Objective To investigate the clinical characteristics,imaging features,laboratory test results,and prognosis of children with acute lymphoblast leukemia(ALL)complicated by cerebral hemorrhage.Methods A retrospective analysis was conducted on the clinical data of 20 children with ALL complicated by cerebral hemor-rhage admitted to the Department of Hematology,Children's Hospital of Soochow University from June 20,2014 to June 20,2024.Results The clinical manifestation of the 20 children with ALL complicated by cerebral hemorrhage were complex and diverse,with disturbance of consciousness being the most common initial symptom.The prognosis varied depending on the size and location of the hematoma and whether it ruptured into the ventricle.Among the 20 cases,14(70％)demonstrated improvement in intracranial lesions,with 8(40％)cases exhibiting substantial lesion absorption and favorable prognosis.Six cases(30％)showed improvement in intracranial lesions but not complete resolution,three cases developed focal encephalomalacia,two cases had residual symptomatic epi-lepsy and one had residual right-sided hemiplegia.Furthermore,three(15％)cases suffered recurrent cerebral hemorrhages at distinct locations from the initial event following improvement of the primary hemorrhage,and 3(15％)cases led to mortality.Conclusions Neurological symptoms in children with acute lymphoblast leukemia(ALL)complicated by cerebral hemorrhage are diverse and often atypical.Timely cranial imaging and laboratory tests are necessary,while surgical intervention and platelet transfusion should be a prudential consideration.

Background and purpose:Prostate cancer and breast cancer are highly prevalent malignant tumors,and there occurrence and development are related to the tumor suppressor genes phosphatase and tensin homolog deleted on chremosome ten(Pten)and the transformation related protein 53 gene(Trp53).The loss of function of Trp53 is closely related.The simultaneous loss of the two can accelerate the malignant progression of tumors and induce therapeutic resistance.The gene-edited spontaneous tumor model of mice based on the Cre-loxP system is a key tool for studying the mechanism of cancer.Studies have shown that prostate-specific promoter(probasin,Pbsn)-driven iCre recombinase(Pbsn-iCre)can induce spontaneous prostate cancer in male mice,but its role in female breast cancer and transgender expression characteristics have not yet been clarified.In this study,we constructed Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+transgenic mouse model which was designed to explore its spontaneous tumor phenotype in prostate cancer and breast cancer,and to verify the expression characteristics of Pbsn in breast tissue.Methods:The Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+mouse model was established using Cre-loxP system by hybridization and continuous backcross screening with Ptenfl/fl mouse,Trp53fl/flmouse,and Pbsn-iCre+mouse(Ethical No.:FUSCC-IACUC-2025115).Pten,Trp53 and Pbsn-iCre genotypes were verified by polymerase chain reaction and agarose gel electrophoresis.The incidence of tumor in transgenic mice was monitored,and the histopathological characteristics of tumor were evaluated by hematoxylin-eosin staining.The protein levels of Pten and p53 in prostate and breast tumor tissues were analyzed by immunohistochemistry,and the distributions of Pbsn in breast,prostate,ovary,heart,liver and kidney were detected.Results:Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+male mouse developed spontaneous prostate tumor at age of 5 month,and female mouse developed spontaneous breast tumor at age of 6 months.The pathological manifestations of prostate cancer were invasive acinar adenocarcinoma structure with glandular structure disorder and basement membrane destruction.The pathological manifestations of breast cancer were invasive ductal carcinoma with ductal epithelial dysplasia and interstitial lymphocyte infiltration.Immunohistochemistry confirmed the complete deletion of Pten and p53 proteins in prostate and breast tumor tissues,which verified the prostate and mammary gland specific gene knockout effect.Immunohistochemistry also confirmed that Pbsn protein was specifically expressed in prostate acinar epithelial cells,ovarian tissue,and mammary duct epithelial cells,but not in heart,liver and kidney.Conclusion:Pbsn-iCre is functionally expressed in female mammary glands,and the simultaneous loss of Pten/Trp53 induced by Pbsn-iCre may drive the development of prostate cancer in male and breast cancer in female mouse.

Background and purpose:Prostate cancer and breast cancer are highly prevalent malignant tumors,and there occurrence and development are related to the tumor suppressor genes phosphatase and tensin homolog deleted on chremosome ten(Pten)and the transformation related protein 53 gene(Trp53).The loss of function of Trp53 is closely related.The simultaneous loss of the two can accelerate the malignant progression of tumors and induce therapeutic resistance.The gene-edited spontaneous tumor model of mice based on the Cre-loxP system is a key tool for studying the mechanism of cancer.Studies have shown that prostate-specific promoter(probasin,Pbsn)-driven iCre recombinase(Pbsn-iCre)can induce spontaneous prostate cancer in male mice,but its role in female breast cancer and transgender expression characteristics have not yet been clarified.In this study,we constructed Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+transgenic mouse model which was designed to explore its spontaneous tumor phenotype in prostate cancer and breast cancer,and to verify the expression characteristics of Pbsn in breast tissue.Methods:The Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+mouse model was established using Cre-loxP system by hybridization and continuous backcross screening with Ptenfl/fl mouse,Trp53fl/flmouse,and Pbsn-iCre+mouse(Ethical No.:FUSCC-IACUC-2025115).Pten,Trp53 and Pbsn-iCre genotypes were verified by polymerase chain reaction and agarose gel electrophoresis.The incidence of tumor in transgenic mice was monitored,and the histopathological characteristics of tumor were evaluated by hematoxylin-eosin staining.The protein levels of Pten and p53 in prostate and breast tumor tissues were analyzed by immunohistochemistry,and the distributions of Pbsn in breast,prostate,ovary,heart,liver and kidney were detected.Results:Ptenfl/fl;Trp53fl/fl;Pbsn-iCre+male mouse developed spontaneous prostate tumor at age of 5 month,and female mouse developed spontaneous breast tumor at age of 6 months.The pathological manifestations of prostate cancer were invasive acinar adenocarcinoma structure with glandular structure disorder and basement membrane destruction.The pathological manifestations of breast cancer were invasive ductal carcinoma with ductal epithelial dysplasia and interstitial lymphocyte infiltration.Immunohistochemistry confirmed the complete deletion of Pten and p53 proteins in prostate and breast tumor tissues,which verified the prostate and mammary gland specific gene knockout effect.Immunohistochemistry also confirmed that Pbsn protein was specifically expressed in prostate acinar epithelial cells,ovarian tissue,and mammary duct epithelial cells,but not in heart,liver and kidney.Conclusion:Pbsn-iCre is functionally expressed in female mammary glands,and the simultaneous loss of Pten/Trp53 induced by Pbsn-iCre may drive the development of prostate cancer in male and breast cancer in female mouse.

OBJECTIVES: To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula (LXJDHYF) for acute-on-chronic liver failure (ACLF) in mice. METHODS: Thirty C57BL/6 mice were randomly divided into blank control group, model group, low- and high-dose LXJDHYF groups, and H151 (a specific cGAS-STING pathway inhibitor) group (n=6). In all but the control group, the mice were treated with CCl₄ to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF. After the treatments, the mouse livers were collected for HE and TUNEL staining, and serum levels of ALT, AST and TBil were determined. In bone marrow-derived macrophages (BMDMs) and liver tissues of ACLF mice, the expressions of cGAS-STING signaling pathway-related mRNAs including IFN‑β, ISG15, IL-6 and TNF-α were determined with RT-qPCR, and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting. RESULTS: Compared with the mice in the model group, the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis. LXJDHYF treatment also significantly lowered serum levels of ALT, AST, TBil, IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs. CONCLUSIONS LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.
Animals ; Signal Transduction/drug effects* ; Mice ; Nucleotidyltransferases/metabolism* ; Mice, Inbred C57BL ; Acute-On-Chronic Liver Failure/etiology* ; Membrane Proteins/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Liver/metabolism* ; Disease Models, Animal ; Interferon Regulatory Factor-3/metabolism* ; Interleukin-6/metabolism* ; Male

Objective:To explore the influencing factors of left ventricular thrombus (LVT) in patients with non-ischemic heart failure (NIHF) and to construct a nomogram prediction model for NIHF patients with LVT.Methods:This study was a case-control study. A total of 2 592 patients with NIHF hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from January 2018 to July 2022 were selected. Fifty-one patients with LVT identified by echocardiography and cardiac magnetic resonance were classified into LVT group. One hundred and sixty patients were selected as the non-LVT group using a 1∶3 propensity score matching based on age and gender. Multivariate logistic regression analysis was used to explore the influencing factors of LVT in patients with NIHF. A nomogram prediction model was constructed, and the area under (AUC) the receiver operating characteristic (ROC) curve was calculated to evaluate the predictive effect of the model.Results:A total of 211 patients were enrolled, with a median age of 40 years old and 160 males (76%). Compared with non-LVT group, LVT group had lower systolic blood pressure ((112±20) mmHg vs. (120±19) mmHg; 1 mmHg=0.133 kPa), lower left ventricular ejection fraction (LVEF; (27±12)% vs. (39±14)% ), lower proportion of patients with history of hypertension (28% (14/51) vs. 44% (70/160)) and atrial fibrillation (8% (4/51)vs.39% (62/160)), higher proportion of patients with New York Heart Association functional class Ⅲ to Ⅳ (class Ⅲ: 59% (30/51) vs. 41% (66/160); class Ⅳ: 28% (14/51) vs. 19% (31/160)), and larger left ventricular end-systolic diameter (LVESD; (56±14) mm vs. (50±15) mm). The levels of hemoglobin ((152±23) g/L vs. (142±30) g/L), D-dimer (508 (300, 1 105) μg/L vs. 158 (68, 379) μg/L), and N-terminal pro-brain natriuretic peptide (3 429 (2 462, 4 734) ng/L vs. 1 288 (422, 2 544) ng/L) were higher in LVT group than in non-LVT group ( P all<0.05). LVT group had a higher proportion of patients using beta-blockers (92% (47/51) vs. 78% (124/160)), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors (88% (45/51) vs. 72% (115/160)), and anticoagulant drugs (98% (50/51) vs. 32% (51/160)) than non-LVT group (all P <0.05). Multivariate logistic regression showed that reduced LVEF ( OR=1.08, 95% CI 1.02-1.15, P=0.008), decreased LVESD ( OR=1.07, 95% CI 1.01-1.12, P=0.013), and increased D-dimer levels ( OR=5.40, 95% CI 1.98-14.74, P=0.001) were independent influencing factors for LVT in patients with NIHF. The ROC curve showed that the AUC of the nomogram for predicting LVT in patients with NIHF was 0.793 (95% CI 0.710-0.876, P<0.001). Conclusion:Reduced LVEF, decreased LVESD, and elevated D-dimer are associated with LVT in NIHF patients. The predictive model developed based on the above indicators has certain value in predicting LVT in NIHF patients.

OBJECTIVE To enrich the polymethoxyflavonoid-rich fraction from Citri Reticulatae Pericarpium using D101 macro-porous resin,and further to analyse the chemical constituents using High-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry(HPLC-Q-TOF-MS).METHODS Citri Reticulatae Pericarpium extract was adsorbed on D101 macro-porous resin and then eluted with different concentrations of ethanol to enrich the polymethoxyflavonoid-rich fraction;the content of the major flavonoid components was determined by high-performance liquid chromatography(HPLC);and the components were further an-alysed by HPLC-Q-TOF-MS.RESULTS The established HPLC method for the simultaneous determination of seven flavonoids in Citri Reticulatae Pericarpium extract was accurate and reliable.The contents of compounds such as nobiletin and tangeritin were signifi-cantly increased in the polymethoxyflavonoid-rich fraction.Using high resolution mass spectrometry(HRMS),70 and 60 compounds were identified from the Citri Reticulatae Pericarpium extract and the polymethoxyflavonoid-rich fraction,respectively,with 53 polyme-thoxyflavonoids being detected in these two extracts.CONCLUSION The results of this study provide an experimental basis for fur-ther identification of the pharmacological substance basis of the polymethoxyflavonoids in Citri Reticulatae Pericarpium and the estab-lishment of quality control methods.

Objective To explore the role of the cGAS-STING signaling pathway in the therapeutic mechanism of Liangxue Jiedu Huayu Formula(LXJDHYF)for acute-on-chronic liver failure(ACLF)in mice.Methods Thirty C57BL/6 mice were randomly divided into blank control group,model group,low-and high-dose LXJDHYF groups,and H151(a specific cGAS-STING pathway inhibitor)group(n=6).In all but the control group,the mice were treated with CC14 to induce liver cirrhosis followed by intraperitoneal injections of lipopolysaccharide and D-amino galactose to establish mouse models of ACLF.After the treatments,the mouse livers were collected for HE and TUNEL staining,and serum levels of ALT,AST and TBil were determined.In bone marrow-derived macrophages(BMDMs)and liver tissues of ACLF mice,the expressions of cGAS-STING signaling pathway-related mRNAs including IFN-β,ISG15,IL-6 and TNF-α were determined with RT-qPCR,and the phosphorylation levels of IRF3 and STING proteins were investigated using Western blotting.Results Compared with the mice in the model group,the LXJDHYF-treated mice exhibited milder hepatocyte necrosis and inflammatory cell infiltration in the liver with significantly reduced hepatocyte apoptosis.LXJDHYF treatment also significantly lowered serum levels of ALT,AST,TBil,IL-6 and TNF-α in ACLF mice and effectively suppressed the expressions of cGAS-STING signaling pathway-related mRNA in both the BMDMs and the liver tissues and the phosphorylation of IRF3 and STING proteins in the BMDMs.Conclusion LXJDHYF can significantly improve liver function and attenuate inflammation in ACLF mice possibly by inhibiting excessive activation of the cGAS-STING signaling pathway.

Objective:To investigate the association between time in target range and risk of vertebral fracture in patients with type 2 diabetes.Methods:The clinical data of 1 032 patients with type 2 diabetes who were hospitalized in endocrine department of Henan Provincial People′s Hospital from June 2017 to July 2021 were collected. Among which 632 patients were included into final analysis. The diabetes-specific risk score for vertebral fracture was used to assess the risk of vertebral fracture. Multivariate linear regression analysis was used to test the association between time in target range and risk score of vertebral fracture. Risk score≥9 was defined as increased risk of vertebral fracture. Multivariate logistic regression was used to estimate the association between time in target range and risk of vertebral fracture. Results:Among the included patients, mean age was(55.0±12.4) years and the percent of male was 72.5%. The mean course of diabetes was(9.4±8.0) years, and mean score of risk of vertebral fracture was 5.6±4.3. Time in target range was negatively correlated with risk score of vertebral fracture( P for trend <0.001), which was independent of potential confounders and continuous glucose monitoring parameters. The included patients were divided into four groups based on quartiles of time in target range. Multivariate logistic regression indicated that the risk of vertebral fracture in the first quartile of time in target range was 4.6 times higherthanthatinthe4thquartile, and the significance remained adjusted for potential confounders, s, CV, or meanamplitudeofglycemicexcursions(MAGE), respectively. Conclusion:Timein target rangewasnegativelycorrelatedwithriskscoreofvertebralfracturein patient with type 2 diabetes. Low time in range level was an independent risk factor for increased risk of vertebral fracture.

Diabetic kidney disease is a severe microvascular complication of diabetes characterized by complex etiology, diverse mechanisms, long course, and poor prognosis, posing a significant threat to patients′ quality of life. In recent years, research on gut microbiota has progressed deeper, and the concept of the gut-kidney axis emerges, introducing novel therapeutic concepts. This article provides an overview of the role of gut microbiota in the development of diabetic kidney disease and explores potential therapeutic strategies involving gut microbiota for the treatment of this condition.

Objective:To investigate the status of anticipatory grief among the main caregivers of maintenance hemodialysis patients, and to analyze its influencing factors.Methods:From April 2021 to July 2021, the main caregivers of 180 patients undergoing maintenance hemodialysis in Xiangdong Hospital Affiliated to Hunan Normal University and Liling Traditional Chinese Medicine Hospital in Hunan Province, were selected by convenience sampling method for the research object. The survey was carried out using the General Information Questionnaire, the Anticipatory Grief Scale and the Zarit Caregiver Burden Interview, multiple linear regression was used to analyze the influencing factors of anticipatory grief in the main caregivers of maintenance hemodialysis patients.Results:The total score of Anticipatory Grief Scale in the main caregivers of maintenance hemodialysis patients was 84.43±12.02, and the total score of Zarit Caregiver Burden Interview was 24.92 ± 7.98, which were positively correlated ( r = 0.557, P<0.01).In the multiple linear regression analysis, the caregiver ′s education level, age, gender, care burden and per capita monthly income and the patient ′s age were the influencing factors of anticipatory grief for the main caregivers of maintenance hemodialysis patients ( t values were -5.54-8.75, all P<0.05), which could explain 54.1% of the total variance. Conclusions:The anticipatory grief of the main caregivers of maintenance hemodialysis patients is at a relatively serious level. Medical care should pay more attention to the caregivers and their sadness in their communication, so as to detect problems in time, so as to take targeted measures to the current situation, which is effective to improve their level of grief and improve the quality of care.