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

Tumor immunotherapy occupies a pivotal position in the field of hematological malignancies.Chimeric antigen receptor(CAR)T-cell therapy has established a new therapeutic pattern for hematological immunotherapy and achieved satisfactory clinical results in the treatment of B-lineage hematological malignancies.However,CAR T-cell therapy has some limitations in the treatment of T-cell acute lymphoblastic leukemia because of the presence of CAR T-cell fratricide,tumor cell contamination,T-cell aplasia,and other clinically relevant problems.Therefore,the current major challenge is overcoming the existing bottlenecks to optimize CAR-T therapy and improve its efficacy against T-ALL while improving the prognosis of patients.

BACKGROUND: The prevalence of hypertension is high among Chinese adults, thus, identifying non-hypertensive individuals at high risk for intervention will help to improve the efficiency of primary prevention strategies. METHODS: The cross-sectional data on 9699 participants aged 20 to 80 years were collected from the China National Health Survey in Gansu and Hebei provinces in 2016 to 2017, and they were nonrandomly split into the training set and validation set based on location. Multivariable logistic regression analysis was performed to develop the diagnostic prediction model, which was presented as a nomogram and a website with risk classification. Predictive performances of the model were evaluated using discrimination and calibration, and were further compared with a previously published model. Decision curve analysis was used to calculate the standardized net benefit for assessing the clinical usefulness of the model. RESULTS: The Lasso regression analysis identified the significant predictors of hypertension in the training set, and a diagnostic model was developed using logistic regression. A nomogram with risk classification was constructed to visualize the model, and a website ( https://chris-yu.shinyapps.io/hypertension_risk_prediction/ ) was developed to calculate the exact probabilities of hypertension. The model showed good discrimination and calibration, with the C-index of 0.789 (95% confidence interval [CI]: 0.768, 0.810) through internal validation and 0.829 (95% CI: 0.816, 0.842) through external validation. Decision curve analysis demonstrated that the model was clinically useful. The model had a higher area under receiver operating characteristic curves in training and validation sets compared with a previously published diagnostic model based on Northern China population. CONCLUSION This study developed and validated a diagnostic model for hypertension prediction in Gansu Province. A nomogram and a website were developed to make the model conveniently used to facilitate the individualized prediction of hypertension in the general population of Han and Yugur.
Adult ; Humans ; Asian People ; China/epidemiology* ; Cross-Sectional Studies ; Health Surveys ; Hypertension/epidemiology* ; Nomograms ; Ethnicity

Objective: Subthreshold attention-deficit/hyperactivity disorder (ADHD) has been suggested to be a “morbid condition” which also needs medical attention. Methods: The present study recruited 89 children with subthreshold ADHD (sADHD), 115 children with diagnosed ADHD (cADHD), and 79 healthy controls (HC) to explore the clinical manifestation, executive functions (EFs) of sADHD, and the caregiver strain. The clinical manifestation was evaluated through clinical interviews and parent-reports. Executive functions were assessed both experimentally and ecologically. Caregiver strain was measured by a parent-reported questionnaire. Results: For the clinical manifestation, both sADHD and cADHD indicated impairments when compared with HC. The comorbidities and the scaled symptoms indicated that the externalizing behaviors were relatively less serious in sADHD than cADHD, whereas the internalizing behaviors between two groups were comparable. For ecological EFs, sADHD scored between cADHD and HC in inhibition and working memory. For experimental EFs, sADHD was comparable to cADHD in inhibition, shifting, and was worse than cADHD in verbal working memory. For the caregiver strain, all scores of sADHD were between that in cADHD and that in HC. Conclusion Our present findings supported the suggestion of subthreshold ADHD as “morbid condition,” which should be treated with caution in clinical practice, especially for the internalizing behaviors and some key components of EFs.

Objective : To analyze the status and influencing factors of the intention of people aged 18 to 25 years to primary medical institutions and their satisfaction for health services in Zhejiang Province, so as to provide basis for the improvement of health services in primary medical institutions. Methods: During November and December in 2019,the 18-25 year-old people in Zhejiang Province were recruited to investigate the general information, intention to seek medical advice and satisfaction for health services in primary medical institutions through WeChat. Logistic regression was performed to analyze the influencing factors of the intention and the satisfaction. Importance matrix was used to analyze the key drivers of the satisfaction. Results: Among the 620 people surveyed, with a response rate of 93.37%, 142 (22.90%) chose primary medical institutions for advice. Actually 516 (83.23%) people went to primary medical institutions last year, and 384 ( 74.42% ) of them were satisfied with the health services. The results of multivariate logistic regression analysis showed that the people aged 18-25 years who were under the new rural cooperative medical care system ( OR=3.062, 95%CI: 1.745-5.373 ) and who had records in community health centers ( OR=0.547, 95%CI: 0.308-0.970 ) were more likely to go to primary medical institutions for medical advice; the ability of doctors ( OR=1.478, 95%CI:1.168-1.871 ) ,the drug notification by medical staff ( OR=1.308, 95%CI: 1.065-1.606 ) , routine examination items ( OR=1.523, 95%CI: 1.227-1.889 ) , the ways of payment ( OR=1.168, 95%CI: 1.017-1.340 ) , the comfort of environment ( OR=1.785, 95%CI: 1.437-2.219 ) and the bulletin boards of health knowledge ( OR=1.302, 95%CI: 1.086-1.561 ) were associated with the satisfaction. The results of importance matrix analysis showed that the ability of doctors and routine examination items were the priorities to improve, followed by the drug notification by medical staff; the comfort of environment had competitive advantages; the ways of payment and the bulletin boards of health knowledge needed to be further analyzed. Conclusions The 18-25-year-old people in Zhejiang Province were less intended to seek medical advice in primary medical institutions, which was associated with the type of medical insurance and records in community health centers. They were satisfied with the health services, the ability of doctors and routine examination items were the key drivers.

Objective To investigate the influences of different mechanical ventilation modes on ventilator?induced diaphragm dysfunction (VIDD). Methods The patients received invasive mechanical ventilation in our ICU after lower abdomen surgery were enrolled into 3 groups according to different ventilation modes. The data of the 3 groups were analyzed. According to the offline results, patients were divided into two groups, the success of weaning as the dependent variable, the clinical indicators with statistical significance as the independent variable, the Logistic regression analysis was performed to analyze the ventilator weaning. Results The mechanical ventilation time, 48 h reintubation rate and the length of ICU stay in the A/C mode group were significantly higher than those in the SIMV mode group and the PSV mode group. The weaning success rate in the A/C mode group was significantly lower than that in the SIMV mode group and the PSV mode group, with significant difference (P<0.05). Weaning success group and weaning failure group had significant differences in the proportion of three ventilation modes (P < 0.05). With weaning as dependent variable, APACHE Ⅱ score, ALB and ventilation mode as independent variables, logistic regression analysis was performed using the enter method. APACHE Ⅱ and ventilation mode were independent influencing factors for weaning. Conclusion Compared with the A/C mode, the SIMV mode and the PSV mode have less influence on VIDD and high weaning success rate in the mechanical ventilation process of patients post?lower abdomen surgery. No significant difference was found between the SIMV mode and the PSV mode in their influence on weaning.

The development trend, countries, institutions, co-authors, and subjects in MEDLINE-covered papers were analyzed by Excel, Ucinet and SciMAT respectively in order to understand the current situation in studies on precision medicine, which showed that precision medicine is in a rapid development stage, the impact power of pa-pers on precision medicine published in United States of America is high, the source journals published in United States of America are the core journals in precision medicine, the academic level of papers on precision medicine published in United States of America is high. Co-authors analysis showed that the co-authors network is of the small world effect. Subject evolution analysis revealed that the subjects involved in studies on precision medicine are increasingly rich with genomics, drug treatment and oncology accounted a large proportion. Analysis of the evo-lution in genomics, drug treatment and oncology displayed that the subjects involved in studies on precision medi-cine have experienced macro-stage, micro-stage, and combined macro- and micro-stage.

Diabetes is the general chronic metabolic disease,with chronic hyperglycemia as the main clinical characteristic.Proteomics discusses and explores the pathogenesis of diabetes more deeply from the overall level of proteins,which has been frequently applied in Chinese medicine research.This paper summarized proteomics application in the study of Chinese medicine intervening diabetes mellitus,including screening and verification of proteomics in Chinese medicine syndromes of diabetes and its complications,as well as proteomics analysis of pharmacological mechanism of related Chinese medicine.This paper also prospected its outlook,in hope toprovide new clues and basis for the pathogenesis theory of diabetes in traditional Chinese medicine (TCM) and functioning targets,and to deepen research on Chinese medicine intervening diabetes.

Sibiraea angustata belongs to the Rosaceae family and it is widely disturbed in Qinghai,Sichuan,Gansu,Yunnan and Tibet.It is one of the commonly used Tibetan medicines.Sibiraea angustata is rich in triterpenes,organic acids,organic esters,alkanes,and etc.And studies showed that Sibiraea angustata has various medicinal effects,such as regulating the metabolism of glucose and lipid,reducing body weight,anti-oxidation,modulating the immune system,liver-protection,anti-tumor,anti-aging,antibacterial activities,and promoting digestion.

Objective To investigate the mortality risk factors of nosocomial infection patients in intensive care unit (ICU), and to guide clinicians to take effective control measures. Methods A retrospectively cohort study was conducted. The relevant information of patients with nosocomial infection treated in ICU of Hengshui Harrison International Peace Hospital Affiliated to Hebei Medical University from June 2009 to December 2015 was analyzed. The patients who admitted to ICU again, with length of ICU stay less than 48 hours, without first etiology of screening within 48 hours of ICU admission, or without complete pathogenic information were excluded. The gender, age, diagnosis, length of ICU stay, invasive operation, nutritional status, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, distribution and drug resistance of the pathogens, and procalcitonin (PCT) levels at 7 days after nosocomial infection were recorded. The risk factors leading to death in patients with nosocomial infection were analyzed by logistic regression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of all risk factors on the outcome of patients with nosocomial infection. Results In 864 enrolled patients with male of 54.75% and mean age of (63.50±15.80) years, 732 (84.72%) patients survived and 132 (15.28%) died. Compared with survivors, the non-survivors had higher age (years: 65.47±15.32 vs. 58.15±13.27), incidence of urgent trachea intubation (32.58% vs. 22.81%), deep venous catheterization (83.33% vs. 63.25%), and multiple drug-resistant infection (65.91% vs. 33.20%), longer length of ICU stay (days: 13.56±4.29 vs. 10.29±4.32) and duration of coma (days: 7.36±2.46 vs. 5.48±2.14), lower albumin (g/L: 23.64±8.47 vs. 26.36±12.84), higher APACHEⅡ score (19.28±5.16 vs. 17.56±5.62), SOFA score (8.55±1.34 vs. 6.43±2.65), and PCT (μg/L: 3.06±1.36 vs. 2.53±0.87, all P < 0.05). There was no significant difference in gender and urinary tract catheterization between survivors and non-survivors (both P > 0.05). The low respiratory tract was the most common site of infection followed by urinary tract and bloodstream in both groups. It was shown by logistic regression analysis that prolonged ICU stay [odds ratio (OR) = 2.039, 95% confidence interval (95%CI) = 1.231-3.473, P = 0.002], APACHEⅡ score (OR = 1.683, 95%CI= 1.002-9.376, P = 0.000), SOFA score (OR = 2.060, 95%CI = 1.208 -14.309, P = 0.041), PCT (OR = 2.090, 95%CI = 1.706-13.098, P = 0.004), and multi-drug resistant pathogens infection (OR = 5.245, 95%CI = 2.213-35.098, P = 0.027) were independent risk factors for ICU mortality in patients with nosocomial infection. The area under ROC curve (AUC) of length of ICU stay, APACHEⅡ score, SOFA score, and PCT level for predicting death of nosocomial infection patients was 0.854, 0.738, 0.786, and 0.849, respectively, the best cut-off value was 16.50 days, 22.45, 6.37 and 3.38 μg/L, respectively, the sensitivity was 83.6%, 90.0%, 81.1%, and 89.6%, and the specificity was 70.3%, 75.6%, 71.3%, and 85.4%, respectively. Conclusions Prol onged ICU stay, nosocomial infection with secondary sepsis and multiple organ dysfunction syndrome were the leading causes of death for nosocomial infection patients in ICU. Prolonged ICU stay, APACHE Ⅱ score, SOFA score, and PCT level could effectively predict death risks for nosocomial infection patients.