BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

BACKGROUND:Spondylolisthesis is a common disease,and there is a lack of effective drugs to treat it.There is still a need to further define the pathogenesis and screen out more suitable therapeutic targets for spondylolisthesis.Mendelian randomization analysis can be used to explore the drugable genes associated with spondylolisthesis and provide valuable guidance for the development of more effective and targeted therapeutic drugs.OBJECTIVE:To explore potential therapeutic targets and effective drugs for spondylolisthesis by means of pharmaceutically available genome-wide Mendelian randomization analysis.METHODS:Using the Finnish database,eQTLGen consortium,drug signature database,drug-gene interaction database,protein-protein interaction database,organic small molecule biological activity database and protein structure database,which contains genome and health information of half a million Finns,data on druggable genes were subjected to two-sample Mendelian randomization analysis and co-localization analysis with data from genome-wide association studies of spondylolisthesis to identify genes highly associated with spondylolisthesis.In addition,GO and KEGG enrichment analysis,protein network construction,drug prediction and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic agents.RESULTS AND CONCLUSION:In this study,we identified 34 potential drug target genes that were significantly associated with spondylolisthesis,particularly the gene APOBEC3G.This gene showed a significant association with spondylolisthesis outcomes through Mendelian analysis and co-localization analysis,suggesting that APOBEC3G may be a priority therapeutic target.As for other potential mechanisms and drugs,we still need to conduct more in-depth research to determine their roles.This study used a database from a European population,which can be used as a reference for the study of population genetics in China.

OBJECTIVE To analyze the homology and drug resistance characteristics of clinical carbapenem-resistant Klebsiella pneumoniae(CRKP)isolates from the children and adults in Kunming area so as to provide guidance for prevention and control of CRKP strains.METHODS Totally 41 strains of clinical CRKP isolates were collected from the children in 4 hospitals of Kunming area in 2023,and 54 strains were collected from the adults.The ho-mology of the strains was analyzed by means of repetitive extragenic palindromic-polymerase chain reaction(REP-PCR);the phenotypes of carbapenemases and the genes in the strains were detected.RESULTS The 95 strains of CRKP were divided into 30 genotypes.There was clustering of genotypes in some strains.The type A enzyme was most common among the strains from the adults(47 strains,87.04％),while the type A enzyme(18 strains,43.90％)and the type B enzyme(23 strains,56.10％)were both detected in the strains from the children.A-mong the strains producing type A enzyme,the strains carrying with KPC gene were both dominant among the strains isolated from the adults(44 strains,81.48％)and the strains isolated from the children(18 strains,43.90％).Among the strains producing type B enzyme,the strains carrying with NDM gene were dominant a-mong the strains from the children(22 strains,53.66％).CONCLUSIONS There is colonization and inter-hospital transmission of CRKP strains in the hospitals of Kunming area.It is necessary for the clinical departments of the children's hospitals to strengthen the active screening of the transferring children and carefully carry out the cleaning and disinfection of nosocomial environment so as to reduce the probability of the CRKP infection among the children.Mean-while,the clinicians of the pediatrics department should comprehensively take all the factors into accounts such as the type of enzyme,formulate the appropriate medication regimens and raise the cure rate of the children with CRKP infection.

Objective To observe the efficacy of self-guided attention network for detecting responsible lesions related to cerebral palsy(CP)in children with periventricular white matter injury(PVWMI).Methods Totally 383 children with PVWMI were retrospectively enrolled and divided into CP group(n=243)and non-CP group(n=140),while 214 children without obvious brain abnormality on brain MRI were taken as control group.ROI of 4 key anatomical structures related to CP,i.e.centrum semiovale,posterior limb of internal capsule,cerebral peduncle and thalamus were delineated on T1WI,while responsible lesions related to CP within the key anatomical structures were labeled on T2WI,and the images were then registrated and used as input of the networks.ResNet34 network was adopted combined with attention and self-guided networks to train the network for detecting responsible lesions related to CP in children with PVWMI,and their efficacies were evaluated.The optimal network was screened,and its efficacy for segmenting the key anatomical structures was evaluated.Results Self-guided attention network was the optimal network,its area under the curve(AUC)for detecting lesions was 0.794-0.914,and the Dice similarity coefficient for segmenting the key anatomical structures was 0.702-0.764.Conclusion Self-guided attention network could be used for preliminarily detecting responsible lesions related to CP in children with PVWMI.

Osteoblasts are the main functional cells of bone formation,and their adhesion to the implants is the premise of biological function.However,most of the common clinical implants are inert metals,which have some problems such as poor biological activity and lack of bone induction,which are not conducive to osteoblast adhesion,so it is often necessary to modify their surface.Nano-morphology is a hot topic in recent years,which refers to the topological structure of implant surface unit and size 1-100 nm,similar to extracellular matrix in structure,with many advantages such as enhanced hydrophilicity,superior biocompatibility and antibacterial properties.However,not all nano-morphologies are conducive to osteoblast adhesion.This paper reviews the adhesion process,common nano-surface structure and surface modification of osteoblasts on nano-surface,in order to provide reference for implant surface nano-modification and clinical application.

OBJECTIVE To analyze the homology and drug resistance characteristics of clinical carbapenem-resistant Klebsiella pneumoniae(CRKP)isolates from the children and adults in Kunming area so as to provide guidance for prevention and control of CRKP strains.METHODS Totally 41 strains of clinical CRKP isolates were collected from the children in 4 hospitals of Kunming area in 2023,and 54 strains were collected from the adults.The ho-mology of the strains was analyzed by means of repetitive extragenic palindromic-polymerase chain reaction(REP-PCR);the phenotypes of carbapenemases and the genes in the strains were detected.RESULTS The 95 strains of CRKP were divided into 30 genotypes.There was clustering of genotypes in some strains.The type A enzyme was most common among the strains from the adults(47 strains,87.04％),while the type A enzyme(18 strains,43.90％)and the type B enzyme(23 strains,56.10％)were both detected in the strains from the children.A-mong the strains producing type A enzyme,the strains carrying with KPC gene were both dominant among the strains isolated from the adults(44 strains,81.48％)and the strains isolated from the children(18 strains,43.90％).Among the strains producing type B enzyme,the strains carrying with NDM gene were dominant a-mong the strains from the children(22 strains,53.66％).CONCLUSIONS There is colonization and inter-hospital transmission of CRKP strains in the hospitals of Kunming area.It is necessary for the clinical departments of the children's hospitals to strengthen the active screening of the transferring children and carefully carry out the cleaning and disinfection of nosocomial environment so as to reduce the probability of the CRKP infection among the children.Mean-while,the clinicians of the pediatrics department should comprehensively take all the factors into accounts such as the type of enzyme,formulate the appropriate medication regimens and raise the cure rate of the children with CRKP infection.

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.

Purpose To achieve intelligent detection of acute pulmonary embolism(APE)in CT pulmonary angiography based on the Res2Net attention mechanism network.Materials and Methods Retrospectively included patients with suspected of APE who underwent CT pulmonary angiography examination and were diagnosed as APE at the First Affiliated Hospital of Henan University of Chinese Medicine from February 2015 to May 2023.The dataset was randomly divided into training,validation and test set in a ratio of 7∶2∶1.The model was trained based on the Res2Net network,combined with atrous spatial pyramid pooling and attention mechanism modules,and was performed five-fold cross internal validation.Using the area under the receiver operator characteristic curve,sensitivity and specificity to assess the diagnostic performance of the model.Dice similarity coefficient,precision and intersection over union(IOU)were used to assess the segmentation performance of thrombus on the test set and plot the corresponding curves.The performance of the Res2Net attention mechanism network was compared with the classic U-Net and CE-Net model.Results A total of 303 patients with APE were included in this study.There were 212,61 and 30 cases in the training set,validation set and test set,respectively.The model's area under the curve was 0.95,sensitivity was 0.90,specificity was 1.00,Dice similarity coefficient was 0.86,precision was 0.90,Pos-IOU was 0.78 and Neg-IOU was 1.00,respectively.The parameter curves and radar chart showed that the Res2Net attention mechanism network performed better than the U-Net and CE-Net models.The visualization results of the segmentation comparison showed that the Res2Net attention mechanism network achieved higher precision in segmenting pulmonary artery thrombus.Conclusion The Res2Net attention mechanism network has good performance for detection of APE.

Osteoblasts are the main functional cells of bone formation,and their adhesion to the implants is the premise of biological function.However,most of the common clinical implants are inert metals,which have some problems such as poor biological activity and lack of bone induction,which are not conducive to osteoblast adhesion,so it is often necessary to modify their surface.Nano-morphology is a hot topic in recent years,which refers to the topological structure of implant surface unit and size 1-100 nm,similar to extracellular matrix in structure,with many advantages such as enhanced hydrophilicity,superior biocompatibility and antibacterial properties.However,not all nano-morphologies are conducive to osteoblast adhesion.This paper reviews the adhesion process,common nano-surface structure and surface modification of osteoblasts on nano-surface,in order to provide reference for implant surface nano-modification and clinical application.

BACKGROUND:Monounsaturated fatty acids are mostly recognized as a fatty acid with beneficial effects on human health,and some studies have suggested that they may contribute to non-inflammatory pain at multiple sites in the body.OBJECTIVE:To investigate the effect of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality,thereby providing potential biomarkers and intervention strategies for low back pain management and prevention.METHODS:A Mendelian randomization method was used to analyze the potential association of monounsaturated fatty acids on the incidence of low back pain and all-cause mortality in conjunction with large sample data from the National Health and Nutrition Examination Survey(NHANES)database.Results were validated and sensitivity analyzed using multiple statistical models(e.g.,inverse variance weighting,MR-Egger regression,simple median,weighted median,and weighted median)to enhance the reliability of causal inferences.In the NHANES study,multivariate Cox proportional risk regression models were used to assess the independent predictive values of different fatty acid ratios and to control for confounders.Potential nonlinear relationships between monounsaturated fatty acids and all-cause mortality were assessed using Kaplan-Meier curves,log-rank tests,and restricted cubic spline curves.RESULTS AND CONCLUSION:Elevated monounsaturated fatty acids have been found to be associated with a significantly higher risk of low back pain,suggesting an unfavorable effect of this fatty acid.Also,monounsaturated fatty acids may increase all-cause mortality in patients with low back pain.This provides new insights into the potential effects of monounsaturated fatty acids on low back pain and all-cause mortality,and provides a scientific basis for nutritional interventions for low back pain.The results support the use of dietary modification as one of the strategies for the prevention and management of low back pain in the European population,but further studies are needed to explore the specific biological mechanisms and potential for clinical application,thereby improving guidance for the prevention and treatment of diseases in China.