Objective : To investigate the effects of immunoglobulin gene superfamily 10 (IGSF10) on prolifera- tion，migration and invasion of lung adenocarcinoma cells． Methods : ioinformatics was applied to study the ex- pression levels of IGSF10 in tumor tissues and normal tissues． Western blot and quantitative real-time PCR ( qPCR) were used to detect the expression level of IGSF10 in lung adenocarcinoma cell lines and normal lung epi- thelial cells．Knockdown of IGSF10，the effect of knockdown of IGSF10 on proliferation，migration and invasion of lung adenocarcinoma A549 cells was examined using cell counting kit-8 ( CCK-8) ，Transwell migration and inva- sion assay，scratch assay and plate cloning assay．The effects of knockdown of IGSF10 on the expression of invasion and migration-related genes in A549 cells were examined by Western blot and qPCR assays. Results : IGSF10 ex- pression in lung adenocarcinoma tissues was lower than that in normal tissues (P ＜0. 05) ．IGSF10 expression in lung adenocarcinoma cell lines was lower than that in lung epithelial cells (P＜0. 05) ．Knockdown of IGSF10 pro- moted the ability of lung adenocarcinoma A549 cells to proliferate ，proliferation ，migration and invasion ( P < 0. 05) ．Knockdown of IGSF10 promoted the expression of regulatory epithelial-mesenchymal transition marker Neu- ral-cadherin (N-cadherin) and key transcription factors Snail family transcriptional repressor 1 (Snail) and Snail family transcriptional repressor 2 (Slug) (P＜0. 05) and inhibited the expression of Epithelial-cadherin (E-cad- herin) (P＜0. 05) ． Conclusion Knockdown of IGSF10 may promote proliferation，migration and invasion of lung adenocarcinoma cells through activation of Snail，Slug / E-cadherin signaling axis，and this result may provide a po- tential new target for clinical diagnosis and treatment of lung adenocarcinoma.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Objective:To investigate the predictive value of dynamic platelet and hemagglutination-related parameters in patients with acute pancreatitis (AP).Methods:The patients admitted to the Department of Emergency Surgery in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2020 were analyzed. According to the inclusion criteria and exclusion criteria, patients with AP were retrospectively enrolled. According to the Chinese Guidelines for the Diagnosis and Treatment of Acute Pancreatitis (Shenyang, 2019), the patients were divided into two groups: severe acute pancreatitis (SAP group) and non-severe acute pancreatitis (non-SAP group) [including mild acute pancreatitis (MAP) and moderate severe acute pancreatitis (MSAP)]. A normal distribution of the maximum and mean aggregation rates of dynamic platelets (arachiidonic acid), plateletcrit (PCT) and bedside index for severity in acute pancreatitis (BISAP) scores and other measurement data were tested by t test, while measurement data of prothrombin time (PT), fibrinogen (FIB) and D-dimer that did not conform to normal distribution were tested by Mann-Whitney U test. χ 2 test was used for the counting data such as sex, age and etiology of patients in the two groups. The prognostic value of statistically significant indicators for non-SAP group and SAP group was further analyzed by receiver operating characteristic (ROC) curve. Results:A total of 146 patients with AP were enrolled, including 50 patients in SAP group and 96 in non-SAP group. The maximum and average aggregation rates of dynamic platelet (aracidonic acid) in the SAP group were (71.76±17.62) % and (67.91±18.10) %, PT (12.02±1.33) s, FIB (4.76±2.08) g/L, D-dimer (3.75±6.04) μg/L, PCT (0.23±0.08) %, and BISAP scores (1.42±1.18), which were all significantly higher than those in the non-SAP group [the maximum and average aggregation rates of dynamic platelet (arachiidonic acid) (46.65±20.11) % and (42.50±20.71) %, PT (11.50±1.51) s and FIB (3.91±1.48) g/L, D-dimer (1.00±1.37) μg/L, PCT (0.19±0.06) %, BISAP scores (0.45±0.66)] (all P<0.05). According to area under the ROC curve, the maximum and average aggregation rates of dynamic platelets (arachiidonic acid) in serum of patients with SAP were 0.83 and 0.82, respectively, and the sensitivities were 0.56 and 0.68, respectively. The specificity was 0.99 and 0.81, respectively, which was better than PT, FIB, D-dimer, PCT and BISAP scores in predicting the severity of AP. Conclusions:The maximum and average aggregation rates of dynamic platelets (arachidonic acid), PT, FIB, D-dimer, PCT and BISAP scores can be used as predictors of the severity of acute pancreatitis. The maximum and average aggregation rates of dynamic platelets (arachiidonic acid) were the best in predicting the severity of AP.

Normal embryonic development is regulated by different genes and related signaling pathways. In recent years, the association between different genes and genes, genes and signaling pathways in the same organization has been widely concerned by scholars at home and abroad. Sp and Wnt gene deletion or mutation can lead to abnormal embryonic development. The results of this review indicate that abnormal embryonic development is due to Sp gene deletion/mutation The zinc finger protein superfamily member Sp1-9 is involved in the development of various tissues and organs , such as the hematopoietic system, respiratory system and skeletal system, and its deletion or mutation can lead to developmental abnormalities in embryonic tissues. In addition, the Sp8 gene is associated with the occurrence of cleft palate. By summarizing the observations about the relationship between the Wnt gene and cleft lip and palate in recent years, we can understand the abnormal expression of Wnt3, Wnt3A, Wnt5A, Wnt9B, Wnt10A and Wnt11 in humans. The occurrence of cleft lip and palate is closely related; Sp5/8 is a key downstream effector of the Wnt signaling pathway during embryonic development and participates in the Wnt signaling pathway. Sp5/8 and the Wnt signaling pathway are involved in the regulation of normal neural crest development and the self-renewal of embryonic stem cells in embryonic mice. In summary, this paper proposes that the Sp and Wnt genes may be involved in the regulation of the formation and occurrence of embryonic cleft palate and provides a reference for further study of the associated mechanisms between the two genes in the cleft palate model.

Objective: To evaluate the association between the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/E') and left atrial pressure (LAP) estimated from invasive catheter measurements in patients with atrial fibrillation (AF). Methods: A total of 46 consecutive patients with non-valvular AF and preserved left ventricular ejection fraction (LVEF) admitted in our department to receive the first radiofrequency ablation from May to July 2017 were included. All patients underwent echocardiography at 24-48 hours before radiofrequency ablation, and LAP was invasively measured during the ablation procedure. According to mean LAP, patients were divided into 2 groups of normal LAP (LAP≤12 mmHg(1 mmHg=0.133 kPa, n=31) and elevated LAP (LAP>12 mmHg, n=15). Linear correlation analysis was used to evaluate the relationship between E/E' and LAP. Results: E/E' correlated well with LAP (septal E/E' (E/E'_sep), r= 0.397, P=0.006; lateral E/E' (E/E'_lat), r=0.433, P=0.003; mean E/E' (E/E'_mean), r=0.431, P=0.003). Using receiver operating characteristic analysis, the optimal cut-off for E/E'_sep was 12.5 (sensitivity 73.3%, specificity 67.7%), E/E'_lat was 10.8 (sensitivity 80.0%, specificity 77.4%), E/E'_mean was 11.0 (sensitivity 86.7%, specificity 64.5%) to predict mean LAP>12 mmHg. Conclusion E/E', especially the E/E'_lat, is positively correlated with LAP in patients with AF and preserved LVEF, and may be used to estimate the diastolic function in AF patients with preserved LVEF.

BACKGROUNDScreening on multidrug-resistant tuberculosis (MDR-TB) has been limited to the serious TB subpopulations excluding the new TB patients. This study aimed to examine MDR-TB burden among the new TB patients.

METHODSWe conducted a study in Zhejiang Province during 2009-2013 to screen for MDR-TB patients among the low MDR-TB risk patients and five subpopulations of high MDR-TB risk patients. The number, prevalence, and trend of MDR-TB were compared while the logistic regression model was used to examine risk factors related to MDR-TB.

RESULTSA total of 200 and 791 MDR-TB cases were, respectively, identified from the 9830 new TB cases and 2372 high-risk suspects who took MDR-TB screening from 2009 to 2013. The MDR-TB rates went down in both of the new TB patients and five MDR-TB high-risk groups over the study time, but the percentage of MDR-TB patients identified from the new TB patients in all diagnosed MDR-TB cases kept stable from 28.3% in 2011 to 27.0% in 2012 to 26.0% in 2013.

CONCLUSIONSThe study indicated that MDR-TB burden among new TB patients was high, thus screening for MDR-TB among the new TB patients should be recommended in China as well as in the similar situation worldwide.

Objective To explore the effect and mechanism of necroptosis related proteins in middle cerebral artery occlusion (MCAO) induced brain ischemia/reperfusion injury in mice.Methods C57BL/6 mice were used to establish the brain ischemia/reperfusion injury model induced by MCAO.MCAO mice were treated with z-VAD.fmk (zVAD,1.1 g/kg),GSK'872 (0.7 g/kg) and combined intervention of zVAD and GSK'872,and neurological defect was evaluated by mNSS while brain infarct volume was measured by TTC staining.Western blot and immunofluorescence assay were used to detect protein expression and location of RIP1,RIP3 and MLKL,respectively.Results Neurological defect and brain infarction were caused by MCAO.Compared with MCAO group,zVAD,GSK'872 and the combined intervention alleviated neurological defect and reduced brain infarct volume significantly (P＜0.05 or P＜0.01).The protein levels of RIP3 and RIP1 MLKL were increased in mice of MCAO group,while GSK'872 and the combined intervention obviously downregulated the aforementioned protein expression [RIP1 (GSK'872:0.64± 0.02 vs MCAO:1.28±0.02,P＜0.01);RIP3 (GSK'872:1.08±0.02 vs MCAO:1.45±0.02,P＜0.01);MLKL (GSK'872:0.54±0.01 vs MCAO:1.00±0.01,P＜0.01)].However,zVAD only slightly reduced protein expression of MLKL (P＜0.05) but didn't change the protein expression of RIP1 and RIP3 (P＞0.05).Conclusion RIP1,RIP3 and MLKL are involved in the execution of necroptosis and contribute to the pathological progress of brain ischemia/reperfusion injury.

Objective To identify the clinical and imaging characteristics in neonatal refractory purulent meningitis. Methods Clinical data of 70 cases of neonatal purulent meningitis admitted to the neonatal intensive care unit at Children's Hospital of Fudan University from January, 2009 to December, 2014 were reviewed retrospectively. The patients were divided into refractory group (n=28) and non-refractory group (n=42) according to the course of antimicrobial therapy.The clinical and brain MRI characteristics of neonatal refractory purulent meningitis were analyzed. Parameters were compared between the two groups using Chi-square or Fisher's exact tests, and Wilcoxon tests where appropriate. Risk factors of neonatal refractory purulent meningitis were investigated by univariate and multivariate Logistic regression analysis. Results Among the 70 cases, 31(44.3%) were positive for cerebrospinal fluid (CSF)/blood culture. The positive rate was higher in the refractory group than in the non-refractory group [75.0%(21/28) vs 23.8%(10/42),χ2=17.843, P<0.01]. The most common pathogenic bacteria isolated in the refractory group were Escherichia coli [8 cases (38.1%)] and group B streptococci [5 cases (23.8%)]. Compared to the non-refractory group, patients in the refractory group were more likely to have seizure, higher CSF white blood cell count, higher CSF protein concentration and lower CSF glucose concentration [53.6%(15/28) vs 7.1% (3/42), 965.0 (463.0-2 200.0)×106/L vs 116.5 (61.0-327.5)×106/L, 3 221.1(2 354.3-4 633.5) mg/L vs 1 487.6(988.2-1 924.1) mg/L, and 0.2 (0.1-0.8) mmol/L vs 1.5 (1.2-1.8) mmol/L; all P<0.01]. Multivariate Logistic regression analysis showed that seizure, low CSF glucose concentration on admission, and a positive CSF/blood culture result neonatal refractory purulent meningitis (OR=9.6, 95%CI: 1.2-76.0; OR=15.0, 95%CI: 5.6-63.3; and OR=7.3, 95%CI: 1.5-36.0, respectively). Abnormal brain MRI findings, including intracranial extracerebral space abnormality, ventricular dilatation and periventricular white matter injury, were more common in the refractory group [100.0%(28/28) vs 61.9%(26/42), χ2=13.827 totally; 64.3%(18/28) vs 21.4%(9/42), χ2=13.023 for intracranial extracerebral space abnormality; 60.7%(17/28) vs 19.0%(8/42), χ2=12.704 for ventricular dilation and 28.6%(8/28) vs 2.4%(1/42) for periventricular white matter injury; all P <0.01]. Compared with the non-refractory group, the refractory group had a longer hospital stay [(48.0±17.4) d vs (26.0±10.2) d, t=6.016, P<0.01] and more adverse events [67.9%(19/28) vs 31.0%(13/42), χ2=9.220, P=0.002], including hearing impairment and requirement of neurosurgical intervention [14/18 ears vs 10/46 ears (21.7%), χ2=4.292, P=0.038]. There was no death in both groups during hospitalization. Conclusions Neonates with seizure, low CSF glucose concentration and positive CSF/blood culture results are more likely to have refractory purulent meningitis. Brain MRI abnormalities are more common in neonatal refractory purulent meningitis.

BACKGROUND:Oligodendrocytes are mostly differentiated from oligodendrocyte precursor cel s. A suitable medium and cel seeding density have a significant impact on the process of the isolation of oligodendrocyte precursor cel s to obtain oligodendrocytes. OBJECTIVE:To explore the optimization of oligodendrocyte culture conditions. METHODS:Oligodendrocyte precursor cel s isolated from the newborn rats 48 hours after birth were cultured in DMEM/high glucose medium or DMEM/F12 medium using seeding densities of 2×104 cel s/cm2, 4×104 cel s/cm2, 8×104 cel s/cm2, 16×104 cel s/cm2, 32×104 cel s/cm2, and 64×104 cel s/cm2, respectively. Oligodendrocyte precursor cel s were induced to differentiate into oligodendrocytes at 72 hours after cel adhesion. Morphology of differentiated oligodendrocyte precursor cel s were observed under a light microscope, and the differentiation results were identified by immunofluorescence staining after 7-day induced differentiation. RESULTS AND CONCLUSION:Morphology of oligodendrocyte precursor cel s were recognized when cultured in DMEM/high glucose medium or DMEM/F12 medium using seeding densities of 2×104 cel s/cm2, 4×104 cel s/cm2, and 8×104 cel s/cm2, respectively. Immunofluorescence staining showed that myelin basic protein-positive cel s were found after 7-day induced differentiation, and the positive cel number were 16.40±3.30, 49.95±2.33, and 76.95±4.86 in DMEM/F12 medium, and 12.65±2.53, 32.10±1.17, and 54.05±1.56 in DMEM/high glucose medium (P<0.05). These findings indicate that DMEM/F12 medium is more suitable for culturing oligodendrocyte precursor cel s compared with DMEM/high glucose medium to some extent. The number of differentiated oligodendrocytes was gradual y increased with the enhanced seeding density of oligodendrocyte precursor cel s, and the seeding densities from 4×104 to 8×104 cel s/cm2 were appropriate for the observation of cel morphology.

_ Objective_ To evaluate the efficacy of unilateral subtotal adrenalectomy in the treatment of bilateral adrenal solitary neoplasma causing Cushing's syndrome and to elaborate the therapeutic principle. Methods From 2007 to 2013, a total of ten patients were diagnosed with Cushing's syndrome caused by bilateral solitary adrenal neoplasma. We compared patients'clinical symptoms, hormone profiles, biochemical and metabolic parameters, and imaging data before and after the surgery. Five of them chose the optimal neoplasma based on the lateralization ratio of adrenal venous sampling result and the other 5 patients chose the optimal neoplasma based on the diameter of the mass reflected by the computed tomography result and were then operated. Results After the unilateral subtotal adrenalectomy,the24-hour urinary free cortisol decreased significantly(P<0.05)and the midnight serum cortisol level also significantly reduced(P<0. 01). Plasma adrenocorticotropic hormone level increased significantly(P<0. 01). Nine patients of them did not need contralateral adrenalectomy and one patient received contralateral adrelectomy because of the remnant of Cushingnoid symptoms. Conclusion Unilateral subtotal adrenalectomy is an effective and safe way to treat Cushing's syndrome caused by bilateral solitary neoplasma.