Objective:This study aims to investigate sex-specific abnormalities?? in gray matter volume (GMV) in Children with autism spectrum disorder (ASD) and their associations with gene expression.Methods:T 1-weighted brain MRI data were collected at the MRI Center of the University of Electronic Science and Technology of China between 2022 and 2023 from 100 children with ASD and 90 typically developing (TD) children. Voxel-based morphometry (VBM) was used to explore GMV differences between ASD boys and TD boys, and between ASD girls and TD girls. Partial least squares regression (PLSR) was performed based on the Allen Human Brain Atlas to identify genes associated with GMV alterations, followed by enrichment analyses. Cell-type-specific expression analyses were used to examine associations across developmental stages and brain structures. Protein-protein interaction (PPI) networks were constructed to identify hub proteins. Results:Compared to TD boys, ASD boys showed increased GMV in the right superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, temporal pole, parahippocampal gyrus, fusiform gyrus, cuneus, and precuneus, as well as in the bilateral orbital part of the superior frontal gyrus and the gyrus rectus. Decreased GMV was observed in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 635 genes were associated with these GMV alterations, enriched in pathways related to DNA-templated transcription, RNA metabolism and biogenesis, and ion binding. Developmental analysis indicated strong associations with the cerebellum during early, middle-to-late childhood, and adolescence, and with the cerebral cortex in early adulthood. Protein-protein interaction (PPI) network analysis highlighted NOB1, GNL3L, ESF1, TFB2M, and WDR75 as specific hub proteins. Compared to TD girls, ASD girls exhibited increased GMV in the right middle and inferior temporal gyri, temporal pole, and fusiform gyrus, and decreased GMV in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 765 genes were associated, enriched in pathways related to ion channel activity, signal transduction, and regulation of membrane potential. These genes showed strong associations with the amygdala during mid-to-late fetal development, middle-to-late childhood, adolescence, and early adulthood; with the cerebellum during late infancy, early childhood, and early adulthood; with the cerebral cortex during the mid-to-late fetal development, early neonatal period, and adolescence; with the hippocampus during middle-to-late childhood and adolescence; with the striatum during adolescence and early adulthood; and with the thalamus during early-to-mid fetal development, early neonatal period, and early adulthood. PPI network analysis identified ANK3, ANK1, SCN4B, NFKB1, and PXN as specific hub proteins. Conclusion:Both ASD boys and ASD girls exhibit GMV abnormalities compared with TD controls. The specific genes associated with GMV alterations are enriched in distinct biological pathways in boys and girls. Cell-type-specific expression analyses further revealed sex-dependent differences in developmental timing and brain structural correlations, and distinct PPI networks were constructed for each group.

Objective:This study aims to investigate sex-specific abnormalities?? in gray matter volume (GMV) in Children with autism spectrum disorder (ASD) and their associations with gene expression.Methods:T 1-weighted brain MRI data were collected at the MRI Center of the University of Electronic Science and Technology of China between 2022 and 2023 from 100 children with ASD and 90 typically developing (TD) children. Voxel-based morphometry (VBM) was used to explore GMV differences between ASD boys and TD boys, and between ASD girls and TD girls. Partial least squares regression (PLSR) was performed based on the Allen Human Brain Atlas to identify genes associated with GMV alterations, followed by enrichment analyses. Cell-type-specific expression analyses were used to examine associations across developmental stages and brain structures. Protein-protein interaction (PPI) networks were constructed to identify hub proteins. Results:Compared to TD boys, ASD boys showed increased GMV in the right superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, temporal pole, parahippocampal gyrus, fusiform gyrus, cuneus, and precuneus, as well as in the bilateral orbital part of the superior frontal gyrus and the gyrus rectus. Decreased GMV was observed in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 635 genes were associated with these GMV alterations, enriched in pathways related to DNA-templated transcription, RNA metabolism and biogenesis, and ion binding. Developmental analysis indicated strong associations with the cerebellum during early, middle-to-late childhood, and adolescence, and with the cerebral cortex in early adulthood. Protein-protein interaction (PPI) network analysis highlighted NOB1, GNL3L, ESF1, TFB2M, and WDR75 as specific hub proteins. Compared to TD girls, ASD girls exhibited increased GMV in the right middle and inferior temporal gyri, temporal pole, and fusiform gyrus, and decreased GMV in the cerebellar vermis and bilateral cerebellar hemispheres. A total of 765 genes were associated, enriched in pathways related to ion channel activity, signal transduction, and regulation of membrane potential. These genes showed strong associations with the amygdala during mid-to-late fetal development, middle-to-late childhood, adolescence, and early adulthood; with the cerebellum during late infancy, early childhood, and early adulthood; with the cerebral cortex during the mid-to-late fetal development, early neonatal period, and adolescence; with the hippocampus during middle-to-late childhood and adolescence; with the striatum during adolescence and early adulthood; and with the thalamus during early-to-mid fetal development, early neonatal period, and early adulthood. PPI network analysis identified ANK3, ANK1, SCN4B, NFKB1, and PXN as specific hub proteins. Conclusion:Both ASD boys and ASD girls exhibit GMV abnormalities compared with TD controls. The specific genes associated with GMV alterations are enriched in distinct biological pathways in boys and girls. Cell-type-specific expression analyses further revealed sex-dependent differences in developmental timing and brain structural correlations, and distinct PPI networks were constructed for each group.

Objective To investigate the causes of false-positive rifampicin resistant results in Xpert MTB/RIF (Xpert) test for samples with extremely low bacterial loads. Methods A total of 346 samples with extremely low bacterial loads and rifampicin-resistance results from Wuhan Pulmonary Hospital between June 2017 and March 2021 were collected. The samples were divided into probe-delayed and probe dropout groups based on amplification results. Mycobacterial culture and proportion method drug susceptibility testing were performed, and Xpert retesting was conducted for strains with discordant drug susceptibility results. Results Out of the 346 samples, 195 samples (56.36%) were positive in culture. Upon Xpert retesting, among the 64 Xpert-resistant but proportion method-sensitive strains, the proportions of samples in the delayed probe group with mutations in the probe D and probe E were 4.55%（1/22） and 13.33%（2/15）, respectively. In the probe dropout group, the proportions of samples with mutations in the probe A and probe E were 75.00% (9/12) and 80.00% (8/10), respectively. The false-positive rifampicin resistance rates in the delayed probe and probe dropout groups were 78.26% (36/46) and 3.36% (5/149), respectively. Conclusion The main reasons for false-positive rifampicin resistance results in the Xpert test for samples with extremely low bacterial loads were probe delay in the D and E probes, followed by low-level drug-resistant mutations in the A and E probes.

Objective To analyze the effect of luteinizing hormone (LH) change amplitude in follicular phase on ovarian response and pregnancy outcome after fresh embryo transfer cycle in infertility patients with normal ovarian function during controlled ovarian hyperstimulation (COH) with antagonist protocol. Methods A total of 277 infertility patients who underwent in vitro fertilization and embryo transfer (IVF-ET) in the Center for Reproductive Medicine of this hospital from January 2019 to December 2021 were se-lected.Patients were divided into the high LH group (n=91),medium LH group (n=93) and low LH group (n=93) according to the tertiles of changes between LH level on the fourth day of COH and basal LH level before COH administration.The basic clinical features,use of exogenous gonadotropin (Gn) during COH, hormone levels at different periods,indexes of ovarian response,laboratory outcomes and pregnancy outcomes during fresh embryo transfer cycle were compared among all groups.Results There was no significant differ-ence in age,infertility duration,infertility types,basal follicle stimulating hormone (FSH),estradiol and tes-tosterone levels among the three groups (P>0.05).The duration of use of Gn in the high LH group was the shortest,the total amount and initiation dose of Gn was the smallest,and the estradiol level,ovarian sensitivity index (OSI),numbers of oocytes,metaphase Ⅱ(MII) oocytes,diprokaryotic fertilization,embryo formation and high-quality embryos were the highest after exogenous Gn stimulation,and the differences were statisti-cally significant compared with the other two groups (P<0.016).There was no significant difference in the clinical pregnancy rate,biochemical pregnancy rate and early miscarriage rate during fresh embryo transfer cy-cle among the three groups (P>0.05).Conclusion The infertility patients with normal ovarian function who have a large decrease in LH level during COH with antagonist protocol can obtain better embryo quantity and quality,but there was no effect on the pregnancy outcome during fresh embryo transfer cycle.

Objective: To study the effect of the inhibitor of Notch signaling pathway-γ-secretase inhibitor DAPT on the ultrastructures of middle ear in the ovalbumin (OVA)-mediated allergic OME in vivo. Methods: Male Sprague-Dawley (SD) rats, weighing 250-300 g, were completely and randomly divided into three groups (5 rats, 10 ears in each group):(1)Control group(2)OME group(3)OME+DAPT group. Rats in the OME group underwent systemic and local sensitization by intraperitoneal and intratympanic injection of ovalbumin to make the model of OVA-induced OME. Rats in the control group were sensitized with PBS. On the basis of establishing the OME model, OME+DAPT group were intraperitoneal injected with DAPT (10 mg/kg) for seven consecutive days and were administered before intratympanic injection of ovalbumin. After the model was successfully established, endoscopy,H&E staining and scanning electron microscopy were used to study the histology and mucous-ciliary ultrastructures of the non-ciliated and ciliated mucosa in the middle ear of each group. One-way ANOVA and Tukey methods were used for statistical analysis. Results: H&E staining showed that the three groups had statistically significant differences in submucosal thickness both in non-ciliated and ciliated regions (non-ciliated area:(6.83±1.47)μm, (38.58±9.57)μm, (32.17±11.89)μm, respectively. F=107.9;cilia area:(26.69±3.22)μm, (30.41±6.75)μm, (26.76±4.06)μm, respectively. F=5.62,both P<0.01). The thickness of the submucosa in the non-ciliated area and the cilia area of the OME group were significantly thicker than that of control group (F=42.08 and 4.40,both P<0.05); the thickness of the non-ciliated area and the ciliated area in OME+DAPT group were reduced compared to OME group(F=1.55 and 2.77,both P<0.05). Scanning electron microscopy showed that the array of cilia on the middle ear mucosa was disorderly arranged and inversed, this phenomenon was relieved in the OME+DAPT group. The number of goblet cells in the control group, OME group, and OME+DAPT group were 9.87±1.92; 15.67±5.77; 10.33±1.99 respectively and the difference between them was statistically significant (F=11.43, P<0.01). The number of goblet cells in the OME group were significantly higher than those in the control group (F=9.00,P<0.01) and the number of goblet cells in the OME+DAPT group were decreased compared to those of OME group (F=8.41, P<0.01). Conclusions: The study demonstrates the pathological changes of the ultrastructure in middle ear in OVA-induced OME and the effect of the γ-secretase inhibitor on it. In OME group, the cilia are disorderly arranged and inversed, the number of goblet cell is increased and they are swelled which suggest the hypersecretion of the mucus. DAPT can regulate OVA-induced allergic inflammation and relieve pathological changes of ultrastructure in middle ear mucociliary transport system through alleviating submucosal inflammation, reducing the hypersecretion of goblet cell and the morphological damage of cilia through the Notch signaling pathway.
Amyloid Precursor Protein Secretases ; Animals ; Ear, Middle ; Male ; Otitis Media with Effusion/drug therapy* ; Ovalbumin ; Rats ; Rats, Sprague-Dawley

Objective: To investigate the effect and mechanism of RNA binding protein Lin28 on the 5-fluorouracil (5-Fu) sensitivity of HepG2 cells. Methods: HepG2 cells were transfected with plasmid pcDNA3.1-Lin28 or si-Lin28 (small interfering RNA of Lin28). qPCR and Western blotting were used to detect the expression of Lin28 in HepG2 cells after transfection. Changes of cell proliferation in transfected cells after 5-Fu treatment was detected by CCK8 assay and the 50% inhibitory concentration (IC50) was calculated. Flow cytometry was used to detect apoptotic rate after 5-Fu treatment and the expression of apoptosis-related protein was assayed by Western blotting. The mRNA expressions of drug-resistant miRNAs (let-7a and let-7b), as well as cancer stem cell markers (Oct4, Nanog and Sox2) after transfection were detected by qPCR. Results: As compared to the HepG2/Vector cells, the mRNA and protein expressions of Lin28 were significantly up-regulated in HepG2/Lin28 cells (P<0.05 or P<0.01). Over-expression of Lin28 significantly suppressed the sensitivity of HepG2 cells to 5-Fu (IC50elevated obviously, P<0.05) and significantly increased cell proliferation while decreased apoptotic rate and expression of apoptotic-related protein caspase-3 (all P<0.01). As compared to si-control group, expression of Lin28 in HepG2/si-Lin28 cells was significantly down-regulated (P<0.01). Lin28 knockdown significantly reduced cell proliferation and IC50 of 5-Fu (all P<0.01) but increased apoptotic rate and expression of apoptosis-related protein (P<0.01). Compared with HepG2/Vector group, expressions of let-7a and let-7b, as well as cancer stem cell markers (Oct4, Nanog and Sox2) were significantly increased in HepG2/Lin28 cells (all P<0.01); while these molecules were significantly decreased in HepG2/si-Lin28 cells as comparing to si-control group (all P<0.01). Conclusion: Lin28 can modulate the chemosensitivity of HepG2 cells by regulating the expression of miRNAs and the formation of cancer stem cells. Targeting Lin28 might be a promising approach to improve the chemotherapy efficacy in HCC.

Objective To explore the application values of GeneXpert MTB/RIF assay (Xpert assay) for rifampicin resistance and multidrug resistant tuberculosis (MDR-TB).Discordance of Xpert and L-J proportion DST of rifampicin was analyzed.Methods Specimens of 1 300patients from January 2014to June 2016in our hospital were collected for solid culture, Xpert assay and L-J proportion drug susceptibility test (DST).Rifampicin resistance detected by Xpert assay was compared with L-J proportion method as a gold standard.Sequencing of rpoB gene and determination of minimum inhibition concentration were accomplished on the discordant MTB strains between Xpert and L-J proportion DST.Results Compared with the DST, the sensitivity, specificity, positive and negative predictive value of Xpert assay for rifampicin resistance were 99.31％, 97.82％, 92.88％and 99.80％, respectively.Among 1 300culture-positive specimens, mutations were detected from 309specimens by Xpert assay, which included 125initial treatment and 184retreatment patients.Among309specimens with rpoB gene mutations, mutations detected by probes E, D and B were common, and the rates were 65.70％, 14.56％and 10.68％, respectively.Totally 239patients were MDR-TB[77.35％ (239/309) ], of which 94initial treatment patients[75.20％ (94/125) ]and 145retreatment patients[78.80％ (145/184) ]were MDR-TB.Among 22strains which were detected rpoB gene mutations by Xpert, but sensitive by L-J proportion DST, 6strains had no mutation in rpoB gene rifampicin resistance determining region (RRDR);16strains had mutations, which were mainly located in L511Pcodon (8strains) and L533Pcodon (4strains).Among 2strains which had no rpoB gene mutation by Xpert, but were resistant by L-J proportion DST, 1strain had no mutation in rpoB gene RRDR region;1strain had mutation which was located in E546G codon outside RRDR region.Conclusion Xpert assay can be used to rapidly detect rifampicin resistance and to screen MDR-TB.Mutations in codon 511and 533are related to low-level resistance to rifampicin.

Objective To compare the clinical effects of of arterialized venous flap (AVF) with different perfusion strategies for repairing hand soft tissue defects. Methods Ninety-six patients with hand soft tissue defects from January 2015 to June 2018 in Gaozhou Traditional Chinese Medical Hospital were collected and randomly divided into two groups: the inverted group (48 patients) treated with anti-valve arterialized venous flap inverted anastomosis and the non-inverted group (48 patients) receiving pro-valve arterialized venous flap non-inverted anastomosis. The excellent and good rate of hand function recovery, flap survival rate,postoperative skin flap response degree and treatment satisfaction between two groups were compared. Results Compared with the inverted group, the flap survival rate in the non-inverted group increased significantly [97.9% (47/48) vs. 83.3% (40/48)], the proportion of mild flap response degree increased [45.8% (22/48) vs. 18.8% (9/48)], the proportion of severe flap response degree decreased significantly [12.5%(6/48) vs. 41.7%(20/48)], and the differences were statistically significant (χ2＝4.391, 7.032, 8.205, P < 0.05). The excellent and good rate of hand function recovery in inverted group and non-inverted group had no significant differences (χ2＝1.233, P＞0.05). There was no significant difference in satisfaction with the shape of skin flaps, finger function and donor site recovery between two groups(P＞0.05). Conclusions Compared with anti-valve arterialized venous flap inverted anastomosis, pro-valve arterialized venous flap non-inverted anastomosis on soft tissue defect repairment of hand can efficiently increase the survival rate of flap and improve the flap response degree after operation.

Objective To investigate the distribution and incidence of hyperuricemia for the Zhoushan island residents in Zhe-jiang province and provide scientific advice for health management.Methods The uric acid reports of island residents were analyzed by a retrospective statistical analysis in the Physical Examination Center of the 413 Hospital from October 2013 to October 2015.The patients with metabolic diseases (such as diabetes,chronic renal failure and other people,etc.)were ex-cluded.According to the different gender and different age groups,the average level of uric acid,hyperuricemia occurrence rate and the difference among the groups were performed statistical analyses.The single factor analysis of variance was used by Microsoft 2003 Excel software.Results The average serum uric acid level of 7 310 island residents was 283±82μmol/L and the incidence of hyperuricemia was 21.2%.The incidence of hyperuricemia was 33.6% in 31~40 years group,and the average level of uric acid was 343±86μmol/L and significantly higher than≤30 years group,significant statistic difference were observed.The incidence of hyperuricemia was more than 15% in≥41 years group,significantly higher than≤30 years group.The population of physical examination was concentrated in the 31~40 years group.The hyperuricemia incidence was 27.9% in 5 214 male residents,and the average serum uric acid level was 368±74μmol/L and higher than the female group (P<0.001).The hyperuricemia incidence was as high as 43.1% in 31~40 years group.But the level of average serum uric acid showed no significant difference with≤30 years group(P>0.05).The level of average serum uric acid level was less in≥61 and 41~50 years group than in ≤30 years group (P<0.05),but the hyperuricemia incidence were higher than ≤30 years group.The incidence of hyperuricemia was 4.6% in 2 096 female residents.The level of average serum uric acid was 257±57μmol/L and lower than the male group in all age groups (P<0.001).The incidence of hyperuricemia was 18.6% in≥60 years old and lower than 10% in the other groups.The incidence of hyperuricemia increased gradually with age.Conclu-sion The hyperuricemia incidence in island residents was higher,and higher in male than in female.The occurrence of hype-ruricemia was significantly younger.Therefore,health education,reasonable diet adj ustment,improvement of lifestyle and eating habits etc.Should be conducted for a long time to prevent the occurrence of hyperuricemia and related diseases.

Background:Gross target volume of primary tumor (GTV?P) is very important for the prognosis prediction of patients with nasopharyngeal carcinoma (NPC), but it is unknown whether the same is true for locally advanced NPC patients treated with intensity?modulated radiotherapy (IMRT). This study aimed to clarify the prognostic value of tumor volume for patient with locally advanced NPC receiving IMRT and to ifnd a suitable cut?off value of GTV?P for prognosis prediction. Methods:Clinical data of 358 patients with locally advanced NPC who received IMRT were reviewed. Receiver oper?ating characteristic (ROC) curves were used to identify the cut?off values of GTV?P for the prediction of different end?points [overall survival (OS), local relapse?free survival (LRFS), distant metastasis?free survival (DMFS), and disease?free survival (DFS)] and to test the prognostic value of GTV?P when compared with that of the American Joint Committee on Cancer T staging system. Results:The 358 patients with locally advanced NPC were divided into two groups by the cut?off value of GTV?P as determined using ROC curves: 219 (61.2%) patients with GTV?P≤46.4mL and 139 (38.8%) with GTV?P>46.4mL. The 3?year OS, LRFS, DMFS, and DFS rates were all higher in patients with GTV?P≤46.4mL than in those with GTV?P>46.4mL (allP<0.05). Multivariate analysis indicated that GTV?P>46.4mL was an independent unfavorable prognostic factor for patient survival. The ROC curve veriifed that the predictive ability of GTV?P was superior to that of T category (P<0.001). The cut?off values of GTV?P for the prediction of OS, LRFS, DMFS, and DFS were 46.4, 57.9, 75.4 and 46.4mL, respectively. Conclusion:In patients with locally advanced NPC, GTV?P>46.4mL is an independent unfavorable prognostic indi?cator for survival after IMRT, with a prognostic value superior to that of T category.