The relationship of α-hydroxybutyrate dehydrogenase with 1-year outcomes in patients with intracerebral hemorrhage: A retrospective study.

Background and aims: Cardiac enzymes are recognized as a valuable tool for predicting the prognosis of various cardiovascular diseases. The prognostic value of alpha-hydroxybutyrate dehydrogenase (α-HBDH) in patients with intracerebral hemorrhage (ICH) was ambiguous and not evaluated. Methods: Two hundred and thirteen Chinese patients with ICH participated in the study from December 2018 to December 2019. Laboratory routine tests and cardiac enzymes, including α-HBDH level, were examined and analyzed. All the patients were classified into two groups by the median value of α-HBDH: B1 <175.90 and B2 ≥175.90 U/L. The clinical outcomes included functional outcome (according to modified Rankin Scale (mRS) score ≥3), all-cause death, and recurrent cerebro-cardiovascular events 1 year after discharge. Associations between the α-HBDH and the outcomes were evaluated using logistic regression analysis. Univariate survival analysis was performed by the Kaplan-Meier method and log-rank test. Results: Of the 213 patients, 117 had α-HBDH ≥175.90 U/L. Eighty-two patients had poor functional outcomes (mRS≥3). During the 1-year follow-up, a total of 20 patients died, and 15 of them had α-HBDH ≥175.90 U/L during the follow-up time. Moreover, 24 recurrent events were recorded. After adjusting confounding factors, α-HBDH (≥175.90) remained an indicator of poor outcome (mRS 3-6), all-cause death, and recurrent cerebro-cardiovascular events. The ORs for B2 vs. B1 were 4.78 (95% CI: 2.60 to 8.78, P = 0.001), 2.63 (95% CI: 0.80 to 8.59, P = 0.11), and 2.40 (95% CI: 0.82 to 7.02, P = 0.11) for poor functional outcomes with mRS ≥ 3, all-cause death, and recurrent cerebro-cardiovascular events, respectively. Conclusion: Increased α-HBDH at admission was independently related to poor functional outcome and all-cause mortality in patients with ICH at 1-year follow-up.

Predictive value of the apolipoprotein B/A1 ratio in intracerebral hemorrhage outcomes.

BACKGROUND AND AIMS: The apolipoprotein B (apoB)/apolipoprotein A1 (apoA1) ratio is a key indicator in predicting future cardiovascular outcomes. However, it is still unclear whether the ratio of apoB/apoA1 is a better predictor of the outcomes after intracerebral hemorrhage (ICH). Therefore, we aimed to assess the relationships between the ratio of apoB/apoA1 and functional outcomes, all-cause mortality, and stroke recurrence in ICH patients. METHODS: Two hundred and sixteen Chinese ICH patients participated in this study from December 2018 to December 2019. Laboratory routine tests including hematology analysis, coagulation tests, and lipid levels were examined. The clinical outcomes included functional outcomes evaluated by the modified Rankin Scale score (mRS), all-cause death, and stroke recurrence 1 year after discharge. Associations between the apoB/apoA1 ratio and the outcomes were evaluated using logistic regression analysis. Based on multivariate analysis, we constructed a nomogram. Univariate survival analysis was performed by the Kaplan-Meier method and log-rank test. All the patients were classified into two groups by the median value of the apoB/apoA1 ratio: B1 < 0.8 and B2 ≥ 0.8. RESULTS: Of the 216 patients, 107 had an apoB/apoA1 ratio ≥ 0.8. Eighty-five patients had poor functional outcomes (mRS ≥ 3), and 32 patients had severe functional outcomes (mRS ≥ 4). During the 1-year follow-up, a total of 18 patients died, and 13 patients had apoB/apoA1 ratio levels ≥0.8 during the 1-year follow-up period. Moreover, 16 recurrent strokes were recorded. Adjustments for age, sex, smoking, alcohol, body mass index, lipid levels, and hematoma site and volume showed that a high apoB/apoA1 ratio was significantly related to adverse functional outcomes and all-cause mortality. The ORs for B2 versus B1 were 3.76 (95% CI: 1.37 to 10.40, p = 0.010), 22.74 (95% CI: 1.08 to 474.65, p = 0.044), and 7.23 (95% CI: 1.28 to 40.88, p = 0.025) for poor functional outcomes with mRS ≥ 3, mRS ≥ 4, and all-cause mortality, respectively. CONCLUSION: An increased apoB/apoA1 ratio at admission was independently related to poor functional outcome and all-cause mortality in ICH patients at the 1-year follow-up.

Serum ceramide concentrations are associated with depression in patients after ischemic stroke-A two-center case-controlled study.

BACKGROUND AND AIMS: The present study aims to correlate the severity of post-stroke depression (PSD) and serum ceramide concentration. MATERIALS AND METHODS: In this two-center case-control study, we prospectively collected clinical and demographical information from age and gender-matched 51 PSD patients, 56 non-post-stroke depression (Non-PSD) patients, and 39 patients with major depression (MD) to perform the suitable biochemical analysis to bring a correlation in causing depression in patients soon after the stroke. The ROC curve method was used to evaluate ceramide's diagnostic efficacy in all three groups of patients. A follow-up analysis was also conducted based on PSD severity to associate serum ceramide levels and neuropsychiatric symptoms. The severity of the patient's depressive symptoms was assessed by using the self-rating depression scale (SDS). RESULTS: In comparison between PSD and MD patients, three serum ceramide species were found to be significantly different. Compared with Non-PSD patients, PSD patients had significantly higher levels of all the four serum ceramides, and increasing levels ofC16:0, C18:0(VS MD) and C16: 0(VS Non-PSD) serve as a diagnostic tool and an independent risk factor in all three categories of patients. Moreover, the follow-up analysis results showed that, as the treatment progressed, the differences in the 3 serum ceramide species were statistically significant. CONCLUSION: There was a stage-specific association between serum ceramides and PSD, and the potential pathophysiological mechanism has to be investigated in future research.

Epidemiology and risk factors of neurosurgical bacterial meningitis/encephalitis induced by carbapenem resistant Enterobacteriaceae.

OBJECTIVES: This is a retrospective observational study conducted in one of the largest clinical center of neurosurgery in China. Our aim was to determine the epidemiological characteristics of carbapenem-resistant Enterobacteriaceae (CRE) related meningitis/encephalitis and to elucidate the risk factors for CRE neurosurgical infections. PATIENTS AND METHODS: We performed a retrospective study between January 2012 and December 2017 of patients who underwent neurosurgery. The medical records of each patient were reviewed, and 20 clinical variables on risk factors were extracted and evaluated by Multivariate logistic analysis for CRE-meningitis/encephalitis. RESULTS: In 2012-2017, the positive rate of neurosurgical meningitis/encephalitis was 7.9% (2947/29605), Enterobacteriaceae accounted for 6.3% (185/2947) of all bacterial infections. Totally, 133 Enterobacteriaceae include 26 CRE isolates were available in this study. Of them, Univariate analysis showed that the risk factors of CRE meningitis were ventilator, bacteremia, Intensive Care Unit (ICU) admission, hospital acquired pneumonia and mortality attribute to infection. Multivariate logistic analysis showed that hospital acquired pneumonia and mortality attribute to infection were independent risk factors for CRE meningitis. CONCLUSION: CRE is one of the most serious drug-resistant bacteria published by World Health Organization (WHO) in 2016, and meningitis/encephalitis caused by CRE is an important sign of the failure of the neurosurgery, which demands the physician's immediate attention.

Antitumor Activity of Asiaticoside Against Multiple Myeloma Drug-Resistant Cancer Cells Is Mediated by Autophagy Induction, Activation of Effector Caspases, and Inhibition of Cell Migration, Invasion, and STAT-3 Signaling Pathway.

BACKGROUND Accumulating evidence suggests that plant-derived molecules may prove extremely beneficial in the development of chemotherapy for deadly cancer types. Multiple myeloma is a rare and incurable type of cancers. Very little research has been directed towards the development of chemotherapy for the management of multiple myeloma. Here, the anticancer effects of a plant-derived triterpenoid, Asiaticoside, were examined against the drug-resistant myeloma cell line KM3/BTZ. MATERIAL AND METHODS Cell viability was determined by CCK-8 assay and autophagy was checked by transmission electron microscopy. ROS levels were determined by flow cytometery. Cell migration and invasion were examined by Transwell assay. Protein expression was assessed by Western blotting. RESULTS The results showed that Asiaticoside inhibits the growth of the KM3/BTZ cells and exhibited an IC50 of 12 µM. Further, it was observed that the anticancer effects of Asiaticoside are due to the induction of autophagy allied with upsurge of the expression of LC3-II. Moreover, the expression of the effector caspases in the KM3/BTZ cells was also altered. Asiaticoside also caused accretion of the ROS in the KM3/BTZ cells and inhibited their migratory and invasive properties via modulation of the STAT-3 signaling pathway. CONCLUSIONS Asiaticoside may prove useful in the management and treatment of the multiple myeloma and needs further investigation.

Effect of sequential treatment with TCM syndrome differentiation on acute exacerbation of chronic obstructive pulmonary disease and AECOPD risk window.

OBJECTIVE: To evaluate the efficacy and safety of the comprehensive interventions based on three Traditional Chinese medicine (TCM) patterns therapy in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and AECOPD risk window. METHODS: A prospective, multi-center, single-blinded, double-dummy and randomized controlled clinical trial is being conducted to test the therapeutic effects of a sequential two stage treatment. A total of 364 patients were enrolled into this study with 182 in each treatment group (TCM and conventional). Patients received medication (or control) according to their assigned group. TCM treatment according to syndrome differentiation for AECOPD were administered twice daily to patients with AECOPD over 7-21days, followed by TCM for AECOPD risk window (RW) over 28days. All patients were followed up for 6 months. Exacerbations were used as the primary outcome measures. Forced expiratory volume in the first second (FEV1) and the modified medical research council dyspnea (MMRC) scale, quality of life and mortality rate were used as secondary outcome measures. RESULTS: Of 364 randomized patients, 353 were included in the intention-to-treat analysis and 290 in the per-protocol analysis. In the TCM group, 16 patients (10.4%) reached the primary end point; 24 (17.7%) in the conventional group (RR 0.59, 95% CI 0.33-1.06; p=0.074). Among patients with a re-exacerbation, the median time to event was 107.5days (interquartile range [IQR], 39.5-129.0) in the TCM and 50days (IQR, 31-130.5) in the conventional group (P=0.011). After exacerbation therapy and a further 180-days follow-up, patients in the TCM group had significant improvements in dyspnea, as measured by MMRC (P=0.003), Patients in the TCM group also had improvements in health-related quality of life (P=0.002), as measured COPD Assessment Test (CAT). There was no difference between groups in death, and recovery of lung function. There were no differences between the TCM and conventional treatment group in adverse events. CONCLUSIONS: In patients presenting to the respiratory department with acute exacerbations of COPD, TCM treatments with syndrome differentiation will have beneficial effects with regard to re-exacerbation, relieving symptoms, improving quality of life for COPD patients.

[Explorations of epileptic network with cortico-cortical evoked potential].

OBJECTIVE: To evaluate the cortico-cortical evoked potential (CCEP) in exploring the network in epileptics. METHODS: Two patients with intractable epilepsy underwent chronic intracranial electrode placement. According to the distribution of icta onset zones and the functional brain mapping, alternating 1 Hz electrical stimuli were delivered to the target electrodes. And CCEPs were recorded by averaging electrocorticograms time-locked to stimuli from subdural electrodes. Then icta onset zones, eloquent areas identified by electrical cortical mapping and CCEP distributions were compared. RESULTS: Typical CCEP responses were observed. The data of one patient was useful for investigating the connectivity associated with various brain networks while another patient was useful for evaluating the cortical excitability. CONCLUSION: The exploration of epileptic network is achieved through cortico-cortical evoked potential by investigating the connectivity associated with various brain networks and cortical excitability.

Jagged-2 enhances immunomodulatory activity in adipose derived mesenchymal stem cells.

Adipose derived Mesenchymal stem cells (AMSCs) are able to expand in vitro and undergo differentiation into multiple cell lineages, yet have low immunogenicity while exhibiting several immunoregulatory characteristics. We sought to investigate the immunomodulatory mechanisms of AMSCs to better understand their immunogenic properties. Following 10 days of chondrogenic differentiation or 48 hours of IFN-γ pretreatment, AMSCs retained low level immunogenicity but prominent immunoregulatory activity and AMSC immunogenicity was enhanced by chondrogenic differentiation or IFN-γ treatment. We found Jagged-2 expression was significantly elevated following chondrogenic differentiation or IFN-γ pretreatment. Jagged-2-RNA interference experiments suggested that Jagged-2-siRNA2 suppresses Jagged-2 expression during chondrogenic differentiation and in IFN-γ pretreated AMSCs. Besides, Jagged-2 interference attenuated immunosuppressive activity by mixed lymphocyte culture and mitogen stimulation experiments. So, the immunoregulatory activity of AMSCs, to some extent dependent upon Jagged-2, might be stronger after multilineage differentiation or influence from inflammatory factors. This may also be why rejection does not occur after allogeneic AMSCs differentiate into committed cells.

The threshold of cortical electrical stimulation for mapping sensory and motor functional areas.

This study aimed to investigate the threshold of cortical electrical stimulation (CES) for functional brain mapping during surgery for the treatment of rolandic epilepsy. A total of 21 patients with rolandic epilepsy who underwent surgical treatment at the Beijing Institute of Functional Neurosurgery between October 2006 and March 2008 were included in this study. Their clinical data were retrospectively collected and analyzed. The thresholds of CES for motor response, sensory response, and after discharge production along with other threshold-related factors were investigated. The thresholds (mean ± standard deviation) for motor response, sensory response, and after discharge production were 3.48 ± 0.87, 3.86 ± 1.31, and 4.84 ± 1.38 mA, respectively. The threshold for after discharge production was significantly higher than those of both the motor and sensory response (both p<0.05). A negative linear correlation was found between the threshold of after discharge production and disease duration. Using the CES parameters at a stimulation frequency of 50 Hz and a pulse width of 0.2 ms, the threshold of sensory and motor responses were similar, and the threshold of after discharge production was higher than that of sensory and motor response.

Surgical treatment of patients with drug-resistant hypermotor seizures.

PURPOSE: To describe the clinical, electrophysiologic, neuroradiologic, and histologic findings in our patients with drug-resistant hypermotor seizures (HMSs) and to evaluate the outcome of their surgical treatment. METHODS: Twenty-three patients were identified by criteria for drug-resistant HMS. Surgical treatment and presurgical evaluation modalities including semiology, magnetic resonance imaging (MRI), interictal/ictal scalp video-EEG (electroencephalography), and intracranial recording were analyzed retrospectively. RESULTS: The common seizure frequency of 60-300 per month was observed among 15 patients. Sixteen patients (69.6%) experienced auras such as fear and palpitation. Marked agitation was observed in 12 patients and mild agitation in 11 patients. Groaning/shouting and asymmetric posturing were common accompanying symptoms. Asymmetric posturing was observed more often in patients with mild agitation than in those with marked agitation (p = 0.027). MRI detected focal abnormalities in six patients. Intracranial recording was conducted in 16 patients. The origins of seizures were localized in mesial frontal cortex in four patients, dorsolateral frontal cortex in four patients, and mesial temporal cortex in two patients. The epileptogenic zones (EZs) were resected from the frontal lobe in 21 patients and from the temporal lobe in 2 patients. The follow-up ranged from 12-60 months. Seventeen patients (73.9%) had been seizure-free, 11 of whom had presented with marked agitation (11 of 12) and 6 with mild agitation (6 of 11) (p = 0.069). Histologic examinations demonstrated focal cortical dysplasia (FCD) in 18 patients. DISCUSSION: The HMSs can originate from both the mesial and dorsolateral frontal cortex, and occasionally from the temporal lobe. Patients with drug-resistant HMSs should be recommended for resective surgical treatment.

Surgical treatment for musicogenic epilepsy.

We report a patient with medically intractable musicogenic epilepsy (ME) who was treated with surgery. Using the non-invasive methods of ictal and interictal electroencephalography (EEG), MRI, interictal single photon emission computed tomography and clinical manifestations, we first localized the musicogenic seizures (MS). The ictal onset zone was then further localized using intracranial EEG to the middle part of the left superior temporal gyrus. Surgical resection of the epileptogenic zone was then performed. The patient had two seizures within 2 weeks post-operatively, but has then had no seizures during the following year (Engel class II). The results suggest that patients who have medically intractable ME combined with unilateral ictal onset zones should be considered for the surgical treatment of epilepsy.

Surgery for perirolandic epilepsy: Epileptogenic cortex resection guided by chronic intracranial electroencephalography and electric cortical stimulation mapping.

SUBJECT: The objective of this study was to assess outcome with regard to seizure status and neurological function in patients undergoing resective surgery involving the perirolandic area. METHOD: All 15 patients who underwent perirolandic cortical resection between October 2006 and September 2007 at the Comprehensive Epilepsy Centre of Beijing Xuanwu Hospital were included in the study. The locations of functional cortical areas, ictal onset zones and epileptogenic lesions were mapped by chronic intracranial EEG recordings and electric cortical stimulation. Seizure outcome was determined using the modified classification of Engel and colleagues. Motor and sensory deficits were monitored. RESULTS: At last follow-up 5 patients (33%) were in Engel class I, 4 (27%) were in class II, 3 (20%) were in class III, and 3 (20%) were in class IV. Nine patients suffered immediate functional deficits; 8 of these recovered completely within 2 weeks to 3 months of surgery. One had mild persistent loss of finger motor control. CONCLUSION: After accurate presurgical evaluation using invasive recordings and functional brain mapping, epileptogenic cortical resection can give excellent results and few deficits in patients with perirolandic epilepsy.