona occludens 1(ZO-1). The results indicate that ZFXN may inhibit neuronal apoptosis and inflammatory response through PI3K/AKT/p53 pathway to protect the blood-brain barrier, thereby slowing down microcirculatory impairment in cerebral hemorrhage.
Animals ; Mice ; Tumor Suppressor Protein p53 ; Proto-Oncogene Proteins c-akt ; Molecular Docking Simulation ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; Microcirculation ; Phosphatidylinositol 3-Kinases/genetics* ; Tumor Necrosis Factor-alpha ; ErbB Receptors ; Cerebral Hemorrhage/drug therapy* ; Neoplasms ; Phosphatidylinositols ; Drugs, Chinese Herbal/pharmacology*

OBJECTIVE: To investigate the clinical characteristics, treatment, and prognosis of seizures in children with acute lymphoblastic leukemia (ALL) during chemotherapy. METHODS: Children with ALL with seizures during chemotherapy admitted to the Department of Pediatrics, Peking University People's Hospital from January 2010 to March 2022 were retrospectively analyzed. Clinical data including the incidence of seizure, time at seizure onset, causes, management, and prognosis were collected retrospectively. RESULTS: A total of 932 children with ALL were admitted during the study period, of whom, 75 (8%) were complicated with seizures during the period of chemotherapy. There were 40 males and 35 females, with a median age of 7.5 (1-17) years, and 43 cases (57.3%) occurred within the first 2 months of chemotherapy. The underlying diseases were reversible posterior encephalopathy syndrome (n=15), cerebral hemorrhage (n=10, one of whom was complicated with venous sinus thrombosis), intrathecal or systemic methotrexate administration (n=11), brain abscess (n=7, fungal infection in 3 cases, and bacterial in 4), viral encephalitis (n=2), febrile seizure (n=7), hyponatremia (n=7), hypocalcemia (n=2), and unknown cause (n=14). Sixty-four children underwent neuroimaging examination after seizure occurrence, of whom 37 (57.8%) were abnormal. The electroencephalograhpy (EEG) was performed in 44 cases and was abnormal in 24 (54.4%). Fifty-five patients remained in long-term remission with regular chemotherapy, 8 patients received hematopoietic stem cell transplantation, 9 died and 3 lost to follow-up. Symptomatic epilepsy was diagnosed in 18 cases (24%), and was well controlled in 16 with over 1 year of seizure-free. Whereas 2 cases were refractory to anti-seizure medications. CONCLUSION Seizures are relatively common in children with ALL, most commonly due to reversible posterior encephalopathy syndrome, methotrexate-related neurotoxicity, and cerebral hemorrhage. Seizures occurred within 2 months of chemotherapy in most cases. Neuroimaging and EEG should be performed as soon as possible after the first seizure onset to identify the etiology and to improve the treatment regimen. Some cases developed symptomatic epilepsy, with a satisfactory outcome of seizure remission mostly after concurrent antiseizure medication therapy.
Adolescent ; Brain Diseases/complications* ; Cerebral Hemorrhage/complications* ; Child ; Electroencephalography ; Epilepsy/drug therapy* ; Female ; Humans ; Male ; Methotrexate/adverse effects* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Prognosis ; Retrospective Studies

To overview of systematic reviews/Meta-analysis of Xingnaojing Injection(XNJ) in the treatment of intracerebral hemorrhage(ICH). The systematic reviews concerning XNJ in the treatment of ICH were retrieved from four Chinese databases, four English databases, Chinese Clinical Trial Registry and ClinicalTrail.gov, with the retrieval time set from their inception to September 2020. Following the independent screening and data extraction by two researchers, a measurement tool to assess systematic evaluation 2(AMSTAR 2) and grades of recommendation, assessment, development and evaluation(GRADE) system were used to evaluate the metho-dological, reporting and evidence qualities of the 10 included systematic reviews. The results showed that XNJ was superior to the wes-tern medicine or conventional treatment in improving the effective rate and National Institutes of Health stroke scale(NIHSS) score, Barthel index(BI), and Glasgow coma scale(GCS) score and Chinese stroke scale(CSS) score, and reducing the mortality and cerebral hematoma volume, without inducing obvious adverse reactions. In general, the methodological, reporting and evidence qualities of the 10 included systematic reviews were poor. The AMSTAR 2 scores showed that key items No. 2 and No. 16 failed to meet the stan-dard, resulting in poor methodological quality. There was only one outcome indicator graded by GRADE as intermediate quality, 43% indicators as low quality, 42% indicators as extremely low quality, and none as high quality. These available evidences have suggested that the methodological, reporting and evidence qualities of the systematic evaluation concerning XNJ for the treatment of ICH need to be improved. Most evidences support that XNJ was better than the western medicine or conventional treatment in the treatment of ICH, but the methodological quality and the reliability of outcome indicators in relevant systematic review were low. More high-quality studies are still required for further verification.
Cerebral Hemorrhage/drug therapy* ; Drugs, Chinese Herbal ; Humans ; Meta-Analysis as Topic ; Reproducibility of Results ; Systematic Reviews as Topic ; United States

To systematically review the efficacy and safety of Angong Niuhuang Pills in adjuvant treatment of cerebral hemorrhage. CNKI, VIP, Wanfang, CBM, PubMed, EMbase, Cochrane Library were retrieved to collect the randomized controlled trial(RCT) from the time of database establishment to November 2020. Two researchers screened out the literatures and extracted the data according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. A total of 13 RCTs were included, involving 1 196 patients with cerebral hemorrhage, with 599 in the treatment group and 597 in the control group, and all of them were treated with internal medicine. The results of Meta-analysis showed that compared with conventional therapy, the combined administration with Angong Niuhuang Pills could improve the effective rate in patients with cerebral hemorrhage(RR=1.25, 95%CI[1.18, 1.34], P<0.000 01), the National Institutes of Health stroke scale(NIHSS)score(MD=-5.18, 95%CI[-8.12,-2.23], P=0.000 6) and Glasgow coma scale(GCS) score(MD=1.12, 95%CI[0.46, 1.78], P=0.000 9), activity of daily living(ADL)(MD=15.70, 95%CI[14.05, 17.36 ], P<0.000 01), reduce the malondialdehyde(MDA)(MD=-1.73,95%CI[-2.81,-0.64],P=0.002), but with no statistically significant difference in hematoma volume changes between the two groups. In terms of safety, the combined administration with Angong Niuhuang Pills reduced the incidence of adverse reactions compared with the single administration of conventional therapy(RR=0.40, 95%CI[0.28, 0.57], P<0.000 01), with no serious adverse events. The existing clinical study evidences show that Angong Niuhuang Pills had a good effect in adjuvant treatment of cerebral hemorrhage, and can improve the treatment efficacy, activity of daily living and symptoms of neurological deficits, and reduce oxidative stress, with a higher safety. However, the methodological quality of the included studies is not high, so the above conclusions still need to be verified with more high-quality studies.
Cerebral Hemorrhage/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Treatment Outcome

Endogenously eliminating the hematoma is a favorable strategy in addressing intracerebral hemorrhage (ICH). This study sought to determine the role of retinoid X receptor-α (RXR-α) in the context of hematoma absorption after ICH. Our results showed that pharmacologically activating RXR-α with bexarotene significantly accelerated hematoma clearance and alleviated neurological dysfunction after ICH. RXR-α was expressed in microglia/macrophages, neurons, and astrocytes. Mechanistically, bexarotene promoted the nuclear translocation of RXR-α and PPAR-γ, as well as reducing neuroinflammation by modulating microglia/macrophage reprograming from the M1 into the M2 phenotype. Furthermore, all the beneficial effects of RXR-α in ICH were reversed by the PPAR-γ inhibitor GW9662. In conclusion, the pharmacological activation of RXR-α confers robust neuroprotection against ICH by accelerating hematoma clearance and repolarizing microglia/macrophages towards the M2 phenotype through PPAR-γ-related mechanisms. Our data support the notion that RXR-α might be a promising therapeutic target for ICH.
Anilides/pharmacology* ; Cerebral Hemorrhage/drug therapy* ; Hematoma/drug therapy* ; Humans ; Macrophages ; Microglia ; Neuroprotection ; PPAR gamma ; Retinoid X Receptor alpha

Background:Blood pressure (BP) variability has been associated with stroke risk. We elucidated the association between systolic BP (SBP) variation and outcomes in patients with nonlobar intracerebral hemorrhage (ICH) following intensive antihypertensive treatment upfront.

MethodsWe screened consecutive patients with spontaneous ICH who underwent intensive antihypertensive treatments targeting BP <140 mmHg between 2008 and 2016. SBPs were monitored hourly during the acute period (≤7 days after symptom onset) in the intensive care unit. SBP variability was determined in terms of range, standard deviation (SD), coefficient of variation (CoV), and mean absolute change (MAC). The primary outcomes included hematoma growth and poor clinical outcome at 3 months (modified Rankin Scale [mRS] score ≥3. The secondary outcome was an ordinal shift in mRS at 3 months.

ResultsA total of 104 individuals (mean age, 63.0 ± 13.5 years; male, 57.7%) were included in this study. In multivariable model, MAC (adjusted odds ratio [OR], 1.11; 95% confidence interval [CI]: 1.02-1.21; P = 0.012) rather than the range of SD or CoV, was significantly associated with hematoma growth even after adjusting for mean SBP level. Sixty-eight out of 104 patients (65.4%) had a poor clinical outcome at 3 months. SD and CoV of SBP were significantly associated with a 3-month poor clinical outcome even after adjusting for mean SBP. In addition, in multivariable ordinal logistic models, the MAC of SBP was significantly associated with higher shift of mRS at 3 months (adjusted OR, 1.08; 95% CI: 1.02-1.15; P = 0.008).

Conclusions:The MAC of SBP is associated with hematoma growth, and SD and COV are correlated with 3-month poor outcome in patients with supratentorial nonlobar ICH. Therefore, sustained SBP control, with a reduction in SBP variability is essential to reinforce the beneficial effect of intensive antihypertensive treatment.

Aged ; Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Cerebral Hemorrhage ; drug therapy ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Treatment Outcome

Spontaneous chronic subdural hematoma (SDH) is a rare condition that could develop in association with hematologic disease. A 66-year-old male developed a chronic SDH as an initial manifestation of chronic myelomonocytic leukemia (CMML). He experienced recurrent chronic subdural hemorrhage and newly developed intracerebral hemorrhage. Considering the scheduled long-term chemotherapy, bilateral middle meningeal artery (MMA) embolization was performed to prevent recurrence of subdural hemorrhage. Although pancytopenia occurred during the 7 months' follow-up period, residual chronic subdural hemorrhage was absorbed without recurrence. To our best knowledge, this is the first report of CMML with spontaneous chronic SDH. MMA embolization is potentially a useful and safe treatment option in the challenging clinical situations with underlying pathologies.
Aged ; Cerebral Hemorrhage ; Drug Therapy ; Follow-Up Studies ; Hematologic Diseases ; Hematoma, Subdural* ; Hematoma, Subdural, Chronic ; Humans ; Leukemia ; Leukemia, Myelomonocytic, Chronic ; Male ; Meningeal Arteries ; Pancytopenia ; Pathology ; Recurrence

OBJECTIVE: The purpose of this pilot study was to examine the safety and function of the newly developed cerebrospinal fluid (CSF) reservoir called the V-Port.METHODS: The newly developed V-Port consists of a non-collapsible reservoir outlined with a titanium cage and a connector for the ventricular catheter to be assembled. It is designed to be better palpated and more durable to multiple punctures than the Ommaya reservoir. A total of nine patients diagnosed with leptomeningeal carcinomatosis were selected for V-Port insertion. Each patient was followed up for evaluation for a month after the operation.RESULTS: The average operation time for V-Port insertion was 42 minutes and the average incision size was 6.6 cm. The surgical technique of V-Port insertion was found to be intuitive by all neurosurgeons who participated in the pilot study. There was no obstruction or leakage of the V-Port during intrathecal chemotherapy or CSF drainage. Also, there were no complications including post-operative intracerebral hemorrhage, infection and skin problems related to the V-Port.CONCLUSION: V-Port is a safe and an easy to use implantable CSF reservoir that addresses problems of other implantable CSF reservoirs. Further multicenter clinical trial is needed to prove the safety and the function of the V-Port.
Catheters ; Cerebral Hemorrhage ; Cerebrospinal Fluid ; Drainage ; Drug Therapy ; Humans ; Intracranial Pressure ; Meningeal Carcinomatosis ; Neurosurgeons ; Pilot Projects ; Punctures ; Skin ; Titanium

PURPOSETraumatic brain injury (TBI) is a leading cause of death and disability. Intracranial hemorrhage (ICH) secondary to TBI is associated with a high risk of coagulopathy which leads to increasing risk of hemorrhage growth and higher mortality rate. Therefore, antifibrinolytic agents such as tranexamic acid (TA) might reduce traumatic ICH. The aim of the present study was to investigate the extent of ICH growth after TA administration in TBI patients.

METHODSThis single-blind randomized controlled trial was conducted on patients with traumatic ICH (with less than 30 ml) referring to the emergency department of Vali-Asr Hospital, Arak, Iran in 2014. Patients, based on the inclusion and exclusion criteria, were divided into intervention and control groups (40 patients each). All patients received a conservative treatment for ICH, as well as either intravenous TA or placebo. The extent of ICH growth as the primary outcome was measured by brain CT scan after 48 h.

RESULTSAlthough brain CT scan showed a significant increase in hemorrhage volume in both groups after 48 h, it was significantly less in the TA group than in the control group (p = 0.04). The mean total hemorrhage expansion was (1.7 ± 9.7) ml and (4.3 ± 12.9) ml in TA and placebo groups, respectively (p < 0.001).

CONCLUSIONIt has been established that TA, as an effective hospital-based treatment for acute TBI, could reduce ICH growth. Larger studies are needed to compare the effectiveness of different doses.

Adult ; Antifibrinolytic Agents ; therapeutic use ; Brain Injuries, Traumatic ; diagnostic imaging ; drug therapy ; Cerebral Hemorrhage, Traumatic ; drug therapy ; Female ; Humans ; Male ; Middle Aged ; Single-Blind Method ; Tomography, X-Ray Computed ; Tranexamic Acid ; therapeutic use

BACKGROUNDThe influence of blood pressure (BP) lowering on intracerebral hemorrhage (ICH) patients is unclear. To assess the safety and efficacy of aggressive antihypertensive therapies in acute ICH patients, we carried out a systematic review and meta-analysis.

METHODSPubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, and VIP database up to July 2014 were searched. High-quality randomized controlled trials were included. Low-quality trials were excluded. Serious adverse events were defined as the primary outcome. The secondary outcomes were hematoma enlargement (HE) at 24 h after onset, mortality, and favorable clinical outcome at 90 days.

RESULTSFour high-quality trials involving a total of 1427 patients met the inclusion criteria and were analyzed. Odds ratios (ORs) of primary outcome was 0.96 (95% confidence interval [CI ]: 0.82-1.13, P = 0.61). ORs of HE at 24 h after onset, mortality and favorable clinical outcome at 90 days were 0.91 (95% CI: 0.72-1.17, P = 0.47), 0.97 (95% CI: 0.79-1.20, P = 0.81), 1.13 (95% CI: 0.98-1.30, P = 0.09) respectively.

CONCLUSIONSAggressive BP management policies are safe and might have a potency of reducing HE and improving clinical outcome.

Antihypertensive Agents ; therapeutic use ; Blood Pressure ; drug effects ; Cerebral Hemorrhage ; drug therapy ; Hematoma ; drug therapy ; Humans ; Randomized Controlled Trials as Topic