Objective: To develop a RHCE genotyping assay based on kompetitive allele-specific PCR (KASP) and assess its clinical accuracy for RhCE blood group determination. Methods: KASP primers were designed to interrogate three RHCE loci: the 109 bp insertion/deletion in intron 2, c. 307T>C, and c. 676C>G. A total of 1 194 RhD-positive inpatients from Chengdu were typed by both KASP genotyping and manual tube serology. Discordant samples (n=10) were retested by both methods and further resolved by Sanger sequencing. An additional 377 cases were tested for the c. 48C>G locus to evaluate the predictive accuracy of individual loci and combined locus testing for RhC antigen. Results: Genotyping concordance with serology was 100.0% for both the c. 676C>G locus (RhE/Rhe) and the c. 307T>C locus (Rhc). For RhC prediction using the 109 bp insertion, overall accuracy was 99.7% (1 191/1 194); the 3 discordant cases were confirmed by Sanger sequencing to be false negatives attributable to 109 bp deletion in intron 2. Testing the c. 48C>G allele for RhC prediction yielded 7 false positives, with an accuracy of 98.1% (370/377). RhC antigen status was determined by combining the 109 bp insertion and the c. 48C allele. After excluding 10 samples with inconsistent results between the two loci, the accuracy reached 100% in the remaining 367 samples. When both loci were applied in combination, accuracy reached 100% in the 367 cases with concordant results. Among the 1 194 patients, CCee (45.8%) and CcEe (31.7%) were the most common RhCE phenotypes. The e antigen had the highest positivity rate (92.2%), and the Ce haplotype was the most frequent (66.9%). Conclusion: The KASP-based RHCE genotyping method achieves high accuracy for clinical RhCE typing. Combining the 109 bp insertion/deletion with the c. 48C allele significantly improves RhC antigen prediction compared with either locus alone. This method was applied to RhCE genotyping of 1 194 RhD-positive inpatients in Chengdu, providing local RhCE phenotype and haplotype distribution data to support RhCE-matched transfusion practice.

Objective In order to understand the current resistance status of Aedes albopictus(Ae. albopictus) adult population to commonly used insecticides and the resistance dynamics development in Zhejiang Province and provide a theoretical basis for the scientific and rational use of hygienic insecticides. Methods Resistance determination was carried out using the diagnostic dose method(GB/T 26347-2010)recommended by WHO in the adult mosquito contact cylinder method to monitor the resistance of Ae. albopictus field populations in 11 cities and districts in Zhejiang Province in 2024. Results The monitoring result showed that adult Ae. albopictus in 11 areas were resistant or suspected resistant populations to both cis-cypermethrin and permethrin; suspected and resistant populations to the organophosphate insecticide malathion were as high as 81.82%; while suspected resistance to the carbamate insecticide residual carbofuran accounted for 45.45%, and the rest of the monitoring sites were sensitive to it. Conclusions The result suggest that the generalized resistance of Ae. albopictus populations to pyrethroids and organophosphorus insecticides in the field in Zhejiang Province needs to be highly emphasized. In future mosquito vector and mosquito-borne disease control, insecticides should be selected based on the resistance monitoring information, while following scientific guidelines for insecticide use.

BackgroundNegative emotions are core predictors of adolescent mental health. While existing research has predominantly focused on the impact of risk factors such as negative life events and rumination on adolescents' emotions， the protective role of the family， particularly parental involvement， has received less attention. Consequently， the integrated mechanism connecting negative life events， rumination， parental involvement and negative emotions remains insufficiently clarified. ObjectiveTo elucidate the mechanisms linking negative life events to negative emotions in adolescents， and to verify the mediating role of rumination and the moderating role of parental involvement， so as to provide a theoretical basis for relevant prevention and intervention. MethodsA cross-sectional study was conducted in June 2025. A total of 600 adolescents from a middle school in Liangshan Yi Autonomous Prefecture， Sichuan Province， were recruited through cluster random sampling. Participants completed the Adolescent Self-rating Life Events Checklist （ASLEC）， the Rumination Response Scale （RRS）， parental involvement subscale of the Perception of Parents Scales （POPS）， and the Chinese short version of Depression Anxiety and Stress Scale （DASS-21）. Pearson correlation analysis was performed to examine the correlations among all variables. Model 4 and model 7 embedded in Process macro 4.1 were employed to separately test the mediating effect of rumination between negative life events and negative emotions of adolescents， as well as the moderating effect of parental involvement. ResultsUltimately， 534 valid questionnaires were obtained， yielding a valid response rate of 89.00%. ASLEC score and RRS score were positively correlated with DASS-21 scores （r=0.580， 0.706， P<0.01）， and ASLEC score was also positively correlated with RRS score （r=0.583， P<0.01）. Rumination acted as a partial mediator between negative life events and negative emotions， with an indirect effect of 0.531 （95% CI： 0.438–0.630）， accounting for 55.60% of the total effect. Parental involvement significantly moderated the first stage of the mediating pathway （β=-0.109， P<0.05）. ConclusionIn adolescents， rumination serves as a partial mediator in the relationship between negative life events and negative emotions， and parental involvement further moderates the predictive relationship from negative life events to rumination.

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To exploring the effect of inflammatory indicators on the outcome of assisted conception of in vitro fertilization/intracytoplasmic sperm injection(IVF/ICSI)in patients with ovarian endometriosis(OEM).Methods The study subjects were selected as the patients with OEM who received IVF/ICSI treatment at the Third Affiliated Hospital of Zhengzhou University from January 2019 to February 2024.Based on whether previous surgery for uterine endometriosis cyst removal had been performed,they were divided into non-surgery group(n=73)and surgery group(n=112).To explore the differences in inflammatory markers between two groups and to determine whether they have an impact on the outcome of assisted reproduction.Results The lymphocytes(L)and blastocyst formation rates of patients in surgery group were significantly higher than those in non-surgery group,platelet to lymphocyte ratio(PLR)and carbohydrate antigen 125(CA125)were significantly lower than those in non-surgery group(P＜0.05).There were no statistically significant differences in the clinical pregnancy rate and live birth rate between two groups of patients(P＞0.05).After adjusting for confounding factors,the results of multivariate Logistic regression analysis showed that L,PLR,and CA125 had no statistically significant impact on the clinical pregnancy rate and live birth rate(P＞0.05).Both maternal age and the number of embryos transferred exerted a certain influence on clinical pregnancy rates and live birth rates(P＜0.05),furthermore,the type of embryo transferred had a significant effect on clinical pregnancy rates(P＜0.05).Conclusion Compared with non-surgery group,surgery group had higher L level and lower PRL and CA125 levels,but these changes did not significantly affect clinical pregnancy or live birth outcomes in OEM patients undergoing IVF/ICSI assisted reproduction.

OBJECTIVE: To explore the mechanism and clinical manifestations of a case with complex structural variations involving chromosomes 5, 7, and 14, and assess the value of Chromosome conformation-based karyotyping (C-MoKa) for its diagnosis. METHODS: Two half-sibs by the same father presented at the First Hospital of Lanzhou University in December 2024 for severe multi-system abnormalities were selected as study subjects. Peripheral blood samples from the their parents were subjected to conventional chromosomal karyotyping analysis. The father was further analyzed using C-MoKa, while both siblings underwent copy number variation sequencing (CNV-seq). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: LDYYSZLLKH2025-05). RESULTS: Conventional karyotype analysis indicated that the father has a karyotype of 46,XY,add(5)(p15.3). CNV-seq identified multiple chromosomal abnormalities in both siblings, including duplications and deletions of chromosomes 14 and 5. C-MoKa analysis further revealed a complex chromosomal structural variation involving chromosomes 5, 7, and 14 in the father. These variations were closely associated with the severe phenotypes noted in both children. CONCLUSION Complex chromosomal structural variations can lead to multi-system abnormalities and significantly impact reproductive health. Compared to conventional karyotyping, the C-MoKa technique has shown significant advantage in identifying such complex rearrangements. The combined application of multiple techniques can improve the accuracy of diagnosis, enabling genetic counseling for carriers to reduce their risk for producing further affected offspring.
Female ; Humans ; Male ; China ; Chromosome Aberrations ; DNA Copy Number Variations/genetics* ; Karyotyping ; Pedigree ; East Asian People/genetics*

Background Job burnout and depressive symptoms are prevalent among occupational populations, with a close relationship between them. Sleep quality, as a potential mediating factor, significantly affects the mental health of workers. Objective To explore the relationship between job burnout, sleep quality, and depressive symptoms, and determine whether sleep quality mediates the relationship between job burnout and depressive symptoms. Methods From April 25 to May 1, 2024, this study employed cluster sampling to conduct a questionnaire survey among individuals engaged in various occupations across five cities in the Ningxia Hui Autonomous Region. The questionnaires included socio-demographic information, as well as the Chinese Maslach Burnout Inventory (CMBI), the Pittsburgh Sleep Quality Index (PSQI), and the Patient Health Questionnaire-9 (PHQ-9) for assessing burnout, sleep quality, and depressive symptoms, respectively. Out of the 4106 questionnaires distributed, a total of 3837 questionnaires were valid, and the valid recovery rate was 93.45%. The distribution among demographic variables in burnout, sleep quality and depressive symptoms were statistically analyzed. A binary logistic regression model was used for multifactor correlation analysis; Pearson correlation was used to test the correlation between burnout, sleep quality, and depressed mood. Modelling and mediated effect path mapping were performed using Amos 24.0 software. Results The postive rate of occupational burnout in the workers was 97.49% (3741/3837), the positive rate of poor sleep quality was 66.77% (2526/3837), and the positive rate of depressive symptoms was 75.68% (2904/3837). There were statistically significant differences in depressive symptoms by ages, shift types, working years, marital status, smoking habits, drinking habits, and exercising frequency (P < 0.05). The logistic model indicated that working years, drinking habits, job burnout, and overall sleep quality were significant factors influencing the occurrence of depressive symptoms (P < 0.05). The correlation analysis revealed positive correlations between depressive symptom scores and job burnout scores (r=0.045, P < 0.01), between depressive symptom scores and sleep quality scores (r=0.480, P < 0.01), and between job burnout scores and sleep quality scores (r=0.054, P < 0.01). Furthermore, the indirect effect of job burnout on depressive symptoms through sleep quality was 0.100 (95%CI: 0.204, 0.252; P < 0.01). Conclusion Job burnout and sleep quality are significant factors associated with the occurrence of depressive symptoms among occupational populations, and sleep quality plays a partial mediating role in depressive symptoms associated with job burnout. This finding may provide a scientific basis for developing intervention strategies to control depressive symptoms among workers.

The mitochondrial unfolded protein response(UPRmt)represents a crucial intracellular stress response mechanism that plays a fundamental role in maintaining mitochondrial and cellular homeostasis. Growing evidence suggests that dysregulation of UPRmt contributes significantly to the pathogenesis of various systemic disorders, including neurodegenerative diseases such as Parkinson's and Alzheimer's diseases, as well as age-related pathologies. Emerging research has particularly highlighted the involvement of UPRmt in ocular diseases, including cataracts, glaucoma, and diabetic retinopathy. This comprehensive review examines the physiological functions of UPRmt and its regulatory mechanisms in age-related eye diseases. The roles of key UPRmt downstream effector molecules in ocular cell populations such as lens epithelial cells, retinal pigment epithelial cells, and retinal ganglion cells are systematically analyzed. Importantly, the dual regulatory nature of UPRmt in ocular pathophysiology is discussed, that is, its moderate activation promotes mitochondrial homeostasis, mitigates oxidative stress, and suppresses inflammatory responses, its chronic or excessive activation triggers apoptotic pathways, induces metabolic dysfunction, and ultimately accelerates disease progression. By elucidating these mechanisms, our review provides novel insights into ocular disease pathogenesis and proposes potential therapeutic strategies targeting UPRmt modulation for the prevention and treatment of age-related eye disorders.