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.

Objective: To assess the effect of 12-year-old children s pit and fissure sealants on the health of first permanent molars, so as to provide evidence for optimizing caries prevention strategies among children. Methods: In March 2025, a cluster random sampling method was used to conduct oral examinations on 965 students aged 12 from Chengdu s 2021 Comprehensive Intervention Program for Pediatric Oral Diseases. Data from the Comprehensive Intervention System for Children s Oral Diseases were referenced. Participants were divided into a sealed group ( n =755) and an unsealed group ( n =210) based on whether they had received sealants on their first permanent molars. Chi square test or analysis of variance were used to compare indicators such as caries incidence, new caries detection rate, and new caries mean (DMFT increment) between the two groups Results: The sealed group showed significantly lower caries incidence, new caries detection rate, and new caries mean (33.38%, 17.65%, 0.59±1.00) compared to the unsealed group (43.81%, 24.70%, 0.87±1.22)( χ 2/F =7.79, 18.26, 9.55, all P <0.05). However, no significant difference was found in the filled teeth ratio between the two groups (20.38% , 20.16%; χ 2=0.01, P =0.94). In girls, the sealed group exhibited significantly lower caries incidence, new caries detection rate, and new caries mean (36.78%, 20.99%, 0.69± 1.10 ) than the unsealed group (57.55%, 33.52%, 1.15±1.29) ( χ 2/F =14.42, 23.76, 10.92, all P <0.05), whereas no significant differences were observed between boys in the sealed (30.47%, 14.85%, 0.50±0.89) and unsealed groups (29.81%, 16.18%, 0.59± 1.08) ( χ 2/F =0.02, 0.41, 0.74, all P >0.05). Boys had significantly lower new caries detection rates and new caries means than girls in both groups ( χ 2/F =16.20, 6.94; 29.93, 11.84, all P <0.05). In urban areas, the sealed group had lower new caries detection rates and new caries means (19.37%, 0.68±1.04) than the unsealed group (24.66%, 0.90±1.20) ( χ 2/F =6.86, 3.94, both P <0.05). In suburban areas, all indicators for the sealed group (24.71%, 13.77%, 0.42±0.87) were significantly lower than those for the unsealed group (38.81%, 24.77%, 0.82±1.28) ( χ 2/F =5.28, 15.36, 6.00, all P <0.05). Indicators from specialized dental institutions (11.25%, 4.81%, 0.16±0.56) were significantly lower than those from county level or above general hospitals (33.33%, 19.11%, 0.38±1.00) and primary healthcare institutions (37.59%, 19.24%, 0.67±1.05) ( χ 2/F =20.99, 34.31, 21.08 , all P <0.01). Conclusions The 12-year-old children s pit and fissure sealants effectively reduce the caries incidence in first permanent molars, particularly showing significant effectiveness in girls and suburban children. Intervention strategies should be optimized according to gender.

As a distinctive resource of Chinese civilization， traditional Chinese medicine （TCM） technology transfer faces significant opportunities under the background of digital and intelligent transformation， while also being constrained by unique challenges such as the complexity of its theoretical system， lengthy industrial chains， and multidimensional policy restrictions， resulting in a "high-value-high-threshold" paradox. At present， TCM technology transfer is deeply trapped in a "threefold reluctance" dilemma， i.e.， unwillingness to transfer， inability to transfer， and lack of capacity to transfer. Specifically， the disconnection between scientific research evaluation systems and market demand leads to low conversion rates of research achievements， unclear ownership and compliance risks suppress innovation incentives， and the absence of professional services intensifies supply-demand mismatches. This article systematically analyzes the specific characteristics of TCM technology transfer and proposes a breakthrough pathway centered on full-chain digital and intelligent transformation. By integrating technologies such as intelligent sorting systems， blockchain-based traceability， and AI diagnostic models， the TCM ecosystem spanning "cultivation-production-service" can be reconstructed. In terms of standardization， promoting the progression from "experience-based data conversion" to "data standardization" and further to "intelligent standardization" is advocated to resolve quality control challenges. For example， a "three-no-one-full" certification system can strengthen quality trust. Policy coordination should focus on optimizing mechanisms for the transformation of scientific and technological achievements， while exploring intellectual property securitization and risk-sharing models to stimulate research momentum. In terms of internationalization， reliance on the Belt and Road Initiative platform to promote the export of geo-authentic medicinal material brands and standards is recommended to build a dual-driven model of "technology plus culture". Looking ahead， through the construction of national-level databases， the cultivation of interdisciplinary talent， and the mutual recognition of international standards， a new paradigm of "scientific intelligent manufacturing" can be formed， providing systematic solutions for the modernization of TCM and global health governance.

ObjectiveJunctophilin-2 (JPH2) is an essential structural protein that maintains junctional membrane complexes (JMCs) in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum, thereby facilitating excitation-contraction (E-C) coupling. Mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM), but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus (MORN) repeat motifs remain incompletely understood. This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis. MethodsA recombinant N-terminal fragment of mouse JPH2 (residues1-440), encompassing the MORN repeats and an adjacent helical region, was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain. Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features. Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells. In addition, site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations, including R347C, was used to evaluate their effects on membrane interaction and subcellular localization. ResultsThe crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6 Å, revealing a compact, elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration, forming a continuous hydrophobic core stabilized by alternating aromatic residues. A C-terminal α-helix further reinforced structural integrity. Conservation analysis identified the inner groove of the MORN array as a highly conserved surface, suggesting its role as a protein-binding interface. A flexible linker segment enriched in positively charged residues, located adjacent to the MORN motifs, was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes. Functional assays demonstrated that mutation of these basic residues impaired membrane association, while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays, despite preserving the overall MORN-Helix fold in structural modeling. ConclusionThis study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2, highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions. The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis. These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.

Objective: To explore the correlation between traditional Chinese medicine (TCM) constitution and depressive symptom among school aged children and adolescents, so as to provide evidences for informing constitution based regulation and prevention of depressive symptom. Methods: From June to December 2024, a total of 4 729 students aged 6-14 were recruited by cluster random sampling from 10 primary schools in Baoding (Hebei Province), Heze and Liaocheng (Shandong Province). General information, TCM constitution and depressive symptom were collected. Restricted cubic spline (RCS) models were used to analyze related factors and threshold effects of depressive symptom. Binary Logistic regression was applied to examine the association between depressive symptom and TCM constitution, with subgroup analyses conducted. Results: The detection rate of depressive symptom among the included children and adolescents was 25.82%. RCS analyses indicated non linear associations between depressive symptom and age (inflection point at 10 years old), bedtime (inflection point at 22:00), and wake up time (inflection point at 6:30 ) (all P non linearity <0.01). Linear associations were observed with body mass index (BMI) and sleep duration (all P non linearity > 0.05 ). After adjusting for covariates such as age, BMI and sleep status, binary Logistic regression analyses showed that Yin deficient constitution ( OR =1.26, 95% CI =1.09-1.45) and Phlegm-dampness constitution ( OR =1.42, 95% CI =1.11-1.82) were significantly associated with depressive symptom among children and adolescents (all P <0.05). Conclusions Depressive symptom among school aged children and adolescents is primarily associated with Yin deficiency and Phlegm dampness constitutions in TCM constitution. Active attention should be paid to susceptible TCM constitution among children and adolescents. Targeted health guidance and interventions should be implemented to improve TCM constitution health status for preventing the occurrence of depressive symptom.

Objective: To investigate the correlation among α2, 6-sialyltransferase (ST6Gal-Ⅰ), CD36 desialylation, and caveolin-1 (Cav-1) in phorbol ester (PMA)-induced MEG-01 cell model, as well as their potential mechanism in immune thrombocytopenia (ITP). Methods: MEG-01 cells were treated with 10 ng/mL PMA for 48 hours (control group: 0.1% DMSO). Flow cytometry was used to detect cell surface markers: desialylation (CD41 RCA ) and α2, 6-sialylation (CD41 SNA ). Western blot was performed to analyze the protein expressions of ST6Gal-Ⅰ, CD36, and Cav-1. Results: Flow cytometry analysis revealed that, compared with the control group (set as 100%), the proportion of CD41 RCA positive cells in the MEG-01 cells after PMA intervention significantly increased to (127.79±2.01)%, while the proportion of CD41 SNA positive cells significantly decreased to (78.09±1.76)% (both P<0.05). Western blot analysis results showed that, compared with the control group, PMA intervention significantly downregulated the expression of ST6Gal-Ⅰ protein (0.602±0.023 vs 0.768±0.068) and Cav-1 protein (1.012±0.028 vs 1.253±0.068) (both P<0.05), while significantly upregulating the expression of CD36 protein (0.936±0.033 vs 0.694±0.070, P<0.05). Conclusion: PMA can significantly inhibit the expression of ST6Gal-Ⅰ, accompanied by increased desialylation (β-galactose exposure), elevated CD36, and downregulated Cav-1. These changes suggest that the increased exposure of CD36 antigen and the disorder of membrane microenvironment may be involved in the pathological process of ITP, providing a new direction for mechanism research.

OBJECTIVE: To observe the effect of acupuncture at "four pharyngeal points" on simple vocal tics with liver hyperactivity disturbed wind in children. METHODS: Sixty children with simple vocal tics of liver hyperactivity disturbed wind were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases). The control group was given Changma Xifeng tablets orally, 3 times a day, while the observation group was treated with acupuncture at "four pharyngeal points" on the basis of the treatment in the control group, 15-20 min a time, once daily for 7 days, with a 3-day break. Both groups were treated for 3 months. The TCM syndrome score and Yale global tic severity scale (YGTSS) score of the two groups were observed before treatment and after 1, 2, 3 months of treatment, the disappearance time of simple vocal tics was recorded, and the therapeutic efficacy was evaluated after treatment. RESULTS: After 1, 2, 3 months of treatment, the TCM syndrome scores and YGTSS scores of the two groups were decreased compared with those before treatment (P<0.01, P<0.05), and the scores of the observation group were lower than those in the control group (P<0.05, P<0.01). The disappearance time of simple vocal tics in the observation group was earlier than that in the control group (P<0.05). The effective rate of the observation group was 93.1% (27/29), which was higher than 73.3% (22/30) in the control group (P<0.05). CONCLUSION Acupuncture at "four pharyngeal points" could improve symptoms in children with simple vocal tics of liver hyperactivity disturbed wind, and shorten the disappearance time of simple vocal tics.
Humans ; Male ; Acupuncture Points ; Female ; Child ; Acupuncture Therapy ; Drugs, Chinese Herbal/administration & dosage* ; Child, Preschool ; Liver/drug effects* ; Tics/drug therapy* ; Treatment Outcome

BACKGROUND: The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections. METHODS: This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups. RESULTS: A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups. CONCLUSION: The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs. REGISTRATION ClinicalTrials.gov , NCT05173493.
Humans ; Helicobacter Infections/drug therapy* ; Helicobacter pylori/pathogenicity* ; Male ; Female ; Prospective Studies ; Middle Aged ; Anti-Bacterial Agents/adverse effects* ; Adult ; Aged ; Treatment Outcome ; Proton Pump Inhibitors/therapeutic use*

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

This study identified 8 members including NjBIN2 of the GSK3 family in Nardostachys jatamansi by bioinformatics analysis. Moreover, the phylogenetic tree revealed that the GKS3 family members of N. jatamansi had a close relationship with those of Arabidopsis. RT-qPCR results showed that NjBIN2 presented a tissue-specific expression pattern with the highest expression in roots, suggesting that NjBIN2 played a role in root growth and development. In addition, the application of epibrassinolide or the brassinosteroid(BR) synthesis inhibitor(brassinazole) altered the expression pattern of NjBIN2 and influenced the photomorphogenesis(cotyledon opening) and root development of N. jatamansi, which provided direct evidence about the functions of NjBIN2. In conclusion, this study highlights the roles of BIN2 in regulating the growth and development of N. jatamansi by analyzing the expression pattern and biological function of NjBIN2. It not only enriches the understanding about the regulatory mechanism of the growth and development of N. jatamansi but also provides a theoretical basis and potential gene targets for molecular breeding of N. jatamansi with improved quality in the future.
Brassinosteroids/metabolism* ; Steroids, Heterocyclic/metabolism* ; Gene Expression Regulation, Plant/drug effects* ; Plant Proteins/metabolism* ; Phylogeny ; Nardostachys/metabolism* ; Plant Growth Regulators/pharmacology* ; Plant Roots/drug effects*