[Objective]To explore the epidemiology and clinical characteristics of kala-azar patients in Kashgar region,so as to improve the diagnosis and treatment.[Methods]A retrospective analysis was conducted on the clinical data of 71 kala-azar patients admitted to the First People's Hospital of Kashgar Region between January 2013 and December 2023.[Results]Among the 71 patients,the majority were aged 0-5 years(52.11%,37/71),with a male-to-female ratio of 0.92:1.Most cases occurred in winter and spring.Common clinical manifestations included fever,fatigue,decreased appetite,splenomegaly and hepatomegaly.Laboratory investigations mainly found pancytopenia,reversed albumin-to-globulin ratio,elevated transaminases,and increased C-reactive protein and procalcitonin.The positive rates of anti-rK39 antibody detection and bone marrow microscopy were 100%(23/23)and 91.38%(53/58),respectively.Metagenomics next-generation sequencing(mNGS)of liver tissue identified Leishmania donovani in one case.The common complications were infectious toxic hepatitis 49.30%(35/71),myocarditis 29.56%(21/71),and bronchopneumonia 23.94%(17/71).[Conclusions]Potential kala-azar should be taken into consideration for patients from the endemic areas with long-term irregular fever accompanied by splenomegaly,hemocytopenia,and reversed albumin-to-globulin ratio.Bone marrow smear microscopy and anti-rK39 antibody detection are recommended for the diagnosis,and mNGS provides a novel diagnostic solution.

BACKGROUND:Bone marrow mesenchymal stem cells possess multipotent differentiation potential and are an important source of cells for cartilage and bone tissue regeneration research.Kartogenin is a small-molecule drug that has been demonstrated to promote stem cell differentiation towards chondrogenesis.However,the ability to promote osteogenic differentiation is still controversial,and the specific effects of kartogenin on the chondrogenic and osteogenic differentiation of stem cells of different species have not been fully elucidated.OBJECTIVE:To investigate the effects of kartogenin on chondrogenic and osteogenic differentiation in rabbit-derived and rat-derived bone marrow mesenchymal stem cells.METHODS:Rabbit-derived and rat-derived bone marrow mesenchymal stem cells were obtained through whole bone marrow separation and adherence methods,and were treated with varying concentrations of kartogenin.Cell proliferation was detected using the CCK-8 assay.Chondrogenic and osteogenic differentiation was assessed via toluidine blue and alizarin red staining,respectively.After screening for the optimal concentration of kartogenin,alkaline phosphatase staining,qRT-PCR,and western blot assay were employed to analyze the expression of osteogenic and chondrogenic-related genes and proteins.RESULTS AND CONCLUSION:(1)Within the concentration range of 0 to 10 000 nmol/L,kartogenin did not significantly affect the proliferation of rabbit-derived or mouse-derived bone marrow mesenchymal stem cells.(2)The differentiation effect of kartogenin on rabbit-derived and rat-derived bone marrow mesenchymal stem cells showed significant differences.In rabbit-derived bone marrow mesenchymal stem cells,kartogenin predominantly promoted chondrogenic differentiation while inhibiting osteogenic differentiation.This was evident from positive toluidine blue staining,whereas alkaline phosphatase and alizarin red staining exhibited no significant changes.qRT-PCR analysis revealed upregulation of chondrogenic-related genes(Col2a1 and Sox9)and downregulation of genes associated with osteogenesis(Alpl,Col1a1,Runx2,and Bglap).Similar results were found in the western blot assay.(3)In contrast,kartogenin in mouse-derived bone marrow mesenchymal stem cells promoted both chondrogenic and osteogenic differentiation.While toluidine blue staining remained largely unchanged,alkaline phosphatase and alizarin red staining revealed increased positivity,indicative of enhanced osteogenesis.qRT-PCR analysis showed upregulation of not only chondrogenic-related genes(Col2a1 and Sox9)but also genes linked to osteogenesis(Alpl,Col1a1,Runx2,and Bglap).The western blot assay results showed similar results.These findings suggest that kartogenin exerts differential regulatory effects on the differentiation of rabbit and rat bone marrow mesenchymal stem cells,potentially stemming from variations in gene expression profiles and underlying signaling pathways.

BACKGROUND:Bone marrow mesenchymal stem cells possess multipotent differentiation potential and are an important source of cells for cartilage and bone tissue regeneration research.Kartogenin is a small-molecule drug that has been demonstrated to promote stem cell differentiation towards chondrogenesis.However,the ability to promote osteogenic differentiation is still controversial,and the specific effects of kartogenin on the chondrogenic and osteogenic differentiation of stem cells of different species have not been fully elucidated.OBJECTIVE:To investigate the effects of kartogenin on chondrogenic and osteogenic differentiation in rabbit-derived and rat-derived bone marrow mesenchymal stem cells.METHODS:Rabbit-derived and rat-derived bone marrow mesenchymal stem cells were obtained through whole bone marrow separation and adherence methods,and were treated with varying concentrations of kartogenin.Cell proliferation was detected using the CCK-8 assay.Chondrogenic and osteogenic differentiation was assessed via toluidine blue and alizarin red staining,respectively.After screening for the optimal concentration of kartogenin,alkaline phosphatase staining,qRT-PCR,and western blot assay were employed to analyze the expression of osteogenic and chondrogenic-related genes and proteins.RESULTS AND CONCLUSION:(1)Within the concentration range of 0 to 10 000 nmol/L,kartogenin did not significantly affect the proliferation of rabbit-derived or mouse-derived bone marrow mesenchymal stem cells.(2)The differentiation effect of kartogenin on rabbit-derived and rat-derived bone marrow mesenchymal stem cells showed significant differences.In rabbit-derived bone marrow mesenchymal stem cells,kartogenin predominantly promoted chondrogenic differentiation while inhibiting osteogenic differentiation.This was evident from positive toluidine blue staining,whereas alkaline phosphatase and alizarin red staining exhibited no significant changes.qRT-PCR analysis revealed upregulation of chondrogenic-related genes(Col2a1 and Sox9)and downregulation of genes associated with osteogenesis(Alpl,Col1a1,Runx2,and Bglap).Similar results were found in the western blot assay.(3)In contrast,kartogenin in mouse-derived bone marrow mesenchymal stem cells promoted both chondrogenic and osteogenic differentiation.While toluidine blue staining remained largely unchanged,alkaline phosphatase and alizarin red staining revealed increased positivity,indicative of enhanced osteogenesis.qRT-PCR analysis showed upregulation of not only chondrogenic-related genes(Col2a1 and Sox9)but also genes linked to osteogenesis(Alpl,Col1a1,Runx2,and Bglap).The western blot assay results showed similar results.These findings suggest that kartogenin exerts differential regulatory effects on the differentiation of rabbit and rat bone marrow mesenchymal stem cells,potentially stemming from variations in gene expression profiles and underlying signaling pathways.

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

[Objective]To explore the epidemiology and clinical characteristics of kala-azar patients in Kashgar region,so as to improve the diagnosis and treatment.[Methods]A retrospective analysis was conducted on the clinical data of 71 kala-azar patients admitted to the First People's Hospital of Kashgar Region between January 2013 and December 2023.[Results]Among the 71 patients,the majority were aged 0-5 years(52.11%,37/71),with a male-to-female ratio of 0.92:1.Most cases occurred in winter and spring.Common clinical manifestations included fever,fatigue,decreased appetite,splenomegaly and hepatomegaly.Laboratory investigations mainly found pancytopenia,reversed albumin-to-globulin ratio,elevated transaminases,and increased C-reactive protein and procalcitonin.The positive rates of anti-rK39 antibody detection and bone marrow microscopy were 100%(23/23)and 91.38%(53/58),respectively.Metagenomics next-generation sequencing(mNGS)of liver tissue identified Leishmania donovani in one case.The common complications were infectious toxic hepatitis 49.30%(35/71),myocarditis 29.56%(21/71),and bronchopneumonia 23.94%(17/71).[Conclusions]Potential kala-azar should be taken into consideration for patients from the endemic areas with long-term irregular fever accompanied by splenomegaly,hemocytopenia,and reversed albumin-to-globulin ratio.Bone marrow smear microscopy and anti-rK39 antibody detection are recommended for the diagnosis,and mNGS provides a novel diagnostic solution.

Objective: To explore the relationship between processed food consumption and blood pressure level of students in a university in Yunnan Province, so as to provide the reference for preventing hypertension in university students. Methods: In October 2021, a cluster sampling method was used to select 4 781 freshmen from a university in Kunming, Yunnan Province. The frequency of processed food consumption of university students was assessed by using the dietary frequency questionnaire, and height, weight and blood pressure were measured. Mann-Whitney test and Kruskal-Wallis test were used to compare the differences in blood pressure level of university students with different demographic variables, and the association between processed food consumption and blood pressure level was analyzed with a generalized linear model. Results: Among the students of a university in Yunnan Province, the detection rates of systolic prehypertension and hypertension were 33.86% and 1.23%, and the detection rates of diastolic prehypertension were 32.13% and hypertension 7.22%. The results of generalized linear model analysis showed that after controlling for demographic variables and other variables that might affect the blood pressure level of university students, the consumption of processed food (bread and cake: β =0.15, 95% CI =0.01-0.29) and ultra processed food (coffee beverage: β =-0.29, 95% CI =-0.54--0.03) were associated with systolic blood pressure level( P <0.05). The consumption of processed food (salted duck egg: β =0.21, 95% CI =0.01-0.41) was correlated with the diastolic blood pressure of college students ( P <0.05). Conclusions Processed food consumption in university students may increase the risk of high blood pressure.The education of healthy eating among college students should be strengthened to reduce the consumption of processed foods.

Objective To evaluate the apparent diffusion coefficient(ADC)values of different bone marrow infiltration patterns in multiple myeloma(MM)patients with MR whole-body diffusion weighted imaging(WB-DWI)and to determine the ADC thresholds for different bone marrow infiltration patterns.Methods Nineteen MM patients diagnosed for the first time were selected.The lesions types of each site(cervical spine,ribs,sternum,humerus,scapula,sacral spine,ilium,femur,thoracic spine,and lumbar spine)after the WB-DWI images were visually evaluated,which were divided into focal group(including focal lesion in combined focal and diffuse infiltration)[region of interest(ROI)=141],pure diffuse infiltration group(ROI=150),diffuse lesion in combined focal and diffuse infiltration group(ROI=127),"salt-and-pepper"group(ROI=54),and normal appearance group(ROI=68).ADC values were measured and compared between each group and the receiver operating characteristic(ROC)curve was drawn to distinguish different patterns of bone marrow infiltration.Results There was no statistically significant difference in ADC values between the diffuse lesion in combined focal and diffuse infiltration group and the"salt-and-pepper"group(P＞0.99),and there was statistically significant difference in ADC values between the other groups(P＜0.05).The ROC curve showed that the area under the curve(AUC)for identifying focal group and the"salt-and-pepper"group was 0.889[95％confidence interval(CI)0.844-0.934],the AUC for identifying pure diffuse infiltration group and the normal appearance group was 0.968(95％CI 0.949-0.987).ADC values were able to accurately and visually differentiate between the different patterns of bone marrow infiltration.Conclusion The ADC values can be used as a quantitative tool to objectively distinguish different bone marrow infiltration patterns in MM patients.

Promoting the integration of party building with business work is a strong political guarantee for the high-quali-ty development of public hospitals in the new era."Party Branch Co-construction at Primary Level"is a vehicle for integrating Party building efforts with the main service tasks and supporting central work activities.This project focuses on the hospital's high-quality development with a goal-oriented and problem-oriented approach,aiming to create"service-oriented"Party branches within functional departments.Through the"Branch Co-construction"activities,it explores:1.Joint organization of activities;2.Business coordination;3.Joint team development.The project aims to integrate the regular organization activities of functional department Party branches with clinical business work,enhancing the awareness of proactive and front-line service in functional departments.It continuously explores ways and methods for"co-construction and joint work"with clinical medical and technical department Party branches,leveraging the exemplary role of Party members and the fighting bastion role of Party branches.

Objective:To compare the therapeutic effects of 0.05% cyclosporine and 0.1% fluorometholone eye drops in patients with moderate and severe dry eye.Methods:A randomized controlled study was conducted.Fifty-two patients (52 eyes) with moderate to severe dry eye in Tianjin Medical University Eye Hospital from August 2021 to December 2022 were enrolled and randomly divided into 0.05% cyclosporine group and 0.1% fluorometholone group by random number table method, with 26 cases (26 eyes) in each group.Patients received 0.05% cyclosporine eye drops (2 times/day) and 0.1% fluorometholone eye drops (2 times/day) combined with calf blood deproteinized extract eye drops (4 times/day) according to the grouping.Before and 1, 3 and 6 months after treatment, clinical symptoms and signs were observed and Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS) score, Schirmer Ⅰ test (SⅠT), non-invasive first tear film break-up time (NIBUTf), and conjunctival goblet cell (CGC) density were recorded.Before treatment and after 6 months of treatment, changes in corneal nerves and dendritic cells (DC) were observed by in vivo confocal microscopy (IVCM).This study adhered to the Declaration of Helsinki and was approved by the Medical Ethics Committee of Eye Hospital of Tianjin Medical University (No.2021KY-17).Written informed consent was obtained from each subject. Results:Compared with the 0.1% fluorometholone group, CFS score decreased after 1 month of treatment, but SⅠT, NIBUTf and CFS score increased after 3 months of treatment, and OSDI score, SⅠT and CFS score decreased after 6 months of treatment in the 0.05% cyclosporine group, showing statistically significant differences (all at P<0.05).Compared with baseline, in the 0.05% cyclosporine group, NIBUTf increased and CFS score decreased after 1 month of treatment, OSDI score and CFS score decreased, SⅠT and NIBUTf increased after 3 and 6 months of treatment, showing statistically significant differences (all at P<0.05).In the 0.1% fluorometholone group, CFS score decreased after 3 months of treatment, OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to baseline, showing statistically significant differences (all at P<0.05).OSDI score and CFS score decreased, SⅠT increased after 6 months of treatment compared to 3 months of treatment in the 0.05% cyclosporine group, and the differences were statistically significant (all at P<0.05).Baseline and CGC densities after 1, 3 and 6 months of treatment were (147.66±17.29), (195.44±15.46), (210.36±19.15) and (282.09±22.63)cells/mm 2 in the 0.05% cyclosporine group and (138.09±17.29), (95.67±15.46), (117.77±19.15) and (109.13±22.63)cells/mm 2 in the 0.1% fluorometholone group, respectively, with a statistically significant overall difference ( Fgroup=11.724, P<0.001; Ftime=4.837, P=0.005).Compared with the 0.1% fluorometholone group, CGC density in the 0.05% cyclosporine group increased after 1, 3 and 6 months of treatment, with statistically significant differences (all at P<0.05).Compared with baseline, the CGC density increased in the 0.05% cyclosporine group after 1, 3 and 6 months of treatment, and the differences were statistically significant (all at P<0.05).Compared with the 0.1% fluorometholone group, the corneal nerve fiber density in the 0.05% cyclosporine group increased after 6 months of treatment, and corneal DC density, area and dendrite number decreased, showing statistically significant differences (all at P<0.05). Conclusions:Cyclosporine 0.05% eye drops combined with calf blood deproteinized extract eye drops can improve symptoms and signs in patients with moderate to severe dry eye, and the long-term effect is better than that of 0.1% fluorometholone plus calf blood deproteinized extract eye drops.