Objective:To explore the causal association between insulin-like growth factor-1(IGF-1)and colorectal cancer(CRC)based on two sample Mendelian randomization(MR)analysis.Methods:A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project.The inverse variance weighted(IVW)method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC.Additional analyses were performed using weighted median(WM),MR-Egger regression,weighted mode estimator(WME),and simple mode(SM)methods.Sensitivity analysis was performed to assess the robustness of the results.Results:A total of 386 single nucleotide polymorphisms(SNPs)were selected as instrumental variables(IVs)with IGF-1 as the exposure factor.The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC[odds ratio(OR)=1.178,95％confidence interval(CI):1.092-1.272)](P＜0.001),and the association remained significant after adjusting for height[OR(95％CI)=1.214(1.111,1.327)](P＜0.001).Cochran's Q-test showed heterogeneity among the IVs(P＜0.05),while the horizontal pleiotropy of IV was not detected by the MR-Egger regression(P＞0.05).The leave-one-out analysis showed that the MR results were robust.Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC[OR(95％CI):1.017(0.997,1.037)](P=0.103).Conclusion:There is a causal relationship between IGF-1 level and CRC,and elevated IGF-1 level could be a risk factor for CRC.

Objective:To discuss the influencing factors of angina pectoris in the patients with diabetes mellitus(DM),to construct a Bayesian network model to explore the network relationships among the influencing factors,and to predict the risk of angina pectoris in the patients with DM.Methods:Based on the UK Biobank(UKB)database,the Logistic regression aralysis model was used to screen the influencing factors of angina pectoris in the patients with DM.The taboo search algorithm was used for structure learning,and the Bayesian parameter estimation method was used for parameter learning to construct the Bayesian network model.Results:A total of 22 712 DM patients were included.The influencing factors of angina pectoris in the patients with DM included 14 variables:gender,age,body mass index(BMI),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HbA1c),hypertension,maternal smoking around delivery,smoking status,alcohol consumption,regular exercise,insomnia,sleep duration,and childhood relative body size(P<0.05).A Bayesian network model was constructed with 15 nodes and 22 directed edges.Among them,age,HbA1c,hypertension,regular exercise,BMI,and sleep duration were directly associated with the occurrence of angina pectoris in the patients with DM,while gender,smoking status,alcohol consumption,TC,TG,insomnia,childhood relative body size,and maternal smoking around delivery were indirectly associated with the occurrence of angina pectoris in the patients with DM.Conclusion:Age,HbA1c,hypertension,regular exercise,BMI,and sleep duration are direct influencing factors of angina pectoris in the patients with DM.Controlling HbA1c,blood pressure,and BMI levels,engaging in regular exercise,and maintaining appropriate sleep duration are beneficial for reducing the risk of angina pectoris in the patients with DM.

Objective:To screen the Alzheimer's disease(AD)-related genes and construct its diagnostic model using bioinformatics technology and machine learning(ML)algorithms,to discuss the immunological characteristics of AD patients,and to provide novel biomarkers for AD diagnosis.Methods:The AD-related gene expression dataset GSE125583 was downloaded from the Gene Expression Omnibus(GEO)database.Differentially expressed genes(DEGs)were identified through differential analysis.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analyses were performed to explore the biological functions and signaling pathways of DEGs.A protein-protein interaction(PPI)network was constructed,and hub genes were screened using Cytoscape software combined with three ML algorithms:Least Absolute Shrinkage and Selection Operator(LASSO),eXtreme Gradient Boosting(XGBoost),and Random Forest(RF).The screened hub genes were utilized to build an AD diagnostic model via RF,followed by feature importance ranking.The model's efficacy and key genes were evaluated using a test set.Single-sample gene set enrichment analysis(ssGSEA)was used for immune cell infiltration analysis between AD group and control group.Results:Differential analysis identified 1 287 DEGs.The GO functional enrichment analysis results revealed that DEGs were primarily involved in biological functions related to neural signaling,synapses,and vesicles.KEGG signaling pathway enrichment analysis indicated significant enrichment of DEGs in ion transport,neurotransmitter,and ligand-gated channel pathways.Nine overlapping hub genes were screened by the three ML algorithms.In the AD diagnostic model,the top four key genes with highest diagnostic performance were adenylate cyclase-activating polypeptide 1(ADCYAP1),brain-derived neurotrophic factor(BDNF),platelet-derived growth factor receptor β(PDGFRB),and C-X-C motif chemokine receptor 4(CXCR4),with corresponding area under the curve(AUC)values of 0.852,0.795,0.820,and 0.756,respectively.The model achieved an AUC of 0.828,accuracy of 81.25%,sensitivity of 84.40%,and specificity of 71.43%.The immune cell infiltration analysis results demonstrated higher infiltration of macrophages,monocytes,natural killer(NK)cells,and lymphocytes in AD tissue.Among these,NK/natural killer T(NKT)cells and plasmacytoid dendritic cells showed significant correlations with the four key genes(P<0.05).Conclusion:The feature genes screened based on bioinformatics and ML exhibit diagnostic potential for AD.Genes such as ADCYAP1 may serve as potential biomarkers for AD diagnosis,offering significant implications for early prevention and treatment.

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

Objective To investigate the risk of chronic obstructive pulmonary disease(COPD)after asthma and explore factors influen-cing the onset and progression of asthma in patients with COPD.Methods A follow-up cohort was established based on the United Kingdom Biobank(UKB)database.The risk of asthma and COPD was predicted,and the influencing factors were analyzed using a mul-tistate model(MSM).Results Without considering the influence of covariates,the cumulative risk from COPD to mortality was the highest,followed by asthma to COPD,and asthma to mortality.Advanced age,male,diabetes mellitus(DM),high waist-to-hip ratio,hyper-tension,increased Townsend deprivation index,increased frequency of smoking,and family history were risk factors for developing COPD in the asthmatic population.Advanced age,male,DM,high waist-to-hip ratio,hypertension,increased Townsend deprivation index,and in creased frequency of smoking were risk factors for mortality in the asthmatic population.Advanced age,male,and DM and increased Townsend deprivation index were risk factors for mortality in the COPD population.Conclusion Advanced age,male,DM,high waist-to-hip ratio,hypertension,increased Townsend deprivation index,increased smoking frequency,and family history increased the risk of COPD in the asthmatic population.This MSM can be used to predict the influencing factors and degree of COPD after asthma,and reveal the change law of disease progression.

Objective:To study the current situation of the operating room nurses′ flourishing, and to explore the mediating role of self-compassion between forgiveness and flourishing, so as to provide a basis for improving the level of flourishing of operating room nurses.Methods:From September to November 2023, a total of 1 182 operating room nurses from 20 hospitals in Henan province were investigated by convenient sampling method. General data questionnaire, the Heartland Forgiveness Scale, Self-Compassion Scale and the Flourishing Scale were used to conduct an online cross-sectional survey. The mediating role of self-compassion in the relationship between forgiveness and flourishing was analyzed.Results:A total of 1 182 valid questionnaires were collected, including 261 males and 921 females. The age ranged from 21 to 54 (33.21 ± 5.72) years. In operating room nurses, the score of the forgiveness was (111.88 ± 18.77) points, the score of the self-compassion was (76.60 ± 10.75) points, the score of the flourishing was (43.48 ± 8.72) points. Forgiveness was positively correlated with self-warmth and flourishing ( r=0.545, 0.590, both P<0.05), forgiveness was negatively correlated with self-cold ( r=-0.365, P<0.05). The flourishing was positively correlated with self-warmth ( r=0.608, P<0.05), and negatively correlated with self-cold ( r=-0.509, P<0.05). self-warmth and self-cold played a mediating role between forgiveness and flourishing. The indirect effects of self-warmth and self-cold were 23.97% and 20.93% of the total mediating effects. Conclusions:The level of flourishing of the operating room nurses is at a relatively high level. Nurses′ forgiveness can affect their flourishing directly as well as indirectly through self-warmth and self-cold.

Objective:To study the current situation of the operating room nurses′ flourishing, and to explore the mediating role of self-compassion between forgiveness and flourishing, so as to provide a basis for improving the level of flourishing of operating room nurses.Methods:From September to November 2023, a total of 1 182 operating room nurses from 20 hospitals in Henan province were investigated by convenient sampling method. General data questionnaire, the Heartland Forgiveness Scale, Self-Compassion Scale and the Flourishing Scale were used to conduct an online cross-sectional survey. The mediating role of self-compassion in the relationship between forgiveness and flourishing was analyzed.Results:A total of 1 182 valid questionnaires were collected, including 261 males and 921 females. The age ranged from 21 to 54 (33.21 ± 5.72) years. In operating room nurses, the score of the forgiveness was (111.88 ± 18.77) points, the score of the self-compassion was (76.60 ± 10.75) points, the score of the flourishing was (43.48 ± 8.72) points. Forgiveness was positively correlated with self-warmth and flourishing ( r=0.545, 0.590, both P<0.05), forgiveness was negatively correlated with self-cold ( r=-0.365, P<0.05). The flourishing was positively correlated with self-warmth ( r=0.608, P<0.05), and negatively correlated with self-cold ( r=-0.509, P<0.05). self-warmth and self-cold played a mediating role between forgiveness and flourishing. The indirect effects of self-warmth and self-cold were 23.97% and 20.93% of the total mediating effects. Conclusions:The level of flourishing of the operating room nurses is at a relatively high level. Nurses′ forgiveness can affect their flourishing directly as well as indirectly through self-warmth and self-cold.

Objective To investigate the risk of chronic obstructive pulmonary disease(COPD)after asthma and explore factors influen-cing the onset and progression of asthma in patients with COPD.Methods A follow-up cohort was established based on the United Kingdom Biobank(UKB)database.The risk of asthma and COPD was predicted,and the influencing factors were analyzed using a mul-tistate model(MSM).Results Without considering the influence of covariates,the cumulative risk from COPD to mortality was the highest,followed by asthma to COPD,and asthma to mortality.Advanced age,male,diabetes mellitus(DM),high waist-to-hip ratio,hyper-tension,increased Townsend deprivation index,increased frequency of smoking,and family history were risk factors for developing COPD in the asthmatic population.Advanced age,male,DM,high waist-to-hip ratio,hypertension,increased Townsend deprivation index,and in creased frequency of smoking were risk factors for mortality in the asthmatic population.Advanced age,male,and DM and increased Townsend deprivation index were risk factors for mortality in the COPD population.Conclusion Advanced age,male,DM,high waist-to-hip ratio,hypertension,increased Townsend deprivation index,increased smoking frequency,and family history increased the risk of COPD in the asthmatic population.This MSM can be used to predict the influencing factors and degree of COPD after asthma,and reveal the change law of disease progression.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.

Purpose: Vaccinia virus is widely used as an oncolytic agent for human cancer therapy, and several versions of vaccinia virus have demonstrated robust antitumor effects in breast cancer. Most vaccinia viruses are modified by thymidine kinase (TK) deletion. The function of the cyclin-dependent kinase inhibitor p21 in breast cancer remains controversial. We explored the impact of p21 gene knockdown (KD) on breast cancer cells and whether p21 KD interferes with the antitumor effect of TK-negative vaccinia virus. Methods: p21 KD MDA-MB-231 and p21 KD MCF-7 cells were prepared, and cell proliferation and migration rates were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and scratch healing assays. The tumor growth of xenografts originating from p21KD MDA-MB-231 cells and control cells was compared in a mouse model. The colony formation and sphere-forming abilities of p21 KD breast cancer cells were also determined using low-melting agarose and serum-free culture. The tumorkilling effect of the vaccinia virus was determined in breast cancer cells and mouse models using an MTT assay and tumor cell xenografts. Results: p21 KD increased the growth and migration of MDA-MB-231 and MCF-7 cells and promoted the cell growth of MDA-MB-231 cells in mice, while decreasing the colony formation and sphere formation abilities. Expression of TK was reduced in p21 KD MDAMB-231 cells. Oncolytic effects of both wild-type and TK-deleted vaccinia viruses were attenuated in p21KD MDA-MB-231 cells. The tumor-killing effect of TK-deleted vaccinia virus was also weakened in xenografted mice bearing p21 KD MDA-MB-231 cells. Conclusion Targeted inhibition of p21 accelerates the proliferation and migration of breast cancer cells and impairs the tumor-killing effect of vaccinia virus, suggesting that p21 levels in cancer cells interfere with vaccinia virus oncolytic therapy.