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 cognitive level of parents' participation in treatment activities during perioperative period and analyze its influencing factors.Methods:A total of 500 parents of perioperative children treated in Jinan Maternity and Child Care Hospital, Children's Hospital Affiliated to Shandong University and Central Hospital Affiliated to Shandong First Medical University from March to October 2021 were selected by the convenient sampling method. The Cognitive Assessment Scale of Inpatients' Participation in Treatment Activities, Caregiver Positive Perception Scale and Overall Health Literacy Scale were used to investigate the patients. A total of 500 questionnaires were sent out in this study and 487 were effectively received, with an effective recovery of 97.4%.Results:The total cognitive score of 487 perioperative Children's parents' participation in treatment activities was (62.25±7.39) , and the average score of each dimension was from high to low as patients' participation cognition, behavior management cognition and treatment cognition. Multiple linear regression analysis showed that parents' age, educational level, marital status, previous caregiving experience, caregivers' positive feelings, health literacy and hospital stay of children were the factors influencing the cognitive level of parents' participation in treatment activities during perioperative period.Conclusions:Parents' age, education level, marital status, previous nursing experience, positive feelings of caregivers, health literacy and length of hospital stay of children are factors that influence the cognitive level of parents' participation in treatment activities during perioperative period. Targeted intervention measures can be taken in the future to improve the cognitive level of parents' participation in treatment activities during perioperative period to promote the recovery of children.

Objective:To evaluate the role of Toll-like receptor 4 (TLR4) in the mechanism by penehyclidine hydrochloride alleviating lipopolysaccharide (LPS)-induced acute lung injury(ALI)in rats.Methods:Twenty-four healthy male Sprague-Dawley rats, aged 10 weeks, weighing 220-250 g, were divided into 4 groups ( n=6 each) according to the random number table method: normal saline group (NS group), endotoxin-induced ALI group (ALI group), penehyclidine hydrochloride + normal saline group (PHC+ NS group) and penehyclidine hydrochloride + endotoxin-induced ALI group (PHC+ ALI group). ALI was induced by intratracheal instillation of LPS 5 mg/kg in anesthetized animals. In group PHC+ ALI, penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of LPS. The equal volume of normal saline was injected into the airway in group NS, and penehyclidine hydrochloride 2 mg/kg was intraperitoneally injected immediately after intratracheal instillation of normal saline in group PHC+ NS. The rats were sacrificed at 6 h after intratracheal instillation of LPS or normal saline, and lungs were removed. The lung was lavaged and broncho-alveolar lavage fluid (BALF) was collected for determination of concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) by enzyme-linked immunosorbent assay. Lung tissues were obtained for microscopic examination of the pathological changes (with a light microscope) and for determination of wet to dry lung weight ratio (W/D ratio) and TLR4 protein and mRNA expression (by immuno-histochemistry or real-time polymerase chain reaction). Results:Compared with group NS and group PHC+ NS, the W/D ratio and concentrations of TNF-α and IL-1β in BALF were significantly increased, the expression of TLR4 protein and mRNA in lung tissues was up-regulated ( P<0.01), and the pathological changes of lung tissues were aggravated in group ALI . Compared with group ALI, the W/D ratio and concentrations of TNF-α and IL-1β in BALF were significantly decreased, the expression of TLR4 protein and mRNA in lung tissues was down-regulated ( P<0.01), and the pathological changes of lung tissues were significantly mitigated in group PHC+ ALI. Conclusions:The mechanism by which penehyclidine hydrochloride reduces endotoxin-induced lung injury may be related to reduction of TLR4 activity and thus inhibition of pulmonary inflammatory responses in rats.

Objective:To analyze the etiological composition and changing trends in chronic kidney disease.Methods:CKD patients from our hospital were in cluded in the study from three separate periods, 173 patients from 1990-1991, 956 patients from 2009-2010, and 1440 patients from 2018-2019. The etiology of CKD in patients between the younger and middle-aged group and the elderly group were compared using the χ2 test, and the Bonferroni method was used to correct the pairwise comparisons.Results:The leading cause of CKD in 1990-1991, 2009-2010, and 2018-2019 was chronic glomerulonephritis (52%), chronic glomerulonephritis (35%), and diabetes (36%), respectively. The distribution of the etiologies was different signficantly among the three cohorts (χ2=74.375, P<0.001). Compared with 1990-1991, the percentage of CKD related to diabetes (χ2=14.847, P=0.001) and hypertension (χ2=12.279, P=0.002) significantly increased, while chronic glomerulonephritis showed a downward trend (χ2=19.976, P<0.001). Among the elderly CKD patients, the leading cause of CKD in the three cohorts was chronic glomerulonephritis (34%), diabetes (40%), and diabetes (43%), respectively. Conversely, diabetes and hypertension have become the predominant causes in 2009-2010 and 2018-2019. Although chronic glomerulonephritis remained the leading cause of CKD in the past 30 years, the percentage declined gradually among the younger and middle-aged patients with CKD. The percentage of CKD related to diabetes (χ2=31.345, P<0.001) and hypertension (χ2=15.485, P<0.001) significantly increased. In addition, in the 2018-2019 cohort, there were 494 patients with end-stage renal disease (ESRD), and the percentage of ESRD related to diabetes and hypertension were 48% and 37%, respectively. Conclusion:Diabetes and hypertension have become the predominant causes of CKD in Chinese elderly patients. Although chronic glomerulonephritis was the leading cause among the younger and middle-aged patients with CKD, the percentage declined gradually. Additionally, diabetes and hypertension were also the predominant causes of ESRD.

Objective:To explore the teaching effect of individualized teaching based on problem-based learning (PBL) that applied in gynecology practice teaching under the background of conflicts between postgraduate examination preparation and clinical internship for medical undergraduates.Methods:A total of 157 medical students of the five-year program who started gynecology internship and meanwhile prepared for the postgraduate entrance examination in 2018 were enrolled in the study and divided into two groups randomly. One group received traditional teaching (control group), and the other group received individualized teaching mode based on PBL (observation group). After the internship, the two groups of students were assessed for their theoretical and clinical skills, and the students' evaluation of the teaching effect was acquired through a questionnaire survey. SPSS 22.0 was used to perform chi-square test.Results:The students in observation group had statistically significant higher scores in theory and skill tests than those in the control group ( P<0.001). The evaluation of boosting their enthusiasm for internship, advancing self-learning ability, conducing to improving learning methods in the future, and enhancing clinical skills and thinking ability in the observation group was significantly better than that in the control group ( P<0.05). Conclusion:The individualized teaching model based on PBL could efficiently alleviate the conflicts between internship and postgraduate entrance examination preparation and improve the effect of gynecology practice teaching.

Objective:To investigate the clinical effect of perforator flap combined with toe transplantation for repairing thumb damage with soft tissue defect of hand.Methods:The retrospective observational study method was used. From May 2014 to June 2019, 8 patients with thumb damage and soft tissue defect of hand were admitted to the 988th Hospital of Joint Logistic Support Force of PLA, including 6 males and 2 females, aged from 25 to 46 years. Among them, thumb damage in 3 cases were degree Ⅱ, 1 case was degree Ⅲ, and 4 cases were degree Ⅳ. All thumb damage were repaired with perforator flap combined with toe transplantation. The skin and soft tissue defects of hand were repaired by free anterolateral thigh perforator flap in 6 cases and free deep inferior epigastric perforator flap in 2 cases. The thumb damage of degree Ⅱ was repaired by the first toe transplantation combined with perforator flap, and thumb damage of degree Ⅲ or Ⅳ was repaired by the second toe transplantation combined with perforator flap. The survival and blood supply of reconstructed thumbs and flaps, and wound healing of donor sites were observed after surgery. All the patients were followed up for 10 to 18 months, the appearance of the reconstructed thumbs, sensory recovery, and foot walking function were observed. At the final follow-up, the functional reconstruction of the thumb was evaluated.Results:All the blood supply and survival of the reconstructed thumbs and flaps were good, and all the wounds of donor sites healed well. During the follow-up, the appearances of the reconstructed thumb and flap were good, the sensation of pain and touch of the finger pulp recovered well, and no significant impact on foot walking function was observed. At the final follow-up, the function of reconstructed thumb was evaluated as excellent in 4 cases, good in 3 cases, and fair in 1 case.Conclusions:The repair method of perforator flap combined with toe transplantation technique can complete the targeted repair of thumb damage with skin and soft tissue defect of hand in one stage, minimizing the foot donor site injury and shortening the course of disease and early rehabilitation, which is one of the ideal methods for the treatment of complex thumb damage.

Objective: To analyze the essential medicines supply of medical institutions at county-level in Shaanxi Province and to provide empirical evidences and suggestions to improve relevant policies. Methods:A strati-fied cluster random sampling method was used to choose the institution samples. A survey was conducted to study the supply of essential medicines in 2012. Indicators include the variety and amount of essential medicines procured, the medicine shortage condition, and the rate of winning the bid for essential medicine. Results:Essential medicines ac-counted for 69 . 1% of all medicines;and procurement of essential medicines accounted for 42 . 4% of all procurement spending on medicines. Of the top 25 chemical products of essential medicines, provincial supplementary medicines accounted for 33. 9%;and among the top 25 traditional Chinese medicines of essential medicines, the provincial sup-plementary medicines accounted for 51. 9%. All 27 medical institutions faced a shortage of medicines. There were 47 kinds of essential drugs in urgent need were out of bid. Conclusion:Essential medicine supply of medical institutions at county-level is in good condition;however, more attention needs to be paid to medicine shortage. We should take measurements to standardize the process of bidding for essential medicines and strengthen the management of medi-cine shortage in order to better meet patients’ needs.

Objective To evaluate the implementation of the national essential medicine system in Shaanxi Province.Methods Using a standardized methodology (2008 Edition) developed by the World Health Organization(WHO) and Health Action International(HAD,data on the prices and availability of 38 essential medicines were collected from 120 primary,secondary and tertiary public hospitals in ten cities of Shaanxi Province from March to May 2012.Results The availability of essential medicines is generally low at public hospitals in Shaanxi province,as the average availability of originator brands is but 5.9％,and that of generics of the lowest prices is but 23.9％,while this availability at tertiary hospitals is higher than hospitals of lower levels.The procurement prices of originator drugs within essential medicines are distinctly higher than the international reference prices for the originator brands,and slightly higher for the lowest priced generics.The procurement prices at primary care hospitals are slightly lower than that of other hospitals.Retail prices of essential medicine are not significantly different among regions of different income levels.Affordability of originator brands is poor,while that of their generic equivalents is good.Conclusion The government is recommended to adjust the national essential medicine list,expand the variety of essential medicine moderately,improve the medicine pricing mechanism,and deepen public hospitals reform.

Objective To study the effects of the antiarrhythmic drugs of propafenone, amiodarone and dilthiazem on c-type Kv1. 4 channels in Xenopus laevis oocytes with two-electrode voltage-clamp technique. Methods Defolliculated oocytes ( stage Ⅴ - Ⅵ) had transcribed cRNAs of ferret Kv1. 4△N channels injected. The oocytes were continuously perfused with control solution or propafenone, amiodarone and dilthiazem under monitoring of software of Clampfit v 9. 0. Results All of the three drugs blocked ferret Kv1. 4△N channel in voltage-, frequency- and concentration-dependent manners. The values of IC50 (50%inhibiting concentration ) of propafenone, amiodarone and dilthiazem were ( 103.4± 2. 2 ) μ mol/L,(501.22 +5.9) μmol/L and (353.62 +9.9) μmol/L, respectively. The currents under the actions of propafenone , amiodarone and dilthiazem were decreased to 41%, 32% and 21% of control group, respectively. Propafenone (100μ mol/L), Amiodarone (500μmol/L), dilthiazem (350μmol/L) inhibited currents to (54. 6 + 1.9 ) %, ( 46. 3 + 3.5 ) %, ( 52. 8 ± 2. 8 ) % of control group in voltage-dependent blockage. Conclusions The results suggested that all the three drugs blocked the kv1. 4△N channel in the open state. The three drugs block the kv1. 4△N channel maybe had the similiar effects in some respects, but each had its unique characteristics.

The effects of the antiarrhythmic drug propafenone at c-type kv1.4 channels in Xenopus laevis oocytes were studied with the two-electrode voltage-clamp techinique. Defolliculated oocytes (stage V-VI) were injected with transcribed cRNAs of ferret Kv1.4 delta N channels. During recording, oocytes were continuously perfused with control solution or propafenone. Propafenone decreased the currents during voltage steps. The block was voltage-, use-, and concentration- dependent manners. The block was increased with positive going potentials. The voltage dependence of block could be fitted with the sum of monoexponential and a linear function. Propafenone accelerated the inactivate of current during the voltage step. The concentration of half-maximal block (IC(50)) was 121 micrometer/L. With high, normal, and low extracellular potassium concentrations, the changes of IC(50) value had no significant statistical differences. The block of propafenone was PH- dependent in high-, normal- and low- extracellular potassium concentrations. Acidification of the extracellular solution to PH 6.0 increased the IC50 values to 463 micrometer/L, alkalization to PH 8.0 reduced it to 58 micrometer/L. The results suggest that propafenone blocks the kv1.4 delta N channel in the open state and give some hints for an intracellular site of action.
Animals ; Anti-Arrhythmia Agents/*pharmacology ; Hydrogen-Ion Concentration ; Inhibitory Concentration 50 ; Kv1.4 Potassium Channel/*antagonists & inhibitors/metabolism ; Oocytes/drug effects/metabolism ; Patch-Clamp Techniques ; Potassium/*metabolism ; Potassium Channel Blockers/*pharmacology ; Propafenone/*pharmacology ; Xenopus laevis