Objective To investigate the expression of histone deacetylase(HDAC)isoforms in the frontal lobe,hippo-campus and liver of offspring rats delivered by rats with maternal immune activation and their correlation with the efficiency of prepulse inhibition(PPI％).Methods Ten pregnant Sprague-Dawley rats were randomly divided into the model group(n=5)and control group(n=5).The rats in the model group were injected with 10 mg·kg-1 polyinosinic-polycytidylic acid(Poly I:C)via the caudal vein on the 9th day of pregnancy,while rats in the control group were given the same volume of sterile physiological saline.After 3 h,blood was collected from the caudal vein,and the levels of interleukin(IL)-1 β,IL-6 and tumor necrosis factor-α(TNF-α)in the plasma of pregnant rats were detected by enzyme-linked immunosorbent assay to evaluate the immune activation status.The pregnant rats in the two groups were fed until natural delivery,the offspring rats were weaned on the 21st day after birth,and the male offspring rats were fed continuously.A prepulse inhibition test was performed at puberty(the 40th day after birth)to evaluate the spatial recognition memory and sensory gating function of the offspring rats.The expression levels of the HDAC gene family in the hippocampus,frontal lobe and liver of offspring rats were detected by real-time fluorescence quantitative polymerase chain reaction.Results The plasma IL-6,IL-1 β and TNF-α levels in the model group were significantly higher than those in the control group(P＜0.05).When the prepulse stimulation was 75 dB,the PPI％of the offspring rats at puberty in the model group was significantly lower than that in the control group(P＜0.05).When the prepulse stimulation was 80 and 85 dB,there was no significant difference in PPI％between the model group and the control group(P＞0.05).In the frontal lobe,the expression levels of HDAC3,HDAC4,HDAC8,HDAC9,HDAC10 and Sirt mRNA in the offspring rats in the model group were significantly lower than those in the control group(P＜0.05),while the expression level of HDAC5 mRNA was significantly higher than that in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC6,HDAC7 and HDAC11 mRNA between the model group and the control group(P＞0.05).In the hippocampus,the offspring rats in the model group had significantly lower expression levels of HDAC1,HDAC8 and HDAC10 mRNA and significantly higher expression levels of HDAC2 and HDAC5 mRNA than those in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC3,HDAC4,HDAC6,HDAC7,HDAC9,HDAC11 and Sirt mRNA between the model group and control group(P＞0.05).In the liver tissue,the expression levels of HDAC6 and HDAC10 mRNA of the offspring rats in the model group were significantly lower than those in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC3,HDAC4,HDAC5,HDAC7,HDAC8,HDAC9,HDAC11 and Sirt mRNA between the model group and the control group(P＞0.05).The expression level of HDAC2 mRNA in the hippocampus of offspring rats in the two groups was negatively correlated with PPI％at 75 dB(r=-0.965,P＜0.05),the expression levels of HDAC10 and Sirt mRNA in frontal lobe tissues were positively correlated with PPI％at 75dB(r=0.946,0.925;P＜0.05).Conclusion Pregnancy Poly I:C infection has significant effects on the expression of HDAC family proteins in offspring rats,and which is related to the impairment of early sensory gating,this may provide new ideas for the research in pathogenesis and drug treatment of schizophrenia.

【Objective】 To evaluate the efficacy of sacral neuromodulation (SNM) in the treatment of neurogenic bladder (NB) with Meta-analysis, so as to provide reference for clinical treatment options for NB. 【Methods】 Relevant literatures regarding the efficacy of SNM in treating NB during Jan.2010 and Dec.2022 were collected from the PubMed and CNKI databases, and screened with inclusion and exclusion criteria.After the quality of literatures was assessed, data were extracted and then analyzed using Review Manager 5.3. 【Results】 The research included 14 studies involving 601 patients.Meta-analysis showed that SNM significantly improved urinary frequency (WMD=4.30, 95%CI: 2.84-5.77, P<0.01), daily episodes of urinary incontinence (WMD=2.92, 95%CI: 2.76-3.07, P<0.01), single void volume (WMD=-113.93, 95%CI: -159.91- -67.98, P<0.01), maximum flow rate (WMD=-3.23, 95%CI: -4.04- -2.42, P<0.01), residual urine (WMD=111.79, 95%CI: 79.93-143.64, P<0.01), maximum bladder capacity (WMD=-65.63, 95%CI: -84.38- -46.88, P<0.01), and bladder compliance (WMD=-4.65, 95%CI: -8.75- -0.55, P=0.03). 【Conclusion】 SNM is effective in the treatment of NB, but more randomized controlled trials are needed to verify the efficacy.

Objective To explore the correlation between functional striatal abnormalities(FSA)scores and symptoms and cognitive function in patients with schizophrenia.Methods A total of 92 patients with schizophrenia admitted to the Second Affiliated Hospital of Xinxiang Medical University from July 2021 to February 2022 were selected as the research subjects,15 patients were excluded due to excessive interference with head movement during image data analysis,and 77 patients were finally included in the statistical analysis.The cognitive function of the patients before treatment and after 8 weeks of treatment was evaluated through a set of cognitive function tests.The severity of symptoms before treatment and after 8 weeks of treatment was evaluated according to the positive and negative symptom scale(PANSS).The patients were divided into the ineffective group(PANSS＜50％,n=33)and the effective group(PANSS ≥ 50％,n=44)according to the PANSS reduction rate.Before treatment and 8 weeks after treatment,the resting-state functional magnetic resonance imaging scans were performed,and FSA scores were calculated.Results There was no significant difference in FSA scores of patients between the effective group and the ineffective group before treatment(P＞0.05).After 8 weeks of treatment,the FSA scores of patients in the two groups were significantly higher than those before treatment(P＜0.05).After 8 weeks of treatment,there was no significant difference in FSA scores of patients between the effective group and the ineffective group(P＞0.05).Before treatment and after 8 weeks of treatment,there was no significant correlation between the FSA scores and the total PANSS scores,positive factor scores,negative factor scores and pathological factor scores in the two groups(P＞0.05).There was no significant corre-lation between the pre-treatment FSA scores and the differences in positive factor scores,negative factor scores and pathological factor scores before and after treatment in both groups(P＞0.05).In the effective group,the FSA score was significantly nega-tively correlated with the spatial span score(P＜0.05)and significantly positively correlated with the category fluency score(P＜0.05)before treatment;however,there was no significant correlation between the pre-treatment FSA score and the scores of trail making,symbol coding,word learning,maze solving,visuospatial memory,2-digit continuous performance,3-digit continuous performance and 4-digit continuous performance(P＞0.05).In the ineffective group,there was a significant negative correlation between the pre-treatment FSA score and the spatial span and 4-digit continuous performance scores(P＜0.05),while there was no significant correlation between the pre-treatment FSA score and the scores of trail making,symbol coding,word learning,maze solving,visuospatial memory,category fluency,2-digit continuous performance and 3-digit continuous performance(P＞0.05).There was no significant correlation between the FSA score and cognitive function scores after treat-ment in the effective group(P＞0.05).There was a significant positive correlation between the FSA score and the trail making score after treatment in the ineffective group(P＜0.05),but there was no significant correlation between the FSA score and the scores of symbol coding,word learning,spatial span,maze solving,visuospatial memory,category fluency,2-digit continuous performance,3-digit continuous performance and 4-digit continuous performance(P＞0.05).Conclusion FSA scores in patients with schizophrenia increase significantly after treatment.FSA scores may not be related to the severity of symptoms or treatment response,but are correlated with the cognitive function of information processing speed.

Objective:To investigate the auxiliary diagnostic value of serum midkine (MK) and thyroid stimulating hormone (TSH) for differentiated thyroid cancer (DTC).Methods:Seventy-one postoperative DTC patients (DTC group) treated with 131I were selected, and 143 patients with benign thyroid lesions (benign thyroid disease group) treated with surgery in Center Hospital of Xiaogan from March 2019 to December 2020 at the same period were also selected. Clinical data such as liver and kidney function indexes, positive rate of anti thyroglobulin antibodies (TGAb) and positive rate of thyroid peroxidase antibody (TPOAb) were collected before treatment, and their fasting blood samples were collected before treatment. Fully automated electrochemiluminescence immunoassay was used to measure free thyroxine (FT 4), free triiodothyronine (FT 3), TSH levels in patients′ serum. The serum MK levels were measured by enzyme-linked immunosorbent assay (ELISA). Binary Logistic regression model was used to screen for independent risk factors for the development of DTC. A receiver operating characteristic curve (ROC) was drawn to evaluate the efficacy of MK, TSH and MK combined with TSH, in aiding the diagnosis of DTC and its staging. Results:Serum TSH and MK levels in DTC group were higher than those in benign thyroid disease group: (3.55 ± 0.61) mU/L vs. (2.97 ± 0.46) mU/L, (394.25 ± 63.36) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). Elevated serum TSH and MK levels were independent risk factors for DTC. When MK combined with TSH was used to diagnose DTC, the area under the curve (AUC), sensitivity and specificity were higher than those of MK and TSH alone (0.925 vs. 0.859 and 0.783, 83.10% vs. 78.87% and 73.24%, 89.51% vs. 85.31% and 79.02%), and the differences were statistically significant ( P<0.05). Serum TSH and MK levels in stage Ⅲ and Ⅳ patients in DTC group were higher than those in stage Ⅰ and Ⅱ patients: (3.79 ± 0.65) mU/L vs. (3.42 ± 0.56) mU/L, (427.88 ± 52.73) ng/L vs. (311.45 ± 42.66) ng/L, and the differences were statistically significant ( P<0.05). The AUC, sensitivity and specificity of MK combined with TSH in the diagnosis of different stages of DTC were higher than those of MK and TSH alone (0.822 vs. 0.657 and 0.666, 73.90% vs. 56.52% and 56.52%, 83.33% vs. 77.08% and 79.17%), and the differences were statistically significant ( P<0.05). Conclusions:Serum TSH and MK levels are independent risk factors for the occurrence of DTC in patients, and the combination of them has certain auxiliary diagnostic value for the identification and staging of DTC.

Objective:A case-control association analysis was performed to investigate if the single nucleotide polymorphisms (SNPs) of N-cadherin(CDH2) gene is implicated in schizophrenia in a Han Chinese population.Methods:A total of 528 patients with paranoid schizophrenia and 528 healthy controls were recruited from northern Henan province to analyze 25 SNPs located in CDH2 gene.The clinical symptoms of 267 first-episode schizophrenia patients were evaluated with positive and negative syndrome scale (PANSS), and the correlation between CDH2 gene and clinical symptoms was analyzed by SNPStats software online.Results:Allele frequencies of rs9951577 and rs1231268 were significantly correlated with schizophrenia( P<0.05), genotype frequency of rs1639387 was significantly correlated with schizophrenia( P=0.044). After gender classification, SNPs rs1789470 and rs28365328 were found to be significantly correlated with schizophrenia in female patients ( P=0.044, 0.019). In addition, the study found that CDH2 was correlated with the clinical characteristics of schizophrenia( P<0.05), and the negative factor score of patients between GG type rs1231268 and the other two genotypes (AG+ AA) ((21.12±8.41) vs (18.87±7.52)) was statistically significant ( P<0.05). Conclusion:CDH2 gene may be one of the susceptibility genes to SZ, and has definite correlation with clinical negative symptoms.

Objective:To explore the identification value of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), cytokeratin 19 fragment (Cyfra211), thyroglobulin (TG), ferritin (Fer) and procalcitonin (PCT) in fine needle aspiration eluent in benign and malignant cervical nodules, and acquire the optimal diagnostic model.Methods:Three hundred and ninety-six single cervical nodule patients who underwent fine needle aspiration biopsy from August 2017 to August 2019 in the Center Hospital of Xiaogan City of Hubei Province were selected. The fine needle aspiration eluent levels of CEA, SCC-Ag, Cyfra211, TG, Fer and PCT were detected by electrogenerated chemiluminescence method. The results of cytopathological diagnosis were regard as "gold standard", and the diagnostic efficiency of single and combined indexes in fine needle aspiration eluent were analyzed by receiver operating characteristic (ROC) curve.Results:Among the 396 patients, malignant nodules was in 101 cases, and benign nodules was in 295 cases. The fine needle aspiration eluent levels of CEA, SCC-Ag, Cyfra211, TG and Fer in patients with malignant nodules were significantly higher than those in patients with benign nodules: (27.73 ± 10.63) μg/L vs. (16.81 ± 8.18) μg/L, (1.59 ± 0.74) μg/L vs. (1.09 ± 0.83) μg/L, (3.31 ± 1.48) μg/L vs. (1.66 ± 0.59) μg/L, (144.96 ± 38.93) μg/L vs. (95.03 ± 47.23) μg/L and (191.18 ± 80.13) μg/L vs. (137.87 ± 63.22) μg/L, the PCT was significantly lower than that in patients with benign nodules: (0.61 ± 0.24) μg/L vs. (1.01 ± 0.52) μg/L, and there were statistical differences ( P<0.01). The ROC curve analysis result showed that the CEA, Cyfra211 and TG had super diagnostic value (area under curve>0.7, Youden index>0.5); the area under curve of CEA, Cyfra211 combined with TG was significantly higher than other combined detection of 2 indexes ( P<0.05). Conclusions:The combined detection of CEA, Cyfra211 and TG in fine needle aspiration eluent can effectively distinguish the benign and malignant cervical nodules.

OBJECTIVE：To identify and evaluate the risk factors of innovative drug clinical trials ，and to provide references for the development of risk management and control strategies. METHODS ：Using the method of literature research ，the risk factors of innovative drug clinical trials were obtained ，classified and sorted out ，and the risk evaluation indicators were initially formed. On this basis ，the questionnaire was designed. By means of interview and questionnaire survey ，54 experts were invited from 4 tertiary hospitals and 1 contract research organization to score. SPSS 24.0 software was used to perform principal component analysis on risk event status data. RESULTS & CONCLUSIONS ：The risk evaluation system included 9 first-class indicators such as policy and legal risk ，clinical trial institution risk and trial scheme design risk ，and 31 second-class indicators such as industrial policy，law and regulation changes ，intellectual property risk . According to the analysis ，the risk factors of innovative drug clinical trials mainly included drug and biological sample management risk ，trial scheme design risk ，clinical trial institution risk ，safety report management risk ，ethical review risk ，policy and legal risk ，and subject management risk. Relevant parties in clinical trials need to focus on monitoring various risk factors ，establish dynamic monitoring and control mechanism and implementation guarantee mechanism ，and effectively prevent and control risk ，to promote the smooth implementation of clinical trials.

Intensive care unit (ICU) in teaching hospital plays important roles in teaching work. The young teachers of critical care medicine are gradually becoming the backbone of teaching work. Improving the teaching ability of young teachers is essential to increase learning motivation of the students and to promote the overall teaching quality of critical care medicine. Therefore, pay attention to help the young teachers of critical care medicine to improve their teaching skill is good for enhancing the faculty developing of critical care medicine, as well as essential for the prosperity and sustainable development of critical care medicine. Based on the problems existing during the teaching process of young teachers of critical care medicine and aimed to train excellent teachers, this article discussed the teaching methods and experience of young teachers of critical care medicine which focuses on teaching program design, class affinity improvement and humanistic education in order to improve the teaching level of young teachers of critical care medicine.

Objective To evaluate the clinical efficacy of different combinations with "Shugan Jianpi" acupuncture and Yintang acupoint magnetic stimulation in the treatment of depression with liver depression and spleen deficiency type.Methods 160 patients with depression treated in hospital from December 2013 to June 2017 were divided into 4 groups according to the random number table,with 40 cases in each group.Group A received basic drug therapy," Shugan Jianpi" acupuncture combined with Yintang acupoint magnetic stimulation,group B received basic drug therapy combined with Yintang acupoint magnetic stimulation,group C received basic drug therapy combined with " Shugan Jianpi" acupuncture treatment,group D was treated with basic medicine only for 4 weeks.Hamilton Depression Scale (HAMD) was used to assess the short-term and long-term efficacy for 4 groups before treatment,after 2 weeks of treatment,after 4 weeks and 2 months after treatment and the safety of these 4 types of therapy was evaluated with the side effects scale (TESS).2 months after the treatment,the quality of life universal scale (SF-36) was evaluated for patients in 4 groups.Results After 2 weeks,4 weeks and 2 months of treatment,HAMD scores in the 4 groups were significantly lower than those before treatment (P＜0.05).After 2 weeks of treatment,HAMD score of A group was (15.28±3.45),and HAMD score of B,C,D group were ((18.30±3.57),(22.50±3.71),(27.30±4.82)) respectively.HAMD score of A group was significantly lower than those of B,C,D group (P＜0.05).After 4 weeks of treatment,HAMD scores in A,B group were significantly lower than those in C,D group (P ＜0.05).After 2 months of treatment,HAMD scores in all the 4 groups were further declined compared with those after 4 weeks of treatment (P＜ 0.05),however,there was no significant difference between the four groups (P＞0.05).The scores of each dimension of SF-36 in group A were significantly higher than those of group B,C and D (P＜0.05),and which in group B and C were significantly higher than those in D group after 2 months of treatment.(P＜0.05).There was no statistical difference among the 4 groups in TESS scores (P ＞0.05).Conclusion The results suggest that there is a synergistic effect in combination of the " ShuganJianpi" acupuncture combined with Yintang acupoint magnetic stimulation in the treatment of depression of liver qi stagnation and spleen deficiency type,and it can effectively reduce the degree and improve their quality of life in patients with depression.

OBJECTIVETo summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors.

METHODSClinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008. Kaplan-Meier method was used to calculate the survival rate. Log-rank test and Cox regression model were used for univariate and multivariate prognostic analyses.

RESULTSAmong 1 165 cases of gastric GIST, 557 were male and 608 were female. The median age of onset was 60 (range 15-89) years. Primary tumors were located in the gastric fundus and cardia in 623 cases(53.5%), gastric body in 346 cases(29.7%), gastric antrum in 196 cases(16.8%). All the cases underwent resection of tumors, including endoscopic resection (n=106), local resection (n=589), subtotal gastrectomy(n=399), and total gastrectomy(n=72). Based on the NIH risk stratification, there were 256 cases (22.0%) at very low risk, 435 (37.3%) at low risk, 251 cases (21.5%) at intermediate risk, and 223 cases (19.1%) at high risk. A total of 1 116 cases(95.8%) were followed up and the median follow-up period was 40 (range, 1-60) months. During the period, 337 patients relapsed and the median time to recurrence was 34 (range 1-60) months. The 1-, 3-, and 5-year survival rates were 98.6%, 86.1% and 73.4%, respectively. The 5-year survival rates of patients at very low, low, intermediate, and high risk were 93.1%, 85.8%, 63.0% and 42.3% respectively, with a statistically significant difference (P=0.000). Multivariate analysis showed that primary tumor site (RR=0.580, 95%CI:0.402-0.835), tumor size (RR=0.450, 95%CI:0.266-0.760), intraoperative tumor rupture(RR=0.557, 95%CI:0.336-0.924), risk classification (RR=0.309, 95%CI:0.164-0.580) and the use of imatinib after surgery (RR=1.993, 95%CI:1.350-2.922) were independent prognostic factors.

CONCLUSIONSThe choice of surgical procedure for gastric GIST patients should be based on tumor size. All the routine procedures including endoscopic resection, local excision, subtotal gastrectomy and total gastrectomy can obtain satisfactory curative outcomes. NIH classification has a high value for the prediction of prognosis. Primary tumor site, tumor size, intraoperative tumor rupture, risk stratification and postoperative use of imatinib are independent prognostic factors in gastric GIST patients.