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.

Objective:To construct four recombinant hemagglutinin (HA) antigens from seasonal influenza viruses and evaluate their immunogenicity in mouse models.Methods:HA coding sequences from four seasonal influenza virus strains Wisconsin (H1N1), Darwin (H3N2), Austria (B/Victoria lineage, BV) and Phuket (B/Yamagata lineage, BY) were optimized and synthesized, and then used to construct four recombinant plasmids. Recombinant baculoviruses were obtained through transformation and transfection. The expression of recombinant HA antigens was identified by SDS-PAGE and Western blot. The recombinant HA antigens were purified by nickel column affinity chromatography and intramuscularly administered to BALB/c mice after formulation with Al(OH) 3 or AddaVax adjuvant. Humoral immune responses were assessed by indirect ELISA and hemagglutination inhibition test, while cellular immune responses were evaluated by ELISPOT. Microneutralization test was used to detect the titers of serum antibodies in mice. Statistical analysis was performed using t test or non-parametric rank sum test. Results:PCR amplification and agarose gel electrophoresis confirmed the correct construction of the recombinant bacmids. Western blot showed verified the successful expression of the four recombinant antigens (H1-HA, H3N2-HA, BV-HA, and BY-HA). SDS-PAGE results showed that the purity of all four recombinant HA antigens exceeded 95%. After three-dose immunization, the total IgG levels in mice immunized with the recombinant H1N1-HA, H3N2-HA, or BV-HA formulated with AddaVax adjuvant were higher than those in the corresponding groups immunized with the same recombinant antigen alone (all P<0.05). The secretion levels of IFN-γ, IL-2, and IL-4 in the group receiving the mixture of all four recombinant HA antigens formulated with AddaVax adjuvant were higher than those in the group immunized with a commercial quadrivalent split influenza vaccine (all P<0.01). Results of the microneutralization test showed that the antibody titer in the quadrivalent split influenza vaccine group was 1∶225, whereas the titer in the group immunized with the mixture of four recombinant HA antigens formulated with AddaVax adjuvant could reach up to 1∶1 200. Conclusions:In this study, four recombinant seasonal influenza virus HA antigens are successfully expressed and demonstrated good immunogenicity in mice when formulated AddaVax adjuvant.

Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.

Objective:To explore the genetic and clinical characteristics of epilepsy related with ATP6V1A gene heterozygous variants.Methods:A case series study was conducted. The clinical data of 10 children of epilepsy associated with ATP6V1A gene variants who were admitted to the Children′s Medical Center, Peking University First Hospital from January 2019 to December 2024 was collected. The characteristics of children′ gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed.Results:Among the 10 children, there were 4 boys and 6 girls. All 10 children with ATP6V1A gene variants were de novo heterozygous variants, including 1 case of mosaic variant. A total of 9 different variants were identified and 7 variants have not been reported previously. The age at epilepsy onset was 28 (9, 48) months. Five children experienced their first seizure as a fever induction. The types of epileptic seizures included focal seizures in 6 children, epileptic spasms in 5 children, tonic spasms and atonic seizures in 1 child respectively. Three children had 2 seizure types. Global developmental delays were exhibited in 8 children, 2 of whom manifested autism spectrum disorder phenotypes. Two children showed normal development. Electroencephalography revealed slowed background activity in 5 children. Interictal epileptiform discharges were recorded in 9 cases, including hypsarrhythmia, focal, multifocal or generalized discharges. Clinical seizures were captured in 4 children. Brain magnetic resonance imaging abnormalities were found in 4 children, including frontotemporal cortical dysplasia, prominent sulci, delayed myelination of white matter, dysplasia of the corpus callosum, bilateral ventricular enlargement, and cerebral atrophy. Five children were diagnosed with developmental and epileptic encephalopathy (DEE), and 4 of them were diagnosed with infantile epileptic spasms syndrome. At the last follow-up, the age was 78 (25, 120) months. Seizures were controlled in 6 children, while 4 children had uncontrolled seizures despite treatment with ≥3 anti-seizure medications. Conclusions:All children with ATP6V1A gene related epilepsy harbored de novo heterozygous missense variants, with few showing mosaic variants. Seizure onset age ranged widely from the neonatal period to childhood. The predominant seizure types were focal seizures and epileptic spasms. The phenotypic spectrum may exhibit DEE, while a minority maintain normal development.

Objective:To summarize the genotype and clinical phenotype characteristics of children with epilepsy associated with the SCN1B gene encoding the sodium channel β1 subunit. Methods:The genotypes and clinical phenotypes of patients with SCN1B variants among suspected genetic epilepsy cases treated at the Children′s Medical Center of Peking University First Hospital between May 2016 and July 2024 were analyzed. These variants were identified using next-generation sequencing and subsequently validated by Sanger sequencing or quantitative polymerase chain reaction methods. Results:A total of 17 patients were analyzed, including 8 males and 9 females. Ten cases of missense variations (including 2 with the same variations), 4 cases of deletion variations, and 1 case each of nonsense variations, splice site variations, and exons 4-5 deletions were identified. Among them, 6 cases had novel SCN1B variations. The variants in 11 cases were inherited from 1 parent. Eleven types of gene variants have not been reported yet. Onset of epilepsy ranged from 3 months to 5 years and 3 months old (median age: 14 months). Types of seizures included generalized tonic-clonic seizures (GTCS) in 14 cases, focal seizures in 9 cases, myoclonic seizures in 3 cases, atypical absence seizures in 2 cases and epilepsy spasms, tonic seizures and atonic seizures in 1 case each. Eleven cases had diverse seizure types. Fourteen cases (14/17) demonstrated fever sensitivity. Electroencephalography revealed focal discharges in 3 cases, coinciding with focal and generalized discharges in 3 additional cases, and multifocal discharges in 6 cases. Seizures were identified in 4 cases: 1 case of myoclonic seizures, 1 case of GTCS, 1 case of atypical absence seizures, and 1 case exhibiting both myoclonic and tonic seizures. Nine cases (9/17) were diagnosed with genetic epilepsy with febrile seizures plus, 1 case diagnosed with myoclonic epilepsy in infancy and 1 diagnosed with infant epileptic spasms syndrome. There were 2 cases of nonspecific developmental epileptic encephalopathy, while the remaining 4 cases could not be diagnosed with a specific epileptic syndrome. Effective antiseizure medications (ASMs) included valproate in 8 cases, levetiracetam in 5 cases, topiramate in 3 cases, clobazam in 2 cases, clonazepam and vigabatrin in 1 case each. Sodium channel blockers exacerbated seizures in 3 cases, specifically oxcarbazepine in 2 cases and lamotrigine in 1 case. At the last follow-up, seizures were controlled for at least 6 months in 14 patients (14/17), while seizures remained uncontrolled in 3 patients despite trialing 2 or more ASMs. Thirteen patients exhibited normal development, while 4 experienced developmental delays. Conclusions:The heterozygous variants in children with SCN1B gene-related epilepsy include missense, deletion, nonsense, splice site variants, and exon deletions. The correlation between different genetic variants and clinical phenotypes remains unclear. These variants are associated with epilepsy onset from infancy to early childhood, presenting with various seizure types, with GTCS being the most common. Phenotypic manifestations can vary significantly in severity, ranging from benign febrile seizures or febrile seizures plus to developmental epileptic encephalopathy. Valproic acid demonstrates the highest effectiveness rate, while the use of sodium channel blockers may worsen seizures in certain patients, necessitating cautious administration.

Objective:To investigate the endoscopic and pathological features and the independent risk factors for early esophageal cancer combined with multiple primary cancer.Methods:Endoscopic and pathological features of 324 patients diagnosed as having early esophageal cancer from January 2013 to January 2022 in Beijing Friendship Hospital were retrospectively collected. Independent risk factors for early esophageal cancer combined with multiple primary cancer were selected by multivariate logistic regression analysis.Results:Among the 324 patients with early esophageal cancer, 47 (14.51%) patients (29 metachronous and 18 synchronous) had multiple primary cancer. Multivariate logistic regression analysis showed that alcohol drinking ≥5 standard drinks/day ( OR=6.23, 95% CI: 2.49-15.57, P<0.001), submucosal layer invasion ( OR=2.80, 95% CI:1.07-7.30, P=0.036), lesion location at lower esophagus ( OR=4.18, 95% CI: 1.98-8.97, P<0.001) and multiple lesions in esophagus ( OR=3.30, 95% CI:1.57-6.92, P=0.002) were independent risk factors for early esophageal cancer combined with multiple primary cancer. Conclusion:Alcohol drinking ≥5 standard drinks/day, submucosal layer invasion, lower lesions location, and multiple lesions in the esophagus are independent risk factors that are more likely to develop multiple primary cancer in patients with early esophageal cancer. It is recommended to prioritize monitoring patients with these factors, and enhance endoscopic follow-up and assessment.

As antibiotic resistance becomes increasingly concerning,antimicrobial peptides,as a new type of antibiotic alternative,have attracted more attention.However,the low enzymatic stability of antimicrobial peptides severely limits their clinical applications.To address this issue,researchers have developed various structural modification strategies,including the introduction of unnatural amino acids,peptide chain cyclization and chemical group modification.This article reviews the basic principles and cases of the above modification strategies analyzes the advantages and disadvantages of different modification strategies and recommends ways these strategies can be optimized.In addition,this article predicts the developments of and potential challenges to strategies for enhancing enzymatic stability of antimicrobial peptides in the hope of providing references for subsequent research and development of antimicrobial peptides.

Objective To compare the efficacy,economic burden,psychological impact,and quality of life between surgical and medical castration following radical prostatectomy(RP)in patients with very high-risk prostate cancer(VHR PCa).Methods Clinical data of 167 patients with VHR PCa who underwent RP in the Department of Urology,the First Affiliated Hospital of Anhui Medical University during Jul.2019 and Mar.2024 were retrospectively collected.Patients were divided into two groups:the surgical castration group(n=44)and medical castration group(n=123).The effects of different castration methods on the biochemical recurrence(BCR)were analyzed with Cox proportional hazards models.The survival curves of BCR-free and progress to castration-resistant prostate cancer(CRPC)were plotted with the Kaplan-Meier method.The differences in functional assessment of cancer therapy-prostate(FACT-P)and hospital anxiety and depression scale(HADS)between the two groups were evaluated with linear regression model.Results The total costs were significantly lower in the surgical castration group than in the medical castration group[(47 422.0±3 998.3)yuan vs.(59 017.2±8 014.1)yuan,P＜0.001].One month postoperatively,the surgical castration group had significantly lower prostate-specific antigen(PSA)level[0.028(0.010,0.159)ng/mL vs.0.100(0.029,0.895)ng/mL,P=0.002].However,no significant differences were observed in the PSA level between the two groups at 3,6,and 12 months postoperatively,or in PSA nadir and time to nadir(P＞0.05).Cox regression analysis suggested a potentially higher risk of BCR in the medical castration group(HR=2.23),but the difference was not statistically significant(P=0.112).The 1-and 3-year BCR-free survival rates were higher in the surgical castration group(90.9％vs.85.4％;86.4％vs.70.7％,respectively),whereas 1-and 3-year progression-free survival rates were comparable between the two groups(97.7％vs.97.6％;95.5％vs.91.9％),with no significant differences(P＞0.05).No significant differences were found in FACT-P[(57.3±10.2)vs.(57.3±7.6)]or HADS[(12.6±5.1)vs.(11.3±4.8)]scores between the two groups(P＞0.05).Conclusion In VHR PCa patients,surgical castration performed following RP is not inferior to drug castration in terms of PSA control,and potential delay of BCR.It had a lower cost and does not significantly increase the psychological burden.As an underutilized strategy,surgical castration can become an optional option for individualized treatment.

Objective To compare the efficacy,economic burden,psychological impact,and quality of life between surgical and medical castration following radical prostatectomy(RP)in patients with very high-risk prostate cancer(VHR PCa).Methods Clinical data of 167 patients with VHR PCa who underwent RP in the Department of Urology,the First Affiliated Hospital of Anhui Medical University during Jul.2019 and Mar.2024 were retrospectively collected.Patients were divided into two groups:the surgical castration group(n=44)and medical castration group(n=123).The effects of different castration methods on the biochemical recurrence(BCR)were analyzed with Cox proportional hazards models.The survival curves of BCR-free and progress to castration-resistant prostate cancer(CRPC)were plotted with the Kaplan-Meier method.The differences in functional assessment of cancer therapy-prostate(FACT-P)and hospital anxiety and depression scale(HADS)between the two groups were evaluated with linear regression model.Results The total costs were significantly lower in the surgical castration group than in the medical castration group[(47 422.0±3 998.3)yuan vs.(59 017.2±8 014.1)yuan,P＜0.001].One month postoperatively,the surgical castration group had significantly lower prostate-specific antigen(PSA)level[0.028(0.010,0.159)ng/mL vs.0.100(0.029,0.895)ng/mL,P=0.002].However,no significant differences were observed in the PSA level between the two groups at 3,6,and 12 months postoperatively,or in PSA nadir and time to nadir(P＞0.05).Cox regression analysis suggested a potentially higher risk of BCR in the medical castration group(HR=2.23),but the difference was not statistically significant(P=0.112).The 1-and 3-year BCR-free survival rates were higher in the surgical castration group(90.9％vs.85.4％;86.4％vs.70.7％,respectively),whereas 1-and 3-year progression-free survival rates were comparable between the two groups(97.7％vs.97.6％;95.5％vs.91.9％),with no significant differences(P＞0.05).No significant differences were found in FACT-P[(57.3±10.2)vs.(57.3±7.6)]or HADS[(12.6±5.1)vs.(11.3±4.8)]scores between the two groups(P＞0.05).Conclusion In VHR PCa patients,surgical castration performed following RP is not inferior to drug castration in terms of PSA control,and potential delay of BCR.It had a lower cost and does not significantly increase the psychological burden.As an underutilized strategy,surgical castration can become an optional option for individualized treatment.

Objective To investigate the governance requirements for real world data(RWD)in China's medical standards and specifications,summarize key technical aspects of data governance,and provide refer-ences for RWD governance-related research.Methods Computerized searches were conducted in CNKI,Wan-fang Data,VIP,and SinoMed,as well as the official websites of 29 national medical societies and the National Standard Information Public Service Platform,covering all records from inception to December 12,2023.A data extraction form was developed,and the included standards and specifications were categorized according to the first six RWD governance processes outlined in the Guidelines for Real World Data Used to Generate Real-World Evidence(Trial)issued by the National Medical Products Administration:data security,data extraction,data cleaning,data transformation,data transmission and storage,and quality control.Relevant content on data governance was systematically summarized and comparatively analyzed.Results A total of 32 standards and specifications were included,comprising 15 foundational medical data standards and 17 data gov-ernance technical specifications.Among these,6 addressed data security,6 covered data extraction,5 focused on data cleaning,5 involved data transformation,6 pertained to data transmission and storage,and 4 discussed quality control.Foundational medical data standards included data description elements,terminology,and format standards,broadly covering essential data elements and meeting basic standardization needs.Data gov-ernance technical specifications primarily provided general guidelines for medical data governance,emphasizing requirements and recommendations.While requirements for data security and extraction were relatively well-de-fined,technical guidance on data transformation and quality control remained limited,and implementation pathways for data cleaning,transmission,and storage were insufficiently detailed.Conclusions As real-world evidence plays an increasingly critical role in healthcare decision-making,China's medical standards and speci-fications have established a preliminary governance framework for RWD.However,technical details and practi-cal implementation of RWD governance still require further refinement.