Background: It is unknown if medication-overuse headache, clinically similar to chronic tension-type headache, has pre-attentive problems which may be related to pain or substance abuse. Methods: Auditory frequency deviance elicited mismatch negativity was recorded from 22 patients with chronic tension-type headache, 26 with medication-overuse headache from underlying chronic tension-type headache and 41 healthy volunteers as controls. Their depression and anxiety scores were noted. Results: There were no signifi cant differences in the N1 latency or amplitude to both standard and deviant stimuli for the different groups. However, the latency and amplitude of mismatch negativity were signifi cantly shortened and reduced at Fz, Cz, and Pz in medication-overuse headache as compared to chronic tension-type headache and normal subjects. Anxiety levels were elevated in chronic tensiontype headache and medication-overuse headache subjects compared to healthy controls but were not correlated with mismatch negativity latency or amplitude in a given group. Conclusions: In medication-overuse headache subjects, the shortened mismatch negativity latency indicates quick involuntary attention switching to auditory change, while its reduced amplitude indicates poor accuracy in discriminating early stimuli, which may be related to medication overuse rather than to the head pain experienced.

Objective: To provide a scientific standard of left ventricular Tei index for healthy people from various region of China, and to lay a reliable foundation for the evaluation of left ventricular diastolic and systolic function. Methods: The correlation and principal component analysis were used to explore the left ventricular Tei index, which based on the data of 3 562 samples from 50 regions of China by means of literature retrieval. hTe nine geographical factors were longitude(X1), latitude(X2), altitude(X3), annual sunshine hours (X4), the annual average temperature (X5), annual average relative humidity (X6), annual precipitation (X7), annual temperature range (X8) and annual average wind speed (X9). ArcGIS sotfware was applied to calculate the spatial distribution regularities of letf ventricular Tei index. Results: hTere is a signiifcant correlation between the healthy people’s letf ventricular Tei index and geographical factors, and the correlationcoeffcients were 0.107 (r1), 0.301 (r2), 0.029 (r3), 0.277 (r4),?0.256(r5),?0.289(r6),?0.320(r7), 0.310 (r8) and 0.117 (r9), respectively. A linear equation between the Tei index and the geographical factor was obtained by regression analysis based on the three extracting principal components. hTe geographical distribution tendency chart for healthy people’s letf Tei index was iftted out by the ArcGIS spatial interpolation analysis. Conclusion: hTe geographical distribution for letf ventricular Tei index in China follows certain pattern. hTe reference value in North is higher than that in South, while the value in East is higher than that in West.

In this paper , based on the analysis of the facing predicament of current situation of medical ethics education , the authors combined with the practice of medical ethics education and the school experience , based on the theory of life education , put forward to experience the activities of public medical treatment building practice of medical students medical ethics education system , promote the educational work to carry out the practice of medical colleges, improve the teaching quality of medical ethics education .

The competence of scientific research ethnical review in domestic hospital was inadequate,which was associated with the development of medical ethnics,values of Chinese traditional society,unsound domestic laws and regulations,weak administrative management,unqualified committee of medical ethnics,the drive of scientific deriving interests and restriction of project funds.Aiming at the above problems,countermeasures were carried out to strengthen the construction of laws and regulations,strengthen the constraint of administrative management,standardize the self-construction of ethnic committee,implement the standard operative procedure,thus to provide a reference for the standardized construction of scientific research ethnical review.

Objective To investigate the effects of soluble endoglin(sEng)on nitric oxide (NO)production and endothelial nitric oxide synthase(eNOS)phosphorylation in cultured human umbilical vein endothelial cells.Methods Human umbilical vein endothelial cells within 3 passages seeded in culture plates of 96 wells,were stimulated by total culture medium(control group)or sEng (1,10 and 100 μg/L)respectively.Cells and medium were collected after cells were cultured for 6,12 and 24 hours respectively.The concentration of the metabolites of NO in each group was measured by nitrate reductase method.The expression of eNOS and eNOS-Ser(p)1177 were detected by Western blot.The expression of eNOS mRNA in each group was detected by real-time fluorescence reverse transcription-polymerase chain reaction.Analysis of variance,LSD method and pearson correlation were used to compare the difference between groups.Results(1)The concentration of the metabolites of NO in 1,10 and 100μg/L sEng groups was(59.25±1.63),(41.08±2.71)and (30.38±1.63)μmol/L respectively after cultured for 6 hours;(54.98±3.34),(35.00±8.60)and (19.82±3.75)μmol/L for 12 hours; and(46.14±4.93),(30.24±2.08)and(12.78±5.01)μmol/L for 24 hours.There was no significant changes in control group with time going by(F=2.30,P=0.14).The concentration of the metabolites of NO was significantly lower in sEng group,and which had negative correlation with culture time(r=-0.98,P＜0.05)and dose(r=-0.88,P＜0.05).(2)The expression of eNOS in 1,10,100 μg/L sEng groups was 0.71 ± 0.00,0.47 ± 0.00 and 0.32±0.00 after cultured for 6 hours; 0.58±0.00,0.42±0.00 and 0.25±0.00 for 12 hours; and 0.49±0.00,0.33±0.00 and 0.18±0.00 for 24 hours.While the expression of eNOS and eNOS-Ser (p)1177/eNOS had no significant changes in control group with time going by(F=3.59 and 0.37,P=0.09 and 0.80).The expression of eNOS protein and eNOS-Ser(p)1177 decreased significantly in sEng groups,which had negative correlation with culture time(r=0.98 and-0.96,P＜0.05)and dose(r=-0.76 and-0.79,P＜0.05).(3)The expression of eNOS mRNA decreased significantly in sEng groups.Which also had negative correlation with culture time(r=-0.51,P＜0.05)and dose(r=-0.82,P＜0.05).Conclusions sEng might inhibit eNOS activity by blocking 1177 Ser phosphorylation to decrease NO production.

Objective To investigate the expression of transforming growth factor-β1 (TGF-β1),endoglin (Eng) and their mRNA in placenta and superficial myometrium of patients with gestational hypertension or preeclampsia and to explore the role of Eng and TGF-β1 in the pathogenesis of gestational hypertension or preeclampsia.Methods One hundred and ten pregnant women were selected in the Second Affiliated Hospital of Tianjin Medical University from April 2009 to April 2010 who underwent cesarean sections and were divided into four groups:gestational hypertension group (n=30),mild preeclampsia group (n=30),severe preeclampsia group (n=30) and control group (normal pregnant women without labor and perinatal complications,n=20).The tissues of placenta and superficial myometrium were collected during cesarean section.Protein levels of Eng and TGF-β1 were detected by Western Blot.Real-time fluorescence reverse transcription polymerase chain reaction was used to detect the Eng and TGF-β1 mRNA expression.One-way ANOVA was used to compare among groups,Student-Newman-Keuls test was used to compare the differences between groups; relation between groups was analyzed by Pearson relation and linear regression.Results In control group,gestational hypertension group,mild and severe preeclampsia group,the Eng mRNA level was 1.00,1.27±0.58,1.54±0.41 and 1.83±0.35,and the TGF-β1 mRNA level was 1.00,1.64 ± 0.33,1.92± 0.38 and 2.23 ± 0.53 in placenta respectively; those figures changed to 1.00,1.32±0.46,1.59±0.37 and 1.93±0.52,and 1.00,1.71 ± 0.45,1.91 ± 0.51 and 2.37 ± 0.46 in superficial myometrium respectively.The Eng and TGF-β1 mRNA levels of control group were lower than those of the other three groups (P＜0.05).The higher the mRNA level,the more severe the disease (P＜ 0.05).In control group,gestational hypertension group,mild and severe preeclampsia group,the Eng protein expression was 0.11±0.07,0.15± 0.05,0.18 ± 0.06 and 0.43 ± 0.04,and the TGF-β1 protein expression was 0.11 ±0.02,0.26 ± 0.05,0.27± 0.03 and 0.88 ± 0.09 in placenta respectively; those figures changed to 0.14±0.06,0.16±0.04,0.20±0.08 and 0.46±0.05,and 0.15±0.03,0.29±0.06,0.31±0.04 and 0.91 ±0.08 in superficial myometrium respectively.The Eng and TGF-β1 protein levels of control group were lower than those of the other three groups (P＜0.05).The higher the protein level,the more severe the disease (P＜0.05).In the gestational hypertension group,mild and severe preeclampsia group,there were positive correlations between Eng and TGF-β1 protein levels in placenta (r=0.57,0.61 and 0.60 respectively,P＜0.05) and superficial myometrium (r=0.59,0.62 and 0.61 respectively,P ＜ 0.05).Conclusions Eng and TGF-β1 might play a role in pathogenesis of gestational hypertension and preeclampsia.

Objective To analyze the influences of maternal high-fat diet on male rat offspring's blood lipid level and hepatic lipid deposition as well as on the expression of two key factors,sterol regulatory element binding protein-1 (SREBP-1) and SREBP cleavage acting protein (SCAP),involved in hepatic cholesterol regulatory cascade during childhood and adulthood.Methods Pregnant Wistar rats were randomly divided into two groups:high fat diet (HF) group and normal intake control (NC) group (both n=20).Rats in the HF group were fed with high-fat diet till delivery before changing to a normal-fat diet,while the NC group was given the normal-fat diet all through the study.Male offspring born appropriate for gestational age (AGA) in different feeding groups were randomly selected as experimental subjects.Physical development,serum lipid levels and hepatic lipid deposition at the age of 7 and 24 weeks were compared between offspring of the two groups.Expression of SCAP and SREBP-1 at protein level was detected with immunohistochemistry.T test or Chi-square test was used for statistical analysis.Results The average birth weight of HF group was higher than that of NC group [(6.95± 0.25) vs (6.79 ±0.78) g,t=2.088,P=0.038].Large for gestational age (LGA),AGA and small for gestational age (SGA) offspring accounted for 18.6％ (21/113),77.9％ (88/113)and 3.5％ (4/113) in HF group and 7.6％ (10/132),87.9％ (116/132) and 4.5％ (6/132) in NC group (x2=13.500,P=0.001).At the age of 7 weeks,the offspring's body weight in HF group was higher than that in NC group [(68.78±7.55) vs (66.61 ±3.92) g,t=2.303,P=0.023].At the age of 24 weeks,the body weight,body length and abdominal circumference of adult offspring in HF group were significantly higher than those in NC group [(251.74±24.04) vs (216.24±33.42) g,(22.60±0.79) vs (21.59± 1.34) cm,(17.93±0.59) vs (16.83±0.88) cm;t=2.220,2.379,2.927,all P＜0.05].At the age of 7 weeks,offspring's serum total cholesterol (TC) level in HF group was higher than that in NC group [(1.94±0.62) vs (1.23 +0.77) mmol/L,t=2.379,P＜0.05].At the age of 24 weeks,adult offspring's liver index,serum TC,triglyceride (TG),low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) levels were all higher in HF group than in NC group,while the high density lipoprotein-cholesterol (HDL-C) level was lower in HF group [(2.75±0.31)％ vs (2.46±0.39)％,(1.98±0.14) vs (1.45±0.27) mmol/L,(2.96±0.21) vs (2.71 ±0.29) mmol/L,(0.97±0.32) vs (0.71 ±0.21) mmol/L,(0.81 ±0.13) vs (0.52±0.17) mmol/L,(1.74±0.20) vs (1.59±0.29) mmol/L;t=2.264,2.333,2.359,2.088,5.336,1.994,all P＜0.05].Comparative analysis of nonalcoholic fatty liver disease activity scores (NAS) between the two groups showed that the liver lobular inflammation in HF group's offspring was more severe at both 7 and 24 weeks of age (2.29±0.49 vs 1.92±0.45,2.83±0.47 vs 2.22±0.55;t=2.157,3.251,all P＜0.05).At the age of 24 weeks,adult offspring in HF group also showed higher liver steatosis scores (2.81 ± 0.35 vs 2.25 ± 0.30,t=4.609,P＜0.05).Immunohistochemical detection showed that there was no significant difference in SCAP protein expressions in liver tissues of 7-week-old offspring between the two groups (P＞0.05),but higher expression of SREBP-1 protein was observed in HF group than in NC group [(34.16±5.08)％ vs (18.09±3.99)％,t=9.697,P＜0.05].At the age of 24 weeks,the expression levels of both SCAP and SREBP-1 proteins in liver tissues were higher in HF group than in NC group [(31.22±6.01)％ vs (17.98+7.89)％,(61.33± 16.25)％ vs (29.76± 11.21)％;t=2.303,2.274,both P＜0.05].Conclusions High-fat intake during pregnancy can increase offspring's birth weight and the risk for LGA offspring.Maternal high-fat diet even up-regulates the expression of SCAP and SREBP-1 in male offspring born AGA in childhood and this impact become more obvious when reaching adulthood,resulting in excessive increase of body weight,body length and abdominal circumference and elevated serum lipid level and liver lipid deposition.

Objective To study the clinical value of simultaneous amplification and testing for detection of Mycobacteria tuberculosis(SAT-TB)in sputum samples and bronchoalveolar lavage fluid(BALF)samples. Methods Totally 169 sputum samples and 151 BALF samples from suspected pulmonary tuberculosis patients were detected by both SAT and Bactec MGIT960.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of the samples using SAT-TB were calculated. Results Taken the results of BD960 as the reference,the sensitivity,specificity,PPV and NPV using SAT-TB of sputum samples were 84.00% (42/50),93.06%(67/72),89.36%(42/47)and 89.33%(67/75)respectively;and those of BALF samples 89.19% (33/37),95.12%(39/41),94.29%(33/35)and 42.39%(39/92)respectively.Taken clinical diagnostic results as reference standard,the sensitivity,specificity,PPV and NPV using SAT-TB of the sputum samples were 57.73% (56/97),93.06%(67/72),91.80%(56/61),and 62.04%(67/108)respectively;and those of BALF samples 51.82%(57/110),94.29%(39/41),96.61%(57/59)and、42.39%(39/92)respectively.The sensitivity,specificity, PPV and NPV using BD960 of the sputum samples were 51.55%(50/97),95.83%(69/72),94.34%(50/53),and 59.48%(69/116)respectively;and those of BALF samples 33.64%(37/110),90.24%(37/41),90.24%(37/41) and 33.64%(37/110)respectively.Conclusion SAT-TB is a rapid and sensitive method for the detection of Myco-bacteria tuberculosis in sputum and BALF samples.It can improve the detection rate of mycobaterium tuberculosis.

Objective:To investigate the predictors of early neurological deterioration (END) in patients with acute ischemic stroke (AIS) based on the Oxfordshire Community Stroke Project (OCSP) classification system.Methods:Patients with AIS admitted to the Department of Neurology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from February 2018 to November 2020 were enrolled retrospectively. According to the OCSP criteria, the patients were classified into total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), posterior circulation infarct (POCI), and lacunar infarct (LACI). END was defined as the National Institutes of Health Stroke Scale (NIHSS) total score within 72 h after onset increased by ≥2 or motor function score increased by ≥1 compared with the baseline. Multivariate logistic regression analysis was used to determine the independent risk factors for END in AIS patients with different OCSP types. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of each index for END in AIS patients with different OCSP types. Results:A total of 405 patients with AIS were enrolled. Their age was 68.84±12.27 years, and 250 were males (61.7%); 132 patients (32.6%) were in the TACI group, 108 (26.7%) were in the PACI group, 61 (15.1%) were in the POCI group, and 104 (25.7%) were in the LACI group. END occurred in 136 patients (33.6%). Multivariate logistic regression analysis showed that homocysteine (Hcy) (odds ratio [ OR] 1.065, 95% confidence interval [ CI] 1.012-1.212; P=0.015), baseline NIHSS score ( OR 1.209, 95% CI 1.095-1.335; P<0.001) and the time from onset to admission ( OR 1.663, 95% CI 1.282-2.082; P<0.001) were significantly and independently correlated with END in the TACI group. Hcy ( OR 1.137, 95% CI 1.040-1.244; P=0.005), fasting blood glucose ( OR 1.714, 95% CI 1.272-2.311; P<0.001), neutrophil to lymphocyte ratio (NLR) ( OR 1.370, 95% CI 1.016-1.848; P=0.039) and the time from onset to admission ( OR 1.266, 95% CI 1.056-1.519; P=0.011) were significantly and independently correlated with END in the PACI group. NLR ( OR 1.446, 95% CI 1.031-2.027; P=0.033) was significantly and independently correlated with END in the POCI group. Fasting blood glucose ( OR 1.301, 95% CI 1.006-1.683; P=0.045), NLR ( OR 1.393, 95% CI 1.025-1.894; P=0.034) and the time from onset to admission ( OR 1.171, 95% CI 1.008-1.361; P=0.039) were significantly and independently correlated with END in the LACI group. ROC curve analysis showed that the areas under the curve (AUC) of Hcy and baseline NIHSS score for predicting END in the TACI group were 0.617 (95% CI 0.521-0.713; P=0.021) and 0.784 (95% CI 0.706-0.862; P<0.001). The optimal cut-off values were 15.91 μmol/L and 19.5 points, respectively. The sensitivity and specificity were 63.7% and 85.2%, 62.0% and 86.9%, respectively. The AUC of Hcy, fasting blood glucose and NLR for predicting END in the PACI group were 0.672 (95% CI 0.548-0.797; P=0.005), 0.794 (95% CI 0.697-0.891; P<0.001) and 0.674 (95% CI 0.560-0.788; P=0.005), respectively. The optimal cut-off values were 15.2 μmol/L, 6.85 mmol/L, and 3.71, respectively. The sensitivity and specificity were 61.3% and 77.9%, 80.6% and 72.8%, 67.7% and 79.4%, respectively. The AUC of NLR for predicting END in the POCI group was 0.850 (95% CI 0.735-0.964; P<0.001). The optimal cut-off value was 5.2. The sensitivity and specificity were 84.2% and 81.4% respectively. The AUC of fasting blood glucose and NLR for predicting END in the LACI group were 0.728 (95% CI 0.614-0.842; P<0.001) and 0.731 (95% CI 0.614-0.842; P<0.001), respectively. The optimal cut-off values were 5.44 mmol/L and 2.71 respectively. The sensitivity and specificity were 80.0% and 62.7%, 76.0% and 79.2%, respectively. Conclusion:The predictors of END in AIS patients with different OCSP types are different.

Objective:To evaluate the utility of whole-exome sequencing (WES) in early diagnosis for children with language delay/disorder.Methods:Children with language delay/disorder who were admitted to the Department of Health Care, Children′s Hospital Affiliated to the Capital Pediatric Institute from January 2019 to December 2020 were analyzed retrospectively. Based on informed consent, the peripheral blood of the children and their parents was collected for WES. Combining the clinical phenotypes of the children, the candidate variants, including single nucleotide variants (SNVs) and copy number variations (CNVs), were selected for validation and family segregation analysis using Sanger sequencing, real-time PCR or CNV-Seq. The pathogenicity of variants was evaluated based on ACMG guideline following with finial genetic diagnosis. Based on whether genetic diagnosis was achieved or not, 125 children with comprehensive examination of the Children Neuropsychological and Behavioral Scale(CNBS-R2016) were sub-grouped (positive/negative group), and the total scores and the detailed scores of five developmental sections (gross motor, fine motor, adaptive ability, language and social behavior ability) between two subgroups were compared.Results:A total of 165 children with language delay/disorder were recruited, including 109 males and 56 females. The ratio of boys to girls was 1.95∶1.The age of the children was (3.2±1.2) years old, the median age was 3.0 years. 45 children carry disease-related pathogenic/likely pathogenic variants, including 36 SNVs and 9 CNVs. The genetic diagnostic yield of this cohort was 27.3% (45/165). The inheritance analysis for core family members showed de novo variant accounted for 86% of genetic diagnosis (31/36). The positive diagnosis rate in girls was 45% (25/56), which was significantly higher than that in boys (18.3%, 20/109, χ2=12.171, P<0.05). There was no significant difference in the rate of positive diagnosis among all age groups (χ2=4.349, P>0.05). Interestingly, the scores of gross motors of positive group were significantly lower than that of negative group (61.5 vs. 69.4, t=-2.610, P<0.05). Otherwise, no significant difference was seen between two groups( t=-0.933, -1.298, -0.114, -0.214, all P>0.05). Conclusions:Language delay/disorder has complex genetic heterogeneity. WES has important application value in early etiological diagnosis for children with language delay/disorder.