ObjectiveThis study aims to explore the potential of different orders of magnitude single-nucleotide polymorphism (SNP) locus combinations for predicting distant kinship relationships. A high-density SNP locus set was constructed, and a comprehensive assessment of its inference capability was conducted. MethodsFirstly, we selected three commercial chip panels, CGA (Chinese genotyping array, Illumina), GSA (Global screening array, Illumina), Affy (23MF_V2 high-density SNP array, Affymetrix) and merged them after quality control, forming a high-density SNP locus panel(1 180 k). Secondly, we selected 161 samples and collected their peripheral blood samples by using whole-genome sequencing technology. Within this sample population, the levels of kinship relationships fully covered the range from level 1 to level 9, and the number of kinship pairs at each level was consistently maintained at over 50 pairs. From 161 samples data of whole-genome sequencing, the 1 180 k locus set was extracted, which is referred to as the high-density SNP locus set in the following text. The kinship inference was conducted using the identity-by-descent (IBD) algorithm with the selected optimal parameters. To comprehensively evaluate the performance of the high-density SNP locus set in kinship inference, we compared it with the three commercial chip panels, the intersection of these three chip loci, and the control sets constructed by randomly reducing the number of the high-density SNP locus set. Based on the changes in the IBD lengths, as well as the dynamic trends in prediction accuracy, we conducted a scientific assessment of the kinship inference capability of the high-density SNP locus set. ResultsAfter screening, a set of 1 184 334 autosomal SNPs was obtained. During the process of screening the optimal IBD length threshold, the result revealed that 0 cM, 1 cM, and 2 cM all demonstrated good applicability. However, to avoid the issue of a large amount of redundant information caused by setting a too low IBD length threshold, this study ultimately selected 2 cM as the optimal threshold. Compared with the average results of three chip panels, the high-density SNP locus set increased the total IBD length and the average IBD length across levels 1-9; the accuracy of the confidence interval for level 8 was 70.97%, which represented a 3.50% improvement; the average confidence interval accuracy for levels 1-8 was 91.39%, representing a 1.00% increase; and the false negative rates at levels 8 and 9 were reduced by 2.42% and 6.76%, respectively. The system efficacy of the high-density SNP locus set for kinship inference of first to eighth degree relationships reached 98.91%. Through random reduction of the high-density SNP locus set results, it is found that increasing the number of SNPs with the panel, the detection efficiency of IBD length showed a significant upward trend. At the same time, the overall trend in the accuracy of kinship relationship prediction as well as the confidence interval accuracy also indicated that both metrics steadily increased with the addition of more loci. ConclusionThe results show that the high-density SNPs panel significantly enhances the efficacy of distant kinship inference, accurately covering kinship degrees, with the average confidence interval accuracy for first to eighth degree relationships stably above 90%. The study finds that increasing the number of SNPs panel can improve the ability to predict distant kinship.

Background Amid global climate change, extreme environmental events are occurring more frequently, and it is imperative to investigate the impacts of combined exposure to fine particluate matter (PM_2.5) and cold spells (CS) on population mortality. Objective To analyze the association between sequential extreme PM_2.5-cold spell (EP-CS) events and non-accidental mortality among residents in Zigong City from 2016 to 2021. Methods Using time-series study design, meteorological data in Zigong were collected from the Zigong Meteorological Bureau for the period from January 1, 2016 to December 31, 2021, while daily non-accidental mortality data were obtained from the mortality surveillance system of the Zigong Center for Disease Control and Prevention. We adopted the percentile method to define extreme PM_2.5 events and cold spells. We analyzed the risk effect of EP-CS events on non-accidental mortality among residents in this city and explored the potential amplification of damage resulting from different patterns of consecutive extreme events by using distributed lag nonlinear model (DLNM). We also conducted stratified analyses based on age, gender, education level, and marital status. Results The EP-CS events demonstrated a significant impact on non-accidental mortality among the local residents, exhibiting a certain lagged effect. The effects on the overall residents lasted from lag0 (RR=1.030, 95%CI: 1.013, 1.048) to lag14 (RR=1.035, 95%CI: 1.019, 1.052). Notably, the effects were more pronounced among females, individuals aged 65 years and above, and those who were never married, divorced, or widowed. Different patterns of EP-CS events all associated with adverse effects, the health impact of EP-CS events was significantly greater than that of individual PM_2.5 pollution or CS events. The analysis of lag effects across different event patterns revealed that the overall effect of EP-CS events with shorter intervals (0–7 d) had a stronger effect compared to EP-CS with longer intervals (8–14 d), and the RR values of lag14 were 1.034 (95%CI: 1.015, 1.054) and 1.017 (95%CI: 1.007, 1.027), suggesting that the damaging effect of compound events occurring in the short term was more significant. Conclusion All sequential extreme EP-CS events have an impact on non-accidental mortality among residents in this city, with compound events demonstrating a stronger effect. Females, individuals aged ≥65 years, and those who were never married, divorced, or widowed are more sensitive to EP-CS events.

Objective To study the efficacy and safety of antiviral therapy in the patients with normal ALT chronic hepatitis B(CHB).Methods The clinical data of the patients with normal ALT CHB visiting in this hospital from December 2019 to December 2023 were collected.The patients were divided into the low vi-ral load group(HBV DNA＜2×106 IU/mL,n=76)and high viral load group(HBV DNA≥2×106 IU/mL,n=10).ETV,TDF and TAF were adopted to conduct the single drug antivirus therapy.The basic informa-tion,demographic characteristics,HBV DNA levels in initial treatment and after 12,24,36,48 weeks of treat-ment,estimated glomerular filtration rate(eGFR)were collected.The rate of complete virological response(CVR)at each time point conducted the statistics for evaluating the effect.The drug safety was evaluated by the eGFR level in 48 weeks of treatment.Results The CVR rates in 12,24,36 weeks of treatment in the low viral load group were 81.6％,94.7％,100.0％and 100.0％respectively,which in the high viral load group were 40.0％,80.0％,80.0％and 80.0％respectively.There was no significant change in eGFR level(109.41±170.57)mL·min-1·1.73 m-2 at 48 weeks of treatment compared with baseline(108.47±110.83)mL·min-1·1.73 m-2(P＞0.05).The ALT and creatinine levels during the treatment process in all the patients were not increased.There was no case of drug withdrawal and drug change due to the drug side effects.Conclusion The overall efficacy and safety of ETV,TDF and TAF monotherapy are good in CHB pa-tients with a family history of cirrhosis or liver cancer and normal ALT.The patients with high viral load at baseline are less likely to achieve CVR in 48 weeks of treatment.

Objective To compare the therapeutic effects of modified Shenqi Maiwei Dihuang Decoction combined with Buzhong Yiqi Pill and Buzhong Yiqi pill alone in the patients with cold and heat mixed type di-abetic foot.Methods A total of 123 patients with cold and heat mixed type diabetic foot receiving the treat-ment in this hospital from April 2022 to December 2023 were selected and divided into the modified Shenqi Mai-Dihuang Decoction and Buzhong Yiqi Pill group(combined group,60 cases)and Buzhong Yiqi Pill group(monotherapy group,63 cases).The wound healing,mean blood flow amount of foot dorsal artery,blood glu-cose and changes in vascular diameter,inflammatory factors and vascular endothelial growth factor after 2 courses of treatment were compared betweeb the 2 groups.Results The ulcer reduction rate in the combina-tion group was significantly higher than that in the monotherapy group(P=0.001).The fasting blood glu-cose and 2 h postprandial blood glucose after treatment in the combination group all were lower than those in the monotherapy group(P=0.001).The average blood flow of foot dorsal artery after treatment in combina-tion group was higher than that in the monotherapy group,and the difference was statistically significant(P=0.013).There were 34 cases of Wagner grade 3 in the combined group and 33 cases of Wagner grade 3 in the monotherapy subgroup respectively.There was statistically significant difference in the CRP level between the two subgroups(P=0.045).Conclusion Shenqi Maiwei Dihuang Decoction combined with Buzhong Yiqi Pill in treating diabetic foot ulcer is more effective than Buzhong Yiqi Pill alone,moreover the safety is high.

Objective:To establish HPLC fingerprint and methods for determining the contents of four iridoid glycosides of Gentiana rigescens; To evaluate the quality of Gentiana rigescens from different origins; To improve the quality control level of Gentiana rigescens medicinal materials.Methods:Using 15 batches of Gentiana rigescens from the main production areas and authentic production areas as raw materials, the common mode of HPLC fingerprints of Gentiana rigescens was established, and the chemical components of the common peaks were identified. Referring to the common mode of fingerprints, similarity analysis was conducted on the fingerprints of Gentiana rigescens from different origins. Using chemometric methods, cluster analysis (HCA), principal component analysis (HCA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were performed on 15 batches of Gentiana rigescens, with the common peak area of fingerprint as the variable. The contents of four types of iridoid glycosides in Gentiana rigescens were determined. Combined with the fingerprints and the content results of four types of iridoid glycosides, the quality of Gentiana rigescens from different origins was evaluated.Results:The fingerprints of Gentiana rigescens contained 9 common peaks, with 4 identified iridoid glycosides. The similarity of the fingerprints of 15 batches of Gentiana rigescens ranged from 0.962 to 0.999. HCA and PCA divided the 15 batches of Gentiana rigescens into two categories. OPLS-DA analyzed 3 significantly different components, namely gentiopicroside, peak 7, and loganic acid. The content determination results showed that the average contents of loganic acid, swertiamarin, and gentiopicroside in Gentiana rigescens from Dali Bai Autonomous Prefecture and Yunnan Province were the highest, and the total amount of four iridoid glycosides was also significantly higher than that from other regions, indicating that the overall quality of Gentiana rigescens from Dali Bai Autonomous Prefecture and Yunnan Province was relatively good.Conclusion:This method is simple, fast, accurate, and can provide reference for improving the quality standards of Gentiana rigescens.

Objective To investigate the expression of T cell subsets in the spleen of BTBR T+Itpr3tf autistic mouse at 4,8,and 12 weeks of age,and to determine the optimal age for studying the relationship between immune abnormalities and autism in BTBR autistic mice.Methods It randomly selected 5～6 male BTBR mouse at 4 weeks,8 weeks,and 12 weeks of age and C57BL/6J mouse of the same gender at corresponding ages for the three-box social interaction test,the self-grooming test,and the marble-burying test;Single cell suspensions were prepared from the spleens of mouse at 8 and 12 weeks of age,and flow cytometry was used to detect 8 subsets of T cells(TH 1,TH2,TH17,TC1,TC2,TC17,TFH,and Treg).Results Compared with C57BL/6J mouse of the same age,BTBR mouse at 4 weeks,8 weeks,and 12 weeks of age showed a decrease in social time(P＜0.001),an increase in grooming time(P＜0.01,P＜0.001),and an increase in the number of marbles buried(P＜0.01,P＜0.001)in BTBR mouse at 8 weeks and 12 weeks of age.As well,the expression of TH 1(P＜0.001),TH2(P＜0.01),TC 1(P＜0.05),TC2(P＜0.001),and TFH(P＜0.01)cells in 8-week-old BTBR mouse were significantly increased,while the expression of Treg(P＜0.001)cells were significantly decreased;The expression of TH 1(P＜0.01),TH2(P＜0.01),TH 17(P＜0.05),TC1(P＜0.01),TC2(P＜0.001),TC 17(P＜0.01),and TFH(P＜0.001)increased in 12-week-old BTBR mouse,while the expression of Treg(P＜0.05)cells decreased.At different age stages(P＜0.050)the ratio of TH 1/Treg and TC 1/Treg in 8-week-old BTBR mouse were significantly higher than those in 12 week old mouse,while the TC 17/Treg ratio decreased.Conclusions BTBR mouse at different developmental stages exhibit varying degrees of abnormal increase in Teff/Treg ratio.Based on result of behavioral test,it is recommended to use 8-week-old BTBR mice for research on autism and immune abnormalities.

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.

Objective:To explore the actor-partner effect of parenting stress and parenting efficacy on children's anger-aggression and anxiety-withdrawal.Methods:A questionnaire survey measuring parenting stress, parenting efficacy and children's social and behavioral problems was conducted among 525 parents of 2-5-year-old children in five kindergartens and parent-child kindergartens in Hunan, Jiangxi and Hainan provinces during April, 2023.The descriptive analysis and Pearson correlation analysis were conducted by SPSS 27.0, the mediation analyses were done with Mplus 7.4, and the actor-partner effect was analyzed by the Web-based program APIM_SEM.Results:(1) Father's parenting stress(3.22±0.67) and mother's parenting stress(2.91±1.02) were significantly related to children's anger-aggression(2.59±1.01) ( rfather=0.31, P<0.01; rmother=0.52, P<0.01) and anxiety-withdrawal(2.64±0.97) ( rfather=0.28, P<0.01; rmother=0.50, P<0.01). (2) Mother's parenting stress negatively predicted maternal parenting efficacy( β=-0.19, P<0.01) and paternal parenting efficacy( β=-0.08, P<0.05), while father's parenting stress negatively predicted paternal parenting efficacy ( β=-0.31, P<0.01) and maternal parenting efficacy ( β=-0.17, P<0.01). Regarding the actor-partner effect, maternal parenting efficacy was dual-mode and paternal parenting efficacy was mixed-mode. (3) The mediation tests showed that, maternal parenting efficacy acted as a partial mediator between maternal parenting stress and children's anger-attack and anxiety-withdrawal, the effects were 0.037(95% CI=0.021-0.056), 0.058(95% CI=0.040-0.078), as well as between paternal parenting stress and children's anger-attack(0.022(95% CI=0.008-0.039)), and anxiety-withdrawal (0.034(95% CI=0.014-0.056)).The paternal parenting efficacy played partial mediation between paternal parenting stress and children's anger-attack and anxiety-withdrawal, the mediation effects were 0.039(95% CI=0.020-0.061) and 0.032(95% CI=0.016-0.052), as well as between maternal parenting stress and children's anger-attack(0.016(95% CI=0.003-0.031)), and anxiety-withdrawal (0.013(95% CI=0.002-0.027)). Conclusion:The parenting stress significantly increase children's anger-attack and anxiety-withdrawal behavior. Parenting stress of fathers and mothers indirectly leads to the increase of children's negative emotions and behaviors by weakening the parenting efficacy of themselves and their partners.

Objective To investigate the practical effects of pediatric rapid sequence intubation(RSI)nursing coordination training based on the LSPPDM(learn,see,practice,prove,do,maintain)framework in order to provide evidence for optimizing pediatric RSI nursing training programs.Methods Nurses from the intensive care unit(ICU)of Children's Hospital,Fudan University during Feb 2023 and Jan 2024 were divided into the experimental group(n=35)and the control group(n=35)by block randomization.The experimental group received LSPPDM framework-based training,while the control group underwent conventional training with theoretical lectures and procedural demonstrations.Outcomes included training satisfaction,theoretical knowledge and procedural skill assessment scores,team collaboration compliance and RSI procedure time were compared between the two groups.Results The experimental group demonstrated significantly higher training satisfaction(123.80±2.04 vs.117.26±9.82,P<0.05),superior post-training theoretical knowledge and procedural skills(P<0.05),enhanced team collaboration compliance(P<0.05),and shorter RSI completion time(P<0.05)compared with the control group.Conclusion Pediatric RSI nursing coordination training based on the LSPPDM framework can effectively increase training satisfaction,promote theoretical and procedural skills and reduce completion time in nurses.

This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.