[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

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.

Objective To predict the lymphovascular invasion(LVI)status of breast cancer patients based on digital breast tomo-synthesis(DBT)intratumoral and peritumoral radiomics nomogram.Methods A total of 192 breast cancer patients from 2 institu-tions were retrospectively selected,in which institution 1 was used for train(n=113)and test(n=49),while institution 2 was used for external validation(n=30).Radiomics features were extracted and selected based on intratumoral and peritumoral 1 mm regions from DBT images.Different machine learning algorithms were used to construct intratumoral,peritumoral,and combined intratumoral and peritumoral models,respectively.Patient clinical data were analyzed by both univariate and multivariate logistic regression analy-ses to identify independent risk factors for the clinical imaging model.The performance of the models was evaluated using the receiver operating characteristic(ROC)curve.The radiomics features with the optimal diagnostic performance and the selected clinical imaging features were combined to construct a comprehensive clinical-radiomics model,and a nomogram was drawn.Results The combined intratumoral and peritumoral model was the optimal radiomics model.Maximum tumor diameter[odds ratio(OR)=1.486,P=0.014],suspicious malignant calcifications(OR=2.898,P=0.015),and axillary lymph node(ALN)metastasis(OR=3.615,P<0.001)were independent risk factors for LVI positive.Furthermore,the area under the curve(AUC)of the comprehensive clinical-radiomics model in the training set,test set and external valida-tion set was 0.889,0.916,and 0.862,respectively,which was higher than those of the combined intratumoral and peritumoral model(0.858,0.849,0.844)and the clinical imaging model(0.743,0.759,0.732).Conclusion The predictive nomogram,derived from both radiomics and clinical imaging features,is relatively accurate in identifying future LVI occurrence in breast cancer,demonstra-ting its potential as an assistive tool for clinicians to devise individualized treatment regimes.

Objective To screen immune-related long non-coding RNAs(LncRNAs)in the TCGA database pancreatic cancer dataset and construct a prognostic risk assessment model with immune-related LncRNAs to explore prognosis-related potential molecular mechanisms.Methods RNA-seq data of 171 pancreatic cancer samples and corresponding clinical information were obtained by The Cancer Genome Atlas(TCGA)database,and two classical immune-related gene datasets(GO0006955/IMMUNE RESPONSE and GO0002376/IMMUNE SYSTERM PROCESS)and gene annotation information were used to identify immune-related LncRNAs.The immune-related LncRNAs associated with pancreatic cancer prognosis were used for univariate and multivariate Cox analyses to establish a model for the assessment of pancreatic cancer prognostic risk based on immune-associated LncRNAs.This risk model was used for survival analysis,clinical correlation analysis,immune cell infiltration analysis,pathway enrichment analysis,and prognostic column line plot modeling.Results We screened 119 immune-related LncRNAs in pancreatic cancer,and five immune-related LncRNAs(AC064836.3,LINC00941,ZNF236-DT,TMEM161B-AS1 and AC068580.2)were identified for the development of pancreatic cancer prognostic risk assessment model.According to the prognostic risk assessment model,pancreatic cancer patients were divided into low-risk group(n=86)and high-risk group(n=85).Compared with the low-risk group,the high-risk group showed a significant negative enrichment trend for immune-related signaling pathways,the 5-year overall survival of pancreatic cancer patients was significantly increased in the low-risk group compared with the high-risk group.The expression of low-risk immune-related LncRNAs(AC064836.3,ZNF236-DT and TMEM161B-AS1)gradually decreased with increasing clinical stage of pancreatic cancer patients.Patient age(P=0.031,risk ratio and 95％CI:1.025/1.002-1.048)and prognostic risk score(P＜0.001,risk ratio and 95％ confidence interval 1.801/1.465-2.215)could be used as independent prognostic risk factors for overall survival in pancreatic cancer.In addition,the prognostic risk assessment model had better predictive efficiency(area under the curve=0.695)compared with the disease predictive ability of common clinical characteristics.Steroid biosynthesis,pentose phosphate pathway,intercellular linkage,cytoskeletal rearrangement and other pathways related to energy metabolism and invasive migration of pancreatic cancer cells were significantly activated in the high-risk group.Meanwhile,pancreatic cancer patients in the high-risk group had lower levels of naive B cells,plasma cells and neutrophils with anti-tumor activity,but their macrophage infiltration levels were significantly higher than those in the low-risk group.Conclusion The prognostic risk assessment model constructed based on five immune-related LncRNAs can effectively predict the survival status,clinical characteristics,molecular pathways,and immune cell infiltration differences of pancreatic cancer patients.Meanwhile,relying on this model,the prognosis of pancreatic cancer patients can be prospectively predicted,which enhances the usefulness of this risk prediction model.

Objective:To establish a quality control method for the standard decoction of Polygoni Avicularis Herba.Methods:Totally 12 batches of decoction pieces from different origins were collected, the standard decoction was prepared and the quality evaluation method was established, the content of index components in the decoction pieces and the standard decoction was determined with HPLC, the index components, solution pH and other parameters were calculated, and the similarity analysis was carried out against the fingerprints.Results:The total content of myricetin in 12 batches of decoction pieces was >0.12%, and the content of myricetin in the standard decoction was >0.03%, which met the standard of the 2020 edition of the Chinese Pharmacopoeia. The pH value was 5.1-5.5, the transfer rate of myricetin components ranged from 50.0%-106.3%, and the fingerprint study showed that there were 7 common peaks. The similarity analysis results indicated that the standard decoction of 12 batches of decoction pieces of Polygoni Avicularis Herba had good consistency.Conclusion:The preparation process is stable and feasible in line with the traditional decoction preparation method, and can be used for the research and quality evaluation of the standard decoction.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Dental implantology has developed rapidly for over half a century,since pure titanium(99.7％)dental cylindrical threaded implants were exploited and osseointegration was introduced in 1960s by Prof.Br?nemark.The long term retention rates of 10 years or more are over 95％.However,the biological complications jeopardize the long term effects of dental implant treatment seriously.The prevalence of dental implant biological complications varies greatly among different reports resulting from the disparities on the defini-tions of dental implant biological complications.After analyzing and summarizing the major opinions proposed internationally in recent years,the consensus for the definition of dental implant biological complications has been reached.Generally the dental implant biologi-cal implications can be classified into early stage(before restoration)biological complications and late stage(after restoration)biological complications.The early stage biological complications include acute and chronic infections,pain,soft tissue deficiency,and osseointegration failure,etc.The late stage complications include peri-implant diseases(peri-implant mucositis and peri-implantitis),soft tissue deficiency around implant,implant loosening and dropping off,etc.The various risk factors related to different dental implant biological complications,the strategies of the prevention and treatment for the dental implant biological complications have been discussed comprehensively,and the consensus has been reached.It is aimed to advocate the dentist to pay more attention to the early prevention of the biological implant complications,to promote more researches on the implant biological complications,and to help elevate the level of dental implantology in our country.

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.

Objective:To explore the effect of contezolid on platelet count in patients with severe pneumonia and analyze the risk factors.Methods:The study was designed as a retrospective case-control study. The research subjects were selected from patients with severe pneumonia who were admitted to the Department of Respiratory and Critical Care Medicine of Shaanxi Provincial People′s Hospital from July 1, 2022 to November 30, 2024 and were treated with contezolid or linezolid. The clinical data of patients were collected and the incidence of thrombocytopenia [platelet count (PLT)<100×10 9/L after medication], the PLT before and at 1 week of treatments, and the lowest PLT value during treatments were compared in patients treated with contezolid and linezolid. The patients were divided into 2 groups based on whether contezolid- related thrombocytopenia occurred. The clinical characteristics of the patients were compared, and the independent risk factors of contezolid-related thrombocytopenia were analyzed by binary logistic regression method. Results:A total of 175 patients were included, among whom 73 received contezolid and 102 received linezolid. There was no statistically significant difference in PLT between the 2 groups before medication ( P=0.364). Compared with patients treated with linezolid, the incidence of thrombocytopenia in patients treated with contezolid was lower [19.2% (14/73) vs. 40.2% (41/102)], and the PLT at 1 week of treatments and the lowest value of PLT during treatments were higher. The differences were all statistically significant (all P<0.05). Compared with patients without contezolid-related thrombocytopenia(59 patients), patients who developed thrombocytopenia after using contezolid had a longer duration of contezolid medication, lower PLT and creatinine clearance rate before medication, and higher procalcitonin and serum creatinine levels before medication. All these differences were statistically significant (all P<0.05). The results of binary logistic regression analysis showed that lower PLT [odds ratio ( OR)=0.971, 95% confidence interval ( CI): 0.950-0.992, P=0.008] and higher procalcitonin level ( OR=7.292, 95% CI: 1.067-49.814, P=0.043) before medication and longer duration of contezolid medication ( OR=1.165, 95% CI: 1.002-1.355, P=0.046) were the independent risk factors of contezolid-related thrombocytopenia. Conclusions:Compared with linezolid, contezolid has a relatively safer profile in the treatment of patients with severe pneumonia and the risk of thrombocytopenia after medication is lower. Patients with lower PLT and higher procalcitonin levels before medication, and those with a longer duration of contezolid medication have a higher risk of contezolid-related thrombocytopenia and should be closely monitored.