Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 2: Modulation of hypoxia, redox status, and mitochondrial protection in a neuroblastoma cell line, SH-SY5Y.

OBJECTIVE: To examine the mitochondrial protective effects of icariin, naringenin, kaempferol, and formononetin, potentially active agents in Bu-Shen-Jian-Pi formula (BSJP) identified using network pharmacology analysis. MATERIALS AND METHODS: Mitochondrial protection activity was determined using a hypoxia-reoxygenation in vitro model based on the neuroblastoma cell line SH-SY5Y and measurements of anti-ferroptotic activity. RESULTS: Icariin, naringenin, kaempferol, and formononetin showed mitochondrial protective activity involving diverse signaling pathways. The cytoprotective effects of formononetin depended on the inhibition of ferroptosis. Hypoxia-reoxygenation stimulation induced ferroptosis in SH-SY5Y cells. DISCUSSION: Ferroptosis is a key mechanism in nervous system diseases and is associated with hypoxia-reoxygenation injury. Naringenin and kaempferol were devoid of anti-ferroptotic activity. CONCLUSION: Evidence has been obtained showing that the core components: icariin, naringenin, kaempferol, and formononetin in BSJP formula have anti-hypoxic and mitochondrial protective activity of potential clinical importance in the treatment of amyotrophic lateral sclerosis and patients with symptoms of hypoxia.

MrERF039 transcription factor plays an active role in the cold response of Medicago ruthenica as a sugar molecular switch.

Cold stress severely restricts plant development, causing significant agricultural losses. We found a critical transcription factor network in Medicago ruthenica was involved in plant adaptation to low-temperature. APETALA2/ethylene responsive factor (AP2/ERF) transcription factor MrERF039 was transcriptionally induced by cold stress in M. ruthenica. Overexpression of MrERF039 significantly increased the glucose and maltose content, thereby improving the tolerance of M. ruthenica. MrERF039 could bind to the DRE cis-acting element in the MrCAS15A promoter. Additionally, the methyl group of the 14th amino acid in MrERF039 was required for binding. Transcriptome analysis showed that MrERF039 acted as a sugar molecular switch, regulating numerous sugar transporters and sugar metabolism-related genes. In addition, we found that MrERF039 could directly regulate ß-amylase gene, UDP glycosyltransferase gene, and C2H2 zinc finger protein gene expression. In conclusion, these findings suggest that high expression of MrERF039 can significantly improve the cold tolerance of M. ruthenica root tissues during cold acclimation. Our results provide a new theoretical basis and candidate genes for breeding new legume forage varieties with high resistance.

Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 1: Biogenic components and identification of targets and signaling pathways in amyotrophic lateral sclerosis patients.

BACKGROUND: There is evidence that Bu-Shen-Jian-Pi (BSJP), a traditional Chinese medicine, has curative effects in patients suffering from amyotrophic lateral sclerosis (ALS), a progressive and potentially fatal hypoxic condition. OBJECTIVE: To identify biogenic components in BSJP extracts having potential pharmacological efficacy in ALS. MATERIALS AND METHODS: Biogenic components in BSJP and their potential pharmacological targets and signaling pathways in ALS were identified and assessed using network pharmacology/hub node analysis. RESULTS: Network pharmacology analysis identified icariin, naringenin, kaempferol, quercetin, and formononetin as core components in BSJP with potential activity involving mitochondrial protection in patients with ALS. CONCLUSION: Network pharmacology analysis proved to be a successful screening tool for obtaining information from scientific databases on the pharmacology of biogenic components in BSJP showing potential therapeutic activity in ALS.

Evidence-based guideline for the prevention and management of perioperative infection

We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

Evidence-based guideline for the prevention and management of perioperative infection.

BACKGROUND: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels. METHODS: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts. RESULTS: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information. CONCLUSIONS: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off.

Malnutrition and Risk of Mortality in Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background and Purpose: Malnutrition is highly prevalent in ischemic stroke patients. We aimed to investigate whether malnutrition indexes may be useful in predicting mortality at 90 days in ischemic stroke patients treated with intravenous thrombolysis. Methods: We retrospectively analyzed consecutive patients who underwent thrombolytic therapy at three comprehensive stroke centers. Malnutrition was assessed using the controlling nutritional status (CONUT) score, geriatric nutritional risk index (GNRI), and prognostic nutritional index (PNI). Results: Of 979 patients (mean age, 66.8 years; males, 63.6%) included in this study, 91 (9.3%; 95% confidence interval [CI]: 8.4-10.2%) died at 3-month follow up. According to the CONUT, GNRI, and PNI scores, 9.9, 33.7, and 7.0% of patients were moderately or severely malnourished, respectively; 64.0% were at least mildly malnourished by at least 1 malnutrition index. In the multivariate regression model after adjusting for potential confounders, malnutrition (severe risk versus normal nutritional status) was significantly associated with an increased risk of mortality for CONUT scores (adjusted odds ratio [OR] 16.16, 95%CI, 7.86-67.11; P < 0.001), GNRI scores (adjusted OR 9.82, 4.10-23.51; P < 0.001) and PNI scores (adjusted OR 12.74, 5.56-29.19; P < 0.001). Similar results were found when the malnutrition scores were analyzed as continuous variables. Adding the three malnutrition indexes to models containing conventional risk factors significantly improved risk reclassification for 3-month mortality. Conclusion: Our study showed that malnutrition may be associated with a higher risk of mortality at 3 months in ischemic stroke after intravenous thrombolysis.

Neutrophil Count, Intracranial Atherosclerotic Stenosis, and Prognosis of Ischemic Stroke After Endovascular Treatment: A Mediation Analysis.

Background and Purpose: Data on the relationship among neutrophil count, intracranial atherosclerotic stenosis (ICAS), and functional outcomes after endovascular thrombectomy (EVT) for ischemic stroke patients remains unclear. We aimed to evaluate the association between neutrophil count and prognosis of EVT patients and to determine whether the association was mediated by ICAS. Methods: We retrospectively analyzed consecutive patients who underwent EVT at two comprehensive stroke centers between June 2016 and December 2019. A remaining stenosis >70%, or a lesser degree of stenosis with a tendency toward re-occlusion or flow impairment during the procedure, was classified as ICAS. A poor outcome was defined as a 90-day modified Rankin Scale score of 3-6. Results: Of the 221 patients (mean age, 65.9 years; males, 61.1%) included in this study, 81 (36.3%) had ICAS, and 120 (54.3%) experienced a poor outcome at 90 days, respectively. In the multivariate adjustment for potential confounders, neutrophil count (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.04-1.36; P = 0.012) and presence of ICAS (OR, 2.65; 95CI%, 1.28-5.45; P = 0.008) were risk factors of poor outcomes. Furthermore, mediation analysis indicated that total ICAS mediated the association between increased neutrophil count and worse functional outcome after EVT (the regression coefficient was changed by 11.7% for poor outcome, and 17.1% for modified Rankin Scale score, respectively). Conclusions: Our study demonstrated that a higher neutrophil count might increase the risk of a poor outcome among ischemic stroke patients who underwent EVT, which was partially mediated by ICAS.

Bispectral Index Values Are Accurate Diagnostic Indices Correlated With Glasgow Coma Scale Scores.

OBJECTIVE: The Glasgow Coma Scale (GCS) is widely used in neurosurgery to evaluate the depth of coma in patients with brain injury. The bispectral index (BIS) was developed primarily to monitor the depth of unconsciousness. Recent evidence suggests that BIS may also help in the assessment of brain injury. This study explores the correlation between GCS scores and BIS values in patients with brain injury. METHODS: Fifty patients were divided into 2 groups-moderate (GCS 9-12) and severe (GCS 3-8)-in this prospective, double-blind, observational study. Bispectral index data were recorded when electromyography was less than 40 and signal quality index was greater than 75 for 5 minutes. Linear regression was used to examine the correlation between BIS and GCS, and receiver operating characteristic curves were plotted. Cutoff points were identified to show the feasibility and accuracy of BIS for assessing brain injury. RESULTS: The mean BIS value of the moderate group was 65.62 ± 12.84, and that of the severe group was 46.27 ± 17.35. Bispectral index values were significantly correlated with GCS (R = 0.729, P < .01). The regression line and 95% confidence interval were determined; the regression equation was BIS = 5.46*GCS + 12.72. The receiver operating characteristic curve showed high diagnostic accuracy when GCS is less than 9; the area under the curve was 0.8164, and the cutoff point (BIS value) corresponding to the maximum sensitivity (0.91) and specificity (0.63) was 60.2. CONCLUSION: BIS values and GCS scores were significantly correlated in patients with brain injury. As a continuous and objective measurement, BIS is a viable evaluation and monitoring tool for brain injury.

Is Intracranial Pressure Monitoring of Patients With Diffuse Traumatic Brain Injury Valuable? An Observational Multicenter Study.

BACKGROUND: Although intracranial pressure (ICP) monitoring of patients with severe traumatic brain injury (TBI) is recommended by the Brain Trauma Foundation, any benefits remain controversial. OBJECTIVE: To evaluate the effects of ICP monitoring on the mortality of and functional outcomes in patients with severe diffuse TBI. METHODS: Data were collected on patients with severe diffuse TBI (Glasgow Coma Scale [GCS] score on admission <9 and Marshall Class II-IV) treated from January 2012 to December 2013 in 24 hospitals (17 level I trauma centers and 7 level II trauma centers) in 9 Chinese provinces. We evaluated the impact of ICP monitoring on 6-month mortality and favorable outcome using propensity score-matched analysis after controlling for independent predictors of these outcomes. RESULTS: ICP monitors were inserted into 287 patients (59.5%). After propensity score matching, ICP monitoring significantly decreased 6-month mortality. ICP monitoring also had a greater impact on the most severely injured patients on the basis of head computed tomography data (Marshall computed tomography classification IV) and on patients with the lowest level of consciousness (GCS scores 3-5). After propensity score matching, monitoring remained nonassociated with a 6-month favorable outcome for the overall sample. However, monitoring had a significant impact on the 6-month favorable outcomes of patients with the lowest level of consciousness (GCS scores 3-5). CONCLUSION: ICP monitor placement was associated with a significant decrease in 6-month mortality after adjustment for the baseline risk profile and the monitoring propensity of patients with diffuse severe TBI, especially those with GCS scores of 3 to 5 or of Marshall computed tomography classification IV.

[Electroacupuncture intervention combined with general anesthesia for craniocerebral operations].

OBJECTIVE: To determine the safety and effectiveness of electroacupuncture (EA) intervention combined with general anesthesia (GA) for craniocerebral tumor-removal surgery involving cerebral eloquent areas. METHODS: A total of 20 patients with cerebral tumors (durosarcoma, neurogliocytoma, metastatic tumor) involving the cerebral eloquent areas were recruited in the present summary. They were equally divided into general anesthesia (GA) group and EA + GA group. Patients of the EA + GA group were treated with EA stimulation (2 Hz/100 Hz) of the bilateral Fengchi (GB 20), Shuaigu (GB 8) and acupuncture stimulation of Quanliao (SI 18), Zulinqi (GB 41) and Taichong (LR 3), and not given intubation during surgery. Patients of the GA group were treated with intravenous administration of Propofol, Fentanyl, Midazolam, Isopropanol, etc. In addition, all the patients were given with controlled hypotension by intravenous injection of Propofol and Fentanyl. Dosages of Propofol and Sulfentanyl used were recorded. Karnofsky performance status scale was used to assess the patient's general well-being and activities of daily life. RESULTS: The craniocerebral tumor-removal surgery was successful in all the 20 patients. Compared with the GA group, the dosages of Sulfentanyl and Propofol of the EA+ GA group were significantly lower (P < 0.05). No significant difference was found between the GA and EA+ GA groups in Karnofsky performance scores (P > 0.05). Patients of the EA+GA group experienced successful tumour-removal surgery without trachea cannula, were awake and could make a good cooperation with the operator during surgery. They had no aggravation of neurofunctional disturbance following the operation. CONCLUSION: EA combined with general anesthesia is safe and effective for patients with craniocerebral tumor-removal operations involving cerebral eloquent areas.

[Numerical analysis on hemodynamics of cerebral aneurysm clip].

Computational fluid dynamics (CFD) was used to numerically investigate the blood flow in 3-D models of human preoperative and posteroperative of cerebral aneurysm clip, and the feasibility of surgical operation was evaluated by the calculated hemodynamics parameters. Mimics software was used to reconstruct the models from CT angiograms, and numerical simulation of blood flow at different time in a cardiac circle was performed. Comparison analysis of blood flow in three models of human preoperative and posteroperative of cerebral aneurysm clip was conducted in terms of blood velocity distribution, wall shear stress (WSS) distribution and pressure distribution. The results demonstrated that blood velocity and WSS were significantly increased, and pressure was obviously decreased.

Evaluation of driver fatigue on two channels of EEG data.

Electroencephalogram (EEG) data is an effective indicator to evaluate driver fatigue. The 16 channels of EEG data are collected and transformed into three bands (θ, α, and ß) in the current paper. First, 12 types of energy parameters are computed based on the EEG data. Then, Grey Relational Analysis (GRA) is introduced to identify the optimal indicator of driver fatigue, after which, the number of significant electrodes is reduced using Kernel Principle Component Analysis (KPCA). Finally, the evaluation model for driver fatigue is established with the regression equation based on the EEG data from two significant electrodes (Fp1 and O1). The experimental results verify that the model is effective in evaluating driver fatigue.

Role of intraoperative microvascular Doppler in the microsurgical management of intracranial aneurysms.

BACKGROUND: The outcome of surgical treatment of intracranial aneurysms may be influenced by incomplete exclusion of the aneurysm or stenosis of the parent vessels. The goal of this study was to evaluate the usefulness and reliability of intraoperative microvascular Doppler (IMD) in guiding optimal clip placement in aneurysm surgery. METHODS: We conducted a retrospective analysis of 79 patients, with a total of 85 intracranial aneurysms, operated between January 2004 and April 2009, who were evaluated with IMD using a 20-MHz probe before and after clip application. IMD was used to examine the aneurysmal sac and adjacent vessels. RESULTS: The findings of IMD helped in adjusting the clip placement. In 9 (10.6%) of the 85 aneurysms, IMD revealed a persistent blood flow through the aneurysmal sac after clip application and the clip was repositioned. IMD showed relevant stenosis of adjacent vessels induced by the clip positioning in 10 of 79 (12.7%) cases. In six cases (7.6%), a blood flow reduction in the artery feeding the aneurysm was evident after clipping; in the other four cases (5.1%), the clip produced a severe blood flow reduction in other adjacent vessels. In addition, in two of these cases, an initial stenosis induced by clip positioning that had escaped detection by visual inspection through the operating microscope was identified by IMD. There were no complications related to the use of IMD. CONCLUSIONS: IMD is a safe, feasible, and very reliable technique and should be used routinely in intracranial aneurysm surgery.

Surgical management of anterior clinoidal meningiomas: a 26-case report.

BACKGROUND: Resection of anterior clinoidal meningiomas remains a major neurosurgical challenge. We determine the surgical technique for removal of tumor and improvement of patient's outcome. METHODS: A retrospective analysis was performed on 26 consecutive patients with anterior clinoidal meningiomas who underwent surgical resection at the Department of Neurosurgery, Renji Hospital, from January 1999 to August 2006. All patients had surgery through the pterional or extended pterional approach. Microvascular Doppler probe was used to protect the internal carotid artery and its branching arteries during dissection of the tumor. Twenty-two of them had severe visual deficits preoperatively. The follow-up period ranged from 3 to 36 months (22.3 +/- 8.8 months). RESULTS: In this series, Simpson grade II resection in 16 cases (61.5%), Simpson grade III resection in 4 cases (15.4%), Simpson grade IV resection in 6 cases (23.1%) were achieved. Sixteen of the patients with preoperative visual impairment experienced significant improvement. No patients died. There was no evidence of tumor recurrence during follow-up. CONCLUSIONS: In the majority of patients, surgery is still the first choice for total resection of the tumors without major complications. Protection of nerves and blood vessels must be a priority concern during removal of tumors.