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.
Mice ; Animals ; Microcephaly/genetics* ; Autistic Disorder/metabolism* ; Autism Spectrum Disorder/metabolism* ; Nerve Tissue Proteins/metabolism* ; Brain/metabolism* ; Mice, Knockout ; Cell Cycle Proteins/metabolism*

As the National Health Commission changes the management of novel corona virus infection, the situation and preventive policies for controlling the epidemic have also entered a new stage in China. Perioperative care strategies for orthopedic trauma such as designated isolation and nucleic acid test screening have also been adjusted in the new stage. Based on the perioperative work experiences in the new stage of epidemic from the frontline anti-epidemic staff of orthopedics in domestic hospitals and combined with the literature and relevant evidence-based medical data in perioperative care of orthopedic trauma patients under the current anti-epidemic policies at home and abroad, Chinese Orthopedic Association and Chinese Society of Traumatology organized relevant experts to formulate the Guideline for clinical perioperative care of orthopedic trauma patients in the new stage of novel corona virus infection ( version 2023). The guideline summarized 16 recommendations from the aspects of preoperative diagnosis and treatment, infection prevention, emergency operation and postoperative management to systematically standardize the perioperative clinical pathways, diagnosis and treatment processes of orthopedic trauma in the new stage of novel corona virus infection, so as to provide a guidance and reference for hospitals at all levels to carry out relevant work in current epidemic control policies.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Since December 2019, novel coronavirus pneumonia (NCP) has been reported in Wuhan, Hubei Province, and spreads rapidly to all through Hubei Province and even to the whole country. The virus is 2019 novel coronavirus (2019-nCoV), never been seen previously in human, but all the population is generally susceptible. The virus spreads through many ways and is highly infectious, which brings great difficulties to the prevention and control of NCP. Based on the needs of orthopedic trauma patients for emergency surgery and review of the latest NCP diagnosis and treatment strategy and the latest principles and principles of evidence-based medicine in traumatic orthopedics, the authors put forward this expert consensus to systematically standardize the clinical pathway and protective measures of emergency surgery for orthopedic trauma patients during prevention and control of NCP and provide reference for the emergency surgical treatment of orthopedic trauma patients in hospitals at all levels.

Objective: To investigate the association between hyponatremia and hemodynamic and prognosis in patients with intermediate-risk acute pulmonary embolism. Methods: We retrospectively recruited 110 intermediate-risk acute pulmonary embolism patients (right ventricular dysfunction was confirmed by echocardiography and CT scan with or without the elevated levels of cardiac injury biomarkers) in the first and the second affiliated hospital of Harbin medical university from January 1,2011 to December 31, 2014. The patients were aged (58.4±14.9) years old.There were 49 males and 61 females.Patients were divided into 2 groups as non-hyponatremia group (plasma sodium>135 mmol/L, 93 cases) and hyponatremia group (plasma sodium≤135 mmol/L, 17 cases). Baseline clinical and hemodynamic parameters were obtained from these patients. All enrolled patients were followed up after discharge. Results: Heart rate ((106.7±21.9) beats per minute vs. (93.4±19.4) beats per minute, P=0.043),N-terminal pro B type natriuretic peptide (NT-proBNP, (5 561±1 593) ng/L vs. (1 738±589) ng/L, P=0.005), mean pulmonary arterial pressure((42.6±12.6)mmHg(1 mmHg=0.133 kPa) vs. (33.9±13.3)mmHg, P=0.046), mean right atria pressure ((20.6±8.1)mmHg vs. (10.2±5.4)mmHg, P=0.014), systolic right atria pressure ((27.3±9.0)mmHg vs. (15.6±6.1)mmHg,P=0.013) and diastolic right atria pressure(6.5(4.3,15.5)mmHg vs. 5.0(2.0,8.0)mmHg,P=0.016) were significantly higher in hyponatremia group than in non-hyponatremia group,and systolic blood pressure was significantly lower in hyponatremia group than in non-hyponatremia group ((113.5±21.9)mmHg vs.(129.5±28.9)mmHg, P=0.048). Pearson correlation analysis showed that hyponatremia was negatively correlated with heart rate (r=-0.262, P=0.043), NT-proBNP (r=-0.227, P=0.048), mean pulmonary arterial hypertension (r=-0.259, P=0.046), mean right ventricular pressure (r=-0.296, P=0.047), mean right atria pressure (r=-0.550, P=0.001), systolic right atria pressure (r=-0.552, P=0.001), and diastolic right atria pressure (r=-0.542, P=0.001). Kaplan-Meier survival analysis showed that the 1-year, 2-year and 3-year cumulative survival rates were 76.5%,70.6%,and 64.7% in the hyponatremia group, and 90.3%,86.0%,and 83.9% in the non-hyponatremia group(log-rank test, P=0.036).Multivariate Cox regression analysis showed that hyponatremia was an independent risk factor of death of intermediate-risk pulmonary embolism patient(HR=4.126, 95%CI 1.982-11.343, P=0.036). Conclusion Hyponatremia is associated with adverse hemodynamic and reduced survival in patients with intermediate-risk pulmonary embolism.

Objective To evaluate the effect of pitavastatin on blood glucose in patients with hypercholesterolemia,and to investigate the efficacy of pitavastatin in diabetic patients combined with hypercholesterolemia.Method This study was a 12-week,multi-center,open-label,without parallel-group comparison,phase Ⅳ clinical trail.Results Contrasting to baseline,the prevalences at week 4 and 12 post-treatment of abnormal fasting plasma glucose (FPG) and glycosylated hemoglobin Alc (HbA1c)( FPG:14.2％ vs 14.1％ and 11.0％ ; HbA1c:14.3％ vs 15.1％ and 16.1％ ) in the safety set subjects without diabetes mellitus (DM),as well as in those with DM but not taking glucose-lowering drugs (FPG:7/7 vs 4/7 and 5/7; HbAlc:5/5 vs 4/4 and 5/5) had no significant changes (all P vaules ＞0.05).Contrasting to baseline,the levels of TC [ (6.51±0.94) mmol/L vs (5.12 ±0.93) mmol/L and (4.54 ±1.00) mmol/L],LDL-C [(4.11 ±0.79)mmol/L vs (3.02 ±0.81) mmol/L and (2.51 ±0.70)mmol/L] and TG [2.10(1.53,2.54) mmol/L vs 1.62(1.26,2.00) mmol/L and 1.35(1.10,1.86)mmol/L]at week 4 and 12 post-treatment in the per protocol set 55 subjects with DM were significantly reduced (all P values ＜ 0.05 ) ; 33.3％ of subjects at high risk and 10.0％ of subjects at very high risk had achieved a TC target value; 55.6％ of subjects at high risk and 40.0％ of subjects at very high risk had achieved a LDL-C target value.Conclusion Pitavastatin has a safe effect on blood glucose and it could be used to treat diabetic patients combined with hypercholesterolemia in China.

ObjectiveTo investigate the association of hypertensive target organ damage with abnormal ankle brachial index (ABI) in high-risk hypertensive patients.MethodsDuring December 2008 to May 2009,a cross-sectional study was conducted to investigated the prevalence of abnormal ABI (ABI ＜ 0.90) in 2674 community-dwelling,hypertensive patients,who aged ＞ 40 years,without coronary heart disease,stroke/transient ischemic attack or known arteriosclerosis,from 18 centers in China. Data were acquired through history,physical examination,laboratory and other diagnostic tests.ResultsThere were 2615 subjects eligible for the full analysis set. The high-risk hypertensive patients with arterial wall thickening,arterial wall thickening and slightly elevated serum creatinine had a higher prevalence of abnormal ABI than their counterparts respectively ( P ＜ 0.05 ). Compared with the normal group,the abnormal ABI group had a higher serum creatinine level on average (P ＜ 0.01 ).After adjustment for certain factors including investigation center,demographic factors,cardiovascular disease (CVD) risk and CVD risk factors using an unconditional logistic regression model,arterial wall thickening ( OR 2.416,95％ CI 1.395-4.183,P =0.0016 ) and slightly elevated serum creatinine ( OR 3.377,95％ CI 1.267-8.997,P =0.0149) were positively associated with abnormal ABI. However,arterial wall thickening (OR 0.988,95％ CI 0.576-1.695,P=0.9664) and microalbuminuria (OR 1.389,95％ CI0.685-2.817,P=0.3621)were irrelevant to abnormal ABI.Conclusions So far as a high-risk hypertensive patient is concerned,there are significant statistical correlations between arterial wall thickening and/or slightly elevated serum creatinine and an abnormal ABI,but no significant statistical correlations between arterial wall thickening or microalbuminuria and an abnormal ABI is observed.

Objective To compare the clinical outcomes of Chinese rapamycin-eluting stents (Firebird stents) and imported paclitaxel-eluting stents ( Taxus stents ) in the treatment of acute myocardial infarction. Methods Ninety-seven patients with ST segment elevated acute myocardial infarction were treated with Firebird stents (in 51 patients) and Taxus stents (in 46 patients). The death rate, re-acute myocardial infarction, target lesion revascularization (TLR) ,and major adverse cardiac event (MACE) within 9 months after percutaneous coronary intervention ( PCI) were observed between the two groups. Results The rate of successful stent-implantation, angina,death, re-acute myocardial infarction, TLR and MACE was 100% ,9. 8% ,0% ,2. 0% ,0% , 11. 8% in the Firebird stent group and 100% ,8. 7% ,0% ,2. 2% ,0% ,0% and 10.9% in the Taxus stents group within 9 months after PCI. There was no significant difference between the two groups. Conclusions There is no significant difference in the clinical effect between the Firebird stent group and Taxus stent group within 9 months after PCI. However, the effect-cost ratio is better in the Firebird stent than the Taxus stent.

Objective:To investigate the role of transforming growth factor β1 (TGFβ1) in the development of Helicobacter pylori ( H. pylori)-associated non-metaplastic atrophic gastritis. Methods:The expressions of TGFβ1, CD68 and smooth muscle actin(SMA) were detected immunohistochemically in 10 patients with mild non-atrophic gastritis, 30 patients with mild non-metaplastic atrophic gastritis, and 32 patients with severe non-metaplastic atrophic gastritis having H. pylori infecion. Meanwhile, three cases of mild non-atrophic gastritis and 4 cases of severe non-metaplastic atrophic gastritis were observed with electron microscope. Results: The count of TGFβ1 positive cells per high-power field (HPF) in severenon-metaplastic atrophic gastritis group (53±22 ) was significantly higher than that in mild non-atrophic gastritis group(22±/HPF) and mild non-atrophic gastritis group(0-3/HPF, P＜0.01). The count of CD68 positive cells in severe non-metaplastic atrophic gastritis group (23±7/HPF) was significantly higher than that in mild non-atrophic gastritis group (13±/HPF) and mild non-atrophic gastritis group (0-3/HPF, P＜0. 01). Correlation analysis showed that the expressions of TGFβ1 and CD68 had a moderate correlation in each group ( r = 0. 634, P＜ 0. 01; r = 0. 699, P＜ 0. 01). Compared with mild non-atrophic gastritis, SMA-positive myofibroblasts and smooth muscle cells in the lamina propria increased in mild and severe non-metaplastic atrophic gastritis. Ultrastructurally, the proliferation of fibroblasts in gastric lamina propria was observed in mild non-atrophic gastritis, while the proliferation of fibroblasts and presence of myofibroblasts could be observed in mild non-metaplastic atrophic gastritis, and there was a parallel phenomenon between myofibroblasts and fibroblasts, as well as smooth muscle cells.Conclusion: Our findings indicate that TGFβ1 expression increases with severity of H. pylori-associated non-metaplastic atrophic gastritis, suggesting that TGFβ1 might play an important role in the development of non-metaplastic atrophic gastritis.

ObjectiveTo evaluate the efficacy and safety of tirofiban in treatment of ST segment elevation acute myocardial infarction(STEAMI) no-reflow and acute thrombosis after emergency percutaneous coronary intervention(PCI). MethodsForty patients which were made definite diagnosis of STEAMI were intra-coronary artary injection fortirofiban after emergency PCI stenting occured no-reflow and acute thrombosis. First,the dose of 0.4μg·kg-1·min-1 was given from intra--coronary artary injection of tirofiban within three minutes, after 30min the dose were given 0.1μg·kg-1·min-1 for 48 hours. ResultsThe no re-flow and acute thrombosis was completely disappeared within five minutes,at the time,side effect with in one week was not observed. ConclusionsTirofiban treatment by direct injection in coronary arteries combined with emergency PCI, can increase the repeffusion rate of infarction related vessel in AMI patients,and improve TIMI reflow. This reperfusion method was effective and safe.