Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Background/Aims: The accuracy of endosonographers in diagnosing gastric subepithelial lesions (SELs) using endoscopic ultrasonography (EUS) is influenced by experience and subjectivity. Artificial intelligence (AI) has achieved remarkable development in this field. This study aimed to develop an AI-based EUS diagnostic model for the diagnosis of SELs, and evaluated its efficacy with external validation. Methods: We developed the EUS-AI model with ResNeSt50 using EUS images from two hospitals to predict the histopathology of the gastric SELs originating from muscularis propria. The diagnostic performance of the model was also validated using EUS images obtained from four other hospitals. Results: A total of 2,057 images from 367 patients (375 SELs) were chosen to build the models, and 914 images from 106 patients (108 SELs) were chosen for external validation. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the model for differentiating gastrointestinal stromal tumors (GISTs) and non-GISTs in the external validation sets by images were 82.01%, 68.22%, 86.77%, 59.86%, and 78.12%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the external validation set by tumors were 83.75%, 71.43%, 89.33%, 60.61%, and 80.56%, respectively. The EUS-AI model showed better performance (especially specificity) than some endosonographers.The model helped improve the sensitivity, specificity, and accuracy of certain endosonographers. Conclusions We developed an EUS-AI model to classify gastric SELs originating from muscularis propria into GISTs and non-GISTs with good accuracy. The model may help improve the diagnostic performance of endosonographers. Further work is required to develop a multi-modal EUS-AI system.

Somatic symptom disorder (SSD) is a somatic disorder characterized by excessive anxiety over various somatic symptoms for a long time, which makes patients feel very painful and the quality of personal life significantly decreased. Previous studies have shown that there is a connection between the clinical manifestations of SSD patients and their cultural background. The patient in this case report was highly affected by Chinese yin-yang culture, displaying obvious Chinese characteristics. We report a patient with SSD, whose clinical manifestations were mainly sexual dysfunction and mood symptoms which were closely related to the Traditional Chinese culture of Yin and Yang. In this case, Hamilton Anxiety Scale, Hamilton Depression Scale, and International Erectile Function Questionnaire were used to evaluate the patients ' anxiety, depression, and sexual function, and the scores were 32, 33, and 9, respectively. The patient was treated with a combination of venlafaxine and mirtazapine. After 5 weeks of treatment, the patient's clinical symptoms improved significantly. The clinical manifestations of some Chinese SSD patients have obvious characteristic relevance to Chinese theory of Yin and Yang, making SSD easily to be misdiagnosed. Therefore, clinicians should pay atlention to this situation. In addition, the combination of venlafaxine and mirtazapine may have a better effect on SSD patients with chronic pain and sexual dysfunction.

OBJECTIVE: To investigate the effects of Notch signal on hypoxic induction factor (HIF-1α) and autophagy-associated genes Beclin1, LC3I, LC3II in oxygen-glucose deprivation (OGD) induced myocardial cell injury. METHODS: The OGD model was established using hypoxic culture box and hypoglycemic DMEM medium. The cells were divided into normal control group, OGD group, OGD + NC siRNA group, OGD + Notch1 siRNA group and OGD + HIF-1α siRNA group. Western blot was used to detect the interference effects of HIF-1α siRNA and Notch1 siRNA. The effects of Notch1 siRNA and HIF-1α siRNA on the activity of myocardial cells in OGD model were detected by the CCK-8 assay. The effects of Notch1 siRNA and HIF-1α siRNA on autophage-associated genes Beclin1, LC3I and LC3II expression were detected by Western blot. RESULTS: The results of Western blot showed that HIF-1α siRNA could effectively knock down the expression of HIF-1α in myocardial cells in OGD model, and Notch1 siRNA could effectively knock down the expression of Notch1 and HIF-1α in myocardial cells in OGD model. The result of CCK-8 assay showed that Notch1 siRNA and HIF-1α siRNA reduced the activity of myocardial cells in OGD model, and there was no statistical difference between the two groups. Western blot results showed that Notch1 siRNA and HIF-1α siRNA could reduce the expressions of the autophagy-associated genes Beclin1, LC3I and LC3II, and reduce the ratio of LC3II to LC3I at mRNA level. CONCLUSION Notch1 plays a role in myocardial protection by regulating the expression of HIF-1α to regulate the autophagy in OGD model cells.
Autophagy ; Beclin-1 ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Glucose ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Myocytes, Cardiac ; cytology ; pathology ; Oxygen ; Receptors, Notch ; metabolism ; Signal Transduction

Objective To understand influence factors of the demission of extra-organizational nurses in Shanghai and measures taken by nursing managers for their demission.Methods In-depth qualitative interviews were carried out in 6 included hospital human resource directors of nursing department in Shanghai from August to November 2016 with the method of purposive sampling. Information was collected, transcribed and the themes were extracted.Results Nursing managers in Shanghai considered that the main 3 aspects of influence factors of the demission of extra-organizational nurses should be the lack of social support system, the increase of nursing professional pressure and the limitation of personal career development. The 6 themes of countermeasures taken by managers included: fading the concept of extra-organizational nurses and organizational nurses; reducing the influence of majeure factors; improving the social status of nurses; strengthening the nurse training; strengthening the humanistic care; using the incentive mechanism.Conclusions Nursing managers in Shanghai think that the demission of extra-organizational nurses is influenced by various factors. Nursing managers can adopt positive and effective measures to reduce the nurses' demission.

This paper reviewed research tools of pressure, pressure source, signs and symptoms, and coping styles of male nurses. Effective strategies for male nurses to cope with stress had been proposed, to instruct male nurses to master and apply pressure management methods, improve mental health, and provide basis for managers to take countermeasures at the same time.

This paper summarizes the concept of male nurses' willingness to quit and tools for measuring the willingness to quit. It is suggested there are three aspects to reduce the turnover rate of male nurses: individual factors; social supporting factors; and organizational management factors. Comprehensive interventions, such as, using professional training to cope with the impact of transition shock on the psychological capital of male nurses, creating supportive atmosphere to reduce adverse factors, building a humanized management platform, establishing pre-cognitive male nurses' separation management mechanism, and understanding the turnover intention of male nurses in time, were studied to retain male nurses.

OBJECTIVETo investigate the correlation between the combination of smoking and the polymorphisms of cytochrome P450 (CYP) 1A1-Msp I and glutathione S-transferase (GST) T1 genes and oral cancer.

METHODSThe genetic polymorphisms of CYP1A1-Msp I and GSTT1 were detected by polymerase chain reaction (PCR) technique in peripheral blood leukocytes of 300 oral cancer cases and 300 non-cancer controls, and the correlation between smoking, the two metabolic enzymes genetic polymorphisms and oral cancer were analyzed.

RESULTSThe frequencies of CYP1A1-Msp I (m2/m2) and GSTT1(-) were 38.33% and 69.33% in oral cancer cases and 21.00% and 44.33% in healthy controls respectively. Statistical tests showed significant difference in the frequencies between the two groups (P<0.01). The risk of oral cancer with CYP1A1-Msp I (m2/m2) was significantly higher than that of controls (OR= 2.34, 95%CI 1.76-4.07). The individuals who carried with GSTT1(-) had a high risk of oral cancer(OR=2.84, 95% CI 1.98-4.54). Combined analysis of the polymorphisms showed that percentage of CYP1A1-Msp I (m2/m2)/GSTT1(-) in oral cancer and control groups was 30.67% and 6.67% respectively (P<0.01). The people who carried with CYP1A1-Msp I (m2/m2)/GSTT1(-) had a high risk of oral cancer(OR=8.27, 95%CI 3.63-11.29). The smoking rate of the case group was significantly higher than that in the control group (OR=2.71, 95%CI 1.31-4.52, P<0.01), and statistic analysis suggested an interaction between smoking and CYP1A1-Msp I (m2/m2)/GSTT1(-) genotypes polymorphisms which increased risk of oral cancer (OR=25.00, 95%CI 11.87-35.64).

CONCLUSIONCYP1A1-Msp I (m2/m2) and GSTT1(-) are the risk factors in oral cancer. Smoking is also related to the susceptibility to oral cancer. There may be a synergetic interaction among CYP1A1-Msp I (m2/m2), GSTT1(-) and smoking on the elevated susceptibility of oral cancer.

Case-Control Studies ; Cytochrome P-450 CYP1A1 ; Genotype ; Glutathione Transferase ; Humans ; Mouth Neoplasms ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Risk Factors ; Smoking

Objective To investigate the mechanism underlying the WNK4 kinasemediated inhibitory effect on BK channel. Methods Cos-7 cells were cotransfected with BK in combination with either CD4 (control group) or wild type WNK4 (WNK4-WT).Immunostaining and confocal microscopy,chemiluminescence,Western blotting analysis were then employed to determine the BK localization in cells,BK surface expression and total protein level,respectively.To further investigate whether the reduction of BK protein expression is due to an increase in degradation through a lysosomal pathway,BK protein level was determined after treated with bafilomycin A1(Baf A1),a proton pump inhibitor affecting lysosomal degradation. Results Immunostaining and confocal microscopic study showed that BK was localized both in plasma membrane and cytosol in the control group.After cells transfected with WNK4-WT,BK expression was markedly reduced.Chemiluminescent assay found that BK surface expression level was 299.9±18.6 in the control group,whereas it was significantly reduced (148.4±13.7,P＜0.01) in the WNK4-WT group.Western blotting analysis showed that total BK protein level was markedly reduced in the presence of WNK4-WT compared to the control group.WNK4-WT was shown to significantly reduce the BK total protein level (42.3％±15.2％) compared to the control group (100％) (P＜0.01).When the cells was treated with Bafilomycin A1 (Baf A1,0.5 μmol/L),WNK4-mediated reduction in BK protein was reversed (82.2％±12.1％,P＜0.05). Conclusions WNK4 inhibits total and surface protein expression of BK in Cos-7 cells whick is likely due to an increase in BK degradation through a lysosomal pathway.

OBJECTIVETo study serum levels and clinical significance of insulin-like growth factor-1 (IGF-1) and growth factor binding protein 3 (IGFBP-3) in children with acute lymphocytic leukemia (ALL).

METHODSSerum samples were obtained from 36 children with ALL before treatment and 6 months after complete remission. Thirty children with surgical diseases severed as the control group. Serum IGF-1 levels were measured using radioimmunoassay (RIA). Serum IGFBP-3 levels were measured using immunoradioassays (IRMA).

RESULTSSerum levels of IGF-1 and IGFBP-3 in the ALL group were 19±4 ng/mL and 1216±132 ng/mL, respectively before treatment, which were lower than those in the control group (32±3 ng/mL and 2104±191 ng/mL respectively) (P<0.01). Serum levels of IGF-1 and IGFBP-3 in the ALL group increased to 30±3 ng/mL and 1941±164 ng/mL respectively 6 months after complete remission, which were significantly higher than those before treatment (P<0.01) and were similar to the levels of the control group.

CONCLUSIONSSerum levels of IGF-1 and IGFBP-3 are reduced in children with ALL, but increase significantly after complete remission, suggesting that IGF-1 and IGFBP-3 might serve as useful markers for the diagnosis and evaluation of therapeutic effects of childhood ALL.

Adolescent ; Biomarkers, Tumor ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; diagnosis