WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice / 神经科学通报·英文版

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.

Discussion on the performance reform of administrative and logistics personnel in a large public hospital / 中华医院管理杂志

Because the work of administrative and logistics personnel in public hospitals is difficult to quantify and evaluate, its performance reform is difficult. A large public hospital in Wuhan has explored and established a distribution incentive mechanism that combines department performance appraisal, individual classification and grading, and secondary distribution within the department. Taking into account the completion of performance appraisal indicators of the national tertiary public hospital in the department, the results of the institutional " Excellent Management Team Ranking" , personal job grades, working years and other factors, a relatively mature and operable system has been formed, which could provide reference for the performance reform of other hospitals.

Clinical efficacy of trimebutine combined with Xiangsha Pingwei in the treatment of functional dyspepsia and its effect on gastrointestinal hormone / 中国综合临床

Objective To investigate the clinical efficacy of trimebutine combined with Xiangsha Pingwei in the treatment of functional dyspepsia and its effect on gastrointestinal hormone.Methods One hundred and twenty cases of functional dyspepsia were randomly divided into the control group and observation group,60 cases in each group.The control group was treated with trimebutine 0.2 g,3 times/d and the observation group was treated with trimebutine 0.2 g,3 times/d and Xiangsha Pingwei 10 g,2 times/d.Both groups were treated for four weeks,a course of treatment.Clinical efficacy and the influence on gastrointestinal hormone levels were compared between the two groups.Results The symptoms scores in both groups all decreased significantly after treatment.While the postprandial fullness scores,early satiety scores and epigastric pain scores in the observation group were significantly lower than those in the control group (0.62±0.12 vs.1.85±0.25,0.56±0.14 vs.1.46±0.21,0.48±0.15 vs.1.32±0.12,t=34.36,27.62,33.87,P<0.05).The total effective rate in the observation group was significantly higher than that in the control group (90.00% vs.73.33%,χ2=5.57,P<0.05).MOT and GAS levels in both groups increased significantly.While MOT and GAS levels in the observation group were significantly higher than those in the control group (MOT: (355.2±78.1) ng/L vs.(288.7±82.4) ng/L;GAS:(96.5±17.6) ng/L vs.(88.4±16.0) ng/L,t=4.54,2.64,P<0.05).The somatostatin (SS) level in both groups decreased significantly.While the SS level in the observation group was significantly lower than that in the control group ((41.1±11.1) ng/L vs.(48.9±12.9) ng/L,t=3.55,P<0.05).Conclusion Trimebutine combined with Xiangsha Pingwei can significantly improve the clinical symptoms and gastrointestinal hormone in patients with functional dyspepsia.

The relationship of plasma homocysteine level and apolipoprotein E gene polymorphism with Alzheimer's disease / 中华老年医学杂志

Objective To investigate the correlations of plasma homocysteine(Hcy)level and apolipoprotein E gene polymorphism with Alzheimer' s disease(AD)and mild cognitive impairment (MCI).Methods A case-control study in 66 AD patients(AD group),64 MCI patients(MCI group) and 54 healthy controls(control group)was conducted.Plasma Hcy level and ApoE polymorphism were determined and analyzed.Results Plasma Hcy levels were significantly higher in AD and MCI groups than in control subjects(both P＜0.001).AD patients also showed increased plasma Hcy levels as compared with MCI patients(P＜0.001).Logistic regression analysis indicated that the increased plasma Hcy level was a risk factor for AD and MCI(OR＝ 1.435 and 1.312,both P＜0.001).ApoE ε3/3 was the most common genotype in AD,MCI and control groups,and ε3/4 and ε4/4 genotypes were more common in AD group and MCI group than in control group(both P＜0.05).The ε4 allele frequency of ApoE was 24.2％ and 23.4％ in AD or MCI group respectively,and 6.5％ in control group(AD or MCI vs.control,P＜0.05).The analysis by multiplicative interaction model showed that the odd ratio for MCI was 23.3 in patients with only hyperhomocysteinemia(Hhcy,Hcy＞ 15 μmol/L),12.6 in patients with carrying ε4 allele,and 46.7 in patients with both Hhcy and carrying ε4 allele,which indicated that there was interaction between hyperhomocysteinemia and carrying e4 allele.Conclusions Hyperhomocysteinemia and ApoE ε4 allele are correlated with dementia and also have additive interactions.

The role of calcium/calmodulin dependent serine protein kinase in embryonic development and related diseases / 中华医学遗传学杂志

Calcium/calmodulin dependent serine protein kinase (CASK), which belongs to the family of membrane associated guanylate kinase (MAGUK) proteins, has several isoforms. CASK expresses differently in embryonic tissues and adult tissues. It can be modulated by phosphorylation and SUMOylation. CASK plays an important role in neural development, spermatozoal development and renal development. Dysfunction of CASK may lead to diseases. CASK is distributed extensively in the brain, regulating synapse formation. Mutation of CASK can lead to several neurologic diseases. CASK is also involved in the development and maturation of sperm and fertilization. It also can influence renal development through interaction with DLG1.

Emergency endoscopic intervention in acute obstructive suppurative cholangitis complicated with septic shock / 中华消化内镜杂志

Objective To evaluate the efficacy of emergency endoscopic intervention in acute obstructive suppurative cholangitis (AOSC) complicated with septic shock.Methods A total of 54 patients with AOSC and septic shock who underwent therapeutic emergency ERCP were included in this retrospective study,and were evaluated by the shock index (SI).Results ERCP was performed for all patients in 24hours after hospitalization,and the average ERCP operation time was 23.8 ± 12.5 min.All 54 patients underwent EST,46 of whom received ENBD,7 biliary stenting and 1 transferred to surgery due to bleeding.The post-ERCP mortality rate was 0,and the complications included 1 case of pancreatitis and 2 cases of pneumonia.The positive rate ofGram-Negative bacillus before ERCP was 46.9％ (15/32).The SI before ERCP was 1.250 ±0.200,which decreased to 0.950 ±0.119 at 2hr after the procedure (P ＜0.001 ),and decreased further to 0.598 ± 0.099 ( P ＜ 0.001 ) at 24 hours after ERCP.Conclusion Therapeutic emergency ERCP is of great importance in the treatments for AOSC complicated with septic shock.

Regulation of the protein stability of POSH and MLK family

Sequential activation of the JNK pathway components, including Rac1/Cdc42, MLKs (mixed-lineage kinases), MKK4/7 and JNKs, plays a required role in many cell death paradigms. Those components are organized by a scaffold protein, POSH (Plenty of SH3's), to ensure the effective activation of the JNK pathway and cell death upon apoptotic stimuli. We have shown recently that the expression of POSH and MLK family proteins are regulated through protein stability. By generating a variety of mutants, we provide evidence here that the Nterminal half of POSH is accountable for its stability regulation and its over-expression-induced cell death. In addition, POSH's ability to induce apoptosis is correlated with its stability as well as its MLK binding ability. MLK family's stability, like that of POSH, requires activation of JNKs. However, we were surprised to find out that the widely used dominant negative (d/n) form of c-Jun could down-regulate MLK's stability, indicating that peptide from d/n c-Jun can be potentially developed into a therapeutical drug.

Characteristics of parental rearing pattern in schizophrenics with brilliant school records / 中国组织工程研究

Objective To explore the features of the parental rearing behavior in schizophrenics with a brilliant school records.Methods 51 schizophrenics in remission with brilliant records were tested by EMBU.36 healthy volunteers were randomized into the controls group.Result Subjects with schizophrenia had abnormal parental rearing behavior,such as overprotection, predilection over intervention and over punishment of parents.Most of them come from peasant family.Conclusion The factors such as abnormal parental rearing behavior probably influence the development of schizophrenics.