Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P＜0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P＜0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P＜0.001,P＜0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

Objective:To analyze the efficiency of human resource allocation and its spatial distribution characteristics of district-level Center for Disease Control and Prevention(CDC)in city N of Jiangsu Province in 2020,in order to provide a strong decision-making reference for optimizing and strengthening the CDC talent team.Methods:The efficiency of human resources of district-level CDC of City N in2020 was measured using the Super-Efficiency SBM model,and the spatial association pattern was analyzed using the natural break point classification method and Moran's index,with the visualization presented through LISA maps.Results:The overall level of human resource efficiency in district-level CDC of City N is relatively high.However,spatially,there are significant differences among the regions,showing a trend of high efficiency in the central areas and low efficiency at the ends.Moran's index and LISA maps indicate a negative spatial correlation in efficiency,with a low-high(L-H)cluster centered on Area L and a high-low(H-L)cluster centered on Area J.The high-high(H-H)cluster pattern has not yet formed,exhibiting a characteristic of interspersed high and low efficiency.Conclusions:There are regional differences in the human resource efficiency of the Disease Control Center in City N,and the spatial cluster pattern needs to be optimized.It is recommended to focus on efficiency improvement in Areas P and L,formulate appropriate policies,and promote coordinated regional development.

Objective:To explore diagnostic value of echocardiography indexes for moderate-severe stenosis in CHD patients and their correlation with cardiac function class.Methods:A total of 90 CHD patients admitted to our hos-pital from Dec 2020 to Dec 2022 were selected as CHD group.According to NYHA classification,CHD group was divided into class Ⅰ～Ⅱ group(n=38)and class Ⅲ～Ⅳ group(n=52).The patients were divided into mild group(n=35)and moderate-severe group(n=55)according to Gensini score.In addition,90 healthy people who sim-ultaneously received physical examination in our hospital were enrolled as control group.LVEF,LVEDd and LVESd were measured in two groups by color ultrasound diagnostic instrument.Cardiac function indexes were com-pared between control group and CHD group,mild group and moderate-severe group,class Ⅰ～Ⅱ group and classⅢ～Ⅳ group.ROC curve was used to analyze the diagnostic value of above cardiac function indexes for moderate-severe stenosis in CHD patients.The correlation among LVEF,LVEDd,LVESd,different stenosis degree and NYHA class in CHD patients was analyzed by Spearman correlation analysis.Results:Compared with the control group,there was significant reduction in LVEF,and significant rise in LVEDd and LVESd in CHD group,P=0.001 all;compared with the mild group,there was significant reduction in LVEF[(45.31±5.08)％vs.(40.34±3.01)％],and significant rise in LVEDd[(53.92±5.09)mm vs.(61.68±4.79)mm]and LVESd[(52.72±4.72)mm vs.(58.06±3.50)mm]in moderate-severe group,P=0.001 all;compared with the class Ⅰ～Ⅱgroup,there was significant reduction in LVEF[(45.07±4.95)％vs.(40.23±3.06)％],and significant rise in LVEDd[(54.50±5.30)mm vs.(61.71±4.91)mm]and LVESd[(52.92±4.63)mm vs.(58.22±3.43)mm]in class Ⅲ～Ⅳ group,P=0.001 all.AUC of combined detection of LVEF,LVEDd and LVESd diagnosing moder-ate-severe stenosis in CHD was 0.909,which was significantly higher than those of single detections(0.733,0.787,0.789)(Z=2.925,2.125,2.043,P＜0.05 or＜0.01).Spearman correlation analysis showed a significant negative correlation between LVEF and NYHA class(r=-0.514),LVEDd and LVESd showed a significant posi-tive correlation with NYHA class(r=0.538,0.546,P=0.001 both),and it showed a significant positive correla-tion between different degrees of coronary stenosis and NYHA class in CHD patients(r=0.875,P=0.001).Con-clusion:The combined detection of LVEF,LVEDd and LVESd possesses high diagnostic value for moderate-se-vere stenosis in CHD patients,and it is significantly correlated with NYHA cardiac function class,which can be used as one of assessing methods for coronary stenosis severity in CHD patients.

Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

In recent years, artificial intelligence (AI) technology has advanced rapidly and has been widely applied in various fields such as medicine and pharmacy, accelerating the drug development process. Focusing on the application of AI in the discovery and optimization of lead compounds, this review provides a detailed introduction to AI-assisted virtual screening and molecular generation methods for discovering lead compounds, while particularly highlighting the cases of AI-drived drugs into clinical trials. Additionally, we briefly outline the application of AI basic algorithm models in quantitative structure-activity relationship (QSAR) and drug repurposing, offering insights for AI-based drug discovery.

Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)in the eNOS gene and genetic susceptibility to systemic lupus erythematosus(SLE)in Hainan.Methods Blood samples were collected from SLE patients(SLE group,n=214)and healthy controls(control group,n=214)from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital.The bases of eNOS gene rs3918188,rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology.Logistic regression was used to analyze the correlation between genotypes,alleles and gene models(dominant model,recessive model,and overdominant model)of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE.Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site.Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE(CC vs.AA:OR=2.449,P<0.05;C vs.A:OR=2.133,P<0.001).In recessive model at rs3918188 locus,CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers(OR=2.774,P<0.001).In contrast,in overdominant model at this locus,AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers(OR=0.385,P<0.001).In addition,polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype,allele type and the 3 genetic models(P>0.05).Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene,but no significant correlation was found between haplotype and genetic susceptibility to SLE(P>0.05).Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan,while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.

The phenomenon of bacterial drug resistance is becoming more and more serious. Natural products, as an important resource for drug discovery, can play a role by regulating protein post-translational modifications related to bacterial infection and inflammatory responses. This provides a valuable compound library for the research and development of new antibacterial drugs. In this present research, dioscin and diosgenin were isolated and identified from Dioscorea nipponica Rhizoma, which both exhibited antibacterial activities, with stronger inhibitory on Gram-positive bacteria (G⁺) than Gram-negative bacteria (G^-). Compared these two compounds, diosgenin showed stronger antibacterial activity than dioscin. In vivo experiments confirmed that diosgenin provided better protection against MRSA-induced sepsis in mice compared to dioscin, which could significantly improve survival rates, reduce bacterial colony counts in infected organs, alleviate pathological damage, and decrease inflammatory cytokine levels in mice. The in vivo study was approved by the Animal Ethics Committee of the PLA Air Force Military Medical University (Grant No. 20230188). Network pharmacology results also revealed that diosgenin could target inflammatory pathways, exerting dual antibacterial and anti-inflammatory activities during bacterial infection therapy.

In this study, the underlying mechanism of Qiwei Guibao Granules(QWGB) in the treatment of premature ovarian fai-lure(POF) was explored by the proteomics technique. Firstly, the POF model was induced in mice by intragastric administration of Tripterygium wilfordii glycosides solution at 50 mg·kg~(-1) for 14 days. Ten days prior to the end of the modeling, the estrous cycle of mice was observed every day to evaluate the success of modeling. From the 1st day after modeling, the POF model mice were treated with QWGB by gavage every day and the treatment lasted four weeks. On the 2nd day after the end of the experiment, blood was collected from the eyeballs and the serum was separated by centrifugation. The ovaries and uterus were collected and the adipose tissues were carefully stripped. The organ indexes of the ovaries and uterus of each group were calculated. The serum estrogen(E_2) level of mice in each group was detected by ELISA. Protein samples were extracted from ovarian tissues of mice, and the differential proteins before and after QWGB intervention and before and after modeling were analyzed by quantitative proteomics using tandem mass tags(TMT). As revealed by the analysis of differential proteins, QWGB could regulate 26 differentially expressed proteins related to the POF model induced by T. wilfordii glycosides, including S100A4, STAR, adrenodoxin oxidoreductase, XAF1, and PBXIP1. GO enrichment results showed that the 26 differential proteins were mainly enriched in biological processes and cellular components. The results of KEGG enrichment showed that those differential proteins were involved in signaling pathways such as completion and coalescence cascades, focal adhesion, arginine biosynthesis, and terpenoid backbone biosynthesis. The complement and coalescence cascades signaling pathway was presumably the target pathway of QWGB in the treatment of POF. In this study, the proteomics technique was used to screen the differential proteins of QWGB in the treatment of POF in mice induced by T. wilfordii glycosides, and they were mainly involved in immune regulation, apoptosis regulation, complement and coagulation cascade reactions, cholesterol metabolism, and steroid hormone production, which may be the main mechanisms of QWGB in the treatment of POF.
Female ; Humans ; Mice ; Animals ; Primary Ovarian Insufficiency/chemically induced* ; Proteomics ; Signal Transduction ; Glycosides/adverse effects*

Objective: To summarize the pathological diagnosis, clinical features, treatment methods and outcomes of pediatric-type follicular lymphoma (PTFL). Methods: Clinical data including the pathology, clinical features, treatment methods, and follow-up results of 9 PTFL patients admitted to Henan Cancer Hospital from February 2017 to February 2023 were analyzed retrospectively. Results: The age of onset in 9 children was 6 to 18 years, all the patients were males. The clinical manifestation was local painless lymph node enlargement in the head and neck, with a stage of Ⅰ-Ⅱ. The histomorphological characteristics of PTFL were similar to those of classic follicular lymphoma (FL). The germinal center of most follicles were enlarged, the mantle zone disappeared, centroblasts were easily visible, and the histological grade were mostly grade Ⅲ, which may be accompanied by the "starry sky" phenomenon. Monoclonal peaks can be seen in B cell clonal rearrangements (BCR). Immunohistochemistry (IHC) showed CD20 positive, CD10 positive, Bcl-6 positive, Bcl-2 negative, C-myc negative, and Ki-67 was 70%-95%. Fluorescence in situ hybridization (FISH) test was negative for t (14, 18), Bcl-2 translocation, and C-myc translocation. Six cases underwent surgical resection, and 3 cases underwent surgical resection combined with chemotherapy. Up to February 2023, with a follow-up time of 45 to 72 months, all children survived without any recurrence and were in a complete remission state. Conclusions: PTFL is mainly characterized by adolescent male onset, with early clinical manifestations and pathological manifestations of high-level histological status, high proliferation index, and lack of t (14; 18)/Bcl-2 translocation and Bcl-2 expression. It is mainly treated by localized surgical excision and has a good prognosis.
Child ; Adolescent ; Humans ; Male ; Female ; Lymphoma, Follicular/pathology* ; Lymphoma, B-Cell/pathology* ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Proto-Oncogene Proteins c-bcl-2/genetics*