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 safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

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:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective To retrospectively analyze the prevention and control effect and epidemic characteristics of elderly tuberculosis in Hubei Province from 2016 to 2020, and to provide a scientific basis for the prevention and treatment of elderly tuberculosis in Hubei Province． Methods The data on tuberculosis patients aged 60 and above who registered their current address in Hubei Province from 2016 to 2020 were collected and analyzed. The registration rates and composition ratios were analyzed using χ² test and χ² test for trend. Results A total of 135 976 tuberculosis patients were reported in Hubei from 2016 to 2020. The annual average registration rate of elderly tuberculosis among the elderly registered residence population (referring to the registration rate of elderly registered residence population aged 60 and above as the denominator, and tuberculosis patients aged 60 and above as the numerator) was 263.51/100 000. The highest rate was 300.02/100,000 in 2017, and the lowest was 188.19/100,000 in 2020 (χ²=70,227.603, P<0.001). In terms of composition, the average annual proportion of tuberculosis patients in the 60-70 years old group was 59.60%, which decreased year by year (χ²_trend=40.448，P<0.001 ). The average annual proportion of males was 73.35%, which was significantly higher than that of females (26.65%). The average annual proportion of farmers was 62.03%. From the perspective of case management, the annual average proportion of major epidemic online reports was 85.17%. The classification of cases was mainly based on clinical diagnosis, accounting for 48.33% annually and showing a decreasing trend year by year (χ²_trend=740.911, P<0.001). The proportion of confirmed cases was 25.08%, which showed an increasing trend (χ²_trend=380.557, P<0.001). From 2016 to 2019, the delay rate of diagnosis and treatment of elder tuberculosis patients was 49.42% (67 876/135 967), and the delay rate decreased year by year (χ²_trend=323.764, P<0.001). Conclusion The elderly population with pulmonary tuberculosis in Hubei Province shows a downward trend. It is necessary to focus on the efforts of designated hospitals to proactively identify cases, increase the proportion of confirmed cases, maintain a high tracking in place, reduce medical delays, and ensure the effectiveness of tuberculosis prevention and treatment for the elderly.

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.

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.

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.

Objective To explore specific magnetic resonance imaging(MRI)features of somatic symptoms in depression by comparing the differences of brain gray matter volume in depression patients with and without somatic symptoms using voxel-based morphometry(VBM).Methods A total of 52 depression patients were recruited and divided into somatic and no somatic symptoms group according to the patient health questionnaire-15 score(＞9 and≤9,respectively).Forty gender-age-matched healthy volunteers were recruited as the control group.All subjects underwent MRI scanning.Imaging data were analyzed to explore the differences in brain gray matter between groups using VBM.Results Compared with control group,gray matter volume increased in the right superior temporal gyrus,and decreased in the right inferior orbitofrontal gyrus,right inferior temporal gyrus,left inferior orbitofrontal gyrus,and left superior temporal gyrus for depressive patients with somatic symptoms(P＜0.001);gray matter volume increased in the right middle temporal gyrus,and decreased in the right superior temporal gyrus and right inferior temporal gyrus for depressive patients without somatic symptoms(P＜0.001).Only the volume in the right tongue and left cingulate gyrus increased in depressive patients with somatic symptoms compared with that in patients without somatic symptoms(P＜0.01).Conclusion VBM-MRI has demonstrated increased volume in the tongue and cingulate gyrus in the somatic symptoms of depression.

Objective To evaluate the molluscicidal effects and costs of spraying 20% suspension concentrate of pyricloben-zuron sulphate (SCPS) with drones against Pomacea canaliculata in paddy environments, so as to provide insights into the extensive applications of pyriclobenzuron against P. canaliculata. Methods On July 2022, a paddy field was selected from Nanchang City, Jiangxi Province as the study area, and 72 independent rectangular plots measuring 2 m × 1 m were allocated in the study area, with 1 m interval between each plot, and 20 P. canaliculata snails gently placed in each plot. The activity of 25% wettable powder of pyriclobenzuron sulphate (WPPS) by manual spraying at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m² against P. canaliculata was tested in 54 plots, and manual spraying of 50% wettable powder of niclosamide ethanolamine salt (WPNES) at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with 9 plots in each group. The activity of SCPS against P. canaliculata was tested in the remaining 18 plots. Based on the molluscicidal tests of WPPS, the molluscicidal effect of SCPS by manual spraying at doses of 0.20, 0.30, 0.40 g/m² and 0.50 g/m² against P. canaliculata was evaluated, and manual spraying of WPNES at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with three plots in each group. On July 2023, 14 paddy fields with a mean living P. canaliculata density of > 5 snails/m² were selected from Yujiang District, Yingtan City, Jiangxi Province for molluscicidal tests. Based on the molluscicidal effect of pyriclobenzuron against P. canaliculata in plots, the molluscicidal effects of WPPS by manual spraying at doses of 0.25, 0.50 g/m² and 1.00 g/m² and manual applications of WPPS at dose of 0.25, 0.50, 1.00 g/m² and 2.00 g/m² mixed with soil were tested, and manual spraying of 0.10 g/m² WPNES served as a chemical control group, while manual spraying of the same volume of clean water served as a blank control, with one paddy field in each group. Based on the effect of pyriclobenzuron against P. canaliculata in plots, the activity of SCPS sprayed with drones at doses of 0.25 g/m² and 0.50 g/m² mixed in water at 2 kg/667 m² and 4 kg/667 m² was tested against P. canaliculata, and spraying of the same volume of clean water with drones served as a blank control. All P. canaliculata snails were captured 3 days and 7 days following chemical treatment in plots and paddy fields and identified for survival, and the mortality and corrected mortality of P. canaliculata snails were estimated. In addition, the areas of chemical treatment, amount of molluscicide use and labor costs of chemical treatment were estimated in molluscicidal tests in paddy fields, and the costs of chemical treatment for an area covering 667 m² by drones and manual applications were calculated. Results The mortality of P. canaliculata snails was all 100% in plots 3 days and 7 days following spraying WPPS at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m², and the mortality rates of P. canaliculata snails were 66.67% to 100.00% 3 days post-treatment with SCPS at various doses (χ² = 277.897, P < 0.05) and 76.67% to 100.00% 7 days post-treatment (χ² = 274.206, P < 0.05). The mortality rates of P. canaliculata snails were 98.19% to 100.00% 3 days post-treatment with WPPS at various doses in paddy fields. There was a significant difference in the mortality of P. canaliculata snails among WPPS treatment groups and controls (χ² = 270.778, P < 0.05), and there were no significant differences between WPPS treatment groups and the chemical control group (all P values > 0.05), while there were significant differences in the mortality of P. canaliculata snails between WPPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 89.83% to 95.31% 3 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 132.892, P < 0.05). There were no significant differences in the mortality of P. canaliculata snails among SCPS treatment groups or water mixture groups (all P values > 0.05), and there were significant differences in the mortality of P. canaliculata snails between SCPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 94.62% to 100.00% 7 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 266.932, P < 0.05), with the highest mortality found following spraying 0.50 g/m² SCPS mixed in 2 kg/667 m² water with drones (P < 0.05). The costs of P. canaliculata snail control by drones and manually were 35.85 Yuan/667 m² and 43.33 Yuan/667 m²; however, the snail control efficiency was 6.67 times higher by drones than by manual applications. Conclusions SCPS sprayed with drones is highly active against P. canaliculata snails in paddy fields. SCPS sprayed with drones is highly efficient and low in cost for P. canaliculata snail control in paddy fields, beaches and river courses.