Computational analysis can accurately detect drug-gene interactions (DGIs) cost-effectively. However, transductive learning models are the hotspot to reveal the promising performance for unknown DGIs (both drugs and genes are present in the training model), without special attention to the unseen DGIs (both drugs and genes are absent in the training model). In view of this, this study, for the first time, proposed an inductive learning-based model for the precise identification of unseen DGIs. In our study, by integrating disease nodes to avoid data sparsity, a multi-relational drug-disease-gene (DDG) graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions. Following the extraction of graph features by utilizing graph embedding algorithms, our next step was the retrieval of the attributes of individual gene and drug nodes. In this way, a hybrid feature characterization was represented by integrating graph features and node attributes. Machine learning (ML) models were built, enabling the fulfillment of transductive predictions of unknown DGIs. To realize inductive learning, this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights, enabling inductive predictions for the unseen DGIs. Consequently, the final model was superior to existing models, with significant improvement in predicting both external unknown and unseen DGIs. The practical feasibility of our model was further confirmed through case study and molecular docking. In summary, this study establishes an efficient data-driven approach through the proposed modeling, suggesting its value as a promising tool for accelerating drug discovery and repurposing.

OBJECTIVE To observe the characteristics of outer membrane vesicles(OMVs)of 1 strain of hypervir-ulent Klebsiella pneumoniae(hvKp)11492.METHODS The hvKp11492,one of major clones of hvKp that were i-solated from patients with bloodstream infection in the First Medical Center of Chinese PLA General Hospital,was chosen as the research subject.The strain was identified by means of matrix-assisted laser desorption/ioniza-tion time of flight mass spectrometry and whole genome sequencing.The hvKp1 1492-OMVs were separated and purified by high speed centrifugation in combination with polymer precipitation,the morphology and particle size of the hvKp11492-OMVs were identified by transmission electron microscopy(TEM)and nanoparticle tracking a-nalysis(NTA),the proteomic characteristics were analyzed through bicinchoninic acid assay(BCA)and liquid chromatography-mass spectrometry(LC-MS)series technique,and the virulence genes were detected by PCR.RESULTS The hvKp11492-OMVs were displayed differently in size,round or oval,and complete double-layer membrane vesicles on TEM.The result of NTA showed that the average particle size of the hvKp1 1492-OMVs was 270 nm.The protein content of hvKp11492-OMVs was(2.448±0.975)μg/μl.The result of subcellular lo-calization indicated that the protein included plasmosin,intracellular membrane protein,periplasmic protein,ex-tracellular membrane protein and nuclear region protein,which were found,by the annotation of GO database,to participate in the biological processes such as oxidation-reduction,interpretation,and metabolism.The hvKp11492-OMVs contained various proteins such as GDP-L-fucose synthetase,iron ion transporter protein and ferritin that were associated with pathogenicity.In addition,the hvKp1 1492-OMVs carried with iutA,iroN,iucA and rmpA virulence genes.CONCLUSIONS The morphologic characteristics,size and proteomic characteris-tics of the hvKp11492-OMVs are identified in the study.It is concluded that the hvKp11492-OMVs carry with va-rious proteins and genes that are association with the virulence and pathogenicity.

Computational analysis can accurately detect drug-gene interactions(DGIs)cost-effectively.However,transductive learning models are the hotspot to reveal the promising performance for unknown DGIs(both drugs and genes are present in the training model),without special attention to the unseen DGIs(both drugs and genes are absent in the training model).In view of this,this study,for the first time,proposed an inductive learning-based model for the precise identification of unseen DGIs.In our study,by integrating disease nodes to avoid data sparsity,a multi-relational drug-disease-gene(DDG)graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions.Following the extraction of graph features by utilizing graph embedding algorithms,our next step was the retrieval of the attributes of individual gene and drug nodes.In this way,a hybrid feature charac-terization was represented by integrating graph features and node attributes.Machine learning(ML)models were built,enabling the fulfillment of transductive predictions of unknown DGIs.To realize inductive learning,this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights,enabling inductive predictions for the unseen DGIs.Consequently,the final model was superior to existing models,with significant improvement in predicting both external unknown and unseen DGIs.The practical feasibility of our model was further confirmed through case study and molecular docking.In summary,this study establishes an efficient data-driven approach through the proposed modeling,suggesting its value as a promising tool for accelerating drug discovery and repurposing.

Objective:To investigate the significance of dynamic quantitative detection of(cytomegalovirus)CMV antibodies in assessing the risk of fetal CMV infection.Methods:A total of 171 pregnant women with positive/weakly positive CMV IgM antibody ELISA screening results from Huizhou Central People's Hospital from August 2019 to March 2022 were selected as the study objects.IgM and IgG levels were measured by electrochemical luminescence(ECLIA),and re-examined 2 to 4 weeks later;at the same time,CMV nucleic acid was detected by real-time PCR fluorescent probe,and the fetal outcome was followed up.Results:In 171 cases,135 CMV IgM antibody ELISA(+)/ECLIA(-)specimens were positive for IgG antibodies and had stable levels after 2～4 weeks,one case was diagnosed with severe β thalassemia at 19+5 weeks,and the remaining fetuses were in good condition.There were 36 cases of IgM antibody ELISA(+)/ECLIA(+)specimens,one was negative for IgG antibody;35 cases had positive IgM antibody and stable IgG antibody level after 2～4 weeks,the fetus was in good condition;one case had IgM antibody level decreased and IgG antibody level increased significantly,urinary CMV DNA level gradually decreased,and was diagnosed as disseminated congenital CMV infection.Conclusion:The false positive rate of CMV IgM antibody detected by ELISA method is significantly higher than that of ECLIA method,and the dynamic quantitative detection can effectively eliminate interference.Maternal women with significant changes in CMV IgM,IgG antibodies and urinary DNA levels are at high risk of intrauterine infection and had a high probability of fetal congeni-tal CMV infection.

OBJECTIVE To observe the characteristics of outer membrane vesicles(OMVs)of 1 strain of hypervir-ulent Klebsiella pneumoniae(hvKp)11492.METHODS The hvKp11492,one of major clones of hvKp that were i-solated from patients with bloodstream infection in the First Medical Center of Chinese PLA General Hospital,was chosen as the research subject.The strain was identified by means of matrix-assisted laser desorption/ioniza-tion time of flight mass spectrometry and whole genome sequencing.The hvKp1 1492-OMVs were separated and purified by high speed centrifugation in combination with polymer precipitation,the morphology and particle size of the hvKp11492-OMVs were identified by transmission electron microscopy(TEM)and nanoparticle tracking a-nalysis(NTA),the proteomic characteristics were analyzed through bicinchoninic acid assay(BCA)and liquid chromatography-mass spectrometry(LC-MS)series technique,and the virulence genes were detected by PCR.RESULTS The hvKp11492-OMVs were displayed differently in size,round or oval,and complete double-layer membrane vesicles on TEM.The result of NTA showed that the average particle size of the hvKp1 1492-OMVs was 270 nm.The protein content of hvKp11492-OMVs was(2.448±0.975)μg/μl.The result of subcellular lo-calization indicated that the protein included plasmosin,intracellular membrane protein,periplasmic protein,ex-tracellular membrane protein and nuclear region protein,which were found,by the annotation of GO database,to participate in the biological processes such as oxidation-reduction,interpretation,and metabolism.The hvKp11492-OMVs contained various proteins such as GDP-L-fucose synthetase,iron ion transporter protein and ferritin that were associated with pathogenicity.In addition,the hvKp1 1492-OMVs carried with iutA,iroN,iucA and rmpA virulence genes.CONCLUSIONS The morphologic characteristics,size and proteomic characteris-tics of the hvKp11492-OMVs are identified in the study.It is concluded that the hvKp11492-OMVs carry with va-rious proteins and genes that are association with the virulence and pathogenicity.

Objective:To investigate the significance of dynamic quantitative detection of(cytomegalovirus)CMV antibodies in assessing the risk of fetal CMV infection.Methods:A total of 171 pregnant women with positive/weakly positive CMV IgM antibody ELISA screening results from Huizhou Central People's Hospital from August 2019 to March 2022 were selected as the study objects.IgM and IgG levels were measured by electrochemical luminescence(ECLIA),and re-examined 2 to 4 weeks later;at the same time,CMV nucleic acid was detected by real-time PCR fluorescent probe,and the fetal outcome was followed up.Results:In 171 cases,135 CMV IgM antibody ELISA(+)/ECLIA(-)specimens were positive for IgG antibodies and had stable levels after 2～4 weeks,one case was diagnosed with severe β thalassemia at 19+5 weeks,and the remaining fetuses were in good condition.There were 36 cases of IgM antibody ELISA(+)/ECLIA(+)specimens,one was negative for IgG antibody;35 cases had positive IgM antibody and stable IgG antibody level after 2～4 weeks,the fetus was in good condition;one case had IgM antibody level decreased and IgG antibody level increased significantly,urinary CMV DNA level gradually decreased,and was diagnosed as disseminated congenital CMV infection.Conclusion:The false positive rate of CMV IgM antibody detected by ELISA method is significantly higher than that of ECLIA method,and the dynamic quantitative detection can effectively eliminate interference.Maternal women with significant changes in CMV IgM,IgG antibodies and urinary DNA levels are at high risk of intrauterine infection and had a high probability of fetal congeni-tal CMV infection.

Objective To analyze the quality of life and its influencing factors among patients with occupational coal workers' pneumoconiosis (hereinafter referred to as "coal workers' pneumoconiosis"). Methods A total of 404 coal workers' pneumoconiosis patients diagnosed in Fengjie County of Chongqing City were selected as the study subjects using the convenient sampling method, and their quality of life was investigated by the SF-36 scale. Results The total score of quality of life of the subjects was (63.1±12.1) points. Their scores in the eight dimensions of physical functioning, role-physical, bodily pain, general health subscales, vitality, social functioning, role-emotional, and mental health subscales were lower than that of norms for Chongqing City and the nation (all P<0.05). The results of multiple linear regression analysis showed that the total score of quality of life of the patients decreased with the increase of age and stage of pneumoconiosis (all P<0.01). The total score of quality of life of patients living in urban areas was higher than that of rural patients(P<0.01). The total score of quality of life of patients who had left their jobs was higher than that of retired patients (P<0.01). The total score of quality of life of smoking patients and those with complications was lower than that of non-smokers and those without complications (all P<0.01). Conclusion Age, place of residence, smoking, stage of pneumoconiosis, work status, and complications of pneumoconiosis were the main influencing factors of quality of life among coal workers' pneumoconiosis patients.

Objective:To explore the clinical manifestations and pathogenic variant in a family with epilepsy, developmental delay and brain deformity.Methods:Clinical data of the child and his family members who had visited the Department of Pediatrics, Linyi People's Hospital on July 2, 2022 were collected. The child, his sister and parents were subjected to high-throughput sequencing, and the result was verified by Sanger sequencing.Results:The child was a 6-year-old boy with developmentally delay and had epileptic seizures with fever sensitivity for four years. Cranial imaging showed brain dysplasia, while the video electroencephalogram showed abnormal discharge. High-throughput sequencing showed the child has harbored a heterozygous c. 5G>T (p.Arg2Leu) variant of TUBB2A gene, which was unreported previously. His sister also carried the variant and had similar clinical manifestations, whilst his parents were of the wild-type and had normal clinical phenotypes. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+ PM2_Supporting+ PM5+ PP1+ PP2+ PP3). Conclusion:The heterozygous c. 5G>T (p.Arg2Leu) variant of the TUBB2A gene, in the form of gonadal mosaicism, probably underlay the disorders in this family.

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

To evaluate the application of medical magnifying loupes in diagnosis of oral mucosal diseases. Twenty-four patients with plaque-type oral lichen planus or homogeneous oral leukoplakia were inspected by naked eyes or assistance with magnifying loupes. Histopathological results were used as the gold standard to evaluate the sensitivity, specificity and accuracy of the two methods in clinical diagnosis. Questionnaires were used to evaluate the subjective effect of magnifying loupes on the diagnosis efficiency of oral mucosal diseases and to explore the most suitable parameters for application. The sensitivity, specificity and accuracy of medical magnifying loupes for the identification of plaque-type oral lichen planus and homogeneous oral leukoplakia were 94.74%, 100.00% and 95.83%, respectively, which were significantly higher than those of naked eye inspection (89.47%, 80.00% and 87.50%). The effective rate of magnifying loupes assisted diagnosis was 91.76% according to physicians' subjective evaluation. The most suitable parameters were 3.5 times magnification and working distance. The medical magnifying loupes can effectively improve the efficiency of the inspection and diagnosis of oral mucosal diseases, and have the characteristics of convenience and real-time. The recommended clinical parameters are 3.5 times magnification and working distance.
Efficiency ; Humans ; Lenses ; Surveys and Questionnaires