Heterozygous loss-of-function variants of FOXP4 are associated with neurodevelopmental disorders (NDDs) that exhibit delayed speech development, intellectual disability, and congenital abnormalities. The etiology of NDDs is unclear. Here we found that FOXP4 and N-cadherin are expressed in the nuclei and apical end-feet of radial glial cells (RGCs), respectively, in the mouse neocortex during early gestation. Knockdown or dominant-negative inhibition of Foxp4 abolishes the apical condensation of N-cadherin in RGCs and the integrity of neuroepithelium in the ventricular zone (VZ). Inhibition of Foxp4 leads to impeded radial migration of cortical neurons and ectopic neurogenesis from the proliferating VZ. The ectopic differentiation and deficient migration disappear when N-cadherin is over-expressed in RGCs. The data indicate that Foxp4 is essential for N-cadherin-based adherens junctions, the loss of which leads to periventricular heterotopias. We hypothesize that FOXP4 variant-associated NDDs may be caused by disruption of the adherens junctions and malformation of the cerebral cortex.
Mice ; Animals ; Ependymoglial Cells/physiology* ; Cadherins ; Neurons/metabolism* ; Cerebral Cortex/metabolism* ; Cell Differentiation ; Cell Movement

Objective:To investigate the safety and the efficacy of percutaneous and surgical approach in femoro-femoral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) cannulation.Methods:All consecutive patients implanted with femoro-femoral VA-ECMO between January 2018 and December 2020 in Beijing Anzhen Hospital, Capital Medical University. Propensity score matching was used to compare outcomes of percutaneous and surgical groups while controlling for confounders.Results:Among the 276 patients who received femoro-femoral VA-ECMO (62 surgical and 214 percutaneous), propensity-score matching selected 52 pairs of patients with similar characteristics with mean age of(59.6±13.0)years old, in which 26 patients were female. There were a lower ECMO cannulation-associated complication (28.8% vs. 48.1%, P=0.044) and a lower hospital mortality (42.3% vs. 67.3%, P=0.010) in the percutaneous group. The circuit blood flow after ECMO initiation was similar in both groups[(3.3±0.8)L·min -1·kg -1 in percutaneous group vs. (3.2±0.7)L·min -1·kg -1 in surgical group, P=0.738]. The serum lactate was declined in both group after ECMO initiation[(5.4±5.8)mmol/L vs. (9.2±6.9)mmol/L, P<0.001 in percutaneous group; (6.3±6.2)mmol/L vs. (10.5±7.0)mmol/L, P=0.003 in surgical group]. Conclusion:Percutaneous approach is a safe and efficient technique in emoro-femoral VA-ECMO cannulation. Compared with surgical cannulation, percutaneous approach is associated with lower ECMO cannulation-associated complication and lower hospital mortality.

OBJECTIVE：To understand the current status of clinical understanding of “prohibiting”“avoiding”“using caution ” in the application of TCM ，and to provide reference for standardizing the connotation and rational application of “prohibiting” “avoiding”“using caution ”of TCM. METHODS ：Based on the theory of “knowledge-attitude-behavior”，doctor-pharmacist questionnaires and patient questionnaires were designed on the basis of literature research and clinical practice. Through the “Tencent questionnaire ”platform，800 doctor-pharmacist questionnaires were distributed to nearly 300 medical institutions from 32 provinces（cities，autonomous regions ）and 800 patient questionnaires were distributed to public patiants who had used TCM nationwide by anonymous online method. After dimensionality reduction of the questionnaire from three dimensions of cognition ， attention and behavior ，the cognition ，attention and behavior of “prohibiting”“avoiding”“using caution ”in the application of TCM were evaluated by 10 points system. RESULTS ：A total of 703 doctor-pharmacist questionnaires were collected ，including 638 valid questionnaires with recovery rate of 87.9％ and effective rate of 90.8％；Cronbach alpha coefficient was 0.90. A total of 644 patient questionnaires were collected ，including 621 valid questionnaires with recovery rate of 80.5％ and effective rate of 96.4％ . The cognition score of doctors and pharmacists to the terms of “prohibiting”“avoiding”“using caution ”in clinical application of TCM was （7.94±1.21），and that of patients was （5.64±1.54）. The score of doctors and pharmacists ’attention to the above terms was （9.47±1.15）（Spearman Rho correlation coefficient with cognition score was 0.077，P＞0.05），and the score of behavioral ability of patients was （7.01±1.71）（Spearman Rho correlation coefficient with cognition score was －0.021，P＞ 0.05）. The score of behavior ability was （7.43 ± 1.72） （Spearman Rho correlation coefficient with cognition score was 0.233，P＜0.01）. TCM textbooks （89.2％），trainingmeetings （66.5％） and herbal prescriptions （58.2％） were the main ways for doctors and pharmacists to learn the above taboos. Medical staff （74.2％）and internet （52.5％）were the main ways for patients to understand the above taboos. CONCLUSIONS ：Doctors，pharmacists and patients pay more attention to the terms of “prohibiting”“avoiding”“using caution ”in the clinical application of TCM ，but their cognition and executive power were low. Clinical cognition of “prohibiting”“avoiding”“using caution ”in the application of TCM is relatively vague，and the corresponding clinical practice behavior is lacking. It is yet to establish clinical specialist consensus in the field of TCM and publicize it actively to improve the level of clinical rational drug use.

Objective:To explore the mediating effect of stigma and loneliness between anxiety and attitude towards seeking professional psychological help among college freshmen.Methods:A sample of 920 freshmen was recruited in the study and they were required to complete self-rating anxiety scale(SAS), attitudes toward seeking professional psychological help scale-short form(ATSPPH-SF), questionnaire of stigma for seeking professional psychological help(SSPPH), University of California, Los Angeles loneliness scale(UCLA). SPSS 24.0 was used for descriptive analysis and correlation analysis.SPSS macro program PROCESS 3.4 was used to analyze the mediating effect.Results:(1) The scores of anxiety, stigma, loneliness and attitude towards seeking professional psychological help of all subjects were (44.70±7.13), (19.14±6.79), (52.30±6.65) and (18.12±3.49). Anxiety was positively correlated with stigma and loneliness( r=0.170, 0.351, both P<0.01). Stigma was positively correlated with loneliness ( r=0.264, P<0.01). Attitude towards seeking professional psychological help was negatively correlated with anxiety, stigma and loneliness( r=-0.085, -0.459, -0.185, all P<0.05). (2) There were three paths that anxiety affected attitude towards seeking professional psychological help.The mediating effect size of stigma was -0.037, accounting for 75.51% of the total indirect effect.The mediating effect size of loneliness was -0.011, accounting for 22.45% of the total indirect effect.The chain mediating effect of anxiety and attitude towards seeking professional psychological help was -0.001, accounting for 2.04% of the total indirect effect. Conclusion:Stigma and loneliness play multiple mediating effects on the relationship between anxiety and attitude towards seeking professional psychological help.

Objective To investigate the prevalence of nutritional risk (NRS2002) and malnutrition inhospitalized stroke patient and their nutritional intervention. Methods The stroke patients admitted to three de-partments of vascular neurology ward including cerebral hemorrhage, cerebral infarction and subarachnoid hemor-rhage in Beijing Tiantan Hospital from January 2018 to January 2019 were recruited using cluster sampling. Nutri-tional risk screening 2002 ( NRS 2002) was used to screen the nutritional risk of inpatients Malnutrition was as-sessed by criteria:(1) body mass index (BMI) <18. 5 kg/m2 with poorer general condition from January 2018 to January 2019;(2) Global leadership initiative on malnutrition ( GLIM) criteria were used except whole body muscle mass measurement from October 2018 to January 2019. The nutritional intervention for patients were closely observed during hospitalization. Results A total of 1532 patients were registered and1036 patients were included in the final analysis considering the inclusion and exclusion criteria. The prevalence of nutritional risk was 33. 0％ ( 342/1036) . The prevalence of malnutrition based on BMI and GLIM criteria was 0. 9％( 9/1036) and 2. 5％ (10/393) respectively. Among the 342 patients with nutritional risk, 112 patients received nutritional support therapy by tube feeding, but only 29 patients received nutritional support that met guideline standards. 81 patients received not standard nutritional support, and 2 patients received highly unregulated nutritional sup-port. No patients received sugar and electrolyte infusion, oral nutritional supplements ( ONS) , oral nutritional a-gents and compound nutrition intervention. The other 230 patients took hospital diet. Conclusion The prevalence of nutritional risk in hospitalized patients with cerebral hemorrhage, cerebral infarction or subarachnoid hemorrhage was high, and the prevalence of malnutrition was extremely low. There was a low proportion of nutri-tional support. High quality of large sample cohort studies will be conducted to show whether reasonable applica-tion of nutritional support therapy in patients with nutritional risk can improve patient outcome.

The laterodorsal tegmentum (LDT) is a brain structure involved in distinct behaviors including arousal, reward, and innate fear. How environmental stimuli and top-down control from high-order sensory and limbic cortical areas converge and coordinate in this region to modulate diverse behavioral outputs remains unclear. Using a modified rabies virus, we applied monosynaptic retrograde tracing to the whole brain to examine the LDT cell type specific upstream nuclei. The LDT received very strong midbrain and hindbrain afferents and moderate cortical and hypothalamic innervation but weak connections to the thalamus. The main projection neurons from cortical areas were restricted to the limbic lobe, including the ventral orbital cortex (VO), prelimbic, and cingulate cortices. Although different cell populations received qualitatively similar inputs, primarily via afferents from the periaqueductal gray area, superior colliculus, and the LDT itself, parvalbumin-positive (PV) GABAergic cells received preferential projections from local LDT neurons. With regard to the different subtypes of GABAergic cells, a considerable number of nuclei, including those of the ventral tegmental area, central amygdaloid nucleus, and VO, made significantly greater inputs to somatostatin-positive cells than to PV cells. Diverse inputs to the LDT on a system-wide level were revealed.

Objective To investigate the incidence and risk factors of acute kidney injury(AKI) requiring continuous renal replacement treatment(CRRT) in patients with acute type A aortic dissection after Sun's operation.Methods A retrospective analysis of consecutive patients with acute type A aortic dissection underwent Sun's operation in Beijing Anzhen Hospital,Capital Medical University from January 2009 to December 2015.These patients were divided into two groups according to whether had severe postoperative AKI requiring CRRT treatment:the dialysis group(AG,65 cases) and the control group(CG,618 cases),we compared the clinical outcomes of patients in two groups and analyzed the related risk factors.Results 50 patients(7.3％) died in hospital.Compared with patients in CG group,patients in AG group had higher age,more patients with preoperative coronary heart disease,pericardial tamponade,and higher rates of intraoperative coronary artery hypass surgery or valve surgery,the results were statistically different between the two groups(P ＜0.05).The patients in AG group had a higher mortality rate in hospital(26.2％ vs.5.3％),and the difference was statistically significant(P ＜0.001).The results of multiple regression analysis suggested that the age ＞ 50 years,preoperative history of pericardial tamponade,intraoperative need for combined coronary artery bypass grafting or valve surgery,and cerebral perfusion time ＞40 min were independent risk factors for CRRT treatment of postoperative severe AKI(P ＜0.05).Conclusion The incidence of severe AKI requiring CRRT treatment in patients with acute type A aortic dissection after Sun's operation was 9.5％,and the discharge survival rate in AG group was lower than that in CG group.An important way to reduce the incidence of severe AKI requiring CRRT after sun's surgery is to shorten the intraoperative cerebral perfusion time as much as possible.

Critical ultrasonography(CUS) is different from the traditional diagnostic ultrasound,the examiner and interpreter of the image are critical care medicine physicians.The core content of CUS is to evaluate the pathophysiological changes of organs and systems and etiology changes.With the idea of critical care medicine as the soul,it can integrate the above information and clinical information,bedside real-time diagnosis and titration treatment,and evaluate the therapeutic effect so as to improve the outcome.CUS is a traditional technique which is applied as a new application method.The consensus of experts on critical ultrasonography in China released in 2016 put forward consensus suggestions on the concept,implementation and application of CUS.It should be further emphasized that the accurate and objective assessment and implementation of CUS requires the standardization of ultrasound image acquisition and the need to establish a CUS procedure.At the same time,the standardized training for CUS accepted by critical care medicine physicians requires the application of technical specifications,and the establishment of technical specifications is the basis for the quality control and continuous improvement of CUS.Chinese Critical Ultrasound Study Group and Critical Hemodynamic Therapy Collabration Group,based on the rich experience of clinical practice in critical care and research,combined with the essence of CUS,to learn the traditional ultrasonic essence,established the clinical application technical specifications of CUS,including in five parts:basic view and relevant indicators to obtain in CUS;basic norms for viscera organ assessment and special assessment;standardized processes and systematic inspection programs;examples of CUS applications;CUS training and the application of qualification certification.The establishment of applied technology standard is helpful for standardized training and clinical correct implementation.It is helpful for clinical evaluation and correct guidance treatment,and is also helpful for quality control and continuous improvement of CUS application.

Objective: To compare the outcome of radiofrequency catheter ablation under local anesthesia/sedation (S) or general anesthesia(GA) in atrial fibrillation patients. Methods: Data of 498 patients with atrial fibrillation undergoing radiofrequency catheter ablation in our departmentfrom January 2014 to December 2015 were retrospectively analyzed. Two hundred and twenty patients assigned to the GA group, the other 278 patients to the S group. Patients were followed clinically every 3 months within one year after procedure. Immediate electrocardiogram was performed in patients with palpitation or choking sensation in chest. The end point of the study was recurrence of any atrial tachyarrhythmia lasting >30 seconds in device interrogation, 24-hour Holter monitoring or 12-lead electrocardiogram after a single procedure. After the ablation procedure, a blanking period of 3 months was allowed according to the guidelines. Procedure time, radiofrequency time, fluoroscopy time, the detection of paroxysmal supraventricular tachycardia, the success rate and the complications were compared between the two groups. Results: There was no difference in the baseline characteristics between the two groups, such as age, gender, BMI, complications, LVEF, LAD (all P>0.05). The duration of procedure ((117.8±51.7)minutes vs.(115.4±36.9)minutes, P=0.79), duration of fluoroscopy((12.5±11.2)minutes vs. (10.4±10.2)minutes, P=0.35), duration of radiofrequency((40.1±12.9)minutes vs. (48.6±44.3)minutes, P=0.48) were similar between the two groups (P>0.05). Compared with S group, discovery of the frequency of atrioventricular node reentrant tachycardia (AVNRT) was significantly lower in GA group (0 vs. 3.6%(10/278), P<0.01), but the difference disappeared with repeat electrophysiological examination when patients become conscious from GA(3.2%(7/220) vs. 3.6%(10/278), P=0.311). The difference of atrioventricular reentrant tachycardia (AVRT) was similar between the two groups(0.9%(2/220) vs. 0.7%(2/278), P=0.841). Compared with S group, reflection of vagus nerve was less in GA group (1.4%(3/220) vs. 8.6%(24/278), P=0.026). After following up of (356±92) days, freedom from atrial fibrillation/atrial flutter/atrial tachyarrhythmia was similar between the two groups(77.9%(162/208) vs. 79.9%(215/269), P=0.818). Conclusion General anesthesia is a promising method to atrial fibrillation ablation, in view of stable patient status and safety for the procedure. There is no difference in complications, recurrence of arrhythmia between the two groups, but detection rate of AVNRT is lower in GA group.