Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

Objective: To explore the correlation between the composition of bone marrow lymphocyte subsets and the clinical attributes observed in de novo AML patients, as well as their influence on prognosis. Methods: A detailed study was carried out on a cohort of 191 de novo acute myeloid leukemia patients who were admitted to our medical center between October 2022 and September 2024. In addition, a group of 24 patients with iron deficiency anemia individuals was carefully chosen as the control cohort. The proportions of lymphocyte subsets within the bone marrow of de novo AML patients were analyzed. Furthermore, an in-depth analysis was performed to investigate the association between the expression levels of these subsets in de novo AML patients and their clinical attributes, as well as their prognostic implications. Results: The proportion of CD19 and CD56 lymphocytes within the bone marrow of de novo AML patients significantly diminished compared to the control cohort (8.5% vs 13.2% P<0.05, and 15.5% vs 18.0%, P<0.05). Conversely, no significant discrepancies were observed in the CD3 , CD3 CD4 , and CD3 CD8 lymphocyte percentages between the AML patients and control group (71.7% vs 72.1%, 32.5% vs 33.7% and 32.8% vs 35.7%, P>0.05). When analyzing the relationships between lymphocyte subsets within the bone marrow of de novo patients and their respective clinical characteristics, patients aged 60 years and above exhibited diminished percentages of CD3 CD8 lymphocytes in the bone marrow compared to their younger counterparts (31.6% vs 34.1%, P<0.05), while the CD56 lymphocyte subsets demonstrated an increased prevalence (17.2% vs 14.4%, P<0.05). Furthermore, patients with leukocytosis (WBC≥100×10 /L) presented lower levels of CD3 and CD3 CD4 lymphocytes in the bone marrow compared with those without it (65.3% vs 72.9% P<0.05, and 28.9% vs 33.2%, P<0.05), respectively. The AML1-ETO fusion gene-positive cohort exhibited a higher prevalence of CD3 CD8 lymphocytes in the bone marrow than in the negative group (38.2% vs 32.3%, P<0.05), whereas the FLT3-ITD mutation-positive group presented a decreased prevalence of CD56 lymphocytes compared with the negative group (12.4% vs 16.8%, P<0.05). In addition, the NPM1 mutation-positive group demonstrated lower levels of CD3 CD8 lymphocytes in the bone marrow than in the negative group (29.1% vs 33.3%, P<0.05). Variables such as tumor protein p53(TP53) mutation positive, the absence of hematopoietic stem cell transplantation, and CD3 CD4 lymphocyte proportions below 25% were identified as independent adverse prognostic indicators for AML patients (P<0.05). Conclusion: The pathogenesis of AML is closely associated with an imbalance in bone marrow lymphocyte subsets. The FLT3-ITD mutation potentially contributes to the dysregulation of CD56 lymphocyte subset expression. The AML1-ETO fusion gene and NPM1 mutation are implicated in the abnormal expression of CD3 CD8 lymphocytes within the bone marrow. Moreover, the percentage of CD3 CD4 lymphocytes in the bone marrow serves as a prognostic factor for de novo AML patients.

Plant-derived natural products have long been a vital source for developing therapeutic drugs. Wedelolactone (WDL), a coumestan isolated from Eclipta prostrata, Wedelia calendulacea, Wedelia chinensis, and Sphagneticola trilobata, demonstrates a broad spectrum of therapeutic potential, including anticancer, anti-inflammatory, anti-obesity, anti-myotoxic, antimicrobial, anti-diabetic, and tissue-protective activities. This review synthesizes information on the isolation, total synthesis, pharmacological activity, underlying mechanisms, and pharmacokinetic properties of WDL. Additionally, it offers insights into potential clinical applications and future drug discovery avenues utilizing WDL or its derivatives, either independently or in combination with other pharmaceuticals.
Coumarins/isolation & purification* ; Humans ; Animals ; Biological Products/chemical synthesis* ; Molecular Structure ; Plant Extracts/chemical synthesis* ; Wedelia/chemistry* ; Eclipta/chemistry*

Objective:To investigate the efficacy and safety of protein A immunoadsorption (PAIA) combined with rituximab (RTX) in highly sensitized patients who underwent haplo-hematopoietic stem cell transplantation (haplo-HSCT) .Methods:The clinical data of 56 highly sensitized patients treated with PAIA and RTX before haplo-HSCT at the First Affiliated Hospital of Soochow University and Soochow Hopes Hematonosis Hospital between March 2021 and June 2023 were retrospectively analyzed. The number of human leukocyte antigen (HLA) antibody types and the mean fluorescence intensity (MFI), humoral immunity, adverse reactions during adsorption, and survival within 100 days before and after adsorption were measured.Results:After receiving the PAIA treatment, the median MFI of patients containing only HLA Ⅰ antibodies decreased from 7 859 (3 209-12 444) to 3 719 (0-8 275) ( P<0.001), and the median MFI of HLA Ⅰ+Ⅱ antibodies decreased from 5 476 (1 977-12 382) to 3 714 (0-11 074) ( P=0.035). The median MFI of patients with positive anti-donor-specific antibodies decreased from 8 779 (2 697-18 659) to 4 524 (0–15 989) ( P<0.001). The number of HLA-A, B, C, DR, and DQ antibodies in all patients decreased after the PAIA treatment, and the differences were statistically significant (A, B, C, DR: P<0.001, DQ: P<0.01). The humoral immune monitoring before and after the PAIA treatment showed a significant decrease in the number of IgG and complement C3 ( P<0.001 and P=0.002, respectively). Forty-four patients underwent HLA antibody monitoring after transplantation, and the overall MFI and number of antibody types decreased. However, five patients developed new antibodies with low MFI, and nine patients continued to have high MFI. The overall survival, disease-free survival, non-recurrent mortality, and cumulative recurrence rates at 100 days post-transplantation were 83.8%, 80.2%, 16.1%, and 4.5%, respectively. Conclusions:The combination of PAIA and RTX has a certain therapeutic effect and good safety in the desensitization treatment of highly sensitive patients before haplo-HSCT.

ObjectiveBased on network pharmacology and transcriptomics， the mechanism of Zishen Qinggan prescription （ZSQGF） in improving glucose and lipid metabolism in type 2 diabetes （T2DM） model rats was explored. MethodBased on network pharmacology analysis of the differential genes between ZSQGF and T2DM， gene ontology（GO）analysis and Kyoto encyclopedia of genes and genomes（KEGG） analysis were conducted， and molecular docking analysis was used to verify the binding between components and targets. A T2DM rat model was established by high-fat feeding and injection of streptozotocin （STZ）. The rats were randomly divided into the control group， model group， metformin （Met， 72 mg·kg^-1） group， and ZSQGF high-， medium-， and low-dose groups （ZSQGF-H， ZSQGF-M， and ZSQGF-L， with 4.8， 2.4， and 1.2 g·kg^-1 raw drug in the solution）. The living status of rats was monitored and the levels of total cholesterol （TC）， total triglycerides （TG）， high density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in rat serum were detected. The liver tissues were subjected to Hematoxylin eosin（HE） staining and oil red O staining. The differential genes were analyzed through transcriptomics， GO and KEGG analysis， and the protein-protein interaction（PPI） network was obtained to screen key targets. With network pharmacology and transcriptomics analysis results， the protein pathways were identified. The expression levels of nuclear factor-κB （NF-κB）， matrix metalloproteinase（MMP）-1 and MMP-9 proteins in liver tissues were detected by Western blot. The mRNA expression of B-cell lymphoma-2（Bcl-2） modifying factor（BMF）， nicotinamide adenine dinucleotide phosphate （NADPH） oxidase 4 （NOX4）， and fatty acid synthase（FASN） was detected by real-time polymerase chain reaction（Real-time PCR）. The expression of MMP-1 and MMP-9 in the liver was detected by immunofluorescence staining. ResultTranscriptomics and network pharmacology analysis suggested that ZSQGF may protect the liver through the glucose and lipid metabolism pathway and the inflammation pathway. Experiments showed that after 8 weeks of administration， the body weight， blood sugar， serum indicators， and pathological staining results of rats were improved. Western blot results indicated a decrease in the relative expression levels of NF-κB， MMP-1 and MMP-9 proteins in the liver. Real-time PCR results showed a decrease in the transcriptional expression of BMF， NOX4， and FASN in the ZSQGF-H group， while immunofluorescence staining results present decreased expression of MMP-1 and MMP-9 in the ZSQGF groups. ConclusionZSQGF can improve the glucose and lipid metabolism by inhibiting the expression of FASN， reducing lipid synthesis， and regulating the NF-κB signaling pathway.

【Objective】 To explore the risk factors for the production of anti-HLA antibodies in patients with hematological diseases before hematopoietic stemcell transplantation. 【Methods】 The results and clinical data of 1 008 patients with hematological diseases in our hospital who underwent anti-HLA antibody testing were collected by using Luminex technology platform before transplantation from 2016 to 2018 for statistical analysis. 【Results】 The total positive rate of anti-HLA antibodies in 1 008 patients was 24.08%. Multivariate analysis showed that independent risk factors associated with the production of anti-HLA antibodies included age≥30 years old(P=0.046, OR1.467, 95%CI1.007-2.136), time from disease diagnosis to antibody testing≥41 days(P=0.000, OR1.830, 95%CI1.306-2.565), initial platelet count<20×10⁹/L(P=0.020, OR1.543, 95%CI1.072-2.220), prior pregnancy(P=0.000, OR5.187, 95%CI3.689-7.293), transfusions before admission(P=0.001, OR1.762, 95%CI1.257-2.470)and total platelet transfusion volumes after admission≥30 U(P=0.000, OR2.352, 95%CI1.638-3.376). Age ≥30 years old(P=0.023, OR=1.839, 95%CI1.088-3.108)and prior pregnancy(P=0.042, OR=5.258, 95%CI1.062-26.038)are associated with the production of anti-HLA class Ⅰ and class Ⅱ antibodies, respectively. The time from disease diagnosis to antibody testing≥41 days(P=0.000, OR=2.873, 95%CI1.612-5.119), initial platelet count<20×10⁹/L(P=0.008, OR=2.164, 95%CI1.225-3.822), prior pregnancy(P=0.002, OR=6.734, 95%CI1.993-22.751), transfusions before admission(P=0.001, OR=2.746, 95%CI1.531-4.925)and total platelet transfusion volumes after admission>30 U(P=0.006, OR=3.459, 95%CI1.416-8.451)are associated with the production of anti-HLA class Ⅰ and Ⅱ antibodies. 【Conclusion】 Older age, longer course of disease, lower PLT count, history of pregnancy and blood transfusion, and higher total amount of PLT transfusion are risk factors which affect the production of anti-HLA antibodies.Therefore, it is advisable to test for anti-HLA antibodies according to the situation before transplantation, which is of great value in guiding donor selection, monitoring antibody changes and improving transplant prognosis.

Objective To investigate the role of member septin family(SEPT12)in human spermatogenesis and its influence on sperm motility and sperm ultrastructure.Methods Whole exome sequencing(WES)was performed on peripheral blood DNA extracted from 375 patients with asthenoteratozoospermia,and a patient with idiopathic in-fertility carrying compound heterozygous mutation of SEPT12 was screened out.Sanger sequencing was performed to verify the mutation,and co-segregation analysis was performed in the family.The morphological abnormalities of sperm were analyzed by hematoxylin-eosin(HE)staining and scanning electron microscopy(SEM),and the ultra-structural defects of sperm were analyzed by transmission electron microscopy(TEM).Then the effects of the muta-tion on the level and position of the protein and the changes of the location and level of the defect structure markers were analyzed by Western blot and immune-fluorescence(IF).Results The compound heterozygous mutations c.C332A(p.Ti111K)and c.406_416 del TGCTCGTATTG(p.q136 VFS*39)in the SEPT12 gene were screened and identified in a patient with asthenoteratozoospermia.The mutations were verified by Sanger sequencing,which was consistent with the co-segregation genetic pattern of the family.The mutations resulted in loss of protein expres-sion,decreased sperm motility and sperm morphological deformities,mainly including short tail,curly tail and ir-regular sperm head.The ultrastructure of sperm showed that the annulus between the mid-piece and the principle-piece was missing,the acrosome membrane of sperm head fell off and the nucleus contained vacuoles.In the mid-piece of sperm flagella,the arrangement of mitochondrial sheath was disordered,most of flagella axoneme central pair was absent,microtubules doublet was missing or disordered,and some radical spoke was absent.By Western blot and IF,the marker proteins of related structural components were detected,and the results showed that the level of SEPT4 protein decreased,SEPT6 protein unchanged,acrosomal related proteins ACTL7A and ACROSIN protein missing,and the expression levels of mitochondrial and axoneme related proteins TOMM20,SPAG6 and RSPH3 protein significantly decreased.Conclusion The deletion of SEPT12 protein caused by SEPT12 gene mu-tation leads to the deletion of the annulus between the mid-piece and the principle-piece,and the abnormal assem-bly of sperm acrosome,mitochondrial sheath and flagella.

Objective To investigate the prevalence of Echinococcus infections in small rodents around human residential areas in Yushu City, Qinghai Province in 2023, so as to provide insights into precision echinococcosis control. Methods One or two quadrats, each measuring 50 m × 50 m, were randomly assigned in Shanglaxiu Township and Longbao Township, Yushu City, Qinghai Province on June 2023, respectively, and 300 plate-type mouse traps, each measuring 12.0 cm × 6.5 cm, were assigned in each quadrat. Small rodents were captured during the period between 10 : 00 and 18 : 00 each day for 4 days. Then, all captured small rodents were identified and dissected, and liver specimens with suspected Echinococcus infections were subjected to pathological examinations. The Echinococcus cytochrome c oxidase 1 (cox1) gene was amplified using PCR assay, and the sequence of the amplified product was aligned to that was recorded in the GenBank to characterize the parasite species. In addition, a phylogenetic tree of Echinococcus was generated based on the cox1 gene sequence using the neighbor-joining method. Results A total of 236 small rodents were captured in Shanglaxiu and Longbao townships, Yushu City, including 65 Qinghai voles and 51 plateau pikas in Shanglaxiu Township, and 62 Qinghai voles and 58 plateau pikas in Longbao Township, and there was no significant difference in the constituent ratio of small rodents between the two townships (χ² = 0.294, P > 0.05). Seven plateau pikas and 12 Qinghai voles were suspected to be infected with Echinococcus by dissection, and pathological examinations showed unclear structure of hepatic lobules and disordered hepatocyte arrangement in livers of small rodents suspected of Echinococcus infections. PCR assay identified E. shiquicus DNA in 7 Qinghai voles, which were all captured from Shanglaxiu Township. Phylogenetic analysis showed that the cox1 gene sequence of Echinococcus in small rodents was highly homologous to the E. shiquicus cox1 gene sequence reported previously. Conclusion Plateau pika and Qinghai vole were predominant small rodents around human residential areas in Yushu City, Qinghai Province in 2023, and E. shiquicus infection was detected in Qinghai voles.

Objective To investigate the spatiotemporal distribution characteristics and potential influencing factors of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, so as to provide insights into the formulation of the echinococcosis control strategy in Qinghai Province. Methods The number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases, number of registered dogs and number of stray dogs were captured from the annual reports of echinococcosis control program in Qinghai Province from 2016 to 2022, and the detection of newly diagnosed echinococcosis cases was calculated. The number of populations, precipitation, temperature, wind speed, sunshine hours, average altitude, number of year-end cattle stock, number of year-end sheep stock, gross domestic product (GDP) per capita, and number of village health centers in each county (district) of Qinghai Province were captured from the Qinghai Provincial Statistical Yearbook, and county-level electronic maps in Qinghai Province were downloaded from the National Platform for Common Geospatial Information Services. The software ArcGIS 10.8 was used to map the distribution of newly diagnosed echinococcosis cases in Qinghai Province, and the spatial autocorrelation analysis of newly diagnosed echinococcosis cases was performed. In addition, the spacetime scan analyses of number of individuals screened for echinococcosis, number of newly diagnosed echinococcosis cases and geographical coordinates in Qinghai Province were performed with the software SaTScan 10.1.2, and the spatial stratified heterogeneity of the detection of newly diagnosed echinococcosis cases was investigated with the software GeoDetector. Results A total of 6 569 426 residents were screened for echinococcosis in Qinghai Province from 2016 to 2022, and 5 924 newly diagnosed echinococcosis cases were found. The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline over years from 2016 to 2022 (χ² = 11.107, P < 0.01), with the highest detection in Guoluo Tibetan Autonomous Prefecture in 2017 (82.12/10⁵). There were spatial clusters in the detection of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2018 (Moran’s I = 0.34 to 0.65, all Z values > 1.96, all P values < 0.05), and the distribution of newly diagnosed echinococcosis cases appeared random distribution from 2019 to 2022 (Moran’s I = −0.09 to 0.04, all Z values < 1.96, all P values > 0.05). Local spatial autocorrelation analysis showed high-high clusters and low-low clusters in the detection of new diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022, and space-time scan analysis showed that the first most likely cluster areas of newly diagnosed echinococcosis cases in Qinghai Province from 2016 to 2022 were mainly distributed in Yushu Tibetan Autonomous Prefecture and Guoluo Tibetan Autonomous Prefecture. GeoDetector-based analysis of the driving factors for the spatial stratified heterogeneity of detection of newly diagnosed echinococcosis cases in Qinghai Province showed that average altitude, number of village health centers, number of cattle and sheep stock, GDP per capita, annual average sunshine hours, and annual average temperature had a strong explanatory power for the spatial distribution of newly diagnosed echinococcosis cases, with q values of 0.630, 0.610, 0.600, 0.590, 0.588, 0.537 and 0.526, respectively. Conclusions The detection of newly diagnosed echinococcosis cases appeared a tendency towards a decline in Qinghai Province over years from 2016 to 2022, showing spatial clustering. Targeted control measures are required in cluster areas of newly diagnosed echinococcosis cases for further control of the disease.