BACKGROUND: Gluconeogenesis is a critical metabolic pathway for maintaining glucose homeostasis, and its dysregulation can lead to glycometabolic disorders. This study aimed to identify hub biomarkers of these disorders to provide a theoretical foundation for enhancing diagnosis and treatment. METHODS: Gene expression profiles from liver tissues of three well-characterized gluconeogenesis mouse models were analyzed to identify commonly differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), machine learning techniques, and diagnostic tests on transcriptome data from publicly available datasets of type 2 diabetes mellitus (T2DM) patients were employed to assess the clinical relevance of these DEGs. Subsequently, we identified hub biomarkers associated with gluconeogenesis-related glycometabolic disorders, investigated potential correlations with immune cell types, and validated expression using quantitative polymerase chain reaction in the mouse models. RESULTS: Only a few common DEGs were observed in gluconeogenesis-related glycometabolic disorders across different contributing factors. However, these DEGs were consistently associated with cytokine regulation and oxidative stress (OS). Enrichment analysis highlighted significant alterations in terms related to cytokines and OS. Importantly, osteomodulin ( OMD ), apolipoprotein A4 ( APOA4 ), and insulin like growth factor binding protein 6 ( IGFBP6 ) were identified with potential clinical significance in T2DM patients. These genes demonstrated robust diagnostic performance in T2DM cohorts and were positively correlated with resting dendritic cells. CONCLUSIONS Gluconeogenesis-related glycometabolic disorders exhibit considerable heterogeneity, yet changes in cytokine regulation and OS are universally present. OMD , APOA4 , and IGFBP6  may serve as hub biomarkers for gluconeogenesis-related glycometabolic disorders.
Machine Learning ; Humans ; Computational Biology/methods* ; Biomarkers/metabolism* ; Diabetes Mellitus, Type 2/genetics* ; Animals ; Mice ; Gluconeogenesis/physiology* ; Gene Expression Profiling ; Transcriptome/genetics* ; Gene Regulatory Networks/genetics* ; Clinical Relevance

Objective:To investigate the rehabilitation effect of Xingyi Baduanjin training on cardiac function and quality of life in postoperative percutaneous coronary intervention(PCI)patients with coronary heart disease.Method:From September 2017 to January 2021,a total of 119 postoperative PCI patients with coronary heart disease in the Department of Cardiovascular Medicine of the First Medical Center of the General Hospi-tal of the People's Liberation Army(PLA)were selected and randomly divided into the experimental group(n=59)and the control group(n=60).In the control group,a conventional cardiac rehabilitation program was executed,while in the experimental group,a rehabilitation program combining the conventional program with Xingyi Baduanjin training was executed.The treatment time was 6 weeks.Before and after the 6 weeks,the exercise endurance of the two groups was measured by cardiopulmonary exercise test,which mainly observed the changes in peak power,peak oxygen consumption,peak metabolic equivalent,peak oxygen pulse,and peak respiratory exchange rhythm.The Quality of Life Scale Brief Version(QOL-BREF)and the MOS 36-Item Short Form Health Survey(SF-36)were used to assess the quality of life and health status in patients.Result:Peak power,peak oxygen consumption,peak metabolic equivalents,peak oxygen pulse and peak re-spiratory exchange rate were not significantly different between the two groups before treatment(P>0.05).Peak power,peak oxygen consumption,and peak metabolic equivalents in both groups after 6 weeks of treat-ment were significantly higher than before treatment(t>3.141,P<0.05),and the experimental group was signif-icantly higher than the control group(t>2.017,P<0.05).Peak oxygen pulse in the experimental group was sig-nificantly higher than before treatment(t=7.459,P<0.05)and was significantly higher than that in the control group(t=5.866,P<0.05).The respiratory exchange rate was significantly lower than before treatment(t=6.281,P<0.05)and was significantly lower than that in the control group(t=2.686,P<0.05).The QOL-BREF scores were not significantly different between the two groups before treatment(P>0.05).The QOL-BREF scores in both groups after 6 weeks of treatment were significantly higher than before treatment(t>23.620,P<0.05),and the experimental group was significantly higher than the control group(t=12.719,P<0.05).The SF-36 scores were not significantly different between the two groups before treatment(P>0.05).The SF-36 scores in both groups after 6 weeks of treatment were significantly higher than before treatment(t>35.255,P<0.05),and the experimental group was significantly higher than the control group(t=16.075,P<0.05).Conclusion:Xingyi Baduanjin training can effectively enhance exercise endurance,which improves the quality of life and health status in postoperative PCI patients with coronary artery disease,and achieves a good reha-bilitation effect.

Objective:To establish an HPLC characteristic chromatogram method to simultaneously determine the content of 6 components in Bombyx Batryticatus and its processed products; To provide a scientific means for quality evaluation.Methods:The HPLC analysis was performed on a Waters Xselect HSS T3 column (250 mm×4.6 mm, 5 μm), with a mobile phase consisting of acetonitrile and 5 mmol/L ammonium acetate solution (adjust pH to 4.5 with acetic acid) in gradient mode at a flow rate of 1.0 ml/min. The column temperature was 30 ℃. The detection wavelength was 260 nm. The injection volume was 10 μl. The SIMCA-P 14.0 software was used for cluster analysis and partial least squares discriminant analysis to evaluate the quality of Bombyx Batryticatus and its processed products.Results:Nine common peaks were identified in the HPLC characteristic spectra of Bombyx Batryticatus and its processed products, and seven common peaks were identified. Cluster analysis and partial least squares discriminant analysis can classify Bombyx Batryticatus and its processed products into two groups, with peak 4, peak 2, peak 1, peak 6, and peak 3 as their mass difference markers. Uric Acid, Hypoxanthine, Uridine, Adenine, Guanosine, and Adenosine showed good linearity ( R2≥0.999 9) within 43.95-879.04, 2.05-41.07, 2.35-47.09, 2.02-40.36, 2.32-46.43, 2.32-46.43 μg/ml, respectively. The precision, stability (24 h), repeatability relative standard deviation (RSD) were all <3.00%. The average spiked recoveries were all in the range of 94.57%-102.01%, and the RSDs were all in the range of 0.96%-3.32%. In 15 batches of Bombyx Batryticatus, the content of the above 6 components, was determined to be 11.51, 0.33, 0.38, 0.42, 0.35, 0.36 mg/g in the following order. And in 15 batches of fried Bombyx Batryticatus, the content of components was determined to be 12.06, 0.35, 0.36, 0.18, 0.21, 0.24 mg/g in the following order. Conclusions:The method established in this study is simple, rapid, and repeatable. PLS-DA can distinguish Bombyx Batryticatus and its processed products, which can provide a reference for the quality evaluation of Bombyx Batryticatus and its processed products.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To investigate the rehabilitation effect of Xingyi Baduanjin training on cardiac function and quality of life in postoperative percutaneous coronary intervention(PCI)patients with coronary heart disease.Method:From September 2017 to January 2021,a total of 119 postoperative PCI patients with coronary heart disease in the Department of Cardiovascular Medicine of the First Medical Center of the General Hospi-tal of the People's Liberation Army(PLA)were selected and randomly divided into the experimental group(n=59)and the control group(n=60).In the control group,a conventional cardiac rehabilitation program was executed,while in the experimental group,a rehabilitation program combining the conventional program with Xingyi Baduanjin training was executed.The treatment time was 6 weeks.Before and after the 6 weeks,the exercise endurance of the two groups was measured by cardiopulmonary exercise test,which mainly observed the changes in peak power,peak oxygen consumption,peak metabolic equivalent,peak oxygen pulse,and peak respiratory exchange rhythm.The Quality of Life Scale Brief Version(QOL-BREF)and the MOS 36-Item Short Form Health Survey(SF-36)were used to assess the quality of life and health status in patients.Result:Peak power,peak oxygen consumption,peak metabolic equivalents,peak oxygen pulse and peak re-spiratory exchange rate were not significantly different between the two groups before treatment(P>0.05).Peak power,peak oxygen consumption,and peak metabolic equivalents in both groups after 6 weeks of treat-ment were significantly higher than before treatment(t>3.141,P<0.05),and the experimental group was signif-icantly higher than the control group(t>2.017,P<0.05).Peak oxygen pulse in the experimental group was sig-nificantly higher than before treatment(t=7.459,P<0.05)and was significantly higher than that in the control group(t=5.866,P<0.05).The respiratory exchange rate was significantly lower than before treatment(t=6.281,P<0.05)and was significantly lower than that in the control group(t=2.686,P<0.05).The QOL-BREF scores were not significantly different between the two groups before treatment(P>0.05).The QOL-BREF scores in both groups after 6 weeks of treatment were significantly higher than before treatment(t>23.620,P<0.05),and the experimental group was significantly higher than the control group(t=12.719,P<0.05).The SF-36 scores were not significantly different between the two groups before treatment(P>0.05).The SF-36 scores in both groups after 6 weeks of treatment were significantly higher than before treatment(t>35.255,P<0.05),and the experimental group was significantly higher than the control group(t=16.075,P<0.05).Conclusion:Xingyi Baduanjin training can effectively enhance exercise endurance,which improves the quality of life and health status in postoperative PCI patients with coronary artery disease,and achieves a good reha-bilitation effect.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To develop a skeleton structure for the flexible manipulator of a robotic system used in natural orifice transluminal endoscopic surgery (NOTES), meeting the performance requirements of surgical actuators.Methods:A flexible manipulator structure and a control strategy for the corresponding structure were designed based on metal braiding technology. Geometric relationship formulas were derived according to the mechanical structure characteristics of the flexible manipulator. A theoretical model was established using the chained beam-constraint-model (CBCM) and mechanical spring theory. The finite element model of the mechanical structure was established, and simulation analysis was performed to verify the accuracy of the theoretical model. The bending stiffness of the metal-braided structure was tested to verify the load capacity of the flexible manipulator.Results:A flexible manipulator structure and a control strategy for the corresponding structure were designed based on metal braiding technology. With proper constraints, the maximum strain of the metal ring as a single stressed unit was about 1.49% when subjected to an axial force of 0.5 N. At this time, the material was in the linear elastic phase and the maximum deformation was about 0.308 9 mm, which was 3.26% higher than the theoretical value. The maximum strain of the manipulator skeleton was about 0.21% in the linear elastic phase. The maximum total deformation was about 7.135 5 mm, which was 6.30% higher than the theoretical value. The flexural stiffness of the manipulator skeleton was calculated to be 3.19 N·mm 2, which was comparable to a flexible manipulator made of shape memory polymers (SMPs) of the same magnitude and size. Conclusions:A skeleton structure for application to NOTES robotic flexible manipulators is developed that meets the support stiffness requirements for performing NOTES surgical tasks.

Objective The present study aimed to explore the effects of CC-chemokine receptor 5 antagonism on tumor growth and immune microenvironment.Methods Cell Counting Kit-8 was used to detect in vitro anti-proliferation activity of maraviroc,a selective CC-chemokine receptor 5 inhibitor,on Lewis cells,a mouse lung adenocarcinoma cell strain.Flow cytometry and real-time quantitative PCR were respectively used to detect cell apop-tosis and Caspase 8 gene expression.In a congenic mouse lung cancer model,the mice were intraperitoneally admin-istered with maraviroc or vehicle.Tumor sizes were measured and tumor infiltrating CD4+,CD8+ and Foxp3+ cells were determined by immunofluorescent staining.Results Our results showed that maraviroc could inhibit the growth of Lewis cancer cells not only in vitro but also in vivo.This in-vitro inhibition was presumably attributable to apoptosis induction by the enhancement of Caspase 8 gene expression after maraviroc blockade.Additionally,more CD4+ and CD8+ cells but less Foxp3+ cells were detected in tumor mass from the mice administered with maraviroc.Conclusions Taken together,it can be speculated that CCR5 blockade may inhibit the growth of Lewis cells by inducing cell apoptosis and impairing the immunosuppressive tumor microenvironment.It is worthy of further investi-gation as a candidate for cancer therapy.

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor prognosis.Anchorage-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary site.However,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune microenvironment.This study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma. Methods:Anoikis-related genes(ANRGs)were obtained from GeneCards.Clinical information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)databases.ANRGs highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)algorithm.Machine learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO cohort.Finally,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor microenvironment. Results:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic model.Significant differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling pathway. Conclusion:The prognostic model based on ANRGs and tumor microenvironment demonstrate good predictive power and provide more personalized treatment options for patients with osteosarcoma.

ObjectTo explore the risk factors related to the intensity of post-stroke depression in patients with cerebral infarction during hospitalization in the rehabilitation department. MethodsThe hospital consultation records of cerebral infarction patients in Beijing Bo'ai Hospital from December, 2019 to February, 2023 were reviewed from the hospital information system, and those who were diagnosed as depression visited the department of psychology were selected. It was collected including general information of sexes, ages, education levels, matrimony; medical features of course, location, affected side, sensory disorders, aphasia, agrypnia, dysphagia, hand-shoulder syndrome, constipation; functioning of muscle strength and Brunnstrom stages; and scores of Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer Assessment (FMA), Fugl-Meyer Assessment-Balance (FMA-B), modified Barthel Index (MBI) and Hamilton Depression Scale (HAMD). Patients with HAMD scores ≤ 20 were as the low group, and those > 20 were as the high group. ResultA total of 2 403 hospitalized stroke patients were included, out of which 269 patients with cerebral infarction were diagnosed as depression and visited the department of psychology; while 103 cases were in the low group and 166 cases were in the high group. The incidence of constipation was less, and the incidence of dysphagia and shoulder-hand syndrome was higher in the high group (χ² > 5.379, P < 0.05), with weaker strength of iliopsoas muscle and quadriceps muscle, earlier of Brunnstrom stage of lower extremities and hands, and worse scores of NIHSS, MMSE, FMA, FMA-B and MBI (|Z| > 2.020, t > 2.171, P < 0.05). Logistic regression showed that constipation (OR = 0.435), quadriceps muscle strength (OR = 0.782) and dysphagia (OR = 2.602) related to the intensity of post-stroke depression in convalescent patients (P < 0.05). ConclusionPost-stroke dysphagia and poor quadriceps muscle strength may exacerbate post-stroke depression; however, constipation may not.