ObjectiveTo investigate the mechanism by which Gegen Qinliantang（GQT） improves skeletal muscle insulin resistance. MethodsThe db/m mice were used as the normal group， while db/db mice were assigned to a model group， low-dose （3.12 g·kg^-1）， medium-dose （6.24 g·kg^-1）， and high-dose （12.48 g·kg^-1） GQT groups， and a Western medicine group （semaglutide， 0.045 mg·kg^-1），n=6 in each group. All groups received corresponding interventions. Intraperitoneal glucose tolerance test （IPGTT）， intraperitoneal insulin tolerance test （IPITT）， and hematoxylin-eosin （HE） staining were used to evaluate insulin resistance and therapeutic efficacy. Serum lipid levels were measured using an automatic biochemical analyzer， and apoptosis in skeletal muscle was assessed via TUNEL assay. Transcriptome sequencing combined with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses was performed to identify differentially expressed genes （DEGs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to validate gene expression. Molecular docking was applied to evaluate the binding patterns between active components of GQT and key regulatory genes to elucidate pharmacological mechanisms. ResultsCompared with the model group， the medium-dose and high-dose GQT groups showed significantly reduced fasting blood glucose （FBG） levels （P<0.01）. Triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） were markedly decreased （P<0.01）， while high-density lipoprotein cholesterol （HDL-C） was significantly increased （P<0.01）. IPGTT， IPITT， and HE staining demonstrated that GQT enhanced insulin sensitivity and restored skeletal muscle morphology. GQT also alleviated apoptosis in skeletal muscle tissue. Transcriptome analysis revealed that GQT primarily affected biological processes such as oxidative phosphorylation， metabolic pathways， cellular processes， and protein binding. Real-time PCR results showed that CBR2， CDK6， F830016B08Rik， IL-1β， Rab27b， and COLEC12 were key regulatory genes. Molecular docking demonstrated that CBR2， IL-1β， Rab27b， and COLEC12 formed stable binding with the main active components of GQT. The therapeutic effects of high- and medium-dose GQT were comparable to those of the semaglutide group. ConclusionGQT improves skeletal muscle insulin resistance， potentially by regulating apoptosis as part of its underlying biological mechanism.

Systemic vascular diseases characterized by a common pathological feature of atherosclerosis are referred to as pan-vascular disease, the incidence and mortality of which are increasing currently. Apolipoproteins are closely related to the occurrence of atherosclerosis due to their genetic polymorphism, and expected to become new biomarkers for prediction and intervention of the disease. This article reviews the research progress on the biological functions of apolipoproteins, and the association of the apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) ratio with the pathogenesis and progress of atherosclerosis. Understanding the ApoB/ApoA1 ratio in different populations with pan-vascular diseases and its effects on different interventions will be conducive to precise and personalized disease management, and to improve clinical outcomes and the quality of life of patients.

Objective To explore the correlation between serum insulin-like growth factor1(IGF-1),insulin-like growth factor binding protein3(IGFBP-3),bone-specific alkaline phosphatase(BAP)and abundance of intestinal flora in children with idiopathic short stature(ISS).Methods A total of 86 children with ISS who were treated with short-acting recombinant growth hormone for the first time in Department of Endocrinology of Baoding Hospital,Beijing Children's Hospital,Capital Medical University,were enrolled from July 2021 to June 2023.Before treatment and at 6 months after treatment,physical indexes(height,weight)and bone age indexes[bone age index(BAI),bone age difference(BAD)]were detected with the same instrument at the same place.The fasting venous blood was collected to detect levels of serum IGF-1,IGFBP-3 and BAP by enzyme-linked immunosorbent assay.The abundances of intestinal floras were monitored by 16s rDNA high-throughput sequencing technology combined with bioinformation analysis technology.A total of 40 healthy children during the same period were enrolled as control group,and differences in different indexes within the same groups or between the two groups were compared by independent sample t test or paired t test.The correlation between abundances of intestinal floras and levels of serum IGF-1,IGFBP-3 and BAP was analyzed by Pearson correlation analysis.Results Compared with the control group.the height,weight,BAD,BAI,levels of serum IGF,IGFBP-3 and BAP,Chaol,Shannon and Pielou e of ISS patients decreased before treatment,and the differences were statistically significant(t=7.119～44.143,all P<0.05).After treatment,height,weight,BAD,BAI,levels of serum IGF,IGFBP-3 and BAP,Chaol,Shannon and Pielou e were increased in ISS children(t=3.145～39.188),the above indexes were still lower than those in control group(t=2.389～69.893),the differences were statistically significant(all P<0.05),respectively.In intestinal floras,dominant bacterial groups at phylum level were Firmicutes,Bacteroidetes,Actinobacteria and Proteobacteria,while dominant bacterial groups at genus level were Blautia,Bifidobacterium,Faecalibacterium and Bacteroides.Compared with the control group,before treatment,the abundances of Actinobacteria and Proteobacteria increased in the ISS group,while the abundances of Bacteroidetes,Bifidobacteria and Bacteroides decreased,and the differences were statistically significant(t=25.224～46.345,all P<0.05).After treatment,abundances of Bacteroidetes,Bifidobacterium and Bacteroides in the ISS group increased compared to before treatment,while abundance of Proteobacteria decreased,and the differences were statistically significant(t=10.055～39.245,all P<0.05).The abundances of Bacteroidetes,Bifidobacterium and Bacteroides in ISS group were lower than those in control group,while abundance of Proteobacteria was higher than that in control group,and the differences were statistically significant(t=6.290～20.540,all P<0.05).The abundances of Bacteroidetes,Bifidobacterium and Bacteroides were positively correlated with levels of serum IGF-1,IGFBP-3 and BAP(r=0.300～0.759,all P<0.05).Conclusion The abundances of intestinal floras are decreased,and the structure is abnormal in children with ISS.The abundances of beneficial bacteria in intestinal floras are related to levels of serum IGF-1,IGFBP-3 and BAP.In clinical treatment of ISS,combined treatment with intestinal flora disorders may be conducted.

BACKGROUND: Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style. METHODS: We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases. RESULTS: The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals. CONCLUSIONS The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans ; Colonoscopy/methods* ; Deep Learning ; Decision Support Systems, Clinical ; Female ; Male

This study aims to investigate the isolate and identify of infectious bronchitis virus(IBV)in chickens,and study its genetic variation and pathogenicity.In 2023,two strains named CK/CH/HN/SQ202301 and CK/CH/HN/SQ202302 were obtained from suspected infectious bronchitis(IB)infected materials collected in a region of Henan Province,China.Further analysis showed that the two isolates belong to the G Ⅰ-13 and GⅥ genotypes,respectively.The cleavage sites of S protein were all RRSRR.The prediction of glycosylation sites showed that the two isolates had 18 and 12 N-glycosylation sites respectively,but no O-glycosylation site.Recombinant analysis shows that C2023-1 was a recombinant strain.Pathogenicity was assessed by infecting 1-day-old SPF chicks with the two isolates,and the results showed that C2023-1 strain infection could cause clini-cal symptoms such as depression and head shaking,as well as death in chicks,with a mortality rate of 37.5％.There were no clinical symptoms or deaths after infection with C2023-2 strain.Viral load test results showed that both isolates continued to detoxify until the 10th day,and had strong rep-lication capacity in the kidney,trachea and bursa of Fabricius.The results indicate significant differences in the genetic characteristics and pathogenicity of the two isolates due to their different genotypes.This study not only provides new epidemiological data on IB,which contributes to a bet-ter understanding of IBV's epidemiological features and control challenges,but also adds valuable bioinformatics resources for IBV by analyzing its variation mechanisms and biological information.

Systemic vascular diseases characterized by a common pathological feature of atherosclerosis are referred to as pan-vascular disease, the incidence and mortality of which are increasing currently. Apolipoproteins are closely related to the occurrence of atherosclerosis due to their genetic polymorphism, and expected to become new biomarkers for prediction and intervention of the disease. This article reviews the research progress on the biological functions of apolipoproteins, and the association of the apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) ratio with the pathogenesis and progress of atherosclerosis. Understanding the ApoB/ApoA1 ratio in different populations with pan-vascular diseases and its effects on different interventions will be conducive to precise and personalized disease management, and to improve clinical outcomes and the quality of life of patients.

To verify whether the two B-cell epitopes Pep1 and Pep4 in the FAdV-4 WZ fiber can be used as candidate epitopes for multivalent epitope vaccines,epitopes Pep1 and Pep4 were tandemly linked with the chicken infectious bronchitis virus strain M41 S1 protein gene in different patterns,and a recombinant fusion plasmid was constructed and expressed in E.coli BL21(DE3).It was confirmed by Western blot and ELISA tests that all four expressed fusion proteins reacted specific-ally with anti-M41 whole virus serum and WZ strain anti-Fiber 2-knob protein serum.After purifi-cation and immunization of BALB/c mice,specific antibodies against the peptide epitopes were de-tected in mouse sera.The results showed that the Pep4 epitope induced a stronger immune re-sponse than the Pep1 epitope.When Pep1 was connected with the amino and carboxyl termini of the fusion protein,respectively,both resulted in the production of the same level of anti-Pep1 anti-bodies in the immunized animals,whereas when Pep4 was connected with the carboxyl terminus of the fusion protein,the immunized animals produced a higher level of anti-Pep4-specific antibodies.This research indicates that the B cell epitopes Pep1 and Pep4 of the reactive WZ strain Fiber 2,when conjugated with proteins to form fusion proteins,can enhance the immunogenicity of Pep1 and Pep4 without affecting the antigenicity of the carrier protein.This study provides technical support and serves as a reference for the design and development of a multivalent epitope vaccine for FAdV-4.

To verify whether the two B-cell epitopes Pep1 and Pep4 in the FAdV-4 WZ fiber can be used as candidate epitopes for multivalent epitope vaccines,epitopes Pep1 and Pep4 were tandemly linked with the chicken infectious bronchitis virus strain M41 S1 protein gene in different patterns,and a recombinant fusion plasmid was constructed and expressed in E.coli BL21(DE3).It was confirmed by Western blot and ELISA tests that all four expressed fusion proteins reacted specific-ally with anti-M41 whole virus serum and WZ strain anti-Fiber 2-knob protein serum.After purifi-cation and immunization of BALB/c mice,specific antibodies against the peptide epitopes were de-tected in mouse sera.The results showed that the Pep4 epitope induced a stronger immune re-sponse than the Pep1 epitope.When Pep1 was connected with the amino and carboxyl termini of the fusion protein,respectively,both resulted in the production of the same level of anti-Pep1 anti-bodies in the immunized animals,whereas when Pep4 was connected with the carboxyl terminus of the fusion protein,the immunized animals produced a higher level of anti-Pep4-specific antibodies.This research indicates that the B cell epitopes Pep1 and Pep4 of the reactive WZ strain Fiber 2,when conjugated with proteins to form fusion proteins,can enhance the immunogenicity of Pep1 and Pep4 without affecting the antigenicity of the carrier protein.This study provides technical support and serves as a reference for the design and development of a multivalent epitope vaccine for FAdV-4.

Objective To explore the correlation between serum insulin-like growth factor1(IGF-1),insulin-like growth factor binding protein3(IGFBP-3),bone-specific alkaline phosphatase(BAP)and abundance of intestinal flora in children with idiopathic short stature(ISS).Methods A total of 86 children with ISS who were treated with short-acting recombinant growth hormone for the first time in Department of Endocrinology of Baoding Hospital,Beijing Children's Hospital,Capital Medical University,were enrolled from July 2021 to June 2023.Before treatment and at 6 months after treatment,physical indexes(height,weight)and bone age indexes[bone age index(BAI),bone age difference(BAD)]were detected with the same instrument at the same place.The fasting venous blood was collected to detect levels of serum IGF-1,IGFBP-3 and BAP by enzyme-linked immunosorbent assay.The abundances of intestinal floras were monitored by 16s rDNA high-throughput sequencing technology combined with bioinformation analysis technology.A total of 40 healthy children during the same period were enrolled as control group,and differences in different indexes within the same groups or between the two groups were compared by independent sample t test or paired t test.The correlation between abundances of intestinal floras and levels of serum IGF-1,IGFBP-3 and BAP was analyzed by Pearson correlation analysis.Results Compared with the control group.the height,weight,BAD,BAI,levels of serum IGF,IGFBP-3 and BAP,Chaol,Shannon and Pielou e of ISS patients decreased before treatment,and the differences were statistically significant(t=7.119～44.143,all P<0.05).After treatment,height,weight,BAD,BAI,levels of serum IGF,IGFBP-3 and BAP,Chaol,Shannon and Pielou e were increased in ISS children(t=3.145～39.188),the above indexes were still lower than those in control group(t=2.389～69.893),the differences were statistically significant(all P<0.05),respectively.In intestinal floras,dominant bacterial groups at phylum level were Firmicutes,Bacteroidetes,Actinobacteria and Proteobacteria,while dominant bacterial groups at genus level were Blautia,Bifidobacterium,Faecalibacterium and Bacteroides.Compared with the control group,before treatment,the abundances of Actinobacteria and Proteobacteria increased in the ISS group,while the abundances of Bacteroidetes,Bifidobacteria and Bacteroides decreased,and the differences were statistically significant(t=25.224～46.345,all P<0.05).After treatment,abundances of Bacteroidetes,Bifidobacterium and Bacteroides in the ISS group increased compared to before treatment,while abundance of Proteobacteria decreased,and the differences were statistically significant(t=10.055～39.245,all P<0.05).The abundances of Bacteroidetes,Bifidobacterium and Bacteroides in ISS group were lower than those in control group,while abundance of Proteobacteria was higher than that in control group,and the differences were statistically significant(t=6.290～20.540,all P<0.05).The abundances of Bacteroidetes,Bifidobacterium and Bacteroides were positively correlated with levels of serum IGF-1,IGFBP-3 and BAP(r=0.300～0.759,all P<0.05).Conclusion The abundances of intestinal floras are decreased,and the structure is abnormal in children with ISS.The abundances of beneficial bacteria in intestinal floras are related to levels of serum IGF-1,IGFBP-3 and BAP.In clinical treatment of ISS,combined treatment with intestinal flora disorders may be conducted.

This study aims to investigate the isolate and identify of infectious bronchitis virus(IBV)in chickens,and study its genetic variation and pathogenicity.In 2023,two strains named CK/CH/HN/SQ202301 and CK/CH/HN/SQ202302 were obtained from suspected infectious bronchitis(IB)infected materials collected in a region of Henan Province,China.Further analysis showed that the two isolates belong to the G Ⅰ-13 and GⅥ genotypes,respectively.The cleavage sites of S protein were all RRSRR.The prediction of glycosylation sites showed that the two isolates had 18 and 12 N-glycosylation sites respectively,but no O-glycosylation site.Recombinant analysis shows that C2023-1 was a recombinant strain.Pathogenicity was assessed by infecting 1-day-old SPF chicks with the two isolates,and the results showed that C2023-1 strain infection could cause clini-cal symptoms such as depression and head shaking,as well as death in chicks,with a mortality rate of 37.5％.There were no clinical symptoms or deaths after infection with C2023-2 strain.Viral load test results showed that both isolates continued to detoxify until the 10th day,and had strong rep-lication capacity in the kidney,trachea and bursa of Fabricius.The results indicate significant differences in the genetic characteristics and pathogenicity of the two isolates due to their different genotypes.This study not only provides new epidemiological data on IB,which contributes to a bet-ter understanding of IBV's epidemiological features and control challenges,but also adds valuable bioinformatics resources for IBV by analyzing its variation mechanisms and biological information.