Single-cell RNA sequencing reveals the heterogeneity of astrocytes / 中国组织工程研究

BACKGROUND:Astrocytes are the most abundant cells in the central nervous system,and various subsets of astrocytes are heterogeneous,performing a variety of special functions.Single-cell RNA sequencing(scRNA-seq)technology developed in recent years has extended our understanding of astrocyte heterogeneity from the perspective of transcriptome profiling. OBJECTIVE:To summarize the heterogeneity of scRNA-seq technology in different time and space,and pathological states and expand our knowledge of astrocyte heterogeneity on both molecular and functional levels. METHODS:The relevant articles on astrocyte heterogeneity and scRNA-seq were searched on PubMed,Elsevier,and CNKI databases.The search terms were"astrocytes,scRNA-seq,heterogeneity,Alzheimer disease,spinal cord injury,multiple sclerosis"in Chinese and English.Finally,74 articles were selected for viewing after screening according to inclusion criteria. RESULTS AND CONCLUSION:scRNA-seq studies related to the heterogeneity of astrocytes have shown that astrocyte is significantly heterogeneous across four aspects:species,developmental stage,central nervous system region,and pathological state.(1)Unique expression of certain genes occurs in astrocytes of different species,and the discovery of species-specific genes is beneficial for the translation of clinical studies.(2)During astrocyte development,differential gene expression emerged in the cellular subtypes identified at each stage,which further refined the cellular lineage of astrocytes and laid the foundation for the study of astrocyte developmental trajectories and mechanisms.(3)The discovery of differential gene expression allows regional localization of different astrocyte subpopulations and assists in the diagnosis and treatment of neurological diseases.(4)Astrocyte heterogeneity revealed by scRNA-seq can provide specific markers at the time of disease diagnosis and identify potential therapeutic targets.(5)The heterogeneity of astrocytes exists in many aspects,interacts with each other and is complex.The mechanisms of its generation,maintenance and transformation remain unclear.At present,molecular research on the single-cell level is still lacking.Linking transcriptionally defined astrocyte subpopulations to cellular activity,behavior and disease markers in real time remains one of the great challenges in the field.

Correlation between serum homocysteine and quantitative electroencephalogram and prognosis of cerebral hemorrhage / 中国综合临床

Objective:To explore the predictive value of admission serum homocysteine levels and quantitative electroencephalogram (qEEG) indicators for adverse outcomes in patients with cerebral hemorrhage.Methods:A retrospective study was conducted on 89 patients, who were collected as the study objects with hemorrhagic stroke treated in the neurology intensive care unit at Kailuan General Hospital from January 2017 to December 2022. Patients were categorized into two groups based on modified Rankin Scale (mRS) scores at discharge: a good prognosis group (mRS≤2) and a poor prognosis group (mRS 3-6). Clinical data and qEEG monitoring of various brain regions were collected. The impact factors of hemorrhagic prognosis were analyzed using multifactorial logistic regression. ROC curve analysis was performed to assess the predictive value of qEEG and admission homocysteine levels for adverse outcomes in hemorrhagic stroke patients.Results:(1) The age of the poor prognosis group was higher than that of the good prognosis group((66.51+13.64) to (60.53+11.69), t=2.15, P=0.034) and admission serum homocysteine levels were significantly higher in the poor prognosis group than in the good prognosis group (17.28(15.52,24.72)mmol/L to 14.50(10.28,16.00)mmol/L, Z=4.14, P<0.001). (2) In the poor prognosis group, power values of δ brain waves in leads Fp1-2, F4, C4, P4, F8, and T4 were higher than those in the good prognosis group (87.99(41.57,196.69) to 50.67(26.64,54.75), Z=2.76, P=0.006); (79.17(40.71,200.00) to 45.06(20.22,61.00), Z=2.10, P=0.036); (72.64(34.97,219.78) to 34.42(19.81,63.4), Z=2.03, P=0.043); (65.06(33.36,177.45) to 28.12(15.88,63.36), Z=2.08, P=0.038); (52.92(25.64,187.91) to 23.61(11.67,43.26), Z=2.21, P=0.027); (66.67(32.56,180.76) to 36.31(17.2,53.78), Z=2.46, P=0.014); (57.30(25.24,127.04) to 29.57(11.91,41.89), Z=2.26, P=0.024). Power values of θ brain waves in leads Fp1-2, F3, F4, C3, C4, P3-4, O1, F7-8, and T3-4 were higher in the poor prognosis group(77.45(47.63,138.72)比35.88(20.92,44.81), Z=3.50, P<0.001); (77.05(35.16,120.22) to 38.74(19.86,58.09), Z=2.27, P=0.023); (85.24(52.53,147.90) to 35.42(14.7,52.59), Z=2.61, P=0.009); (75.81(37.90,124.97) to 36.85(17.92,55.43), Z=2.30, P=0.021); (72.00(43.92,123.54) to 28.37(14.02,51.9), Z=2.22, P=0.027); (67.08(32.01,104.05) to 31.32(17.98,45.28), Z=2.10, P=0.035); (55.33(32.29,94.30) to 25.64(11.87,34.01), Z=2.24, P=0.025); (48.84(20.64,96.28) to 19.85(9.83,28.58), Z=2.30, P=0.022);(48.46(25.06,81.78) to 23.95(8.80,29.16), Z=2.51, P=0.012); (64.46(39.38,112.44) to 26.85(15.74,39.58), Z=2.80, P=0.005); (65.68(31.78,102.00) to 31.09(15.98,46.96), Z=2.38, P=0.017); (45.26(28.34,73.14) to 21.45(10.57,36.59), Z=2.04, P=0.042); (43.50(22.58,78.67) to 25.45(11.91,32.26), Z=2.22, P=0.027). Power values of slow-wave index in leads Fp1-2, F3-4, C3-4, P4, F7-8, and T4, as well as the overall brain average, were higher in the poor prognosis group (6.64(2.98,10.42) to 3.65(2.31,4.30), Z=2.65, P=0.01); (6.53(3.96,11.65) to 3.53(2.56,4.51), Z=2.30, P=0.022); (7.38(4.62,13.12) to 3.83(1.70,4.71), Z=2.38, P=0.017); (5.88(4.02,12.15) to 3.18(2.21,4.46), Z=2.29, P=0.022); (6.13(3.83,11.22) to 2.97(1.53,4.58), Z=2.01, P=0.044); (6.07(3.53,9.39) to 2.74(2.00,3.81), Z=2.40, P=0.016);(4.11(2.51,9.23) to 2.18(1.37,2.82), Z=2.25, P=0.024); (5.71(3.81,10.44) to 3.22(1.86,4.04), Z=2.28, P=0.023); (6.00(3.65,10.37) to 3.04(2.00,4.00), Z=2.39, P=0.017); (4.08(2.56,8.33) to 2.08(1.60,3.14), Z=2.50, P=0.013), with significant statistical differences noted (5.45(3.31,10.08) to 3.17(2.02,4.88), Z=3.62, P=0.005). (3) Logistic regression results showed that admission homocysteine levels ( OR 1.311,95% CI 1.008-1.705, P=0.044), admission NIHSS scores ( OR 1.588,95% CI 1.074-2.349, P=0.020), and overall brain average slow-wave index were influencing factors for poor prognosis in cerebral hemorrhage ( OR 8.596,95% CI 1.088-67.889, P=0.041). (4) ROC curve analysis revealed that the AUC for predicting adverse outcomes in cerebral hemorrhage was 0.768 (95% CI (0.665, 0.872)) for admission homocysteine levels, 0.743 (95% CI (0.634, 0.852)) for the overall brain average slow-wave index, and 0.896 (95% CI (0.827, 0.965)) for admission NIHSS. The cutoff values were 15.67, 3.62, and 8.5, respectively. Sensitivity was 77.8%, 71.1%, and 68.9%, and specificity was 59.4%, 68.7%, and 100%, respectively. The Youden indices were 0.372, 0.398, and 0.689. Conclusion:In the acute phase of cerebral hemorrhage, electroencephalographic physiological changes manifest shows an increase in the δ, θ, and slow-wave index throughout the entire brain. Higher admission homocysteine levels suggest a worse prognosis in patients with cerebral hemorrhage. Admission homocysteine levels and overall brain average slow-wave index have certain predictive value for adverse outcomes in acute cerebral hemorrhage.

Intestinal markers assist in evaluating the advantages and disadvantages of early enteral nutrition in patients with different degrees of shock / 中华急诊医学杂志

Objective:To evaluate whether early enteral nutrition could benefit patients with different degrees of shock by dynamic changes of intestinal biomarkers intestinal fatty acid-binding protein (I-FABP) and citrulline.Methods:(1) From February 2021 to February 2023, 133 target patients in the Intensive Care Unit of Suzhou Hospital Affiliated to Nanjing Medical University were enrolled. The observation period was 7 days after admission, and intestinal biomarkers were monitored three times: 24 hours after admission (D1), the third day after admission (D3), and the seventh day after admission (D7). (2) The enrolled patients were divided into two groups according to the dose of norepinephrine received within 48 hours after admission: safe dose group [receiving norepinephrine < 0.3 μg/(kg·min)] and hazardous dose group [receiving norepinephrine ≥0.3 μg/(kg·min)]. The safe dose group was given early enteral nutrition according to the guidelines, and the dangerous dose group was randomly (random number) given early enteral nutrition (EEN) and delayed enteral nutrition (DEN).(4)The dynamic changes of intestinal fatty acid binding protein and citrulline in three groups were observed; The differences of intestinal biomarkers at different time points of dangerous dose of EEN/DEN were compared. The survival time of EEN/DEN group within 28 days was recorded, and Kaplan-Meier survival curve was drawn. Univariate and multivariate regression analyses of 28-day mortality were performed for the included population.Results:(1) The baseline data, APACHEⅡ score, arterial blood lactic acid, AGI grade, feeding interruption, total feeding time within 7 days, and 28-day survival number were statistically different between safe dose EEN group and hazardous dose EEN group ( P < 0.05). Compared the baseline data of the dangerous dose EEN group and the dangerous dose DEN group, only the number of feeding interruptions was statistically different ( P < 0.05). (2) The trend of change in the safe dose EEN group was the same as that in the dangerous dose DEN group: I-FABP decreased significantly from D3 to D7 ( P < 0.05); Citrulline decreased from D1 to D3, but increased from D3 to D7 ( P < 0.05). In dangerous dose EEN group, I-FABP had no significant change during the monitoring period ( P > 0.05). Citrulline decreased significantly from D1 to D3 ( P < 0.05). The EEN/DEN ratio at dangerous dose was significantly different only for D7-I-FABP ( P < 0.05). Compared with the survival curve of EEN/DEN at risk dose, DEN could improve the early survival rate of critically ill patients at risk dose (Breslow test P = 0.0447). (4) Age( OR=1.069,95% CI: 1.002-1.140, P=0.044) was independent risk factor for 28-day death . BMI ( OR= 0.772, 95% CI: 0.604-0.987, P=0.039), no feeding interruption ( OR=0.044,95% CI: 0.004-0.455, P=0.009), total feeding time within 7 days ( OR=0.959, 95% CI: 0.923-0.997, P=0.036) were the protective factors. Conclusions:EEN at the safe dose and DEN at the dangerous dose can effectively reverse the necrosis of enterocyte and promote the recovery of enterocyte function. EEN is not a clear risk factor for death at 28 days, but it not only increases the incidence of feeding interruption, but also do not conduct the recovery of intestinal cell function from the perspective of intestinal biomarkers.

Clinical features and stroke etiology in 10 patients with bilateral middle cerebellar peduncle infarctions: a preliminary study / 中华神经科杂志

Objective:To characterize clinical and neuroimaging features, etiologies, and mechanisms of bilateral middle cerebellar peduncle (MCP) infarctions.Methods:Consecutive patients with bilateral MCP infarctions treated in the Beijing Tiantan Hospital, Capital Medical University between January 1, 2020 and April 30, 2022 were enrolled in this retrospective study. The demographic data, vascular risk factors, clincial manifestations and the National Institutes of Health Stroke Scale (NIHSS) scores were collected. Brain diffusion-weighted imaging was used to assess the regions of cerebral infarction, and the extracranial and intracranial segments of the vertebrobasilar artery were evaluated using magnetic resonance angiography, or computed tomography angiography. The stroke etiology and underlying mechanism were evaluated according to the Chinese Ischemic Stroke Subclassification.Results:Ten patients with bilateral MCP infarctions (8 men and 2 women) were analyzed ultimately. The onset age were 51.0-86.0 (64.8±11.4) years. NIHSS scores were 2.0-12.0 (4.9±2.9) points at admission. All patients had vascular risk factors, most of which were hypertension (10 cases) and dyslipoproteinemia (8 cases). The most common clinical manifestations were vertigo (10 cases), followed by ataxia (9 cases) and dysarthria (8 cases). Four cases were isolated bilateral MCP infarctions, while 6 patients were combined with other vertebrobasilar artery infarctions, 4 of which were combined with cerebellar hemisphere infarctions, consistent with the clinical symptoms. The etiology in all patients was large atherosclerosis (severe stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery; 9 cases). Five patients were classified as hypoperfusion/impaired emboli clearance, while 4 patients were considered as artery-to-artery embolism, and 1 was considered as the parent artery (plaque or thrombosis) occluding penetrating artery.Conclusions:Bilateral MCP infarctions are an extremely rare cerebrovascular disease characterized by vertigo, ataxia, and dysarthria. Cerebral infarction can be isolated or often combined with cerebellar hemisphere infarction. The etiology was mostly stenosis or occlusion of V4 segment of vertebral artery and anterior inferior cerebellar artery.

High levels of platelet-to-lymphocyte ratio may predict reduced risk of end stage of renal disease in Chinese patients with MPO-ANCA associated vasculitis / 中南大学学报(医学版)

OBJECTIVES@#Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.@*METHODS@#The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality.@*RESULTS@#A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801).@*CONCLUSIONS@#PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

A multicenter study of brain T 2WI lesions radiomics machine learning models distinguishing multiple sclerosis and neuromyelitis optica spectrum disorder / 中华放射学杂志

Objective:To investigate the efficacy of a machine learning model based on radiomics of brain lesions on T 2WI in differentiating multiple sclerosis (MS) from neuromyelitis optica spectrum disorders (NMOSD). Methods:Totally 223 MS and NMOSD patients who were treated from January 2009 to September 2018 in Beijing Tiantan Hospital Affiliated to Capital Medical University, Donghu Branch of the First Affiliated Hospital of Nanchang University, Tianjin Medical University General Hospital, and Xuanwu Hospital of Capital Medical University were analyzed retrospectively, and according to the proportion of 7∶3, 223 patients were completely randomly divided into training set (156 cases) and test set (67 cases). A total of 74 patients with MS and NMOSD who were treated in Huashan Hospital Affiliated to Fudan University and China-Japan Friendship Hospital of Jilin University from January 2009 to September 2018 and in Xianghu Branch of the First Affiliated Hospital of Nanchang University from March 2020 to September 2021 were collected as an independent external validation set. All patients underwent brain cross-sectional MR T 2WI, radiomics features were extracted from T 2WI, and features were selected by max-relevance and min-redundancy and least absolute shrinkage and selection operator algorithms. Then various machine learning classifier models (logistic regression, decision tree, AdaBoost, random forest or support vector machine) were constructed to differentiate MS from NMOSD. The area under curve (AUC) of receiver operating characteristics was used to evaluate the performance of each classifier model in the training set, test set and external validation set. Results:Based on multi-center T 2WI, a total of 11 radiomics features related to the discrimination between MS and NMOSD were extracted and classifier models were constructed. Among them, the random forest model had the best efficiency in distinguishing MS from NMOSD, and its AUC values for distinguishing MS from NMOSD in the training set, test set and external validation set were 1.000, 0.944 and 0.902, with specificity of 100%, 76.9% and 86.0%, and sensitivity of 100%, 92.1% and 79.7%, respectively. Conclusion:The random forest model based on the radiomic features of T 2WI of brain lesions can effectively distinguish MS from NMOSD.

Elevated levels of platelet-to-lymphocyte ratio may predict the reduced risk of MPO-ANCA associated vasculitis in Chinese patients with end stage of renal disease / 中南大学学报(医学版)

Objective: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality.Methods:The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. Results:A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95％CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95％CI 0.591 to 1.976, P=0.801).Conclusion: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.

The value of MR amide proton transfer weighted imaging technique in predicting the pathological grade of brainstem glioma / 中华放射学杂志

Objective:To evaluate the clinical application value of MR amide proton transfer weighted imaging (APTWI) in predicting the pathological grade of brainstem glioma (BSG).Methods:The data of 41 BSG patients in Beijing Tiantan Hospital, Capital Medical University from August 2019 to June 2020 who underwent both MRI and APTWI 2 weeks before surgery and had pathological grading results were retrospectively analyzed. According to the pathological results, 41 patients were classified into high-grade BSG (20 patients) and low-grade BSG (21 patients). Combined with conventional MR images, the signal intensity (%) of amide proton transfer (APT) in the parenchymal area of the tumor was obtained on APTWI images. χ 2 test or independent sample t-test was used to analyze the differences in gender distribution, age and APT signal intensity between patients with high and low grade BSG. Receiver operating characteristic (ROC) curve was drawn to predict the efficacy of APT signal intensity in the differential diagnosis of high and low grade BSG, and Youden index was calculated to obtain the optimal diagnostic threshold; the predictive ability of APT signal intensity was analyzed in combination with Hosmer-Lemeshow goodness of fit test. Results:There was no significant difference in age [(23±18) years, (20±17) years, t=0.97, P=0.340] and gender distribution (9/11, 9/12 for males/females, χ 2=0.02, P=0.890) between high-grade and low-grade BSG patients. The APT signal intensity of high-grade BSG [(3.9±0.9)%] was significantly higher than that of low-grade BSG [(2.8±0.9)%], and the difference had statistical significance ( t=4.16, P<0.001). The area under the ROC curve of APT signal intensity to distinguish high-grade and low grade BSG was 0.836, and with 2.85% as the optimal diagnostic threshold of APT signal intensity, its sensitivity for the diagnosis of high-grade BSG was 90.0% and specificity was 71.4%. The Hosmer-Lemeshow test showed that APTWI had a good predictive ability for BSG grade (χ 2=13.33, P=0.101). Conclusion:APTWI can be applied in distinguishing high grade BSG from low grade BSG, and has clinical value in predicting glioma grading.

Population pharmacokinetics of capecitabine in Chinese breast cancer patients / 中国临床药理学与治疗学

AIM: To investigate the population pharmacokinetic characteristics of capecitabine and its possible influencing factors in Chinese patients of breast cancer. METHODS: 78 cases of Chinese patients with breast cancer were chosen as the objects in this study. Following treatment with capecitabine (0.6 g, 0.15 g/piece, 4 pieces, orally), blood samples were collected and concentrations of capecitabine in plasma were analyzed by high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. The nonlinear mixed-effects software (NONMEM) was used to analyze the data and the population pharmacokinetic model was constructed accordingly. RESULTS: The final established model of absorption and elimination is one-compartment model. The clearance (CL/F) in pharmacokinetic formula of the model is as follows: CL/F=291×e

Characteristics of somatosensory changes in patients with acute middle cerebral artery infarction and its relationship with neurological impairment / 中国综合临床

Objective:To observe the changes of somatosensory evoked potential (SEP) in the upper limbs of patients with acute middle cerebral artery (MCA) cerebral infarction, and to explore its relationship with neurological impairment.Methods:From January 2015 to December 2016, 62 patients with 38 cases of male and 24 women of cerebral infarction who were treated in the department of neurology, Kailuan General Hospital were selected for a retrospectively prospective cohort study, including 38 males and 24 females.aged (66.7 ± 10.9) years old and ranging from 33.0 to 85.0 years old.According to the side of cerebral infarction, 37 cases were divided into left MCA group and 25 cases into right MCA group.During the 48 hours of admission, the electromyography evoked potential meter was used to detect the upper limb SEP, and the peak latency, amplitude and electrical activity waveform of the cerebral cortex potentials N20, P25 and N35 were recorded.Results:The results of SEP in the contralateral limbs of the left and right MCA cerebral infarction group were as follows: 1 case (2.70%) and 5 cases (20.00%) of normal median nerve; 36 cases (97.30%) and 20 cases (80.00%) of abnormality.The ratio of median nerve abnormalities in the group was statistically significant (χ 2=12.577, P<0.001). The ulnar nerve was normal in 3 cases (8.11%), 4 cases (16.00%); 34 cases (91.89%) and 21 cases (84.00%) were abnormal.There was no statistically significant difference between the two groups (χ 2=2.320, P=0.128). The peak latency and/or amplitude of each peak decreased in 34 groups (60.71%) and 33 cases (60.00%) of the ulnar nerve; the waveform of electrical activity disappeared, 22 cases (39.29%) of median nerve and 22 cases of ulnar nerve (40.00%). The peak latency and/or amplitude decreased, the electrical activity waveform disappeared, and the median nerve and ulnar nerve were compared, and the difference was not statistically significant (χ 2=0.021, P=0.885). The National Institue of Health Storke Scale(NIHSS) scores of left and right MCA cerebral infarction group were 34 (91.89%) and 19 (76.00%) respectively.Among them, the disappearance of electrical activity waveform were 18 cases (52.94%) and 4 cases (21.05%)of median nerve; 18 cases (52.94%) and 4 cases (21.05%) of ulnar nerve.The SEP electrical activity waveform disappeared in patients with moderate or higher neurological impairment, and the median nerve and ulnar nerve were statistically significant (χ 2=20.613, 20.613, all P<0.001). Conclusion:The median nerve and ulnar nerve SEP of the contralateral upper limb, which is dominated by the acute middle cerebral artery cerebral infarction, were abnormally changed.The main manifestations were that the latency of each peak of N20, P25 and N35 was prolonged and/or the amplitude was significantly decreased, and the waveform of SEP electrical activity disappeared.In addition, the disappearance of SEP wave activities only occurred in moderate and above neurological damage

Effect and Mechanism of Modified Banxia Xiexintang on Depression During Perimenopause / 中国实验方剂学杂志

Objective::To observe the effect of modified Banxia Xiexintang on depression during perimenopause, in order to study itseffecton 5-hydroxytryptamine (5-HT) and proinflammatory factors. Method::One hundred and thirty-nine patients were randomly divided into control group (69 cases) and observation group (70 cases) by random number table.Patients in control group got tibolone tablets, 2.5 mg/time, 1 time/day, and paroxetine hydrochloride tablets, 20 mg/time, 1 time/day.In addition to the therapy in control group, patients in observation group were added with modified Banxia Xiexintang, 1 dose/day.The course of treatment was 8 weeks.And before and after treatment, Hamilton depression scale for-17 items (HAMD-17), Zung's self-rating depression scale (SDS), hamilton anxiety scale (HAMA), improvement Kupperman(KI), liver depression and spleen deficiency syndrome, menopause-specific quality of life questionnaire (MENQOL) and treatment emergent symptom scale (TESS) were scored, and levels of 5-HT, rain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected. Result::After treatment, scores of HAMD-17 and SDS in observation group were lower than those in control group (P<0.01). And the effect on trea depression in observation group was better than that in control group (Z=2.074, P<0.05). The degree of depression in observation group was ligher than that in control group (Z=2.157, P<0.05). And scores of HAMA, KI and liver depression and spleen deficiency syndrome were lower than those in control group (P<0.01). The severity of perimenopausal syndrome was ligher than that in control group (Z=2.046, P<0.05). And scores of vasomotor symptoms and psychological symptoms of MENQOL scale and the total scores were lower than those in control group (P<0.05). Levels of 5-HT and BDNF were higher than those in control group (P<0.01), while levels of IL-1β, TNF-α and TESS were lower than those in control group (P<0.01). Conclusion::In addition to theroutine western medicine, modified Banxia Xiexintang can alleviate the severity of depression, release the symptoms of depression, anxiety and perimenopausal syudrome(PMS), improve the quality of life, inhibit pro-inflammatory factors, and enhance the expressions of 5-HT and BDNF, with no adverse event.

Clinical characteristics for connective tissue disease complicated with cryptococcal meningitis / 中南大学学报(医学版)

To investigate the clinical characteristics and prognosis for connective tissue disease (CTD) with cryptococcal meningitis (CM). 
 Methods: Clinical data of 18 patients with CTD complicated with cryptococcal meningitis diagnosed by Rheumatology and Immunology Department, Xiangya Hospital, Central South University from January 2000 to January 2017, were retrospectively analyzed.
 Results: The common symptoms of CTD patients with CM were headache, fever, nausea, and vomiting. Patients with severe clinical manifestations, such as convulsions and disturbance of consciousness, all died. Logistic regression analysis showed that disturbance of consciousness and decreased peripheral blood lymphocyte count might be the related factors of poor prognosis of CTD patients with CM (P<0.05). The mortality rate of CTD with CM was 61.11%, and the effective rate of treatment for this disease was 38.89%.
 Conclusion: CTD patients with cryptococcal meningitis have a high risk of death. Severe clinical symptoms, such as disturbance of consciousness and lower peripheral blood lymphocyte count, are associated with its poor prognosis.

Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice / 中国天然药物

The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.

Validation of vancomycin population pharmacokinetic model for pediatric patients / 中国药学杂志

OBJECTIVE: To choose a PPK model of vancomycin most suitable for Chinese pediatric patients, in order to guide the dosage adjustment. METHODS: Based on the database of PubMed and CNKI, all studies regarding vancomycin population pharmacokinetics were investigated and their basic information including PPK models was extracted. The data of Chinese pediatric patients who were administered vancomycin and received therapeutic drug monitoring (TDM) were introduced into the reported final PPK models, and the fitting was conducted by model fitting graphics. RESULTS: Twelve vancomycin PPK studies during 1986-2014 were included. As judged by the correlation coefficient (R) and R-square (R2) between predicted concentration and measured concentration, the models 4 and 9 presented a relatively better fitting with the data of Chinese pediatric patients we collected. The VPC fitting demonstrated that number 1 model achieved the best fitting. However, because the limited data used in this study was based on irregular sampling time, so the VPC test results were difficult to be distinguished and could only be used as a secondary reference. On the other hand, NPDE has corresponding statistical test, and its evaluation ability for the model is not affected by the factors of the experimental design. NPDE analysis showed that one-compartment model was better than two-compartment model, and model 4 and model 9 achieved better fitting to the collected data than others. CONCLUSION: The fitting effects of most reported vancomycin PPK models, except individual models, were poor for the TDM data of Chinese pediatric patients, therefore it is necessary to establish a vancomycin population pharmacokinetic model particularity for Chinese pediatric patients, in order to guide dosage adjustment more accurately.

Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice.</p><p><b>METHODS</b>Data including the patients' serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables.</p><p><b>RESULTS</b>Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (Δ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = -3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; Δ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; Δ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups.</p><p><b>CONCLUSION</b>The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.</p>

Trends in incidence and clinical feature of hypertriglyceridemic acute pancreatitis: clinical review of 20 years / 中华胰腺病杂志

Objective To retrospectively investigate the clinical features and incidence trends of hypertriglyceridemic acute pancreatitis (HLAP) in Guangzhou First People's Hospital for 20 years.Methods The medical records of 1 362 patients,who were admitted to Guangzhou First People's Hospital with acute pancreatitis during January 1991 to December 2010,were reviewed and 99 patients met the HLAP criterion.These patients were divided into four groups according to years (1991 ～ 1995,1996 ～2000,2001 ～2005,and 2006 ～2010).The incidence and clinical features were compared among the 4 groups.Results Among the 99 patients,there were 61 males and 38 females,the mean age was (44 ± 12) years old,and young male was predominant in HLAP.HLAP accounted for 7.3％ of all AP patients,and the incidence was increased 1.5 times during the 20 years period (5.4％,5.7％,6.7％,and 8.3％ respectively).The serum amylase level was (513.3 ±462.7) mmol/L,TG level was (12.7 ± 7.0) mmol/L,Ranson score was (1.2 ± 1.1),CTSI score was 2.2 ± 1.1,incidence of SIRS was 36.4％,and the incidence of MODS was 18.2％,and the incidence of pancreatic pseudocyst was 5.1％,but the incidence and mortality of SAP was not changed with time.The incidence and mortality of SAP of HLAP were significantly higher than those of acute biliary pancreatitis (20.2％ vs 8.5％,6.1％ vs 2.8％).The rate of blood purification increased from 0 to 10.7％,and the hospital stay was decreased from 26 d to 14 d,and the difference between the two groups was statistically significant (P ＜ 0.05).Conclusions Incidence of HLAP is increased gradually,with a trend towards more severe disease,but the prognosis is improved.

Clinical study of invasive fungal infection secondary to systemic lupus erythematosus / 中南大学学报(医学版)

OBJECTIVE@#To study the clinical characteristics of invasive fungal infection secondary to systemic lupus erythematosus (SLE).@*METHODS@#We observed the clinical features and experimental examination in 91 patients treated in Xiangya Hospital in recent years, of which 48 patients with invasive fungal infection and 41 patients without invasive fungal infection.@*RESULTS@#The invasive fungal infection secondary to SLE mainly occurred in the lungs, nervous system, and urinary system. The fungi were mainly Candida albins and Aspergillus. The rate of invasive fungal infection in SLE patients and the level of CRP and TNF-α in these patients were significantly increased. The occurrence of invasive fungal infection was positively correlated with the prolonged course of disease, long-term use of immunosuppressants and antibiotics, and occurrence of complications, such as hypoproteinemia, leukocytopenia, and so on. The levels of C-reactive protein (CRP) and tumor necrosis factor-α(TNF-α) were increased in SLE patients with invasive fungal infection.@*CONCLUSION@#The clinical features of SLE patients with invasive fungal infections are long course of disease, long-time use of immunosuppressants or antibiotics, and occurrence of complications, such as hypoproteinemia or leukopenia. The level of CRP and TNF-α can be used as an important reference index for diagnosing invasive fungal infections.

Infliximab on intestinal barrier injure in rats with acute necrotizing pancreatits / 中华胰腺病杂志

Objective To evaluate the effects of infliximab (TNF-α monoclonal antibody ) on intestinal barrier injury in ANP complicated with MODS in a rat model.MethodsThirty SD rats were randomly divided into sham operation group (SO),ANP group and infliximab treatment group.Sodium taurocholate (4.5％) was injected into the pancreatic duct to induce ANP complicated with MODS model.Infliximab (8 mg/kg) was injected via tail vein in 6h after modeling in infliximab group.Same amount of 0.9％ NS was injected into the pancreatic duct in SO group.After 24 h of modeling,all rats were sacrificed,intestine and pancreas samples were collected for pathologic examination.The blood samples were harvested.The serum levels of amylase,TNF-α,diamine oxidase( DAO),D-lactate,and the rate of carbon propelling in ileum were measured.ResultsThe serum levels of amylase were ( 1125 ± 331 ),( 11024 ± 2203 ),( 545 ±30) U/L in SO group,ANP group and infliximab group; the serum levels of TNF-α were (12.1 ± 4.0),(107.6 ± 18.5),(75.8 ±5.9) U/L; the pathological scores of pancreas were 2.25 ±0.38,14.10 ±0.22,3.93 ± 0.67,the difference among the 3 groups was statistically significant ( P ＜ 0.05 ).The pathological scores of intestine were 2.29 ± 0.32,6.61 ± 0.58,3.91 ± 0.41 ; the DAO levels were ( 87.88 ± 34.51 ),(146.30 ±12.99),(115.00 ± 18.58) ng/ml; the D-lactate levels were (1.50 ±0.49),(2.32 ± 0.35),(2.02 ± 0.25 )mmol/L; and the rates of carbon propelling in ileum were (0.64 ± 0.04 )％,(0.28 ±0.08)％,(0.52 ±0.09)％,the difference among the 3 groups was statistically significant (P ＜0.05).ConclusionsInfliximab can effectively prevent dysfunction of intestinal barrier and improve motility in ANP rats.

Ultrastructure and electrophysiology of astrocytes differentiated from adult adipose-derived stromal cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adipose-derived stromal cell (ADSC) differentiation into neural cells in vitro is becoming widely studied. However, there are few reports on astrocytes following differentiation, and particularly on maturation and electrophysiology. In this study, we used various methods to determine ADSC-derived astrocyte maturity.</p><p><b>METHODS</b>Chemical induction with isobutylmethylxanthine (IBMX) was used to differentiate adult ADSCs into astrocytes followed by hematoxylin-eosin (HE) staining to observe morphology and transmission electron microscopy for cellular ultrastructure assessment. Immunofluorescence was used to detect expression of neural stem cell marker nestin as well as glial markers glial fibrillary acidic protein (GFAP) and S-100. In addition, we measured membrane potentials in bis-(1,3-dibarbituric acid) trimethine oxanol-labeled ADSCs and astrocytes by stimulation with a high potassium solution under an inverted fluorescence microscope. Finally, cell cycle distribution was detected by flow cytometry.</p><p><b>RESULTS</b>Typical astrocyte morphology was shown by HE staining after 48-hour differentiation. Glial fibril was observed with transmission electron microscopy. GFAP and S-100 were not expressed in the control group, but were expressed within 24-hour differentiation and reached a maximum at day 14 with no change up to day 28. Nestin was weakly expressed in control cells and also reached a maximum at day 14 with the percentage of positive cells constant until day 21 followed by a decrease. Differentiated cell membrane potentials after stimulation with potassium were slightly increased, and then gradually declined over time. There was no significant membrane potential change in the control group. Flow cytometry showed that the percentage of cells in G0/G1 phase was 93% and only 5% in S phase.</p><p><b>CONCLUSION</b>ADSCs were differentiated into mature astrocytes with typical characteristics including morphology, ultrastructure, marker protein expression, mature potassium channels and mitotic capacity.</p>

Study on the time of amounted to peak of human adipose-derived stromal cells differentiation into neural precursor cells in vitro / 中华行为医学与脑科学杂志

Objective To reseach the time point of the highest percentage of neural precursor cells derived from adipose stromal cells (ADSCs) in vitro, and to observe the ultrastructure features of neural precursor cells. Methods Used the β-mercaptoethanol to induce ADSCs to differentiate into neural precursor cells and neuron-like cells. The morphology of the uninductedcells and inducted cells were observed with inverted phase contrast microscope. The expression of nestin which was the marker of neural precursor cell in each group was detected using immunofluorescence staining method. The ultrastructural feature of cells which was induced for 3 hours were observed. Results The highest ratio of positive expression of nestin was 3 hours following induction,with the ratio ( 86.25 ± 4.82) %. There were many protuberance on the cell membrane under transmission electron microscopy.There were plenty of organelles in the neural precursor cells. The neural precursor cells had a large size nucleus,large nucleoplasmic index, much extended chromatin,and less condensed chromatin. The nucleus had double-layer nuclear envelope, more nuclear pore on the nuclear envelope. Conclusion The time point of the highest percentage of neural precursor cells derived from ADSCs is 3 hours,and the ultrastructral feature of induced neural precursor cells confirm that cells at this time point are in a state of split active period.