BackgroundSchizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia. ObjectiveTo uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia. MethodsData from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship. ResultsIVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship. ConclusionThis study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Objective:To investigate the risk factors of amputation in patients with diabetic foot ulcer (DFU) in order to improve the prognosis and reduce the amputation rate.Methods:The clinical data of 359 DFU patients admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2017 to August 2021 were retrospectively analyzed, and they were divided into amputation group (161 cases) and non-amputation group (198 cases) according to whether amputation surgery was performed. Demographic characteristics, Wagner grading and other data of the two groups were collected. Forward step logistic regression analysis was used to identify independent risk factors for amputation, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of each risk factor for amputation in DFU patients.Results:There were significant differences between the amputation and non-amputation groups in terms of previous amputation history, peripheral vascular diseases (PVD), diabetic foot secondary osteomyelitis, diabetic nephropathy (DN), history of angioplasty, Wanger grade, K +, age, white blood cell count, C-reactive protein, high density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate, cardiac troponin T, and cardiac troponin I, lactic acid (all P<0.05). Previous amputation history ( OR=2.329, 95% CI: 1.092-4.970, P=0.029), DN ( OR=4.091, 95% CI: 2.222-7.532, P<0.001), PVD ( OR=2.556, 95% CI: 1.487-4.395, P=0.001), diabetic foot secondary osteomyelitis ( OR=6.332, 95% CI: 3.595-11.153, P<0.001), Wagner grade were independent risk factors for amputation in DFU patients, HDL-C ( OR=0.392, 95% CI: 0.182-0.842, P=0.016) were protective factors for amputation in DFU patients. Moreover, the combined accuracy of the above factors in predicting amputation in DFU patients was high, and the area under ROC curve was 0.839 (95% CI: 0.798-0.880), sensitivity was 83%, and specificity was 73% ( OR=0.05). Conclusions:Previous amputation history, DN, PVD, diabetic foot secondary osteomyelitis and Wagner grade are independent risk factors for amputation in DFU patients, while HDL-C is a protective factor for amputation in DFU patients. Further investigation will help to establish a stratified system for predicting the risk of diabetic foot, so as to achieve better individualized treatment.

Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4～6 weeks of age;the ductal portion expanded to the growth boundary at 8～9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8～12 weeks of age,and advanced breast cancer at 10～14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

Bronchial asthma is a common chronic heterogeneous airway disease that is pathologically characterized by airway hyperresponsiveness and chronic inflammation.The pathogenesis of this disease is complex.Essentially,it is an airway inflammatory response driven by abnormal activation of the immune system.Its occurrence and development involve the participation of various immune cells and immune factors,including B lymphocytes,T lymphocytes,mast cells,macrophages and dendritic cells,as well as key cytokines such as interleukin(IL)-4,IL-5,IL-13,and interferon(IFN)-γ.And key cytokines such as interleukin(IL)-4,IL-5,IL-13 and interferon-γ.The complex interactions between these immune cells and mediators cause a series of pathological changes such as increased airway mucus secretion,smooth muscle contraction and airway remodeling,ultimately leading to the appearance of clinical symptoms,such as chest tightness,shortness of breath,wheezing and coughing.This article conducts systematically reviews current understanding of the immunological pathogenesis of bronchial asthma,thereby providing theoretical references for drug development and clinical diagnosis and treatment.

Objective This study aimed to investigate the tumorigenic properties of MMTV-PyMT breast cancer transgenic mice at different ages(in weeks)and the changes in the composition of immune cells in the tumor microenvironment.Methods Eight groups of 4,6,8,10,12,14,16 and 18 weeks of age MMTV-PyMT female mice(FVB mice as the background)and one group of 8 weeks of FVB female mice were prepared for routine blood testing,the pathological changes of the mammary gland and lung metastases were observed by histopathological sections,and the immune cells in blood,spleen,and tumor were analyzed by flow cytometry.Results MMTV-PyMT mice showed adenular ductal lesions at 4～6 weeks of age;the ductal portion expanded to the growth boundary at 8～9 weeks of age,and then gradually broke through the glandular boundary to form early breast cancer at 8～12 weeks of age,and advanced breast cancer at 10～14 weeks of age.At 12 weeks of age,metastases were visible in the lungs of some mice,and at 14 weeks of age,the number of metastases in the lungs increased significantly.As the age of the mice increased,the number of white blood cells,neutrophils,and platelets in their blood increased gradually,while the lymphocytes and erythrocytes showed a gradual downward trend.Flow cytometry showed that with the increase in age,the proportion of T cells in the spleen and tumor gradually decreased,the MDSCs in the blood,spleen,and tumor gradually increased,and the NK cells in the tumor also gradually increased.Conclusions This study analyzed routine blood tests,pathology,and immune cells in the tissues of MMTV-PyMT mouse models of different weeks of age,providing a novel perspective on the dynamic alterations of the tumor immune microenvironment during the malignant progression of breast cancer.

Bronchial asthma is a common chronic heterogeneous airway disease that is pathologically characterized by airway hyperresponsiveness and chronic inflammation.The pathogenesis of this disease is complex.Essentially,it is an airway inflammatory response driven by abnormal activation of the immune system.Its occurrence and development involve the participation of various immune cells and immune factors,including B lymphocytes,T lymphocytes,mast cells,macrophages and dendritic cells,as well as key cytokines such as interleukin(IL)-4,IL-5,IL-13,and interferon(IFN)-γ.And key cytokines such as interleukin(IL)-4,IL-5,IL-13 and interferon-γ.The complex interactions between these immune cells and mediators cause a series of pathological changes such as increased airway mucus secretion,smooth muscle contraction and airway remodeling,ultimately leading to the appearance of clinical symptoms,such as chest tightness,shortness of breath,wheezing and coughing.This article conducts systematically reviews current understanding of the immunological pathogenesis of bronchial asthma,thereby providing theoretical references for drug development and clinical diagnosis and treatment.

Objective To investigate the clinical efficacy and safety of endoscopic ultrasonography-guided(EUS-guided)enterocolon anastomosis in treating patients with malignant bowel obstruction(MBO).Methods The clinical data of 12 patients with MBO,who underwent EUS-guided enterocolon anastomosis at the Nanjing Drum Tower Hospital of China from April 2023 to December 2023,were collected.The perioperative clinical efficacy and safety were retrospectively analyzed.Results Successful EUS-guided enterocolon anastomosis was accomplished in all the 12 patients,with a technical success rate of 100％(12/12).The clinical success rate was 83.3％(11/12),one patient developed obstruction of the stent.The clinical symptoms were relieved in 2-68 hours after treatment,and the time to resume defecation and exhaust was(18.02±15.75)hours.Within one week after the operation,4 patients took liquid diet and 8 patients took semi-fluid diet.Each dimension score of the Quality of Life Core-30 scale of The European Organization for Research and Treatment of Cancer(EORTC QLQ-C30)was remarkably improved,the patient's overall health score was increased from preoperative median 5 points to postoperative 8 points(P＜0.001).During the operation,stent displacement occurred in 2 patients,and the operation was successfully completed after promptly taking remedial measures.After operation,11 patients developed fever(37.5-39.4 ℃),and all the patients were discharged smoothly after symptomatic treatment.No complication such as bleeding,perforation,or stent displacement occurred.Conclusion EUS-guided enterocolon anastomosis is clinically safe and effective,it can effectively relieve the clinical symptoms and improve the quality of life of patients with MBO.

Objective:To investigate the risk factors of amputation in patients with diabetic foot ulcer (DFU) in order to improve the prognosis and reduce the amputation rate.Methods:The clinical data of 359 DFU patients admitted to the People′s Hospital of Xinjiang Uygur Autonomous Region from January 2017 to August 2021 were retrospectively analyzed, and they were divided into amputation group (161 cases) and non-amputation group (198 cases) according to whether amputation surgery was performed. Demographic characteristics, Wagner grading and other data of the two groups were collected. Forward step logistic regression analysis was used to identify independent risk factors for amputation, and receiver operating characteristic (ROC) curves were used to evaluate the predictive value of each risk factor for amputation in DFU patients.Results:There were significant differences between the amputation and non-amputation groups in terms of previous amputation history, peripheral vascular diseases (PVD), diabetic foot secondary osteomyelitis, diabetic nephropathy (DN), history of angioplasty, Wanger grade, K +, age, white blood cell count, C-reactive protein, high density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate, cardiac troponin T, and cardiac troponin I, lactic acid (all P<0.05). Previous amputation history ( OR=2.329, 95% CI: 1.092-4.970, P=0.029), DN ( OR=4.091, 95% CI: 2.222-7.532, P<0.001), PVD ( OR=2.556, 95% CI: 1.487-4.395, P=0.001), diabetic foot secondary osteomyelitis ( OR=6.332, 95% CI: 3.595-11.153, P<0.001), Wagner grade were independent risk factors for amputation in DFU patients, HDL-C ( OR=0.392, 95% CI: 0.182-0.842, P=0.016) were protective factors for amputation in DFU patients. Moreover, the combined accuracy of the above factors in predicting amputation in DFU patients was high, and the area under ROC curve was 0.839 (95% CI: 0.798-0.880), sensitivity was 83%, and specificity was 73% ( OR=0.05). Conclusions:Previous amputation history, DN, PVD, diabetic foot secondary osteomyelitis and Wagner grade are independent risk factors for amputation in DFU patients, while HDL-C is a protective factor for amputation in DFU patients. Further investigation will help to establish a stratified system for predicting the risk of diabetic foot, so as to achieve better individualized treatment.

Over-expression of glutathione S-transferase(GST)can promote Cisplatin resistance in hepatocellular carcinoma(HCC)treatment.Hence,inhibiting GST is an attractive strategy to improve Cisplatin sensi-tivity in HCC therapy.Although several synthesized GST inhibitors have been developed,the side effects and narrow spectrum for anticancer seriously limit their clinical application.Considering the abundance of natural compounds with anticancer activity,this study developed a rapid fluorescence technique to screen"green"natural GST inhibitors with high specificity.The fluorescence assay demonstrated that schisanlactone B(hereafter abbreviated as C1)isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo.Importantly,C1 can selectively kill HCC cells from normal liver cells,effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression.Considering the high GST levels in HCC patients,this compound demon-strated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.