ObjectiveTo explore the relationship between negative life events and depression severity in adolescent patients with depressive disorder， as well as the chain mediating role of insomnia symptoms and quality of life. Methods374 outpatient patients and hospitalized patients with adolescent depressive disorders were enrolled. The Adolescent Life Event Scale （ASLEC）， the Insomnia Severity Index （ISI）， the World Health Organization Quality of Life Questionnaire Short Form （WHOQOL-BREF）， and the Center for Epidemiology Depression Scale （CES-D） were used to evaluate the negative life event situation， insomnia symptoms， quality of life level and depression severity of the subjects， respectively. In addition， the PROCESS 4.0 macroprogram was used to analyze the chain mediating effect of insomnia symptoms and quality of life between negative life events and depression severity in patients with adolescent depressive disorder. ResultsThe results of correlation analysis showed that there was a significant correlation between negative life events and insomnia symptoms， quality of life， and depression severity （all P<0.05）. In addition， the results of chain mediation showed that negative life events had a significant direct effect on depression severity， with an effect size of 0.12 （P<0.001）. Insomnia symptoms and quality of life played a mediating role in the relationship between negative life events and depression severity in patients with adolescent depressive disorders， with indirect effect sizes of 0.062 （95%CI： 0.040-0.087） and 0.091 （95%CI： 0.059-0.123）， respectively. It could also play a chain mediation role， and the effect size was 0.039 （95%CI： 0.024-0.057）. ConclusionNegative life events experienced by patients with adolescent depressive disorder not only directly affect the severity of depressive symptoms， but may also indirectly exacerbate depression through insomnia symptoms and quality of life.

Post-stroke anxiety disorder （PSA） is a common psychiatric complication of stroke， which jeopardizes patients' recovery and their quality of life. Recent studies suggest that inflammation plays an important role in the pathogenesis of PSA. Therefore， this paper reviewed the related licture about the association between PSA and serum inflammatory biomarkers in order to provide references for the intervention of PSA. In this study， a comprehensive search was performed in China National knowledge Infrastructure （CNKI）， Wanfang Data， Web of Science and PubMed database to identify the well qualified literature focusing on the relationship between PSA occurrence and serum inflammatory biomarkers， and a total of 13 studies were retrieved. Analysis indicates a certain association between PSA occurrence and serum inflammatory biomarkers， and denotes that the elevation of inflammatory biomarkers may be a trigger for the disease occurrence and its progression， but the specific mechanism underlying this relationship requires further study.

ObjectiveTo explore the current status and issues regarding the application of ancient books in clinical practice guidelines and expert consensus of traditional Chinese medicine （TCM） published in China， and to provide methodological recommendations for the incorporation of ancient books in the development of TCM guidelines. MethodsWe searched China National Knowledge Infrastructure （CNKI）， WanFang Data， VIP， SinoMed， PubMed， Embase， as well as six industry websites including China Association of Chinese Medicine， National Group Standards Information Platform， and Chinese Association of the Integration of Traditional and Western Medicine，etc. TCM clinical practice guidelines or expert consensus issued during January 1st， 2017， to November 26th， 2022 were searched. Clinical practice guidelines or expert consensus that explicitly referred to ancient books were included， and the content regarding the searching for ancient books， sources of access to ancient books， methods of evaluating the level of evidence， methods of evaluating the level of recommendation， and methods of evaluating the evidence for the ancient books were analysed. ResultsA total of 1,215 TCM clinical practice guidelines or expert consensus were retrieved， with 442 articles explicitly mentioning the application of ancient books， including 300 （67.87%） clinical practice guidelines and 142 （32.13%） expert consensus. Sixty of the 442 publications explicitly reported that ancient books searching had been conducted （13.57%）； among these 60 publications 27 （45.00%） explicitly reported ancient books searching strategies， and the most frequent method was manual searching with a total of 24 articles （40.00%）. The most popular search source was Chinese Medical Dictionary， a TCM classics database， with a total of 18 articles. 197 articles （44.57%） explicitly reported the evaluation criteria for the level of evidence， of which 141 articles （71.57%） involved the evaluation criteria for the ancient books； 413 articles （93.44%） mentioned ancient books in the recommendations， and only the source of formula name was mentioned in 409 （99.03%） of the publications. ConclusionThe current application of ancient books in TCM clinical practice guidelines and expert consensus is limited， with issues of non-standard searching and evaluation methods. Standar-dization and uniformity are needed in evidence grading and recommendation standards. Future research should clarify the scope and methods of applying ancient book， emphasize their integration with modern research evidence， and enhance their value and quality in the development of TCM clinical practice guidelines.

Objective To investigate the effect of ankyrin-repeat domain-containing protein 22(ANKRD22)on the proliferation,invasion,and migration of human hepatoma cells and its molecular mechanism.Methods The TCGA database was used to analyze the expression level of ANKRD22 in normal liver tissue and hepatocellular carcinoma tissue and its association with prognosis.Western Blot and qRT-PCR were used to measure the expression of ANKRD22 in human normal liver cells(L-02)and human hepatoma cells(Huh7,HepG2,MHCC-97H,SK-HEP-1,and SMMC-7721);CCK-8 assay,EdU,wound healing assay,and Transwell assay were used to observe the effect of ANKRD22 on the proliferation,invasion,and migration of hepatoma cells;Western Blot was used to investigate the association of ANKRD22 with cyclins and EMT-related proteins;KEGG and ssGSEA analyses were performed to investigate the mechanism of action of ANKRD22 in hepatoma cells,and related experiments were conducted for validation.The independent-samples t-test was used for comparison of continuous data between two groups;a one-way analysis of variance was used for comparison between multiple groups,and the least significant difference t-test was used for further comparison between two groups.Results In the TCGA database,the expression level of ANKRD22 in hepatoma tissue was significantly higher than that in normal liver tissue(t=5.083,P<0.05),and the patients with a high expression level of ANKRD22 had longer overall survival and disease-related survival than those with a low expression level of ANKRD22(P<0.05).The expression level of ANKRD22 in various human hepatoma cell lines was higher than that in human normal liver cells(all P<0.05).Cell proliferation assay showed that the ANKRD22 overexpression group had significantly higher EdU positive rate and proliferation rate than the Vector group(t=19.60 and 6.72,both P<0.001),and compared with the si-NC group,the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower EdU positive rate and proliferation rate(all P<0.001).Compared with the Vector group,the overexpression group had significantly higher expression levels of Cyclin E1,Cyclin D1,CDK7,and CDK4(t=3.54,4.95,6.34,and 5.19,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).The overexpression group had a significantly lower expression level of P27 than the Vector group(t=6.12,P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).Invasion and migration experiments showed that compared with the Vector group,the ANKRD22 overexpression group had significantly higher migration rate and number of crossings through the membrane(migration group and invasion group)(t=5.01,25.60,and 3.67,all P<0.05),and compared with the si-NC group,thesi-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower migration rate and number of crossings through the membrane(migration group and invasion group)(all P<0.01).The overexpression group had significantly higher expression levels of N-cadherin,Vimentin,and Snail than the Vector group(t=12.13,8.85,and 13.97,all P<0.001),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001);the overexpression group had a significantly lower expression level of E-cadherin than the Vector group(t=4.98,P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had a significantly higher expression level than the si-NC group(both P<0.001).The KEGG enrichment analysis and the ssGSEA analysis showed that ANKRD22 was associated with the PI3K/AKT/mTOR signaling pathway in hepatocellular carcinoma,and the overexpression group had significantly higher expression levels of p-AKT/AKT,p-PI3K/PI3K,and p-mTOR/mTOR than the Vector group(t=12.21,3.43,and 9.75,all P<0.01),and the si-ANKRD22#2 group and the si-ANKRD22#3 group had significantly lower expression levels than the si-NC group(all P<0.001).Conclusion ANKRD22 is highly expressed in hepatoma cells and can promote the proliferation,invasion,and migration of hepatoma cells and the activation of the PI3K/AKT/mTOR signaling pathway.

Objective:To summarize the clinical phenotypes and genetic variations of children with epilepsy related to CLCN4 gene mutations. Methods:A retrospective analysis was conducted on 9 children with epilepsy who were diagnosed with CLCN4 gene mutations through whole-exome sequencing of family members. These children were treated at the Department of Pediatrics, Peking University First Hospital from December 2016 to March 2024. Their clinical manifestations, electroencephalogram, cranial imaging characteristics, and treatment follow-up were reviewed. Results:Among the 9 children, 6 were male and 3 were female. All cases involved de novo mutations. Three cases carried the c.823G>A/p.V275M variant, 2 cases carried the c.2152C>T/ p.R718W variant, 1 case carried the c.1630G>A/pG544R variant, and 1 case carried the c.2167C>T/ p.R723W variant. Two cases carried the unreported new variant c.848G>T/p.S283I and c.818G>A/ p.G273E. The onset age of epilepsy ranged from 55 days to 10 years, with a median onset age of 14 months. Seven out of 9 children had epilepsy onset before the age of 2 years. The types of seizures varied: 8 had focal seizures, 1 had generalized tonic-clonic seizures, 2 had myoclonic seizures, 1 had epileptic spasms, and 1 had atypical absence seizures. Three children experienced multiple types of seizures. All 9 children exhibited developmental delays to varying degrees: 8 had global developmental delay and 1 had cognitive developmental delay. Developmental delays were observed in 7 children before the onset of epilepsy. Clinically, 1 child was diagnosed with infantile epileptic spasms syndrome, 7 with unclassified developmental and epileptic encephalopathy, and 1 with focal epilepsy with developmental delay. At the last follow-up, the age of the children ranged from 2 years and 5 months to 13 years and 9 months. Seizures had been controlled in 3 children for a duration of 4 to 12 months. Conclusions:De novo variants are common in CLCN4 variants. Most seizures onset in infancy, seizure types are various, and focal seizures are common. Most of them have developmental delay and drug-resistant epilepsy, and some of them have developmental delay before seizure onset, which is consistent with the characteristics of developmental and epileptic encephalopathy.

Objective:To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE).Methods:Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children′s Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children′s characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications.Conclusions:The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.

Objective:To summarize the clinical features of epilepsy and (or) developmental delay associated with KCNB1 gene variants in children.Methods:A case series study was conducted on 24 children with KCNB1 gene variants associated with epilepsy and (or) developmental delay who were treated at the Children′s Medical Center of Peking University First Hospital and the Department of Neurology of Shenzhen Children′s Hospital from July 2015 to June 2024. The manifestations of seizures, electroencephalogram (EEG) and genetic test results of those children were analyzed.Results:All the KCNB1 gene variants were de novo, involving 20 different variation, including 15 missense variations, 3 frameshift variations and 2 nonsense variations. There were 7 novel variations. Among the 24 developmental and epileptic encephalopathy children, there were 14 boys and 10 girls. The last follow-up age ranged from 9 months to 13 years and 9 months. Seizures were present in 21 children (88%), with onset ranging from 1 month to 7 years, and 76% (16/21) began before 2 years of age. The seizure types included focal seizures in 15 children (71%), epileptic spasms, myoclonic seizures, and generalized tonic-clonic seizures in 6 children respectively, atypical absence seizures in 4 children, and myoclonic atonic seizures in 1 child. Seventeen children (81%) had a cluster of seizures and 5 had a history of focal status epilepticus with impaired consciousness. All 24 children had varying degrees of developmental delay, with 3 presenting solely developmental delay. EEG abnormalities were present in all the 21 children with seizures, including focal or multifocal discharges in 20 children, generalized discharges in 10 children, hypsarrhythmia in 2 children, and electrical status epilepticus during sleep in 3 children. Magnetic resonance imaging abnormalities were found in 5 of the 24 children. Among the 21 children with seizures, 57% (12/21) achieved seizure control.Conclusions:KCNB1 gene variants are predominantly de novo missense variation. Most affected children present with epilepsy, though some may exhibit only developmental delay. Epilepsy often begins before 2 years of age, with focal seizures being the most common type. About 80% of patients experience clustered seizures. Although most patients achieve seizure control, they still exhibit varying degrees of developmental delay, consistent with developmental epileptic encephalopathy.

Objective: Excessive daytime sleepiness (EDS) and insomnia symptoms are common in patients with major depressive disorder (MDD), which might lead to a poor prognosis and an increased risk of depression relapse. The current study aimed to investigate the prevalence, and sociodemographic and clinical correlates of EDS and insomnia symptoms among adolescents with MDD. Methods: The sample of this cross-sectional study included 297 adolescents (mean age=15.26 years; range=12–18 years; 218 females) with MDD recruited from three general and four psychiatric hospitals in five cities (Hefei, Bengbu, Fuyang, Suzhou, and Ma’anshan) in Anhui Province, China between January and August, 2021. EDS and insomnia symptoms, and clinical severity of depressive symptoms were assessed using Epworth sleepiness scale, Insomnia Severity Index, and Clinical Global Impression-Severity. Results: The prevalence of EDS and insomnia symptoms in adolescents with MDD was 39.7% and 38.0%, respectively. Binary logistic regression analyses showed that EDS symptoms were significantly associated with higher body mass index (odds ratio [OR]=1.097, 95% confidence interval [CI]=1.027–1.172), more severe depressive symptoms (OR=1.313, 95% CI=1.028–1.679), and selective serotonin reuptake inhibitors use (OR=2.078, 95% CI=1.199–3.601). And insomnia symptoms were positively associated with female sex (OR=1.955, 95% CI=1.052–3.633), suicide attempts (OR=1.765, 95% CI=1.037–3.005), more severe depressive symptoms (OR=2.031, 95% CI=1.523–2.709), and negatively associated with antipsychotics use (OR=0.433, 95% CI=0.196–0.952). Conclusion EDS and insomnia symptoms are common among adolescents with MDD. Considering their negative effects on the clinical prognosis, regular screening and clinical managements should be developed for this patient population.

This study delves into the pivotal factors influencing the consensus process within traditional Chinese medicine guideline development, with the objective of augmenting the quality of this process through methodological recommendations aimed at elevating standardization.

Objective To investigate the role of intestinal flora in the development of irritable bowel syndrome with diarrhea(IBS-D).Methods The mice treated with antibiotics were randomly assigned to experimental group or control group.IBS-D mouse feces and normal mouse feces were given to the experimental group and control group for fecal microbiota transplantation,respectively.The fecal water content,intestinal transit time,and intestinal sensitivity were observed.qRT-PCR was used to determine the mRNA expression of nuclear factor kappa-B(NF-κB),Toll like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),interleukin-1β(IL-Iβ),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α)in colon tissue.Western blotting was used to determine the protein levels of the above-mentioned parameters.Results IBS-D related symptoms presented in the mice of the experimental group,such as increased fecal water content and intestinal sensitivity,and shortened intestinal transit time.The expression levels of inflammatory factors(IL-Iβ,IL-6,and TNF-α),NF-κB,TLR4,and MyD88 in the colon tissue of experimental group were significantly higher than those in the control group(P<0.05).Conclusion Intestinal flora inbalance is involved in the development and progression of IBS-D as an initiating important driver.Dysbiosis-induced hypo-inflammation of the intestinal mucosa and abnormal activation of NF-κB-related pathways may play key roles in this process.