Objective:To explore the efficacy and safety of endoscopic radial incision (ERI) for congenital membranous duodenal stenosis (MDS).Methods:The clinical data of 13 children with MDS receiving ERI in the Department of Gastroenterology of Xi'an Children's Hospital from May 2017 to December 2021 were reviewed and analyzed. The perioperative management, surgical procedures, postoperative complications and follow-up were summarized.Results:There were 5 boys and 8 girls with a median disease duration of 8 (2-20) months, and the median age of diagnosis was 13 months (5-30 months). The septum of 10 cases (10/13) was located in the descending part of the duodenum, and that of 3 cases (3/13) in the horizontal part. The papilla of 1 case (1/13) opened on the septum, that of 3 cases (3/13) within 5 cm of the mouth side of the septum, and that of 9 cases (9/13) within 5 cm of the anal side of the septum. The median diameter of the septal aperture was 3 mm (2-6 mm). All 13 children successfully underwent ERI with a median operation time of 20 min (15-32 min). The average surgical incision was 3 strokes (2-4 strokes), and the endoscope with outer diameter 9.9 mm could pass stenosis after ERI. The median incision diameter was 10 mm (10-12 mm). All patients achieved relief of clinical symptoms after ERI. One patient (1/13) suffered from the postoperative delayed bleeding, which was stopped by endoscopic titanium clamping. No intestinal perforation or duodenal papilla injury occurred, and median postoperative hospital stay was 6 days (5-10 days). The upper gastrointestinal angiogram and gastroscopy were repeated 3 months after ERI, and the median diameter of stenosis was 12 mm (10-15 mm), which was significantly dilated compared with before. The mean body weight increase at 1 month after ERI was 1.20 kg (0.50-1.80 kg), and the mean body weight increase at 3 months was 3.50 kg (2.50-4.00 kg), which reached the normal body weight of the same age.Conclusion:ERI is safe and effective for the treatment of MDS in children, and shows good clinical application and promotion value.

Objective:To unveil the pathological changes associated with demyelination in schizophre-nia(SZ)and its consequential impact on interstitial fluid(ISF)drainage,and to investigate the thera-peutic efficacy of ursolic acid(UA)in treating demyelination and the ensuing abnormalities in ISF drainage in SZ.Methods:Female C57BL/6J mice,aged 6-8 weeks and weighing(20±2)g,were randomly divided into three groups:control,SZ model,and UA treatment.The control group received intraperitoneal injection(ip)of physiological saline and intragastric administration(ig)of 1％carboxy-methylcellulose sodium(CMC-Na).The SZ model group was subjected to ip injection of 2 mg/kg dizo-cilpine maleate(MK-801)and ig administration of 1％CMC-Na.The UA treatment group underwent ig administration of 25 mg/kg UA and ip injection of 2 mg/kg MK-801.The treatment group received UA pretreatment via ig administration for one week,followed by a two-week drug intervention for all the three groups.Behavioral assessments,including the open field test and prepulse inhibition experiment,were conducted post-modeling.Subsequently,changes in the ISF partition drainage were investigated through fluorescent tracer injection into specific brain regions.Immunofluorescence analysis was employed to examine alterations in aquaporin 4(AQP4)polarity distribution in the brain and changes in protein expres-sion.Myelin reflex imaging using Laser Scanning Confocal Microscopy(LSCM)was utilized to study modifications in myelin within the mouse brain.Quantitative data underwent one-way ANOVA,followed by TukeyHSD for post hoc pairwise comparisons between the groups.Results:The open field test re-vealed a significantly longer total distance[(7 949.39±1 140.55)cm vs.(2 831.01±1 212.72)cm,P＜0.001]and increased central area duration[(88.43±22.06)s vs.(56.85±18.58)s,P=0.011]for the SZ model group compared with the controls.The UA treatment group exhibited signifi-cantly reduced total distance[(2 415.80±646.95)cm vs.(7 949.39±1 140.55)cm,P＜0.001]and increased central area duration[(54.78±11.66)s vs.(88.43±22.06)s,P=0.007]compared with the model group.Prepulse inhibition test results demonstrated a markedly lower inhibition rate of the star-tle reflex in the model group relative to the controls(P＜0.001 for both),with the treatment group dis-playing significant improvement(P＜0.001 for both).Myelin sheath analysis indicated significant demy-elination in the model group,while UA treatment reversed this effect.Fluorescence tracing exhibited a significantly larger tracer diffusion area towards the rostral cortex and reflux area towards the caudal thala-mus in the model group relative to the controls[(13.93±3.35)mm2 vs.(2.79±0.94)mm2,P＜0.001 for diffusion area;(2.48±0.38)mm2 vs.(0.05±0.12)mm2,P＜0.001 for reflux area],with sig-nificant impairment of drainage in brain regions.The treatment group demonstrated significantly reduced tracer diffusion and reflux areas[(7.93±2.48)mm2 vs.(13.93±3.35)mm2,P＜0.001 for diffusion area;(0.50±0.30)mm2 vs.(2.48±0.38)mm2,P＜0.001 for reflux area].Immunofluorescence staining revealed disrupted AQP4 polarity distribution and reduced AQP4 protein expression in the model group compared with the controls[(3 663.88±733.77)μm2 vs.(13 354.92±4 054.05)μm2,P＜0.001].The treatment group exhibited restored AQP4 polarity distribution and elevated AQP4 protein expression[(11 104.68±3 200.04)μm2 vs.(3 663.88±733.77)μm2,P＜0.001].Conclusion:UA intervention ameliorates behavioral performance in SZ mice,Thus alleviating hyperactivity and anxiety symptoms and restoring sensorimotor gating function.The underlying mechanism may involve the improve-ment of demyelination and ISF drainage dysregulation in SZ mice.

Objective:To compare the antiplatelet effects of vicagrel and clopidogrel in patients with different cytochrome P450 (CYP) 2C19 genotypes.Methods:This is a post-hoc analysis of a phase Ⅱ clinical trial of vicagrel, which included patients with coronary heart disease who underwent percutaneous coronary intervention from August 2018 to June 2019 in 18 centers. Patients were categorized based on the presence of CYP 2C19 *2 or *3 loss-of-function (LOF) alleles into LOF carrier group ( n=111) and non-LOF carrier group ( n=90). Each group included patients received vicagrel 5 mg, 6 mg, 7.5 mg, or clopidogrel 75 mg for 28 days per study protocol. P2Y 12 reaction units (PRU) were measured using VerifyNow at baseline, 6 to 8 hours after loading dose, 7 to 10 days after randomization, and 28 days after randomization and the percentage inhibition of platelet aggregation (%IPA) was calculated. The primary endpoint was %IPA on day 28. Within the patients from the General Hospital of Northern Theater Command, 8 to 12 patients in each study arms were enrolled in a prespecified pharmacokinetic sub-study, measuring the time to reach maximum plasma concentration (T max), peak plasma concentration (C max), and area under the plasma concentration-time curve (AUC). Results:Among 201 patients, the age was (58.8±8.5) years, and 139 (69.2%) were male. In non-LOF carriers, there was no significant differences in PRU values and %IPA between the vicagrel 5 mg, 6 mg, 7 mg, and clopidogrel groups at all time points (all P>0.05). In LOF carriers, %IPA was significantly higher in the vicagrel-treated groups than in the clopidogrel group at 6-8 hours after loading dose (22.9 (14.2, 31.5)% vs. 19.8 (11.0, 28.6)% vs. 29.5 (20.9, 38.0)% vs. 12.9 (3.9, 21.9)%, P=0.038) and 7-10 days after randomization (22.4 (14.2, 30.5)% vs. 34.4 (26.1, 42.6)% vs. 39.8 (31.8, 47.9)% vs. 24.7 (16.3, 33.2)%, P=0.001), with a trend towards higher %IPA in the vicagrel-treated groups at day 28 (30.4 (21.3, 39.6)% vs. 36.5 (27.2, 45.7)% vs. 40.8 (31.8, 49.8)% vs. 30.7(21.2, 40.2)%, P=0.056). Pharmacokinetic results of 35 patients showed that the C max and AUC of the active metabolite M15-2 of vicagrel was similar to that of clopidogrel in non-LOF carriers, but AUC between vicagrel 5 mg, 6 mg, 7 mg and clopidogrel were significantly different in LOF carriers ((5.6±0.6) h·μg -1·L -1 vs. (6.8±2.7) h·μg -1·L -1 vs. (9.2±3.3) h·μg -1·L -1 vs. (4.2±1.9) h·μg -1·ml -1, P=0.020). Conclusion:Vicagrel and clopidogrel have similar antiplatelet effects in non-LOF carriers, but vicagrel exhibits superior antiplatelet effects in LOF carriers.

Interstitial lung disease is a common lung disease of connective tissue disease,which seriously affects the survival rate and quality of life of patients with connective tissue disease.Interstitial lung disease may occur in the whole course of connective tissue disease.Therefore,imaging plays an important role in the whole disease cycle of connective tissue-associated interstitial lung disease.At present,high-resolution computed tomography is the cornerstone of screening,diagnosis and follow-up of connective tissue-associated interstitial lung disease,but ionizing radiation is a potential limiting factor in its clinical application.In recent years,new imaging techniques have developed rapidly,and some promising research results have been achieved in the early screening,diagnosis and efficacy evaluation of connective tissue-associated interstitial lung disease,and they are gradually moving towards non-invasive,low-radiation and accurate imaging analysis techniques.This article reviews the advances in imaging research of connective tissue-associated interstitial lung disease,and analyzes the advantages and disadvantages of various new imaging techniques,as well as the challenges and prospects.

Objective:To investigate the diagnostic and therapeutic value of one-time biliopancreatic-duct-imaging-system (eyeMax)-assisted endoscopic retrograde appendicitis therapy (ERAT) for children.Methods:A total of 11 children who were diagnosed as having uncomplicated acute appendicitis by imaging in Xi′an Children′s Hospital from August to November 2022 were enrolled. All patients received subscope-assisted ERAT. Subscope was intubated into the appendix cavity to observe the mucosa directly. Appendicitis was treated through cleansing, fecalith extraction, stent drainage. The clinical manifestations under subscope were recorded, as well as the treatment success rate, intubation success rate, the effective rate, complication incidence during and after the operation.Results:The age of 11 children was 7.93±2.67 years old. Appendix intubation was successful in all patients. Congestion and swelling of the mucosa in appendiceal orifice and appendix cavity were seen under the subscope in 11 children. There were 6 cases with appendiceal fecaliths, 8 cases with pus and 6 cases with luminal distortion or stenosis. Perforation was observed in 1 case during the operation and no other complication occurred. All patients were treated under subscope, including flushing appendiceal cavity (11 cases), fecalith extraction with extraction basket (3 cases), and appendiceal drainage with stenting (2 cases). The symptoms and signs were relieved after the operation, and the effective rate within 48 hours was 10/11. There were no procedure-related complications or recurrence during postoperative follow-up for 1 week to 4 months.Conclusion:Acute appendicitis could be diagnosed by observing the appendix cavity directly under one-time biliopancreatic-duct-imaging-system-assisted ERAT, and also could be treated with the system, where appendix could be preserved and radiation damage could be avoided with safety and effectiveness.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

Objective: To investigate abnormal spinal curvature among primary and secondary school students in Sichuan Province, so as to provide evidence for scientific prevention. Methods: Using a stratified cluster random sampling method, a total of 210 713 students of grade 4 to grade 12 from 21 cities (prefectures) in Sichuan Province were selected for spinal curvature screening and questionnaire survey from September to November 2022. Chi-square test and multivariate Logistic regression model were used to analyze the influencing factors of abnormal spinal curvature. Results: The detection rate of abnormal spinal curvature was 3.42%, with urban areas (4.54%) higher than that in suburban areas(2.57%), girls (3.86%) higher than that in boys(2.98%), high school students (4.70%) higher than that in middle school students (3.80%) and elementary school students(2.21%), the differences were statistically significant ( χ 2=606.96, 123.81, 645.24, P <0.01). Multivariate Logistic regression analysis showed that urban area, junior and senior high school, girl, carrying backpack on one shoulder, desks and chairs adjusted for student height less than ≤1 time every school year, moderate-to-vigorous physical activity less than 1 h per week, and indoors sedentary time more than 10 h/d were positively associated with abnormal spinal curvature ( OR=1.72, 1.75, 1.87, 1.26, 1.09, 1.07, 1.10, 1.25 , P <0.05). Conclusion The detection rate of abnormal spinal curvature of primary and secondary school students may be affected by the urbanicity, educational stage as well as gender in Sichuan Province. More attention should be paid to urban high school girls, and targeted strategies should be explored to reduce the incidence of abnormal spinal curvature.

Objective:To evaluate the safety and effectiveness of capsule endoscopy for the diagnosis of intestinal diseases in children.Methods:Clinical data of 113 pediatric patients who received capsule endoscopy in Xi'an Children's Hospital from October 2018 to September 2020 were retrospectively analyzed. The completion rate, passage time of stomach and small intestine, lesion detection rate, adverse reactions and complications of capsule endoscopy were analyzed.Results:Among 113 pediatric patients, 78 (69.03%) were male and 35 (30.97%) were female. The age was (99.8±44.7) months (9-195 months), and 31 (27.43%) were under 7 years old. The minimum weight was 9 kg and the minimum height was 70 cm. Eighty-seven pediatric patients (76.99%) swallowed capsules orally (the oral group) with the minimum age of 4 years and 3 months. Capsules were implanted in 26 pediatric patients (23.01%) under gastroscopy (the gastroscopic group), with the maximum age of 9 years and 2 months. Unexplained abdominal pain (47.79%) and unexplained gastrointestinal bleeding (31.89%) were common in the pediatric patients. The completion rate of capsule endoscopy was 97.35% (110/113), and the detection rate of lesions in small intestine was 31.81% (35/110). The passage time of small intestine in the gastroscopic group was significantly longer than that of the oral group (461.04±129.27 min VS 288.23±107.84 min, t=5.646, P<0.01). There was no significant difference in the passage time of stomach or small intestine among different genders, different ages or different endoscopic examination results ( P>0.05). The positive results of capsule were not correlated with the method of ingestion ( P=0.401, OR=2.562, 95% CI:0.284-23.077), gender ( P=0.154, OR=2.352, 95% CI:0.726-7.616), age ( P=0.949, OR=1.007, 95% CI:0.816-1.242), examination reason ( P=0.246) or small intestine passage time ( P=0.219, OR=1.003, 95% CI:0.998-1.008). No complications such as capsule retention occurred in any pediatric patient. Conclusion:Capsule endoscopy in children is noninvasive, rapid and simple, which can improve the diagnostic rate of small intestinal diseases in children, and can be further promoted in pediatric patients.

Objective:To explore the relationship between drug evidence and core prescription for depression.Methods:We retrieved literature of TCM for depression from CNKI, VIP and Wangfang databases to November 2019, 30th as well as there cords from Ancient and Modern Medical Records Cloud Platform (V 1.5). The Excel 2010 was used to establish the standardized database of medical records. After the standardization of medicines, Ancient and Modern Medical Records Cloud Platform (V1.5) statistics methodswere used for association rules analysis, complex networks, and analysis of drugs’ frequency, medical characteristics, core prescription drugs.Results:A total of 632 effective prescriptions were included, involving a total of 527 drugs. The results of frequency of herbs showed that 23 kinds of high-frequency herbs were obtained. Bupleuri Radix was the most frequently used medicine. Most herbs are warm or flat, with pungent, sweet and bitter in taste, belonging to the lung, liver, heart and spleen meridians. A total of 25 drug-pair association and 13 TCM association were obtained by association rule analysis. Conclusions:TCM treatment for depression is mainly based on soothing the liver and regulating qi, clearing the heart and calming the nerves. Bupleuri Radix, Curcumae Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, Ziziphi Spinosae Semen are the basic prescriptions. Angelicae Sinensis Radix, Ophiopogonis Radix, Albiziae Cortex, Polygalae Radix, Poria are used as reference.

Objective:To evaluate high resolution esophageal manometry (HREM) in peroral endoscopic myotomy (POEM) for pediatric achalasia of cardia (AC).Methods:Data of 30 AC children who received POEM in Xi′an Children′s Hospital from January 2013 to September 2019 were reviewed. HREM was performed before and 6 months after POEM. Preoperative and postoperative lower esophageal sphincter pressure (LESP), 4-second integrated relaxation pressure (4sIRP), Eckardt scores and nutritional status were compared.Results:Children with AC aged between 4-14 years. Postoperative LESP was 5.50±1.13 mmHg (1 mmHg=0.133 kPa), which was significantly lower than that before operation (26.23±4.47 mmHg) with significant difference ( t=-24.623, P<0.001). Postoperative median 4sIRP was 5 mmHg, which was 20 mmHg lower than that before operation (25 mmHg) with significant difference ( Z=-4.786, P<0.001). Postoperative median Eckardt symptom score decreased significantly compared with that before (1 VS 8, Z=-4.796, P<0.001). Severe malnutrition of the AC children improved evidently to normal( Z=-5.166, P<0.001). Conclusion:POEM can significantly improve the characteristics of esophageal dynamics in children with AC, and HREM can be an important indicator for follow-up evaluation of POEM.