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

Objective:To evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C, without cirrhosis or compensated stage cirrhosis.Methods:Patients with chronic hepatitis C (without cirrhosis or compensated stage cirrhosis) were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group (100 mg group) or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group (200 mg group) in a 1∶1 ratio. The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal. The drug safety profile was assessed concurrently with the observation of the sustained virological response (SVR12) in the two patient groups 12 weeks following the drug cessation. The intention-to-treat concept was used to define as closely as possible a full analysis set, including all randomized cases who received the experimental drug at least once. The safety set was collected from all subjects who received the experimental drug at least once (regardless of whether they participated in the randomization group) in this study. All efficacy endpoints and safety profile data were summarized using descriptive statistics. The primary efficacy endpoint was SVR12. The primary analysis was performed on a full analysis set. The frequency and proportion of cases were calculated in the experimental drug group (antaitasvir phosphate capsules combined with yiqibuvir tablets) that achieved "HCV RNA

Objective:To study the differences of intestinal flora between neonatal rats with intrauterine hypoxia and healthy neonatal rats using high-throughput sequencing technology to determine the effects of intrauterine hypoxia on neonatal intestinal flora.Methods:Intrauterine hypoxia model were established in neonatal rats. On d1 and d7 after birth, intestinal samples were collected from intrauterine hypoxic group and normal control group and assigned into INH1 group (intrauterine hypoxia d1), INH7 group (intrauterine hypoxia d7), NOR1 group (normal control d1) and NOR7 group (normal control d7). 16S rRNA sequencing were conducted using these samples and the differences in the diversity, richness and composition of the flora among the groups were compared.Results:(1) The Alpha diversity of the intestinal flora in the INH1 group was higher than the NOR1 group. Specifically, both sobs and chao indices, representing the richness of the flora, in INH1 group were significantly higher than the NOR1 group (sobs index: 114.5±35.6 vs. 50.5±21.3, chao index: 135.6±38.5 vs. 73.9±28.8)( P<0.05). Compared with the NOR7 group, the mean values of sobs, ace, chao, simpson and shannon indices in the INH7 group showed no significant differences ( P>0.05). (2) At the phylum and genus level, the dominant bacterial groups in the intrauterine hypoxia group on d1 were firmicutes and streptococcus and proteus and escherichia for the normal control group. The difference of intestinal flora between intrauterine hypoxia group and the normal control group on d7 was smaller than the difference between the two groups on d1. Compared with INH1 group, the INH7 group had increased escherichia composition and decreased streptococcus composition. Conclusions:Intrauterine hypoxia changes the initial colonization and later affects the abundance and structural composition of the intestinal flora in newborn rats.

Objective:To provide a scientific basis for reducing the rate of invalid ambulance attendance and the establishment of grades dispatch system through a retrospective analysis of the invalid ambulance attendance in prehospital emergency care.Methods:The data of the invalid ambulance attendance was collected in Huazhong University of Science and Technology Union Shenzhen Hospital (the only tertiary hospital of in Nanshan District) from 2014 to 2018, and the reasons of the invalid ambulance attendance, the time period during the invalid ambulance attendance occurred (every 3 hours was divided into one time period), and the reasons of ambulance calling were statistically analyzed.Results:① The invalid ambulance attendance rates showed a fluctuating decrease trend year by year from 2014 to 2018, the rates were 31.22% (2 515/8 055), 26.94% (2 147/7 970), 29.80% (2 398/8 046), 25.69% (1 844/7 177) and 21.89% (1 686/7 703), respectively. The total invalid ambulance attendance rate was 27.19% (10 590/38 951) in the five years. ② The top three reasons for the invalid ambulance attendance were cancelled calls, departure before the ambulance arrived, and going to hospital by themselves, accounting for 36.87%, 25.08%, and 17.03%, respectively. The constituent ratios of the causes of invalid ambulance attendance in each year were different with statistical significance (χ 2 = 217.626, P < 0.001). ③ The top three time period of invalid ambulance attendance occurred at 21:00-23:59, 18:00-20:59 and 09:00-11:59, accounting for 16.86%, 14.95% and 13.54%, respectively. There was no statistical significance in the distribution of time period in each year (χ 2 = 32.571, P = 0.252). ④ The top five reasons for ambulance calling of invalid ambulance attendance were fainting/syncope, trauma, alcoholism, traffic accident injuries, and brawls, accounting for 20.13%, 15.67%, 9.97%, 8.64%, and 6.45%, respectively, and there was statistically significant difference in the distribution of the reason for ambulance calls in each year (χ 2 = 194.213, P < 0.001). Conclusion:The invalid ambulance attendance rate is high in Nanshan District of Shenzhen. Improving the professional level and triage ability of the dispatchers, improving the system construction of prehospital emergency care system and increasing social education are conducive to reduce invalid ambulance attendance rate.

Schizophrenia is a serious neurological disorder characterized by incoordination among thinking, cognition, emotion and behavior, and its pathogenesis remains unclear now. In recent years, an increasing number of reports have found that the occurrence of schizophrenia shares a close relationship with prefrontal cortex (PFC), while the later plays an important role in numerous advanced cognitive functions, including working memory, learning and decision making. This review focuses on the recent development of neural circuits, including neurodevelopment, neurotransmitters, synaptic transmission, functional connectivity of brain regions and neural synchrony oscillation in PFC. Hopefully, this review will help to elucidate the pathogenesis of schizophrenia, and provide approaches and ideas for the treatment of relevant psychiatric disorders.

European psychiatric specialist training system has been maturely developed for 6 decades.The institutional framework for psychiatric training during specialization has been conformed to European standards,including training content,assessment and training base.In Europe,psychiatry specialist education lasts 5-7 years.Trainees should have experience of psychiatric internships and get assessed prospectively.After the training,trainees will receive the qualifications of the association for psychiatric training in Europe.While in China,the training time of psychiatrists is 3 years,the training of related departments is nearly 1 year,and psychiatric training is only 2 years.The training time of psychotherapy and clinical practice of psychiatry is still not enough.There is also a lack of consistency in the implementation of theoretical and practical training in all the bases in China.Therefore,by comparing the advantages and disadvantages of the Chinese and European psychiatry training system,this paper proposes optimizing the training program in China,increasing the students' humanistic cultivation and psychological care,and further improving the input of special training funds.

Objective To determine if the cardiac index (CI) measured with arterial pressure-based cardiac output (APCO) agrees with that measured with pulmonary artery catheter (PAC) during cesarean section in parturients with congenital heart disease and severe pulmonary hypertension.Methods Thirty parturients with congenital heart disease and severe pulmonary hypertension,scheduled for elective cesarean section,were enrolled in the study.APCO and PAC were used for cardiac output and other parameters of hemodynamics monitoring during operation in all patients.Continuous epidural anesthesia was performed.CI was recorded immediately before epidural administration (T1),at 5 and 10 min after epidural administration (T2-3),immediately before delivery (T4),and at 2 and 5 min after delivery (T5-6).The correlation was tested by Pearsone correlation analysis.CI derived from APCO and PAC was compared by Bland-Altman analysis for agreement.Results CI measured with PAC was significantly higher than that measured with APCO (P ＜ 0.05).Compared with the baseline value at T1,no significant difference in CI measured with PAC and APCO was found at T11-T4 and T6 (P ＞ 0.05),and CI measured with PAC and APCO was significantly increased at T5 (P ＜ 0.05).Bland-Ahman analysis showed poor agreement between CI measured with the two methods.The correlation analysis showed that there was positive correlation between CI derived from the two methods at T1-6 (the correlation coefficient was 0.93,0.95,0.94,0.89,0.96 and 0.91 at T1-6,respectively,P ＜ 0.05).Conclusion CI value obtained with APCO agrees poorly with that obtained with PAC during cesarean section in parturients with congenital heart disease and severe pulmonary hypertension,but agrees well in monitoring the changing trend of CI.

Objective To study the effects of the staging acupuncture combined with physical therapy on the neural function, motor function and activities of daily living in stroke patients. Methods 166 cases were divided into two groups: 83 cases in the treatment group were treated with staging acupuncture combined with physical therapy; 83 cases in the control group were treated with traditional acupuncture combined with physical therapy. They were evaluated with modified Edinburgh-Scandinavia Stroke Scale (MESSS)，Fugl-Meyer Assessment (FMA), and Bathel Index (BI) before and 2 months after treatment. Results There was no significant difference between these 2 groups before treatment (P>0.05), but were significant differences in MESSS, FMA and BI (P<0.05) after treatment. The incidence of recovery after treatment was 90.36% in treatment group, significantly better than that of the control group (74.49%, P<0.05). Conclusion In comparison with the traditional acupuncture, the staging acupuncture can significantly improve the effect on stroke based on the physical therapy.

Objective To compare the difference in quercetin against oxidative stress response in mouse and in NIH-3T3 cells before and after H2O2 treatment,to explore the underlying mechanism for the quercetin antioxidant.Methods The cultured NIH-3T3 cells were randomly divided into 4 groups: quercetin(Q) pre-protective group(Qb) firstly treated with quercetin for 24 h followed by incubation with H2O2 for 30 min;post-protective group(Qa) treated with H2O2 for 30 min followed by incubation with quercetin for 24 h;H2O2 group(H2O2) after exposure to H2O2 for 30 min,incubated with DMEM medium and the control group(C) only cultured with DMEM medium.The survival rate and apoptotic rate were detected respectively with MTT and TUNEL in NIH-3T3 cell sus-pension samples.The expression of cyclin D1,PTEN,NF-?B,HSP-70,BCl-2,BAX and caspase-3 were examined with immunocytochemistry and immunoblotting.Besides,20 Wistar rats were divided into control group and experimental group,the latter was given with quercetin in the doze of 0.13 mmol/kg.The levels of T-AOC,SOD,GSH-Px,GSH,MDA,NOS and NO2-/NO3-were detected both in the cleaved NIH-3T3 cells and in the plasma from both experimental and control animals prior to and post-1 h,2 h and after 24 h.Results When the Qb group was compared with H2O2 or Qa group,the survival rate was higher and the apoptotic rate was lower.When the H2O2 group was compared with C group,the expression of cyclin D1、PTEN or BCl-2 was down-regulated;while that of BAX、HSP-70、NF-?B or caspase-3 was up-regulated;the level of T-AOC,SOD,GSH-Px or GSH was decreased;that of NOS、NO2-/NO3-or MDA enhanced in the cleft NIH-3T3 cells.When the plasma level of the anti-oxidative enzyme system prior to-compared with post-1h and 2h-treatment with Q,the level of T-AOC,SOD,GSH-Px and GSH,especially the former two,were higher;MDA,lower;NOS or NO2-/NO3-promoted.However,the above parameters basically became normal 24 h after treatment with Q.Conclusion Quercetin down-regulates the promoted expression of HSP70,NOS,NO2-/NO3-and NF-?B etc.in H2O2-treatment NIH-3T3 cells.Qb could reverse the H2O2 damage effects more markedly.Moreover,the quercetin exerts anti-oxidant protective effect through modulating the anti-oxidative enzyme system both in vivo and in vitro.However,based on the cell heterogeneity in none-or pre/post-H2O2-treatment state,a difference in quercetin antioxidant response is noted.