With the rapid development of human genomics technologies and their clinical applications， relevant ethical issues have induced complex ethical governance challenges. These challenges mainly manifest in the dilemma of reconstructing a new social contract under data open sharing， the moral conflict between the collective nature of group data and individual benefits， the problem of structural inequality under precision medicine， the risk of imbalance between costs and benefits， the dilemma of genetic modification from a eugenic perspective， and the issue of proxy consent and privacy protection. International governance practices indicate that these challenges can be addressed to some extent by improving legislation， issuing initiatives， strengthening the functions of ethics committees and corresponding institutions， and focusing on the ethicality of research projects. However， issues such as legal lag and insufficient binding force of initiatives still exist. Meanwhile， although China’s ethical governance work has made continuous progress in top-level design， international exchanges and theoretical research， specialized legislation and cross-subject collaboration mechanisms still necessitate improvement. A systematic ethical governance framework requires establishing a pre-regulatory system， refining ethical review， and promoting specialized legislation and case approval systems. It is also vital to improve genomic data governance， refine cloud platform management mechanisms， and promote hierarchical governance of the data. Furthermore， it is crucial to clarify the responsibilities of the scientific research community， standardize ethical review， strengthen public communication， and build a moral community with the collaborative cooperation of the government， medical and healthcare institutions and their technical personnel， the public， and research subjects. Through the construction of an ethical governance system for human genomics research， this ensures that genomics technologies benefit humanity without transgressing ethical boundaries， thereby achieving the safety， fairness， and sustainability of their research and application.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Cancer multidrug resistance (MDR) impairs the therapeutic efficacy of various chemotherapeutics. Novel approaches, particularly the development of MDR reversal agents, are critically needed to address this challenge. This study demonstrates that tenacissoside I (TI), a compound isolated from Marsdenia tenacissima (Roxb.) Wight et Arn, traditionally used in clinical practice as an ethnic medicine for cancer treatment, exhibits significant MDR reversal effects in ABCB1-mediated MDR cancer cells. TI reversed the resistance of SW620/AD300 and KBV200 cells to doxorubicin (DOX) and paclitaxel (PAC) by downregulating ABCB1 expression and reducing ABCB1 drug transport function. Mechanistically, protein arginine methyltransferase 1 (PRMT1), whose expression correlates with poor prognosis and shows positive association with both ABCB1 and EGFR expressions in tumor tissues, was differentially expressed in TI-treated SW620/AD300 cells. SW620/AD300 and KBV200 cells exhibited elevated levels of EGFR asymmetric dimethylarginine (aDMA) and enhanced PRMT1-EGFR interaction compared to their parental cells. Moreover, TI-induced PRMT1 downregulation impaired PRMT1-mediated aDMA of EGFR, PRMT1-EGFR interaction, and EGFR downstream signaling in SW620/AD300 and KBV200 cells. These effects were significantly reversed by PRMT1 overexpression. Additionally, TI demonstrated resistance reversal to PAC in xenograft models without detectable toxicities. This study establishes TI's MDR reversal effect in ABCB1-mediated MDR human cancer cells through inhibition of PRMT1-mediated aDMA of EGFR, suggesting TI's potential as an MDR modulator for improving chemotherapy outcomes.
Humans ; Protein-Arginine N-Methyltransferases/antagonists & inhibitors* ; Drug Resistance, Neoplasm/drug effects* ; ErbB Receptors/genetics* ; Animals ; Cell Line, Tumor ; Drug Resistance, Multiple/drug effects* ; Methylation/drug effects* ; Saponins/administration & dosage* ; Mice ; Mice, Nude ; Mice, Inbred BALB C ; ATP Binding Cassette Transporter, Subfamily B/genetics* ; Doxorubicin/pharmacology* ; Paclitaxel/pharmacology* ; Female ; Repressor Proteins

Objective To evaluate the efficacy of vitamin AD combined with step-up therapy in children with asthma and its impact on humoral immunity,pulmonary function and recurrence.Meth-ods A total of 94 children with asthma were enrolled,and randomly divided into study group(n=47)and control group(n=47)using random number table method.The control group adopted the step-up treatment plan on the basis of conventional treatment,while the study group was treated with vitamin AD on the basis of the control group.The clinical efficacy,pulmonary function indicators[forced vital capacity(FVC),forced expiratory volume in one second(FEV,),FEV1/FVC and peak expiratory flow rate(PEF)]and humoral immunefunction[immunoglobulin G(IgG),immuno-globulin A(IgA),immunoglobulin M(IgM)and immunoglobulin E(IgE)]after treatment were compared between the two groups.The recurrence rateand safety of the two groups after treatment were compared.Results The total effective rate of clinical efficacy in the study group was 93.62％,which was significantly higher than 78.72％in the control group(P＜0.05).After treatment,FVC,FEV1,FEV1/FVC and PEF levels were significantly higher in both groups compared to pre-treatment values,and the study group showed significantly better improvement than the control group(P＜0.05).After treatment,serum IgG and IgA levels in the study group were significantly higher than those in the control group,whereas IgM and IgE levels were significantly lower(P＜0.05).At 12 months after treatment,the recurrence rate in the study group was 4.26％(2/47),which was sig-nificantly lower than 19.15％(9/47)in the control group(P＜0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion Vitamin AD combined with step-up therapy effectively alleviates clinical symptoms,modulates humoral immune balance,improves pulmonary function,and reduces recurrence rates in children with asthma,and has high safety.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective:To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China.Methods:The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed.Results:From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age.Conclusion:From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.

Objective: To investigate the relationships among psychological resilience, parental control, and behavioral problems in middle school students, aiming to provide evidencebased recommendations for the prevention and intervention of behavioral issues in middle school students, as well as for the development of related policies. Methods: A stratified cluster sampling method was used to select 2 745 participants from three cities in Guizhou Province with different levels of economic development from August to December 2021. The Child Behavior Checklist (CBCL), Parental Control Questionnaire, and Psychological Resilience Questionnaire were administered to junior high school students and their parents. A network analysis method was employed to construct a network analysis model of factors influencing behavioral problems. Results: The detection rate of behavioral problems among junior high school students in Guizhou Province was 22.62%. The scores for psychological resilience (goal focus, emotional control, positive cognition, family support, and interpersonal assistance) and proactive inquiry in behavior control were higher in the group without behavioral problems than in the group with behavioral problems. Scores for psychological control (inducing guilt, with drawing affection, and asserting authority) were higher in the group with behavioral problems than in the group without behavioral problems, with statistically significant differences (t=9.80, 17.76, 6.21, 12.20, 13.18, 6.28, 11.58, 11.10, 10.74, P<0.05). The network model showed that among the same variable factors, the strongest connection weight was between inducing guilt and withdrawing affection, with a weight of 0.79. Between different variables, there were negative correlation between behavioral problems and psychological resilience (goal focus, emotional control, positive cognition, family support, interpersonal assistance) and behavior control (proactive inquiry, behavioral restraint) with correlation coefficients (r=-0.25, -0.42, -0.16, -0.31, -0.33, -0.17, -0.03, P<0.05), respectively. There were positive correlation between psychological control factors (inducing guilt, withdrawing affection, and asserting authority) and behavioral problems (r=0.29, 0.27, 0.27), and a negative correlation between these psychological control factors and psychological resilience factors (goal focus, emotional control, positive cognition, family support, interpersonal assistance)(r=-0.53--0.13)(P<0.05). The strongest connection weight was between withdrawing affection and family support, with a connection weight of -0.53. Family support was an important bridge symptom connecting the entire behavioral problem network model, with a high centrality. Conclusions The detection rate of behavioral problems among junior high school students in Guizhou Province is relatively high. Assisting adolescents in establishing a supportive family environment facilitates the cultivation of their psychological resilience, thereby mitigating the occurrence of behavioral problems.

Objective:To explore the impact of self-disclosure on demoralization syndrome in patients with permanent enterostomy for colorectal cancer, so as to provide reference for clinical nursing interventions for those patients.Methods:From January to May 2023, convenience sampling was used to select 207 patients with permanent enterostomy for colocrctal cancer of the Wound Ostomy Clinic of Laoshan Campus of the Affiliated Hospital of Qingdao University as the research subjects. A survey was conducted on patients using the General Information Questionnaire, Distress Disclosure Index, Social Support Rating Scale, and the Demoralization Scale Mandarin Version.Results:Among 207 patients with permanent enterostomy for colorectal cancer, the scores of self-disclosure, social support, and demoralization syndrome were 35.00 (26.00, 47.00) , 32.00 (26.00, 39.00) , and 35.00 (23.00, 47.00) , respectively. A total of 128 patients (61.8%) were in moderate demoralization, and 37 patients (17.9%) were in severe demoralization. Multiple linear regression analysis showed that place of residence, self-care of stoma, self-disclosure, and social support were the influencing factors for demoralization syndrome in patients with permanent enterostomy for colorectal cancer ( P<0.05) . Conclusions:Patients with permanent enterostomy for colorectal cancer have a high overall score of demoralization syndrome, and a high proportion of patients with moderate to severe demoralization. Medical and nursing staff should focus on patients in remote rural areas and those with poor self-care abilities to stomas, develop targeted intervention measures to improve patients' negative emotions, enhance their self-disclosure, and pay attention to strengthening social support to relieve their demoralization syndrome, thereby improving their quality of life.

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRAS^G12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFR^L858R and EGFR^Δ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFR^T790M showed no difference compared to classical activating mutations without EGFR^T790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRAS^G12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFR^T790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Extracellular Matrix Proteins/genetics* ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins p21(ras)/genetics* ; Treatment Outcome

Objective: To explore the social functioning characteristics of children with co ocurrence of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) for intervention reference. Methods: The Chinese Version of Swanson Nolan and Pelham, Version IV Scale-Parent Form(SNAP-IV), the Chinese Version of Weiss Functional Impairment Scale-Parent(WFIRS-P), and the Questionnaire-Children with Difficulties (QCD) were applied to 192 children with ADHD, 243 children with co occurrence of ADHD and ODD, who firstly visited the Department of Children Psychological Health of Zhuhai Maternal and Child Health Care Hospital, and 118 healthy control children from a school in Zhuhai. Results: The scores of attention deficit factor in SNAP-Ⅳ scale of children in three groups were[1.9(1.7, 2.1), 1.8(1.6, 1.9), 1.0(0.6, 1.2)], the scores of hyperactive impulsivity were[1.8(1.4, 2.1), 1.6(1.1, 1.8), 0.7(0.2, 1.0)] the scores of oppositional defiant were[1.6(1.5, 1.9), 1.0(0.8,1.1), 0.8(0.5, 1.0)], the differences were statistically significant( H=268.44, 237.97, 418.66, P <0.01). The dimensions and total scores of the three groups of children s WFIRS-P scale were family[0.8(0.6, 1.1), 0.6(0.3, 0.8), 0.3(0.1, 0.6)]; learning and school[0.8(0.5, 1.1), 0.8(0.5, 1.0), 0.3(0.1, 0.5)]; life skills[1.0(0.7, 1.2), 0.8(0.6, 1.0), 0.6(0.4, 0.8)]; self management [1.0(0.3, 1.0), 0.7(0.3, 1.0), 0.3(0.0, 0.7)]; social activities [0.7(0.4, 1.0), 0.6(0.3, 0.9), 0.3(0.0, 0.4 )]; adventure activities[0.3(0.2, 0.5), 0.2(0.1, 0.4), 0.1(0.0, 0.2)]; the total score[0.8(0.6, 1.0), 0.6(0.5, 0.8), 0.4( 0.2 , 0.6)], the difference between the groups was statistically significant( H=108.82, 122.45, 60.17, 40.58, 96.17, 76.57, 138.30, P <0.01). The difference between the QCD scale scores of children in the three groups was statistically significant[30.0( 24.0 , 37.0), 32.0(27.0, 40.0), 47.0(37.0, 52.3), H=124.65, P <0.01). Multiple regression analysis showed that attention deficit, and oppositional defiant symptoms were associated with both the total WFIRS-P score and the QCD score of children( R 2= 0.40 , 0.25, P <0.05). Conclusion Children with co occurrence of ADHD and ODD have more severe deficits in all dimensions of social functioning than children with ADHD, which might be associated with attention deficit and oppositional defiant symptoms.