Subthalamic nucleus deep brain stimulation in primary Meige syndrome: motor and non-motor outcomes.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) has emerged as a promising treatment for movement disorders. This prospective study aims to evaluate the effects of bilateral subthalamic nucleus DBS (STN-DBS) on motor and non-motor symptoms in patients with primary Meige syndrome. METHODS: Thirty patients who underwent bilateral STN-DBS between April 2017 and June 2020 were included. Standardized and validated scales were utilized to assess the severity of dystonia, health-related quality of life, sleep, cognitive function and mental status at baseline and at 1 year and 3 years after neurostimulation. RESULTS: The Burke-Fahn-Marsden Dystonia Rating Scale movement scores showed a mean improvement of 63.0% and 66.8% at 1 year and 3 years, respectively, after neurostimulation. Similarly, the Burke-Fahn-Marsden Dystonia Rating Scale disability scores improved by 60.8% and 63.3% at the same time points. Postoperative quality of life demonstrated a significant and sustained improvement throughout the follow-up period. However, cognitive function, mental status, sleep quality and other neuropsychological functions did not change after 3 years of neurostimulation. Eight adverse events occurred in six patients, but no deaths or permanent sequelae were reported. CONCLUSIONS: Bilateral STN-DBS is a safe and effective alternative treatment for primary Meige syndrome, leading to improvements in motor function and quality of life. Nevertheless, it did not yield significant amelioration in cognitive, mental, sleep status and other neuropsychological functions after 3 years of neurostimulation.

Analysis of Changes in KPS Scores and Imaging Signs in Deep Brain Gliomas by DWI Combined with Intraoperative Ultrasound Resection.

Objective: This study investigates the efficacy of DWI combined with intraoperative ultrasound for deep brain glioma treatment, analyzing changes in Karnofsky performance status (KPS) scores and imaging signs. Objectives include elucidating the approach's advantages, addressing knowledge gaps, and contributing insights into its effectiveness for enhancing deep brain glioma management. Methods: In this retrospective study, we analyzed a total of 346 patients with deep brain glioma who underwent surgical treatment at our hospital from July 2015 to January 2022. After applying inclusion and exclusion criteria, 310 patients were selected and categorized into a control group (n = 150) and an observation group (n = 160) based on different auxiliary techniques of surgical treatment. The degree of resection and Karnofsky performance status (KPS) scores were assessed at 1 day preoperatively, 1 week, and 1 month postoperatively for both groups. Additionally, we conducted a comprehensive analysis of DWI and ultrasound imaging signs among patients with different grades of deep brain glioma. The study duration covered the specified period, and statistical analyses were performed to evaluate the outcomes. Results: In our study, the observation group demonstrated significantly improved resection degrees, with a total resection rate of 82.50% compared to the control group's 65.33%. Preoperative Karnofsky performance status scores showed no significant difference between groups (P > .05), but postoperative scores at 1 week and 1 month were significantly higher in the observation group (P < .05). Intraoperative ultrasound and DWI revealed distinct imaging signs differentiating low-grade and high-grade patients. These results highlight the efficacy of DWI combined with intraoperative ultrasound resection in enhancing resection outcomes and influencing postoperative Karnofsky performance status. Conclusions: DWI combined with intraoperative ultrasonic resection in deep brain glioma has a significant effect, with specific imaging signs, which can effectively improve the total resection rate and KPS score, and is worthy of clinical promotion. DWI combined with intraoperative ultrasound has important clinical significance in the resection of deep brain gliomas. The better resection results and improved postoperative Karnofsky performance-status score that we observed suggest a possible benefit in patient outcomes, which could influence treatment strategies. The precise imaging signs identified by this method provide valuable guidance for targeted and effective tumor resection.

Raddeanin A (RA) reduced acute inflammatory injury in mouse experimental cerebral hemorrhage by suppression of TLR4.

Spontaneous intracerebral hemorrhage (ICH) is associated with high mortality and disability rates. The microglia-induced inflammatory response is a critical factor determining brain tissue damage after ICH. Raddeanin A (RA) is a natural triterpenoid compound with anti-inflammatory effects, although its effects on ICH and the underlying molecular mechanism have not been elucidated. In this study, we found that RA reduced the volume of cerebral hematoma and cerebral edema, attenuated neuronal apoptosis and improved the behavioral indices in a murine model of acute cerebral hemorrhage. Mechanistically, RA downregulated the TLR4-mediated pro-inflammatory effectors, reduced infiltration of microglia in peri-intracerebral hemorrhage and inhibited apoptosis of neurons co-cultured with activated microglia. In conclusion, RA can alleviate ICH-related tissue damage and promote the recovery of neuronal function by suppressing microglia-induced inflammation and apoptosis.

Association of intraocular pressure and postoperative nausea and vomiting after microvascular decompression - a prospective cohort study.

BACKGROUND: Postoperative nausea and vomiting is common in patients receiving microvascular decompression. In the current study, we examined whether postoperative nausea and vomiting is associated with reduced intraocular pressure (IOP) after microvascular decompression, a measure that reflects intracranial pressure. METHODS: This is a prospective cohort study. Adult patients scheduled for microvascular decompression surgery for hemifacial spasm between January 2020 and August 2020 were eligible. IOP was measured immediately before anesthesia induction and 30 min after patients regained complete consciousness using non-contact tonometry. IOP reduction was defined by at least 1 mmHg decrease vs. preoperative baseline. The primary outcome was vomiting on postoperative day 1. RESULTS: A total of 103 subjects were enrolled. IOP was reduced in 56 (54.4%) subjects. A significantly greater proportion of patients with IOP reduction had vomiting on postoperative day 1 (51.8% (29/56) vs. 23.4% (11/47) in those without IOP reduction; p = 0.003). In the multivariate regression analysis, vomiting on postoperative day 1 was associated with female sex [odds ratio = 7.87, 95% CI: 2.35-26.32, p = 0.001] and IOP reduction [odds ratio = 2.93, 95% CI: 1.13-7.58, p = 0.027]. CONCLUSIONS: In patients undergoing microvascular decompression surgery, postoperative IOP reduction is associated with postoperative vomiting. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2000029083 . Registered 13 January 2020.

Recent Insights Into the Protective Mechanisms of Paeoniflorin in Neurological, Cardiovascular, and Renal Diseases.

ABSTRACT: The monoterpene glycoside paeoniflorin (PF) is the principal active constituent of the traditional Chinese herbal medicines, Radix Paeoniae Alba and Radix Paeoniae Rubra, which have been used for millennia to treat cardiovascular diseases (eg, hypertension, bleeding, and atherosclerosis) and neurological ailments (eg, headaches, vertigo, dementia, and pain). Recent evidence has revealed that PF exerts inhibitory effects on inflammation, fibrosis, and apoptosis by targeting several intracellular signaling cascades. In this review, we address the current knowledge about the pharmacokinetic properties of PF and its molecular mechanisms of action. We also present results from recent preclinical studies supporting the utility of PF for the treatment of pain, cerebral ischemic injury, and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, new evidence suggests a general protective role of PF in heart attack, diabetic kidney, and atherosclerosis. Mechanistically, PF exerts multiple anti-inflammatory actions by targeting toll-like receptor-mediated signaling in both parenchymal and immune cells (in particular, macrophages and dendritic cells). A better understanding of the molecular actions of PF may lead to the expansion of its therapeutic uses.

Improving recovery after microvascular decompression surgery for hemifacial spasm: experience from 530 cases with enhanced recovery after surgery (ERAS) protocol.

OBJECTIVE: To assess the efficacy of microvascular decompression (MVD) for hemifacial spasm with an enhanced recovery after surgery (ERAS) protocol. METHODS: 984 hemifacial spasm patients who underwent MVD from Jan 2017 to Dec 2017 were analyzed. They were divided into the conventional treatment group (control; n = 453) and the later ERAS group (n = 531). The multimodal ERAS protocol consists of 23 perioperative elements. Time to feeding, mobilization, and urinary catheter removal, wound pain, postoperative nausea and vomiting (PONV), and total, preoperative, and perioperative hospital length of stay (LOS), along with outcomes and complications, were analyzed. RESULTS: The patients in both groups had similar clinical characteristics. Patients in the ERAS group had significantly higher rates of early feeding (469 [88.5%], ERAS, vs. 183 [40.6%], control; p < 0.05), early mobilization (497 [93.7%], ERAS, vs. 215 [47.7%], control; p < 0.05), and early removal of urinary catheter (458 [86.4%], ERAS, vs. 175 [38.8%], control; p < 0.05). The ERAS group also had a significantly lower incidence of wound pain (135 [25.5%], ERAS, vs. 348 [77.2%], control) and PONV (173 [32.6%], ERAS, vs. 251 (55.7%), control) (p < 0.05) and significantly shorter preoperative (0.9 ± 0.3 d, ERAS, vs. 2.3 ± 0.6 d, control), postoperative (4.1 ± 0.4 d, ERAS, vs. 5.8 ± 0.7 d, control), and total LOS (5.2 ± 0.3 d, ERAS, vs. 8.8 ± 0.6 d, control) (p < 0.05). There was no significant difference in outcomes or surgical complication rates between two groups. CONCLUSIONS: Implementation of the ERAS protocol for patients undergoing MVD procedures for the treatment of HFS improved the quality of perioperative care without an increase in adverse events.

Subthalamic Nucleus Deep Brain Stimulation in Primary Meige Syndrome: A 1-Year Follow-Up Study.

OBJECTIVE: To investigate the efficacy of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Meige syndrome. MATERIALS AND METHODS: Fifteen consecutive patients who underwent STN-DBS at the Peking University People's Hospital between September 2017 and June 2018 were included in this study. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) movement score and the BFMDRS disability score were obtained prior to surgery, and at specific time points after surgery. Patients' sleep status was also assessed before and after surgery. RESULTS: The BFMDRS movement scores decreased from 15.3 ± 4.6 to 5.2 ± 6.2 after STN-DBS, with a mean improvement of 68.6% (p < 0.05). The BFMDRS disability scores were also significantly decreased, from 6.9 ± 3.3 to 3.5 ± 2.9, with a mean improvement of 51.7% (p < 0.05). The eye, mouth, speech, and swallowing movement scores also decreased significantly after STN-DBS compared to baseline (p < 0.05). The sleep quality of the patients was also improved after surgery. CONCLUSIONS: These findings demonstrate that the STN is an effective brain target for the treatment of patients with Meige syndrome. STN-DBS was not only able to improve patients' motor symptoms, but also their sleep status.

[Application of Methylprednisolone Sodium Succinate Combined with Tropisetron in Prevention of Nausea and Vomiting under Microvascular Decompression of Hemifacial Spasm].

Objective To evaluate the effect of methylprednisolone sodium succinate combined with tropisetron on postoperative nausea and vomiting(PONV)under microvascular decompression of hemifacial spasm.Methods From January to June 2019,485 patients undergoing microvascular decompression for facial spasm at Department of Neurosurgery,Peking University People's Hospital were randomly assigned into two groups with random number table method.For group A(n=242),2 ml saline was administrated by intravenous drip before induction and 5 mg tropisetron after operation.For group B(n=243),40 mg methylprednisolone sodium succinate was administrated by intravenous drip before induction and 5 mg tropisetron after operation.The anesthesia time,operation time,and incidence of PONV in 0-24 h and 24-48 h were recorded for the comparison of the remedial treatment rate of nausea and vomiting between the two groups.Results There was no significant difference in age,gender,smoking history,body mass index value,American Society of Anesthesiologists score,medical history,surgical side,PONV history,operation time or anesthesia time between the two groups(all P > 0.05).The incidence of PONV in group A was 35.5% and 18.2% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(18.5%,χ 2=7.331,P=0.007;8.2%,χ 2=4.364,P=0.037)in group B.The application rate of antiemetic drugs in group A was 15.2% and 8.7% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(5.3%,χ 2=5.327,P=0.021;2.0%,χ 2=4.432,P=0.035)in group B.Conclusion The combination of methylprednisolone sodium succinate and tropisetron can effectively prevent PONV under microvascular decompression of hemifacial spasm,with the performance superior to single drug treatment.

Sex differences in the structure and function of rat middle cerebral arteries.

Epidemiological studies demonstrate that there are sex differences in the incidence, prevalence, and outcomes of cerebrovascular disease (CVD). The present study compared the structure and composition of the middle cerebral artery (MCA), neurovascular coupling, and cerebrovascular function and cognition in young Sprague-Dawley (SD) rats. Wall thickness and the inner diameter of the MCA were smaller in females than males. Female MCA exhibited less vascular smooth muscle cells (VSMCs), diminished contractile capability, and more collagen in the media, and a thicker internal elastic lamina with fewer fenestrae compared with males. Female MCA had elevated myogenic tone, lower distensibility, and higher wall stress. The stress/strain curves shifted to the left in female vessels compared with males. The MCA of females failed to constrict compared with a decrease of 15.5 ± 1.9% in males when perfusion pressure was increased from 40 to 180 mmHg. Cerebral blood flow (CBF) rose by 57.4 ± 4.4 and 30.1 ± 3.1% in females and males, respectively, when perfusion pressure increased from 100 to 180 mmHg. The removal of endothelia did not alter the myogenic response in both sexes. Functional hyperemia responses to whisker-barrel stimulation and cognition examined with an eight-arm water maze were similar in both sexes. These results demonstrate that there are intrinsic structural differences in the MCA between sexes, which are associated with diminished myogenic response and CBF autoregulation in females. The structural differences do not alter neurovascular coupling and cognition at a young age; however, they might play a role in the development of CVD after menopause.NEW & NOTEWORTHY Using perfusion fixation of the middle cerebral artery (MCA) in calcium-free solution at physiological pressure and systematically randomly sampling the sections prepared from the same M2 segments of MCA, we found that there are structural differences that are associated with altered cerebral blood flow (CBF) autoregulation but not neurovascular coupling and cognition in young, healthy Sprague-Dawley (SD) rats. Understanding the intrinsic differences in cerebrovascular structure and function in males and females is essential to develop new pharmaceutical treatments for cerebrovascular disease (CVD).

Pallidal deep brain stimulation in primary Meige syndrome: clinical outcomes and psychiatric features.

OBJECTIVES: To study the efficacy and safety of bilateral globus pallidus internus deep brain stimulation (GPi-DBS) in refractory Meige syndrome (MS) and evaluate the psychiatric disorders before and after surgery. METHODS: Twenty-two patients with MS treated with bilateral GPi-DBS were retrospectively analysed before surgery and after continuous neurostimulation. Before surgery, patients were assessed by the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Self-Rating Depression Scale, Medical Outcomes Study 36-Item Short-Form General Health Survey (SF-36) and Pittsburgh Sleep Quality Index (PQSI), which corresponded to motor symptoms, depressive state, quality of life and sleep quality, respectively. The implantable pulse generator of each patient was activated at 1 month after surgery. At 1 month, 3 months, 6 months and 12 months after continuous neurostimulation, all patients were evaluated by the same scales above. RESULTS: The BFMDRS movement scores decreased from 15.0±5.3 before surgery to 3.5±4.5 at 12 months after neurostimulation, with a mean improvement of 78% (p<0.001). The BFMDRS disability scores improved from 7.4±4.9 before surgery to 4.0±4.6 at 12 months after neurostimulation, with a mean improvement of 56% (p<0.001). The postoperative SF-36 scores had the remarkable improvement compared with baseline scores. Impaired sleep quality was found in 82% of patients and depression in 64% before surgery, which didn't neither obtained amelioration after continuous neurostimulation. CONCLUSIONS: Bilateral pallidal neurostimulation is a beneficial therapeutic option for refractory MS, which could improve the motor symptoms except for depression and sleep quality.

Verbascoside suppresses the migration and invasion of human glioblastoma cells via targeting c-Met-mediated epithelial-mesenchymal transition.

Verbascoside (VB), a glycosylated phenylpropanoid compound, is derived from the plant Syringa vulgaris (Oleaceae) and has been shown to have antitumor effects in multiple human cancers, including glioblastoma (GBM); however, the underlying mechanism has not been completely elucidated. Epithelial-to-mesenchymal transition (EMT) is the pivotal event in tumor progression. c-Met, a receptor tyrosine kinase, plays an important role in GBM aggressiveness via promoting EMT. The current study aimed to explore whether VB suppresses c-Met-induced EMT and investigated the mechanism of c-Met degradation. We found that VB inhibited GBM cell growth and downregulated c-Met and the EMT markers (snail, vimentin, and zeb1) in vitro and in an orthotopic xenograft mouse model. In addition, overexpressing c-Met in glioblastoma cells abolished the effects of VB on EMT. We also used a microscale thermophoresis (MST) assay to show that VB could directly bind to the c-Met protein, and we showed that VB degraded the c-Met protein via the ubiquitination-proteasome pathway. Our study is the first to identify a new mechanism for the anticancer effects of VB, namely, the inhibition of EMT by directly targeting c-Met; the inhibition of EMT results in c-Met protein degradation through the ubiquitination-proteasome pathway. Our current research indicates that VB is a potential agent to treat GBM via the ubiquitin-mediated degradation of c-Met.

[Clinical Application of New Antiepileptic Drugs].

Epilepsy has high incidence and complex etiologies,and its treatment remains challenging.For around 70% of people with epilepsy,seizures can be controlled after proper antiepileptic treatment.The availability of some new antiepileptic drugs in recent years has offered new options for epileptic patients.A solid knowledge on the pharmacokinetics,efficacy,and tolerability profiles of these new antiepileptic drugs will help to provide safe,proper,reasonable,and standardized treatment for patients.

Paeoniflorin Inhibits Migration and Invasion of Human Glioblastoma Cells via Suppression Transforming Growth Factor ß-Induced Epithelial-Mesenchymal Transition.

Paeoniflorin (PF) is a polyphenolic compound derived from Radix Paeoniae Alba thathas anti-cancer activities in a variety of human malignancies including glioblastoma. However, the underlying mechanisms have not been fully elucidated. Epithelial to mesenchymal transition (EMT), characterized as losing cell polarity, plays an essential role in tumor invasion and metastasis. TGFß, a key member of transforming growth factors, has been demonstrated to contribute to glioblastoma aggressiveness through inducing EMT. Therefore, the present studies aim to investigate whether PF suppresses the expression of TGFß and inhibits EMT that plays an important role in anti-glioblastoma. We found that PF dose-dependently downregulates the expression of TGFß, enhances apoptosis, reduces cell proliferation, migration and invasion in three human glioblastoma cell lines (U87, U251, T98G). These effects are enhanced in TGFß siRNA treated cells and abolished in cells transfected with TGFß lentiviruses. In addition, other EMT markers such as snail, vimentin and N-cadherin were suppressed by PF in these cell lines and in BALB/c nude mice injected with U87 cells. The expression of MMP2/9, EMT markers, are also dose-dependently reduced in PF treated cells and in U87 xenograft mouse model. Moreover, the tumor sizes are reduced by PF treatment while there is no change in body weight. These results indicate that PF is a potential novel drug target for the treatment of glioblastoma by suppression of TGFß signaling pathway and inhibition of EMT.

Ursolic acid inhibits glioblastoma through suppressing TGFß-mediated epithelial-mesenchymal transition (EMT) and angiogenesis.

Found in many fruits and plants, Ursolic acid (UA), a pentacyclic triterpene that occurs naturally, is recognized for its anti-cancer effects, especially in combating glioblastoma. However, the intricate molecular mechanisms underpinning its anti-tumor actions are still not fully understood, despite the recognition of these effects. By examining the functions of epithelial-mesenchymal transition (EMT) and angiogenesis, crucial for glioblastoma progression, and their regulation through Transforming Growth Factor Beta (TGFß) - a key marker for glioblastoma, our research aims to fill this knowledge gap. This study explores how ursolic acid can block the progression of glioblastoma by precisely targeting TGFß-triggered EMT and angiogenesis. The findings show that UA successfully blocks the spread, movement, and invasion of glioblastoma cells. Accompanying this, there is a significant reduction in the expression of TGFß and crucial EMT indicators like snail and vimentin. Furthermore, UA shows a reduction in angiogenesis that depends on the dosage, highlighted by decreased vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs). Interestingly, increased TGFß expression in U87 and U251 glioblastoma cell lines was found to weaken UA's anti-tumor properties, shedding more light on TGFß's critical function in glioblastoma's pathology. Supporting these laboratory results, UA also showed considerable inhibition of tumor growth in a glioblastoma xenograft mouse model. Overall, our research emphasizes Ursolic acid's promise as a new treatment for glioblastoma and clarifies its action mechanism, mainly by inhibiting TGFß signaling and thereby EMT and angiogenesis.

Association Between Neurodegenerative Diseases and an Increased Risk of Epilepsy Based on Single Nucleotide Polymorphisms: A Mendelian Randomization Study.

Epilepsy is a common neurological disorder characterized by transient brain dysfunction, attributed to a multitude of factors. The purpose of this study is to explore whether neurodegenerative diseases, specifically Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), have a causal effect on epilepsy. Mendelian randomization (MR) methods were used to analyze the causal association between neurodegenerative diseases (AD, PD, ALS, and MS) and epilepsy based on single nucleotide polymorphisms from genome-wide association studies, including inverse-variance weighted, weighted median, MR-Egger, and weighted mode methods. The reliability and stability of the MR analysis results were assessed by the MR-Egger intercept, MR-PRESSO, and heterogeneity tests. Forty-three SNPs were selected for the MR analysis of MS and epilepsy. The inverse-variance weighted method showed a significant causal association between MS and increased risk of epilepsy (odds ratio 1.046; 95% confidence interval 1.001-1.093; P = 0.043). However, AD (P = 0.986), PD (P = 0.894), and ALS (P = 0.533) were not causally associated with epilepsy. Sensitivity analysis showed that the results were robust. The MR study confirmed the causal relationship between genetically predicted MS and epilepsy but did not support the causal relationship between genetically predicted AD, PD, and ALS on epilepsy.

Transcutaneous electrical acupoint stimulation to prevent dizziness after microvascular decompression for hemifacial spasm: A randomized controlled trial.

BACKGROUND: Dizziness often occurs after microvascular decompression (MVD), and therapeutic options are limited. The aim of this trial was to determine the potential efficacy of transcutaneous electrical acupoint stimulation (TEAS), against dizziness and its safety in patients undergoing MVD. METHODS: Adult patients scheduled to undergo MVD for hemifacial spasm under total intravenous anesthesia were randomized at a 1:1 ratio to receive, after extubation, 30-min TEAS in the mastoid region as well as Fengchi acupoints (GB20) and Neiguan acupoints (PC6) or 30-min sham stimulation. The primary outcome was the incidence of dizziness at 2 h after surgery. Secondary outcomes included dizziness, postoperative nausea and vomiting (PONV) or headache severity, rescue medication, changes in intraocular pressure before and after surgery, length of stay, dizziness symptoms 4 weeks after discharge, and surgical complications. RESULTS: A total of 86 patients (51.9 ± 9.4 years of age; 67 women) were enrolled. One patient (in the TEAS arm) was excluded from analysis due to conversion to sevoflurane anesthesia. The rate of dizziness at 2 h after surgery was 31.0 % (13/42) in the TEAS arm vs. 53.5 % (23/43) in the sham control arm (P = 0.036). TEAS was also associated with significantly lower severity of dizziness, based on a 10-point scale, during the first 24 h after surgery. None of the other secondary efficacy outcomes differed significantly between the two arms. All postoperative complications were Clavien-Dindo grade I or II. The rate of postoperative complications was 21.4 % (9/42) in the TEAS arm vs. 16.3 % (7/43) in the sham control arm (P = 0.544). CONCLUSIONS: Compared with sham control, TEAS was associated with a lower incidence of dizziness within 2 h and lower severity of dizziness within 24 h post-operatively, but no improvement in other outcomes, in adult patients undergoing MVD for hemifacial spasm.

The mechanism of Zhenzhu Pills treating intracerebral hemorrhage secondary injury based on network pharmacology and molecular docking.

BACKGROUND: Intracerebral hemorrhage (ICH) secondary injury is serious and affects patient's prognosis. The Zhenzhu Pills used to treat subacute ICH in Tibet has shown to have a certain curative effect. Network pharmacology and molecular docking technology are employed to explore the potential mechanism of Zhenzhu Pills. The components and potential targets of Zhenzhu Pills were screened from the Traditional Chinese Medicine Systems Pharmacology database. The Gene Expression Omnibus Series 24265 was used to screen differentially expressed genes between perihematomal tissue and normal brain. METHODS: The herbs-components-targets network was established, with weighted eigenvalue to identify the core components and targets of Zhenzhu Pills treatment of ICH secondary injury. Targets' bioinformatics enrichment was proceeded by gene ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis. Finally, molecular docking was used to identify the hydrogen bonding activity between the key components and action targets. RESULTS: Five herbal drugs were screened from Traditional Chinese Medicine Systems Pharmacology database, with a total of 48 components and 234 targets. The Gene Expression Omnibus Series 24265 dataset was evaluated and 920 differentially expressed genes were identified. A total of 29 intersection targets of Zhenzhu Pills were explored in the treatment of ICH secondary injury. Drugs-components-targets network analysis showed that the pivotal targets were prostaglandin G/H synthase 2, interleukin 6, heme oxygenase-1, vascular endothelial growth factor, and vascular cell adhesion molecule 1, and the core components were quercetin, luteolin, and kaempferol. Gene ontology and KEGG pathway enrichment analysis showed that biological processes such as cell chemotaxis, wound healing, leukocyte migration, and regulation of body fluid levels played an important role in the secondary injury of ICH. The results of KEGG pathway analysis were mainly related to advanced glycation end products-receptor for advanced glycation end products signal pathway and tumor necrosis factor signal pathway. Molecular docking of 3 flavonoids with 5 core targets with the results also showed active hydrogen bonding. CONCLUSIONS: This study provides insights into the potential mechanisms of Zhenzhu Pills in the treatment of secondary injuries resulting from ICH and highlights specific components, targets, and molecular pathways involved in this therapeutic effect. These possible therapeutic mechanisms include inhibiting inflammation, edema, oxidative stress, and so on.

The maximum tolerated dose of gamma radiation to the optic nerve during γ knife radiosurgery in an animal study.

BACKGROUND: The safety of gamma knife radiosurgery should be considered when treating pituitary adenomas. OBJECTIVES: To determine the maximum tolerated dose of radiation delivered by gamma knife radiosurgery to optic nerves. METHODS: An animal model designed to establish prolonged balloon compression of the optic chiasm and parasellar region was developed to mimic the optic nerve compression caused by pituitary adenomas. Twenty cats underwent surgery to place a balloon for compression effect and 20 cats in a sham operation group received microsurgery without any treatment. The effects of gamma knife irradiation at 10-13 Gy on normal (sham operation group) and compressed (optic nerve compression group) optic nerves were investigated by pattern visual evoked potential examination and histopathology. RESULTS: Gamma knife radiosurgery at 10 Gy had almost no effect. At 11 Gy, P100 latency was significantly prolonged and P100 amplitude was significantly decreased in compressed optic nerves, but there was little change in the normal optic nerves. Doses of 11 Gy and higher induced significant electrophysiological variations and degeneration of the myelin sheath and axons in both normal and compressed optic nerves. CONCLUSIONS: Compressed optic nerves are more sensitive to gamma knife radiosurgery than normal optic nerves. The minimum dose of gamma knife radiosurgery that causes radiation injury in normal optic nerves is 12 Gy; however, the minimum dose is 11 Gy in compressed optic nerves.

Platycodin D suppresses proliferation, migration, and invasion of human glioblastoma cells through regulation of Skp2.

BACKGROUND: Platycodin D (PD) is a major bioactive component of Platycodon grandiflorum, a medicinal herb that is widely used in China, and is effective against various human cancers, including glioblastoma multiforme (GBM). S phase kinase-related protein 2 (Skp2) is oncogenic and overexpressed in various human tumors. It is highly expressed in GBM and its expression is correlated with tumor growth, drug resistance and poor prognosis. In this study, we investigated whether inhibition of glioma progression by PD is mediated by decreasing expression of Skp2. METHODS: Cell Counting Kit-8 (CCK-8) and Transwell assays were used to determine the effects of PD on GBM cell proliferation, migration, and invasion in vitro. mRNA and protein expression were determined by real time polymerase chain reaction (RT-PCR) and western blotting, respectively. The U87 xenograft model was used to verify the anti-glioma effect of PD in vivo. Expression levels of Skp2 protein were analyzed by immunofluorescence staining. RESULTS: PD suppressed proliferation and motility of GBM cells in vitro. The expression of Skp2 in U87 and U251 cells was significantly reduced by PD. PD mainly decreased the cytoplasmic expression of Skp2 in glioma cells. Skp2 protein expression was downregulated by PD, resulting in upregulation of its downstream targets, p21and p27. The inhibitory effect of PD was enhanced by Skp2 knockdown in GBM cells and reversed in cells with Skp2 overexpression. CONCLUSION: PD suppresses glioma development by regulation of Skp2 in GBM cells.

Acute paraplegia after aneurysmal subarachnoid hemorrhage: Case report of a rare complication with a 2­year follow­up.

The current overall incidence of subarachnoid hemorrhage (SAH) is ~9/100,000 individuals/year and rupture of an intracranial aneurysm is the main cause of SAH, accounting for ~85% of cases. Only a small number of cases of paraplegia after intracranial aneurysmal SAH have so far been reported and its pathogenesis has remained to be fully elucidated. The present study reports the case of a patient with an aneurysm localized in the medial and inferior lateral wall of the C5 segment of the right internal carotid artery that was treated by coil interventional embolization. The muscle strength of both lower extremities of the patient was grade I and grade 0 before and after the operation, respectively. Lumbar and thoracic magnetic resonance imaging examinations revealed slight hematoma in the subarachnoid space below the L2 level. At two weeks after the operation, the muscle strength of both lower extremities was grade II, while the muscle strength was grade III and grade V at 30 and 60 days after the operation, respectively.