Objective To analyze the adolescent tuberculosis reported in Haikou region between 2018 and 2021 and factors influencing the outcome. Methods The data on adolescent tuberculosis cases reported in Tuberculosis Information Management System in the Haikou Regional Centre for Disease Control and Prevention (RCDC) from 2018 to 2021 were collected. A follow-up survey was carried out until 31 December 2022. The changes in reported incidence of adolescent tuberculosis in Haikou was analyzed, and multivariate Cox proportional hazards regression models were used to identify independent factors influencing the outcome of adolescent tuberculosis. Results A total of 265 cases of tuberculosis in adolescents were reported between 2018 and 2021, of which 55 were reported in 2018, 74 in 2019, 67 in 2020, and 69 in 2021. The total number of reported cases of tuberculosis was 140 among male adolescents, which was slightly higher than 125 among female adolescents. The number of reported cases of tuberculosis was 134 in adolescents ≥15 years of age and 131 in adolescents <15 years of age. No statistically significant difference was reported between good outcome group and poor outcome group in age, gender, place of residence, nationality, and domicile place (P>0.05), whereas difference was found in the history of tuberculosis between two groups (P<0.05). Multivariate Cox proportional hazards regression model denoted that retreated tuberculosis (HR: 2.172, 95%CI: 1.483-3.007), complicating underlying disease (HR: 1.451, 95%CI: 1.080-1.985), and number of sputum smears (HR: 2.617, 95%CI: 1.531-3.458) were the risk factors for adverse outcomes in adolescent tuberculosis. Conclusion From 2018 to 2021, the number of reported adolescents of pulmonary tuberculosis in Haikou increased, suggesting that the management and prevention of adolescents should be strengthened to improve the prognosis rate of adolescents.

Objective·To explore the molecular regulatory mechanism of neural tube defect(NTD)induced by retinoic acid(RA)in mouse embryos,and reveal the gene expression regularity of neural tube closure in mice.Methods·Based on the high-quality brain vesicle transcriptome data of mouse embryo during the critical period of neural tube closure[embryonic day 8.5(E8.5),E9.5 and E10.5],the gene expression trend data of the NTD group and the control group were obtained by using Short Time-series Expression Miner(STEM)software.Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed for genes with different expression trends between the NTD group and the control group.Some candidate genes were screened for validation.Pregnant mice were divided into the NTD group and control group,with 9 mice in each group.Pregnant mice in the NTD group were treated with RA and those in the control group were treated with sesame oil by gavage at E7.5.Foetal rat brain vesicle tissues were collected at E8.5,E9.5 and E10.5 for experiments.Based on the above animal tissues,the screened candidate genes were validated by quantitative real-time PCR(RT-PCR).Results·A total of 18 255 genes were detected in the transcriptome data of the control group,and the expression patterns of these genes could be summarized into 7 significant profiles.A total of 19 037 gene expression data were detected in the transcriptome data of the NTD group,and gene expression patterns could be summarized into 6 profiles with significant significance.A total of 46 genes in the control group showed an upward trend but a downward trend in the NTD group.They were enriched in the positive and negative regulation of organ development,neuronal apoptosis,oligodendrocyte proliferation,and fibroblast growth factor signaling pathway at the biological process level.At the cellular component level,they were mainly involved in the basic structure of cells and neurons;At the molecular functional level,they were mainly related to the binding of fibroblast growth factor receptor.A total of 61 genes showed a downward trend in the control group but an upward trend in the NTD group.These genes were enriched in functions such as cell lysis and amino acid/ion transport at the biological process level.At the cellular component level,they were enriched in intracellular molecules,particles,extracellular region,intercellular space,etc.At the molecular function level,they were related to the activity of a series of enzymes and transporters.The results of RT-qPCR showed that the transcriptome sequencing data were authentic and reliable.Conclusion·RA intervention causes abnormal cellular activities and stress responses during mouse embryo development,leading to abnormal embryo development,activation of signalling pathways related to organismal self-protection,and suppression of genes that maintain normal embryo development.

Objective:To investigate the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumor (GIST) with initial surgical resection.Methods:The retro-spective cohort study was conducted. The clinicopathological data of 847 GIST patients who under-went initial surgical resection in Tianjin Medical University Cancer Institute & Hospital from January 2011 to December 2020 were collected. There were 405 males and 442 females, aged (60±10)years. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the nonparameter rank sum test. The Kaplan-Meier method was used to calculate survival rates. Univariate analysis was conducted using the Log-rank test. Multivariate analysis was conducted using the COX regression model. Results:(1) Clinicopatholo-gical characteristics. Of 847 patients, the tumor primary location was stomach in 585 cases, jejunum and ileum in 142 cases, duodenum in 76 cases, colorectum in 10 cases, esophagus in 3 cases, and extra-gastrointestinal in 31 cases. There were 13 cases with liver metastasis and 22 cases with abdominal metastasis. The tumor maximum diameter was (7±5)cm, and the number of nuclear divisions was 4(range, 0-60) cells/50 high-power field or 5 mm 2. According to risk classification of National Institutes of Health (NIH), 31 cases were of extremely low risk, 238 cases were of low risk, 213 cases were of moderate risk, 365 cases were of high risk. There were 839 of 847 patients positive for CD117, 788 cases positive for Dog-1, 710 cases positive for CD34, respectively. There were 272 cases with Ki-67 <5%, 214 cases with Ki-67 of 5%- 9%, 198 cases with Ki-67 ≥10%, 163 cases with missing data. R 0 resection was in 814 cases and non-R 0 resection was in 33 cases. (2) Gene testing and postoperative adjuvant therapy of GIST patients. ① Gene testing. Of 847 patients, 424 underwent genetic testing. The proportion of genetic testing was 1.89%(1/53) in 2011, 9.76%(8/82) in 2012, 8.45%(6/71) in 2013, 15.66%(13/83) in 2014, 50.00%(40/80) in 2015, 55.26%(42/76) in 2016, 73.86%(65/88) in 2017, 68.27%(71/104) in 2018, 80.65%(75/93) in 2019, 88.03%(103/117) in 2020, respectively. Of 424 with genetic testing, 338 cases had KIT mutation, 31 cases had PDGFRA mutation, 55 cases were wild type. ② Adjuvant therapy. Of 847 patients, 253 patients underwent postoperative adjuvant therapy. The proportions of postoperative adjuvant therapy were 8.82%(21/238), 41.78%(89/213), 39.18%(143/365) in patients of low risk, moderate risk, high risk. Of 578 patients with moderate to high risk, the proportion of postoperative adjuvant therapy was 15.15%(5/33) in 2011, 14.71%(10/68)in 2012, 22.45%(11/49) in 2013, 29.09%(16/55) in 2014, 41.38%(24/58) in 2015, 46.15%(24/52) in 2016, 32.81%(21/64)in 2017, 60.00%(45/75) in 2018, 60.42%(29/48) in 2019, 61.84%(47/76) in 2020, respectively. Of 253 patients underwent postoperative adjuvant therapy, 247 cases received imatinib had 6 cases received sunitinib. (3) Comparison of clinicopathological characteristics of GIST with non-gastric origin and gastric origin. Of 847 patients, 262 cases had non-gastric origin and 585 cases had gastric origin. There were significant differences in gender, the number of tumor, tumor maximum diameter, Ki-67 index, risk classification of NIH, and R 0 resection between the two groups ( χ2=8.62, 8.40, 12.97, 6.57, Z=-6.15, χ2=17.19, P<0.05). (4) Analysis of influencing factors for recurrence-free survival rate in GIST patients. Results of multivariate analysis showed that the year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classification of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy were independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection ( hazard ratio=0.58, 0.61, 2.00, 1.71, 5.81, 2.56, 0.65, 0.38, 95% confidence interval as 0.39-0.85, 0.45-0.83, 1.46-2.74, 1.24-2.35, 3.16-10.69, 1.63-4.02, 0.46-0.94, 0.25-0.56, P<0.05). Conclusions:GIST with initial surgical resection is common located in stomach, with high positive rate in CD117 and Dog-1. The number of people undergoing genetic testing and targeted therapy for GIST is increasing year by year. There are significant differ-ences in clinicopathological characteristics between GIST with non-gastric origin and gastric origin. The year of initial diagnosis, primary site, tumor maximum diameter, mitotic image, risk classifica-tion of NIH, R 0 resection, genetic testing and postoperative adjuvant therapy are independent factors influencing recurrence-free survival rate in GIST patients with initial surgical resection.

Objective To study the effect of recombinant human platelet activating factor acetylhydrolase (rPAF-AH) on candidate plasticity-related gene 15 (CPG15) expression in focal cerebral ischemia rats.Methods Forty-five SD rats were randomly divided into sham operation group,saline group and rPAF-AH group (15 in each group).A middle cerebral artery occlusion model of rats was established for the latter two groups.Each group was divided into 2 d group,7 d group,14 d group.Five rats in each of 2 d group,7 d group,14 d group were used in experiment.The total protein was extracted from coronary sections using homogenate.CPG15 protein expression was detected by Western blot.Results The CPG15 protein expression level was significantly higher in saline group and rPAF-AH group than in sham operation group on days 2,7,14 and reached its peak on day 7,and in rPAF-AH group than in saline group on day 7 (1.48±0.04 vs 1.12±0.05,P＜0.01).Conclusion PAF-AH plays a positive role in neuroplasticity of cerebral ischemia by upregulating the CPG-15 expression in focal cerebral ischemia rats.

OBJECTIVE To compare the effect of four 5-hydroxytryptamine type 4 (5-HT4) receptor agonists:cisapride,zacopride,macopride and 2-[1-(4-piperonyl) piperazinyl]-benzothiazole (BZTZ),on rat cardiac inward rectifier potassium channel (IK1)and heart rhythm.METHODS The whole-cell configuration of patch-clamp technique was used to record effects of 5-HT4 receptor agonists onIk1 in enzymatic dissociated rat ventricular myocytes or Kir2.1 transfected HEK 293 cells.Western blotting was used to observe the expression of Kir2.1 channel exposed 24 h to agents in ventricular myocytes.Langendorff-perfused hearts were perfused with four agents respectively for 30 min.The electrocardiogram was recorded simultaneously.RESULTS BZTZ,cisapride and mosapride 0.1-10 μmol· L-1 decreasedIk1 in a concentrationdependent manner.At the same concentration (1 μmol· L-1),BZTZ showed the most potent inhibition onIκ1 (P＜0.01),followed by cisapride.Mosapride showed slight inhibition efficiency.However,zacopride enhanced Iκ1 (P＜0.01).In Kir2.1 heterologous expression systems,zacopride activated Kir2.1 current (P＜0.01) while mosapride had no effect.In ex vivo Langendorff-perfused hearts,BZTZ and cisapride 1μmol· L-1 elicited singnificant rhythm disturbances,and the total of premature ventricular beats (PVB) were 159±28 and 61±13.50％ (4/8) (P＜0.05) and 25％ (1/8) of the hearts exhibited ventricular tachycardia (VT),while 37.5％ (3/8) and 12.5％ (1/8) of the hearts exhibited ventricular fibrillation (VF),respectively.Mosapride and zacopride had no side effects on heart rhythm.Zacopride also suppressed BZTZ-or cisapride-induced arrhythmias.BZFZ had the strongest proarryhthmic potency among the 5-HT4 agonists,followed by cisapride,mosapride and zacopride.CONCLUSION Iκ1 might be an independent risk factor for arrhythmogenesis and a new target for screening safe 5-HT4 receptor agonists and gastrointestinal prokinetic agents.

Aim To examine the influence of tetramethylpyrazine on learning and memory function of hypoxic hypoxia rats, and the expression of gamma aminobutyric acid(GABA) receptor and forkhead box P2(FOXP2) in hippocampus of rats.Methods A total of 120 Sprague Dawley rats were randomly divided into low hypoxic hypoxia and high hypoxic hypoxia groups, then according to different time points every group was divided into 1 d, 3 d, 7 d 15 d, 30 d group, with 12 rats per each group.Experiment group and the control group were treated with tetramethylpyrazine and 0.9% normal saline, respectively.The hypoxic hypoxia environment was achieved by putting the rats in a hypobaric chamber at a simulated altitude of 5 500 meters for different days.The capabilities of learning and memory of rats were detected by Morris water maze test.The expression of GABA receptor and FOXP2 protein in hippocampus of rat was determined by Western blot.Results ① Morris water maze test showed that the total distance of rats in the simulated hypobaric hypoxia control group was longer than that in the tetramethylpyrazine group(P<0.01) and the number of crossing the bestride platform increased compared with that in the hypobaric hypoxia control group(P<0.01) from the third day;② Western blot results showed that the expression of GABAAα1 receptor have no statistical significance(P>0.05);however,GABAB1 receptor and FOXP2 protein rose from the third day(P<0.05).The expression of GABAAα1 receptor and FOXP2 protein expression were correlated to total distance of Morris water maze in the control group(r=-0.738, P<0.05;r=-0.693, P<0.05), and the expression of GABAB1 receptor was correlated with FOXP2 protein level(r=0.834, P<0.05).Conclusion The simulated high-altitude hypobaric hypoxia can decrease the learning and memory abilities of rats, which may be ameliorated by tetramethylpyrazine intervention, and this effect might be related to the increase of GABAB1R receptor and FOXP2 expression in hippocampus of rats.

Objective: To evaluate the reliability and validity of warning signs checklist developed by the National Health and Family Planning Commission of the People′s Republic of China (NHFPC), so as to determine the screening effectiveness of warning signs on developmental problems of early childhood. Method: Stratified random sampling method was used to assess the reliability and validity of checklist of warning sign and 2 110 children 0 to 6 years of age(1 513 low-risk subjects and 597 high-risk subjects) were recruited from 11 provinces of China. The reliability evaluation for the warning signs included the test-retest reliability and interrater reliability. With the use of Age and Stage Questionnaire (ASQ) and Gesell Development Diagnosis Scale (GESELL) as the criterion scales, criterion validity was assessed by determining the correlation and consistency between the screening results of warning signs and the criterion scales. Result: In terms of the warning signs, the screening positive rates at different ages ranged from 10.8%(21/141) to 26.2%(51/137). The median (interquartile) testing time for each subject was 1(0.6) minute. Both the test-retest reliability and interrater reliability of warning signs reached 0.7 or above, indicating that the stability was good. In terms of validity assessment, there was remarkable consistency between ASQ and warning signs, with the Kappa value of 0.63. With the use of GESELL as criterion, it was determined that the sensitivity of warning signs in children with suspected developmental delay was 82.2%, and the specificity was 77.7%. The overall Youden index was 0.6. Conclusion The reliability and validity of warning signs checklist for screening early childhood developmental problems have met the basic requirements of psychological screening scales, with the characteristics of short testing time and easy operation. Thus, this warning signs checklist can be used for screening psychological and behavioral problems of early childhood, especially in community settings.

Objective To study on the effect of DNA vaccine, p(Aβ3-10) 10-mIL-4, immunization on behavior and brain Aβ deposition in APP/PS1 transgenic mice.Methods DNA vaccine p(Aβ3-10) 10-mIL-4 was constructed which expressed fusion protein of ten tandem repeats of Aβ3-10 and mouse IL-4.APP/PS1 transgenic mice were vaccinated with p (Aβ3-10) 10-mIL-4.Aβ42 peptide and pcDNA3.1 (+) were injected to the control groups.Anti-Aβ antibody titers were detected before and after vaccination by enzyme-linked immunosorbent assay (ELISA) ,the spatial learning and memory ability of the mice were evaluated by Morris water maze.The senile plaques in mouse brains were detected by immunohistochemistry.Results Compare with pcDNA3.1 (+) group,immunization with the vaccine p (Aβ3-10) 10-mIL-4 in APP/PS1 mice induced high-titer Anti-Aβ antibodies ((27.49±4.51) μg/ml, P＜0.01) ,decreased Aβ deposition (reduced senile plaque number in the cortex and hippocampus by 52.86％ and 58.29％ respectively, P＜0.01) and improved their cognitive ability.Conclusions The immunization with p(Aβ3-10)10-mIL-4 in APP/PS1 mice achieve an ideal effect of vaccination, and p(Aβ3-10) 10-mIL-4 can be an alternative Alzheimer's disease vaccine to further study.

BACKGROUND:For pediatric patients with aplastic anemia in China, it is difficult to find human leucocyte antigen-matched sibling donors that are mostly replaced by parental donors.
OBJECTIVE:To retrospectively analyze the clinical efficacy and safety of parental haploidentical peripheral blood hematopoietic stem cel transplantation in children with relapsed and refractory severe aplastic anemia.
METHODS:Seventeen children with relapsed and refractory severe aplastic anemia who had no matched sibling or unrelated donor and failed to respond to immunosuppressive therapy were subjected to parental haploidentical peripheral blood hematopoietic stem cel transplantation. A conditioning regimen of fludarabine+cyclophosphamide+rabbit anti-human thymocyte immunoglobulin antibody and the triple therapy of methotrexate, cyclosporine A and mycophenolate mofetil were applied to prevent graft-versus-host disease.
RESULTS AND CONCLUSION: (1) Of the 17 children, 16 cases (94%) reached hematopoietic reconstitution, and the median time of neutrophils≥ 0.5×109/L and platelets≥ 20×109/L was 13 (11-15) days and 17 (12-28) days, respectively. (2) Incidence of acute graft-versus-host disease was 47% (8 of 17 cases), including 29% (5/17) of grades I-II and 18% (3/17) of grades III-IV. Incidence of chronic graft-versus-host disease was 41% (7/17). (3) With a median folow-up duration of 268 (43-753) days, the overal survival rate was 70.6% (12/17). Five dead cases (29%) belonged to transplantation-related death, including one case of fungal skin infections, one case of graft-versus-host disease, three cases of severe lung infection. No relapse case was reported. These findings indicate that if there are no matched sibling or unrelated donors and the immunosuppression effect is poor, parental haploidentical peripheral blood hematopoietic stem cel transplantation is a safe and effective salvage treatment for children with relapsed and refractory severe aplastic anemia.

Objective To investigate the effects of a highly selective dopamine D4 receptor (ABT-724)on behaviors in Spontaneously hypertensive rats (SHR),a rat model of attention-deficit hyperactivity disorder (ADHD).Methods After intervention of methylphenidate(5mg/kg) and three different doses of ABT-724(0.04mg/kg,0.16mg/kg,0.64mg/kg),behaviors of SHR were verified by open-field test,Morris water maze and Làt maze.Results Number of square crossing after intervention of methylphenidate and ABT-724 in SHR( 70.67 ± 8.59,76.50 ± 10.75,79.17 ± 10.44,65.67 ± 20.62) was less than the saline control group( 130.33 ± 1 1.40) (P＜0.05).During Morris water maze,SHRs(52.50 ± 4.04,52.17 ± 2.99,61 ± 8.15,53.83 ± 9.87 ) after intervention of both had a better spatial memory ability than control group(38.83 ±7.17) (P＜0.05).In Làt maze,number of rearing after intervention of both in SHRs(57.17 ± 5.67,60.83 ± 8.28,55.17 ± 9.45,65.33 ± 9.50 ) was less than saline control group(78.00 ± 13.84) (P＜0.05).Conclusion ABT-724 could improve behaviors of spontaneous locomotor activity,cognitive ability,non-selective attention in SHR.