Objective To investigate the population density and seasonal fluctuations of Aedes albopictus in Guangzhou City, Guangdong Province, from 2021 to 2023, so as to provide insights into A. albopictus control and management of dengue fever. Methods The surveillance of A. albopictus density was performed in all surveillance sites assigned across all streets (townships) in Guangzhou City during the period from January to December from 2021 to 2023. The surveillance frequency was twice every half month from May to September, and once every month for the rest of a year. In each surveillance period, A. albopictus mosquito larvae were captured from indoor and outdoor small water containers in residential areas, parks, medical facilities, schools, other government sectors and social organizations, construction sites, special industries and others for mosquito species identification. Adult mosquitoes were captured using electric mosquito suction apparatus for species identification and gender classification. Adult mosquitoes and mosquito eggs were collected with mosquito and egg traps at the breeding and dwelling places of Aedes mosquitoes for identification. The mosquito oviposition index (MOI), Breteau index (BI), adult mosquito density index (ADI) and standard space index (SSI) were calculated. The A. albopictus density was classified into grades 0, 1, 2 and 3 in each surveillance site, with Grade 0 density defined eligible, and the eligible rate of A. albopictus density was calculated at all surveillance sites each year from 2021 to 2023. In addition, the changing trends in MOI, SSI, BI and ADI of A. albopictus were analyzed in Guangzhou City from 2021 to 2023. Results The eligible rates of A. albopictus density were 61.69%, 68.75% and 55.15% in surveillance sites of Guangzhou City from 2021 to 2023 (χ² = 297.712, P < 0.001), and appeared a tendency towards a reduction followed by a rise each year, which gradually reduced since January, maintained at a low level during the period between May and October, and gradually increased from November to December. The MOI, SSI, BI and ADI of A. albopictus all appeared a tendency towards a rise followed by a reduction in Guangzhou City during the period between January and December from 2021 to 2023. The BI of A. albopictus peaked in the first half of June in 2021 (4.03), the first half of July in 2022 (3.89) and the last half of August in 2023 (5.02), and the SSI of A. albopictus peaked in the last half of June in 2021 (0.93), the last half of May in 2022 (0.59), and the last half of June (0.94) and the first half of September in 2023 (1.12). In addition, the MOI of A. albopictus peaked in the first half of May in 2021 (8.64), the first half of June in 2022 (8.96), and the last half of May (10.21) and the last half of June in 2023 (10.89), and the ADI of A. albopictus peaked in the first half of June in 2021 (3.41), the last half of June in 2022 (4.06), and the first half of July in 2023 (3.61). Conclusions The density of A. albopictus is high in Guangzhou City during the period from May to October, and the risk of local outbreak caused by imported dengue fever is high. Persistent intensified surveillance of the density and seasonal fluctuation of A. albopictus is recommended and timely mosquito prevention and control is required according to the fluctuation in the A. albopictus density.

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.

Transfer learning is a method of learning new tasks in related domain using existing knowledge from source data.In rare disease research,data are often limited.Transfer learning can effectively use data from other related diseases or fields to enhance model performance and research efficiency.This approach helps researchers rapidly identify characteristics and develop potential treatments of rare disease.Currently,transfer learning has been applied in the systematic characterization and drug development of rare diseases.It also shows potential in optimizing rare disease classification,accelerating early diagnosis,and supporting multi-task research.However,challenges arise in the application of transfer learning in rare disease research.In the future,if transfer learning can be combined with techniques such as reinforcement learning,federated learning,and deep learning,greater breakthroughs are expected to be achieved in the field of rare diseases.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

Objective:To identify genetic etiology of ischemic stroke(IS)based on pleiotropy of obe-sity related genes.Methods:A discordant sib-pair study was designed based on the Fangshan family co-hort in Beijing.Body mass index(BMI)polygenic risk score(PRS)was first constructed under different P values.Using the polygenic transmission disequilibrium test(pTDT),we then compared the actual BMI genetic risk of siblings with IS to their expected risk,to analyze whether higher BMI was over-trans-mitted to siblings with IS.The single nucleotide polymorphism(SNP)that comprised the PRS over-trans-mitted with IS and that corresponded to the highest heritability of IS were identified as a pleiotropy SNPs set between BMI and IS.This set was then utilized as a candidate set to identify and verify risk SNPs as-so-ciated IS by transmission disequilibrium test.Finally,we identified independent genomic risk loci and mapped to genes,we then explored the biological function of the identified risk loci and genes by func-tional annotation and pathway enrichment.Results:A total of 541 participants were enrolled,with an average age of(58.4±8.1)years,including 326 discordant sib pairs of ischemic stroke.Compared with non-IS participants,IS participants with males,education level below junior high school,hypertension and hyperlipidemia accounted for a higher proportion(P＜0.05).For all the BMI PRS,we found that the actual genetic risk of BMI in siblings with IS was higher than their expectation,suggesting that genetic risk associated with high BMI was over-transmitted with IS.Compared with other SNP sets,the set(P＜5 × 10-4)corresponded to the best analytical statistics of pTDT and the highest heritability of IS and was identified as the pleiotropy SNP set between BMI and IS.Within this set,there were 45 SNPs having linkage and association with IS,which were located in 43 independent genomic risk loci and mapped to 40 genes.These genes were significantly enriched in the lipid metabolism pathway.The rs2232852 cor-rected by multiple tests was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway.Conclusion:Pleiotropy between BMI-related genes and IS was observed.Forty-five SNPs were found with linkage and association with IS in the pleiotropy gene set and mapped to 40 genes,which were functionally enriched in lipid metabolic pathways.The rs2232852 corrected by multiple tests during association analysis validation was mapped to CYB5R1 and ADIPOR1,which were related to lipid metabolism and the ferroptosis pathway,suggesting that lipid metabolism and ferroptosis played an important role in the development of IS.

Objective:To explore the spousal correlations of total cholesterol(TC),total triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and to investigate the reasons behind these spousal correlations.Methods:Participants and data were from the baseline survey of family-based cohort studies in Fangshan,Beijing and Tulou,Fujian.The ori-gin of spousal correlations were explored from perspectives of convergence,assortative mating,social ho-mogamy.Pearson's correlation and generalized linear models(GLM)were used to estimate the spousal correlation.Convergence was assessed by Pearson's correlation between the phenotypic differences be-tween couples and the duration of marriage,with GLM used for further validation.Pearson's correlation of genetic risk scores(GRS)and couple-specific Mendelian randomization(MR)were calculated to assess the genetic correlation and possible causal relationships between spouses.Two-independent-sample t-tests were used to compare GRS consistency across subgroups divided by education attainment,couple-specific MR and Q statistics used to test assortative mating in subgroups and intergroup differences.Results:In the study,342 couples(287 couples from Fangshan and 55 couples from Fujian)were included,with the average age of(64.91±8.76)years.Spousal correlations of TC,TG,HDL-C,and LDL-C showed statistically significant associations both before and after adjusting for covariates,with effect sizes of 0.229(95％CI:0.125-0.327),0.257(95％CI:0.155-0.354),0.179(95％CI:0.074-0.280),and 0.181(95％CI:0.076-0.282).For convergence,for each additional year of marriage,ΔTC increased by 0.016 mmol/L(95％CI:0.001-0.033 mmol/L),and ΔLDL-C increased by 0.017 mmol/L(95％CI:0.002-0.031 mmol/L).For assortative mating,GRS correlations and results of couple specific MR didn't show any statistical significance.For social homogamy,no differences in GRS or assortative mating were found between subgroups stratified by education attainment.Conclusion:The blood lipid in participants exhibit spousal phenotypic correlations,however,no effects of convergence,assortative mating or social homogamy were observed.More independent studies with larger sample sizes are warranted to further validate these findings in the future.

Transfer learning is a method of learning new tasks in related domain using existing knowledge from source data.In rare disease research,data are often limited.Transfer learning can effectively use data from other related diseases or fields to enhance model performance and research efficiency.This approach helps researchers rapidly identify characteristics and develop potential treatments of rare disease.Currently,transfer learning has been applied in the systematic characterization and drug development of rare diseases.It also shows potential in optimizing rare disease classification,accelerating early diagnosis,and supporting multi-task research.However,challenges arise in the application of transfer learning in rare disease research.In the future,if transfer learning can be combined with techniques such as reinforcement learning,federated learning,and deep learning,greater breakthroughs are expected to be achieved in the field of rare diseases.

Genomic imprinting refers to the phenomenon of differential expression of two alleles due to their different parental origins. Genes that produce genomic imprinting are usually called imprinted genes. The genetic effect caused by the presence of imprinted genes is called parent-of-origin effect. Parent-of-origin effect and genomic imprinting play important roles in the pathophysiological mechanism and occurrence and development of cardio-metabolic diseases. In-depth exploration of the law and potential roles of imprinted genes and parent-of-origin effects will help to better understand the mechanism of cardio-metabolic diseases, and also provide important theoretical basis for the precise treatment of diseases related to imprinted genes.