Zearalenone(ZEN)is a mycotoxin that extensively contaminates food and feed,posing a significant threat to public health.However,the mechanisms behind ZEN-induced intestinal immunotoxicity remain unclear.In this study,Sprague-Dawley(SD)rats were exposed to ZEN at a dosage of 5 mg/kg/day b.w.for a duration of 14 days.The results demonstrated that ZEN exposure led to notable pathological alterations and immunosup-pression within the intestine.Furthermore,ZEN exposure caused a significant reduction in the levels of apolipoprotein E(ApoE)and liver X receptor(LXR)(P＜0.05).Conversely,it upregulated the levels of myeloid-derived suppressor cells(MDSCs)markers(P＜0.05)and decreased the presence of 27-hydroxycholesterol(27-HC)in the intestine(P＜0.05).It was observed that ApoE or LXR agonists were able to mitigate the immunosuppressive effects induced by ZEN.Additionally,a bioinformatics analysis highlighted that the downregulation of ApoE might elevate the susceptibility to colorectal,breast,and lung cancers.These find-ings underscore the crucial role of the 27-HC/LXR/ApoE axis disruption in ZEN-induced MDSCs proliferation and subsequent inhibition of T lymphocyte activation within the rat intestine.Notably,ApoE may emerge as a pivotal target linking ZEN exposure to cancer development.

Objective:To develop the Self-Stigma Scale for Drug Addicts(SSSDA),and test its validity and reliability.Methods:On the basis of literature analysis,open questionnaire survey,semi-structured interview and ex-pert consultation,the theoretical structure of the questionnaire was developed,and 943 drug addicts were test-ed.Sample 1(n=483)was used for item analysis and exploratory factor analysis,and sample 2(n=460)was used for confirmatory factor analysis,criterion related validity and internal consistency reliability analysis.Sixty-four drug addicts were retested 4 weeks later for test-retest reliability test.The criterion related validity was tested with the Drug Stereotype Threat Scale.Results:The scale consisted of 6 dimensions and 31 items,including self-negative cognition,stereotype identity,confidentiality,social avoidance,stigma experience,and stigma experience in the process of detoxification(factor loadings were from 0.41 to 0.81),which explained 64.09％of the total vari-ance.The 6-factor structure model fitted the data well(x2/df=2.82,RMSEA=0.06,CFI=0.92,GFI=0.85,TLI=0.91).The total scores and factor scores of the SSSDA were positively correlated with the DSTS scores(ICC=0.10-0.22,Ps＜0.05).The Cronbach α coefficients for the total scale and each dimension were between 0.80 and 0.95,and the test-retest reliability coefficients(ICC)were between 0.82 and 0.94.Conclusion:The Self-stigma Scale for Drug Addicts(SSSDA)initially developed in this study has satisfactory reliability and validity.

Objective:As the cesarean section rate increases year by year,the treatment of previous cesarean scar defects(PCSD)poses a significant challenge.This study aims to evaluate the clinical value of preoperative magnetic resonance imaging(MRI)technology and analyze relevant influencing factors for patients with abnormal uterine bleeding(AUB)associated with cesarean scar defects who underwent laparoscopic surgery.Methods:A retrospective cohort analysis was performed on women who underwent laparoscopic surgery for PCSD-related AUB at the Department of Gynecology,the Third Xiangya Hospital of Central South University from 2018 to 2022.A total of 57 patients who underwent laparoscopic surgery for the treatment of AUB associated with PCSD were divided into 2 groups based on their postoperative clinical cure status:The clinically-cured group(n=28,49.1%)and the non-clinically-cured group(n=29,50.9%).After a postoperative follow-up period of 3 months for all participants,logistic regression analysis was conducted to explore the correlation between the clinical cure rate of AUB associated with cesarean scar defects treated by laparoscopic surgery and various factors.These factors included patient age,clinical symptoms,obstetric history,history of cesarean section,basic clinical information,preoperative MRI parameters,and postoperative menstrual conditions.Results:There were no significant differences in many aspects,including the patient's age at the time of previous cesarean section,number of pregnancy,time since the previous cesarean section,the uterus position assessed by preoperative T2 signal MRI,defect length,defect width,residual muscle layer thickness,adjacent uterine muscle layer thickness,and distance from the defect to the external cervical os between the 2 groups(all P>0.05).However,the time of onset of AUB symptoms(P=0.036,OR=1.019,95%CI 1.002 to 1.038)and the depth of the defect on the preoperative MRI(P=0.010,OR=5.793,95%CI 1.635 to 25.210)were identified as risk factors affecting the clinical cure rate.Conclusion:The time of onset of AUB symptoms and the depth of the defect on preoperative MRI are risk factors that influence the clinical cure rate of laparoscopic surgery for the treatment of AUB associated with PCSD,which could be helpful for evaluating the prognosis of disease.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl

Objective:To study the clinical and genetics features of two families with dentatorubral-pallido-luysian atrophy (DRPLA), and to summarize the correlation between genotypes and phenotypes.Methods:The peripheral blood, clinical data and auxiliary examination results of probands and related members in 2 families with hereditary epilepsy and ataxia were collected from July 2018 to March 2019 in Peking University First Hospital.By whole exome sequencing and detecting the cytosine-adenine-guanine (CAG) repeats with capillary electrophoresis and fragment analysis, the genetic testing was conducted on the probands and their family members.The clinical and genetic characteristics of all affected members in the 2 families were also analyzed.Results:Two families were diagnosed with DRPLA.All 11 patients presented with psychomotor retardation, and 7 of them had seizures (including myoclonus, focal seizures and generalized tonic-clonic seizures, etc.). There were significant differences in clinical manifestations among different patients in the same family, and the filial generation had seizures at an earlier age with a more severe phenotype than the parental generation.The youngest onset age was 2 years old, and the largest was 45 years old.Five cases had seizures in childhood.Of the 11 patients, 5 cases were deceased, and the cause of death included seizure attacks, sudden unexpected death in epilepsy (SUDEP) and disease progression.The number of CAG repeat times in the fifth exon of the ATN1 gene were found abnormal in 6 surviving patients.The grandfather of the proband in pedigree 2 had normal clinical manifestations, but he also showed abnormal CAG repeats in the fifth exon of the ATN1 gene, which might be an intermediate allele. Conclusions:DRPLA is mainly featured by epilepsy, ataxia, psychomotor retardation and anticipation in clinical.This disease is rare in children with seizures as the first symptom, and has poor prognosis.An early diagnosis can facilitate genetic counseling.

Objective:This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China.Methods:Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods.Results:A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes ( P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk ( OR=0.84, 95% CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA ( P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance ( P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion:The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.

Objective: To summarize the clinical phenotypes of epilepsy in patients with GABRA1 gene variants. Methods: A total of 11 epileptic patients (4 boys and 7 girls) who were treated in the Department of Pediatrics, Peking University First Hospital from March 2016 to July 2019 and detected with GABRA1 gene heterozygous pathogenic variants by targeted next-generation sequencing were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively. Results: A total of 11 epileptic patients carried GABRA1 gene pathogenic variants, of whom 10 were de novo variants and the other one was inherited from the patient′s mother. Two patients had the same variants. Six variants were novel. Ages at seizure onset ranged from 3 to 14 months, and the median age was 8 months. The seizure was first observed within 1 year in 10 patients and beyond 1 year of age in 1 patient. Multiple seizure types were observed, including focal seizures in 10 patients, generalized tonic clonic seizures (GTCS) in 3 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. There were 5 patients with multiple seizure types. Sensitivity to fever was observed in 9 patients, among whom 6 patients had a history of status epilepticus. Two patients had photoparoxysmal response. Five patients had abnormal EEG background, and 6 patients had abnormal discharges in EEG during interictal phase. Brain magnetic resonance imaging (MRI) was normal in all patients. Developmental delay in various degrees was present in 9 patients. Among the 11 patients, Dravet syndrome was diagnosed in 5 patients, West syndrome in 2 patients, undiagnosed early-onset epileptic encephalopathy in 1 patient, and focal epilepsy in the other 3 patients. The ages at the last follow-up ranged from 8 months to 12 years. During follow-up, 8 patients were seizure-free for 6 months to 8 years, and 1 patient had discontinuation of medication. Conclusions In epilepsy associated with GABRA1 gene variants, de novo pathogenic variants are more common than inherited. Most epilepsy caused by GABRA1 gene variants occurs in infancy. Most patients have multiple seizures and focal seizures are common. Most patients have a comparatively favorable prognosis, but they may still have varied degrees of developmental delay.

Objective: To analyze the clinical characteristics of patients with PCDH19-female limited epilepsy (PCDH19-FE). Methods: The clinical data of 60 female epilepsy patients with PCDH19 gene heterozygous variations at the Department of Pediatrics, Peking University First Hospital from October 2007 to December 2018 were collected and analyzed retrospectively, their clinical manifestations, accessory examination and follow-up treatment were summarized. Results: Data of a total of 60 cases of PCDH19-FE were collected. The seizure onset occurred between 4 and 42 months of age (median: 11 months of age). Focal seizures occurred in 47 patients (78%), generalized tonic-clonic seizures (GTCS) occurred in 30 patients (50%), and other rare types of seizures included atypical absence, myoclonic, clonic, tonic, and atonic seizures. Two or more seizures types existed in 24 patients (40%), and seven patients (12%) had attacks of status epilepticus. Sensitivity to fever was observed in 47 out of them (78%) and clustering of seizures as found in all patients. During the interictal phase, focal discharges were monitored in 22 cases (22/45, 49%), multifocal discharges in 12 cases (12/45, 27%), widely discharging in 2 cases (4%), and both focal and widely discharging in 9 cases (20%). Clinical seizures were detected in 30 patients during the electroencephalogram (EEG) recording, including focal seizures in 22 cases, GTCS seizures in 8 cases, tonic seizure in three cases, myoclonic seizure followed by GTCS in one case, and two types of seizures in four cases. Before seizure onset, 57 patients had normal development and three patients had delayed language development. After seizure onset, varied degrees of intelligence disability were present in 38 cases (63%), language delay in 36 cases (60%), and gait instability in 10 cases (17%). Autistic features occurred in 17 cases (28%); and other behavioral problems like learning difficulties, personality, or emotional disorders existed in 33 cases (55%). Age at last follow-up ranged from one year and 3 months to 22 years and 3 months of age, 17 patients (28%) were seizure-free for more than 2 years (5 to 22 years at the last follow-up). The efficiency of antiepileptic drugs were 65% (33/51) in sodium valproate, 63% (27/43) in levetiracetam and 59% (20/34) in topiramate. Conclusions The clinical features of PCDH19-FE are characterized by clustering of seizures, focal seizures in most cases, sensitivity to fever mostly, focal discharges principally in EEG, varied degrees of intellectual disability or movement disorder, combined with autism spectrum disorders in partial and high efficiency in sodium valproate or levetiracetam treatment.

Objective: To summarize the clinical phenotype and genotype features of 3 children with progre-ssive myoclonic epilepsy (PME) caused by KCNC1 gene mutations, and to review the related literatures. Methods: The phenotype and genotype of 3 children with KCNC1 mutations in the Department of Pediatrics, Peking University First Hospital from October 2016 to January 2019 were analyzed.The 25 patients with KCNC1 mutations which had been reported internationally were also collected and analyzed. Results: Three children in this study were identified with KCNC1 de novo mutations, in which 2 children were identified with c. 959G>A (p.Arg320His) mutation, and 1 child with c. 1262C>T (p.Ala421Val) mutation.The clinical features of 3 children were consistent with PME, and the seizure onset ages were 3 months, 10 years and 11 years, respectively.Three children all had myoclonic seizures, among whom 1 child had generalized tonic-clonic seizure and 2 children had focal seizures.Three children all had intellectual and/or motor development delay.The electroencephalograph showed generalized spike and waves or polyspike and waves in 3 children, and focal discharge in 2 children.The brain imaging of 3 children was normal.The last follow-up ages were 3 years old, 13 years old and 12 years old, respectively.Until March 2019, there were 25 cases with KCNC1 gene mutations reported internationally.Including 3 patients in this study, there were 28 patients in total, of which 25 patients were diagnosed with PME.In these 25 patients, 24 patients were identified with p. Arg320His variant in the transmembrane area, 1 patient was identified with p. Ala421Val variant in the transmembrane area.The remaining 3 patients were only found with psychomotor developmental delay without seizures, and they were identified with p. Arg339X variant in the intracellular area.In the 28 patients, 16 cases received cranial imaging data, in which 12 patients had ce-rebellar atrophy and 4 cases were normal.Of the 28 patients, 18 cases were mentally retarded, 27 cases were development retardation or retrogression among whom 9 cases could not walk independently.Ten patients were over 30 years old when reported, and only 1 patient died of pneumonia and respiratory failure at 63 years old. Conclusions KCNC1 gene mutation mainly leads to PME phenotype, and a few patients can only show mental retardation.p.Arg320His is the most common variant of KCNC1 gene.The variants in different structural regions result in different clinical phenotypes, and variants in the transmembrane region can lead to severer clinical phenotypes.The 3 patients with KCNC1 gene mutations in this study are firstly reported cases in China.