【Objective】 To analyze the genetic variation characteristics and clinical phenotypes of a family with primary microcephaly (MCPH) caused by RTTN gene variation, and to provide reference for genetic counseling and prenatal diagnosis. 【Methods】 Clinical data of the three patients (including 2 fetuses and 2-year-old proband,and one fetus with clinical diagnosis) and their parents were collected and analyzed. Two of the children and their parents were tested by trio whole exome sequencing (trio-WES), sanger sequencing validation sites, and the hazard of their compound heterozygous variants was predicted. Literature review was conducted through domestic and international databases to collect reported RTTN gene mutation cases. 【Results】 Three patients in this family had anomalies of the septum pellucidum, hypoplasia of the corpus callosum and other brain malformations during fetal period. The proband (G2) and fetus (G3) showed intrauterine growth retardation and MCPH in late pregnancy; besides, G2 was born with global developmental delay. Trio-WES detected a c.2101(exon16)C>T(p.Arg701Ter,1526) nonsense and a c.2863(exon22)G>A(p.Glu955Lys)missense in the RTTN gene of G2 and G3, which were inherited from their father and mother, forming a compound heterozygous variant. According to the American College of Medical Genetics and Genomics (ACMG) variant classification guidelines, two variants were likely to be pathogenic (LP) and uncertain significance (VUS). Among them, c.2863(exon22)G>A was a newly discovered missense, which was predicted by the software to be harmful to the gene product. 【Conclusions】 Complex heterozygous variations of RTTN gene (c.2101C>T and c.2863G>A) are the genetic cause of MCPH in this family. This report has enriched the variation spectrum of RTTN gene, provided guidance for prenatal diagnosis and reproduction of this family, as well as material and reference for further understanding of the diseases caused by this gene mutation.

Objective:To investigate the efficacy and safety of intravenous thrombolysis and antiplatelet therapy in patients with stroke warning syndrome (SWS), as well as influencing factors of the outcome in patients with SWS.Method:Patients with SWS admitted to the 521 st Hospital of Ordnance Group from June 1, 2018 to December 31, 2023 were retrospectively included. Some patients were treated with ateplase intravenous thrombolysis, followed by oral antiplatelet therapy; some patients only received antiplatelet therapy. The main outcome measure was the modified Rankin Scale score at 90 days after onset, with a score of 0-2 defined as good outcome. Results:A total of 35 patients with SWS were included, including 26 males (74.3%) with an age of 58.29±11.06 years. Nineteen patients (54.3%) received intravenous thrombolysis, and 27 (77.1%) had good outcome at 90 days. There was no statistically significant difference in demographic, baseline data, and good outcome between the intravenous thrombolysis group and the antiplatelet therapy group. One patient had new stroke and one had transient ischemic attack in the intravenous thrombolysis group. There were statistically significant differences in ABCD2 score, systolic blood pressure, low-density lipoprotein cholesterol, fasting blood glucose, highest National Institutes of Health Stroke Scale (NIHSS) score at onset, and symptom duration between the good outcome group and the poor outcome group (all P<0.05). Conclusions:The efficacy of intravenous thrombolysis is similar to that of antiplatelet drugs alone in treating SWS. ABCD2 score, systolic blood pressure, low-density lipoprotein cholesterol, fasting blood glucose, highest NIHSS score at onset, and duration of symptoms may be influencing factors for the outcome of patients with SWS.

ObjectiveTo explore the activation of motor cortex and brain lateralization of healthy male subjects during mirror visual feedback (MVF) of dominant and non-dominant hands. MethodsFrom March to September, 2021, 17 right-handed male subjects were recruited in Shenyang Sport University. The eego^TMmylab electroencephalography (EEG) system was applied to acquire the EEG and surface electromyography (sEMG) signals of digital extensor muscle during MVF. The subjects were completed unilateral finger stretching exercise, including left/right hand MVF and left/right hand visual feedback (VF). Each paradigm was repeated 80 trials, and the four paradigms were divided into two experiments, with one week between each experiment. The time-domain characteristics of sEMG signals and the time-frequency characteristics of α-band (8 to 13 Hz) and β-band (13 to 20 Hz) EEG signals which were closely related to motion were analyzed. Activation and asymmetry of motor cortex during MVF in dominant and nondominant hands were measured with event-related desynchronization/synchronization (ERD/ERS) and asymmetric index (AI). ResultsWhen the relaxed hand was right hand, the sEMG amplitude of digital extensor muscle were more in MVF and VF than in resting state (P < 0.05). In α bands, the main effect of training state on ERD/ERS was significant (F = 14.125, η_p² = 0.469, P = 0.002), and it was higher in MVF than in VF. In β band, the main effect of training state on ERD/ERS was significant (F = 9.704, η_p² = 0.378, P = 0.007), the interaction effect of moving hand and training state was significant on ERD/ERS (F = 8.014, η_p² = 0.334, P = 0.012); for VF, ERD/ERS was higher in right hand movement than in left hand movement (F = 7.267, η_p² = 0.312, P = 0.016); for right hand movement, ERD/ERS was higher in MVF than in VF (F = 17.530, η_p² = 0.523, P = 0.001). At the position of C4 electrode, ERD/ERS was higher in right hand movement than in left hand movement under VF (t = -3.201, P = 0.006, Cohen's d = 0.776), and ERD/ERS was higher in MVF than in VF under right hand movement (t = -4.060, P = 0.001, Cohen's d = 0.985). Main effect of training state was significant on AI at β band (F = 5.796, η_p² = 0.266, P = 0.028), and it was higher in MVF than in VF. ConclusionMVF may improve the activity of motor cortex neurons on the ipsilateral side of the motor hand through recruitment of frontal and parietal mirror neurons and reduction of interhemispheric and intracortical inhibitory activities, and it is more effective for the dominant hand training.

Objective: To explore the action mechanism of miR-139-5p inhibiting proliferation and invasion of epithelial ovarian cancer (EOC) cells by targetedly regulatingNotch1.Methods: A total of 24 pairs of EOC tissues and its corresponding para-cancerous tissues from patients, who underwent surgical resection in the DepartmentofGynecology,Nanyang Central Hospital of Henan Province, were collected for this study; in addition, human ovarian cancer cell lines (SKOV3, ES2, HEY-T30) and human ovarian epithelial cell line IOSE80 were also collected. Real-time quantitative PCR (qPCR) was applied to detectmRNAexpressionofmiR-139-5pandNotch1 in EOC tissues and cell lines. The miR-139-5p over-expression vector and recombinant plasmid pLV-Notch1 were transfected into SKOV3 cells. Blank control group (Ctrl group) and negative control group (NC group) were set up. Dual luciferase reporter gene assay was applied to verify the targeting relationship between miR-139-5p and Notch1 3'-UTR. CCK-8, Transwell and Scratch healing experiments were applied to detect cell proliferationinvasionandmigration, respectively. Western blotting was applied to detect expressions of proliferation and migration related proteins in cells. Results: Compared with para-cancerous tissues and IOSE80 cells, the expression of miR-139-5p was significantly decreased in EOC tissues and cell lines, while the expression of Notch1 mRNA was significantly increased (all P<0.01). The results of Dual luciferase reporter showed that Notch1 was the downstream target gene of miR-139-5p. Compared with NC group, cell proliferation, invasion and migration ability, expression levels of Notch1, NICD, Cyclin D1, Cyclin A1, Snail1, β-catenin and N-cadherin were all significantly decreased on 3 d in miR-139-5p mimic group (all P<0.01), while expression of E-cadherin was significantly increased (P<0.01); meanwhile, over-expression of Notch1 could reverse the inhibitory effect of miR-1395p on proliferation, invasion and migration of SKOV3 cells. Conclusion: miR-139-5p can targetedly regulate Notch1 to inhibit proliferation, invasion and migration of EOC cells, which may be related to its down-regulation of NICD, Cyclin D1, Cyclin A1, Snail1, βcatenin and N-cadherin, and up-regulation of E-cadherin.

Objective To investigate the influence and significance of methylprednisolone(MP) on the genetic expression and distribution of peripheral blood mononuclear cells (PBMCs) IL-23 and IL-17 as well as Th17 and Treg in patients with ankylosing spondylitis (AS). Methods 30 patients in the active period of ASwere selected as study group and treated with short-term and high-dose MP. The treatment regimen was 2. 5-4 mg/kg, Qd, 3-4 d/course, 3-4 d interval and 2-3 courses. 30 healthy persons were selected as control group and given isometric normal saline by the same administration time and method. RT-PCRtest was used to assess the expression of PBMCs IL-23 P19 mRNAand IL17AmRNA, and FCMwas used to assess the cell distributions of PBMCs Th17 and Treg in control group and study group before and after treatment. Associations of them with clinical symptoms and indicators of disease activity were analyzed. Results 1. Cell distribution of Th17 and genetic expression of IL-23 and IL-17 in study group were higher than those in control group, and positively associated with BASDAI, hypnalgia, erythrocyte sedimentation rate(ESR) and CRP. Cell distribution of Treg in study group was lower than that in control group, and negatively associated with indicators mentioned above. 2. In study group, cell distribution of Th17, genetic expression of IL-23 and genetic expression of IL-17 were positively associated with each other, and the genetic expression of IL-23 and the cell distribution of Th17 were negatively associated with the cell distribution of Treg respectively. 3. In study group, BASDAI, BASFI, hypnalgia, ESRand CRPafter treatment were lower than those before treatment while cell distribution of Treg after treatment was higher than that before treatment. All the differences above were statistically significant. Conclusion The axis of IL-23/IL-17 and the unbalance of Th17/Treg could be involved in the attack and disease activity of AS. MPcould improve the clinical symptoms of ASand reduce the disease activity by inhibiting the secretion of proinflammatory factors IL-23 and IL-17, and correcting the unbalance of Th17/Treg.

Objective To explore the DNA expression of human cytomegalovirus (HCMV) in glioma and the association between HCMV infection and prognosis of glioma patients.Methods Used for this study were 89 specimens of glioma which had been surgically ablated and pathologically confirmed from the patients between January 2007 and December 2016 at Department of Neurosurgery,The First Affiliated Hospital of Zhengzhou University,and Department of Neurosurgery,The First Hospital of China Medical University.Of them,32 belonged to WHO grade Ⅱ,31 to WHO grade Ⅲ and 26 to WHO grade Ⅳ.Ten specimens of normal brain tissue were excised as controls from the contemporary patients receiving resection for essential epilepsy.Nested PCR was used to analyze the DNA expression of HCMV in the glioma tissue and normal brain tissue,and in the peripheral blood from the glioma and control patients.Prognosis of the glioma patients was evaluated using the Kaplan-Meier survival analysis.Results The DNA expression of HCMV was positive in 46 of the 89 specimens of glioma,involving 14 cases of WHO grade Ⅱ,16 ones of WHO grade Ⅲ and 16 ones of WHO grade Ⅳ.The DNA expression of HCMV was negative in all the 10 specimens of normal brain tissue.There was a significant difference in the DNA expression of HCMV between the glioma tissue and normal brain tissue (P=0.002).The HCMV DNA was measured in the peripheral blood from 26 glioma patients,involving 10 cases of WHO grade Ⅱ,8 ones of WHO grade Ⅲ and 8 ones of WHO grade Ⅳ.No HCMV DNA was detected in the peripheral blood from the 10 control patients.There was a significant difference between the brain glioma and control groups in gene expression of HCMV in peripheral blood (P=0.048).There were no significant differences in the survival rate between the patients with positive or negative DNA expression of HCMV in the glioma tissue or in the peripheral blood from the glioma and control patients (x2=1.849,P=0.174;x2=0.082,2=0.774).Conclusion HCMV infection may play an active role in pathogenesis and development of glioma.

Objective: To study the effect of berberine (BR) on ventricular remodeling in experimental rats with myocardial infarction (MI) and its mechanisms.
Methods: The MI model of experimental rats was established by ligation of the left anterior descending coronary artery and the MI animals were randomly divided into 3 groups: MI+BR group, in which the rats received BR 20 mg/kg.d, Sham group and MI group, the rats in those 2 groups received the same volume of normal saline. All animals were treated for 8 weeks. The cardiac function and structure were assessed by echocardiography, cardiac interstitial collagen deposition was evaluated by Masson stain, the myocardial cell apoptosis was detected by Tunel method, and the activation of nuclear factor (NF-κB) was also examined.
Results: For echocardiography, MI group had enlarged left ventricular end diastolic diameter (7.28 ± 0.29) mm than Sham group (6.86 ± 0.36) mm,P<0.05, but it decreased in MI+BR group (6.89 ± 0.99) mm,P>0.05. MI group had increased left ventricular end systolic diameter (5.88 ± 0.33) mm than Sham group (4.61 ± 0.31) mm, but it decreased in MI+BR group (4.68 ± 1.17) mm, allP< 0.01. MI group showed increased left ventricular posterior wall compensatory hypertrophy (1.81 ± 0.85) mm than Sham group (1.67 ± 0.16 mm),P<0.05, while in MI+BR group, it was deereased to (1.65 ± 0.14) mm. MI group presented decreased LVEF (45.77 ± 3.17) % than Sham group (67.28 ± 4.15) %, but it increased in MI+BR group (64.64 ± 5.82) %, allP<0.01. For Masson stain, cardiac interstitial collagen deposition in MI group (11.39 ± 0.45) % was higher than Sham group (2.65 ± 0.45) %, but less in MI+BR group (7.00 ± 0.87) %, allP<0.01. For Tunel examination, the myocardial cell apoptosis index was increased in MI group (21.31 ± 2.34) than Sham group (0.99 ± 0.38), but decreased in MI+BR group (14.15 ± 1.62), allP<0.01. For NF-κB activation study, the nuclear protein p65 content was higher in MI group (0.14 ± 0.02) ng/ml than Sham group (0.06 ± 0.01) ng/ml, but lower in MI+BR group (0.10 ± 0.02) ng/ml, allP<0.01.
Conclusion: Application of BR may improve the ventricular remodeling and cardiac function in experimental MI rats, it might be because of BR partially inhibit NF-κB activation, reduce collagen deposition and help anti-apoptosis in myocardial cells.

ObjectiveTo research the endothelial dysfunction and early changes in arterial elasticity in patients with hyperlipidemia and effects of atorvastatin on these changes.Methods40 patients with hyperlipidemia but without any treatment in our hospital were selected as a study group,and 30 healthy people were selected as control group.Use the Flow mediated dilation,FMD detection which bases on the echo-trackingtechnology,eTRACYING to evaluate the right brachial atherosclerosis parameters and vascular diastolic parameters,including the pressure strain elastic modulus(Ep) ;stiffness index (β) ;compliance (AC) ;FMDs and FMDd.The study group take atorvastatin 20mg per day,then retested above parameters and TC,LDL-C after 12 weeks and analyzed all parameters.ResultsThe values of β and Ep in study group are significantly higher than the control group (all P ＜ 0.001 ),but AC;FMDs and FMDd are significantly lower than the control group( all P ＜ 0.001 ).The results of the study group after the treatment of atorvastatin are as follwing:TC,LDL-C,β and Ep are lower than before,AC,FMDs and FMDd are higher than before;and the differences are of significance in statistics ( all P ＜ 0.001 ).ConclusionHyperlipidemic patients had shown the vascular endothelial injury and vascular early hardening before the abnormal changes in intimal,but the atorvastatin intervention could reverse these changes.

Objective To observe the effect of aspirin on phtelets activation markers in patients with coronary heart disease and set up a diagnostic criteria of aspirin resistance.To preliminarily predict the incidence of aspirin resistance in hospital patients.Methods The subjects were divided into 3 groups:aspirin group(103 cases),control group(24 eases),and healthy control group(23 cases).Using whole blood samples,we detected the ratio of CD62P,PAC-1 expression by flow cytometry(FCM)before and after 7-day treatment and compared the changes of CD62P and PAC-1 expression ratio,then calculated the inhibition ratio of platelets glycoprotein,set up the diagnostic criteria of aspirin resistance with receiver operator characteristic curve(SOC)and calculate the incidenee of aspirin resistance in hospital patients.Results The statisticsl reaults are listed as below:in asptirin group,before treatment CD62P(10.16±6.80)%,PAC-1(14.66±10.56)%,and after treatment CD62P(5.70±4.28)%,PAC-1(8.93±7.08)%,P＜0.01.In control group,before treatment CD62P(9.14±6.52)%,PAC-1(17.67±11.53)%,and after treatment CD62P(7.81±5.72)%,PAG-1(14.97±8.05)%,P＜0.05.According to ROC,the inhibition ratio of CD62P＜21.5% or PAG-1＜17.7% was individually set up asdiagnostic criteria of AR.Our study indicate that the incidence of aspirin resistance in hospital CHD patients is 17.5%.Conclusion There exists platelet activation in CHD patients.CD62P and PAC-1 could be considered as the sensitive index of platelet activation and used in the evaluation of anti-platelet therapy.Aspirin can decrease the expression of CD62P and PAC-1,and inhibit the activation of platelet.According to this study,aspirin resistance really exists in CHD patients.By FCM,the diagnostic criteria of aspirin resistance in CHD is the inhibition ratio of CD62P＜21.5% or PAC-1 ＜17,7% due to aspirin.The incidence of aspirin resistance in hospital CHD patients is 17.5%.

Objective To evaluate the protective effect and mechanism of luomaishutong(LMST)on acute myocardial ischemia-reperfusion injury in rabbits.Method Twenty-four New Zealand white rabbits were randomly divided into 3 groups:the LMST group,the control group and the sham-operated group.The AMI reperfusion model was established by removing the blockade after the occlusion of coronary artery for 2 hours.The changes of hemodynamics,oxygen free radical and clearance system were measured in all rabbits.Results (1)Compared with the control group,left ventricular systolic pressure(LVSP)and maximal changing rate of left ventricular innner pressure(?dp/dt_(max))increased remarkably in the LMST group after reperfusion,meanwhile, LVEDP decreased significantly.(2)In the control group,MDA level of cardiocyte was noticeably higher,while SOD and NOS levels were lower than in the sham-operated group.Compared with the control group,MDA level in the LMST group was significantly lower.Furthermore,SOD and NOS levels were higher in LMST group,and the infarcted area was smaller in the LMST group as well.Conclusions LMSF can protect myocardium after ischemia-repcrfusioninjury and improve cardiac function through inhibiting induced by oxygen free radicals.