T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Objective:To investigate the diagnostic efficacy of time-dependent diffusion MRI (t d-dMRI)-derived microstructural parameters for clinically significant prostate cancer (csPCa) and their associations with the pathological grade of prostate cancer(PCa) based on the International Society of Urological Pathology (ISUP) grades. Methods:This cross-sectional study prospectively enrolled 196 patients suspected of PCa from March 2023 to March 2024 at the First Affiliated Hospital, Sun Yat-Sen University. All patients underwent multiparametric MRI and t d-dMRI to obtain microstructural parameters, including cell diameter (d), intracellular volume fraction (f in), extracellular diffusion coefficient (D ex), cellularity, and apparent diffusion coefficient (ADC) value at oscillation frequencies of 33 Hz, 17 Hz, 0 Hz (ADC 33, ADC 17, and ADC 0). Pathologically, 95 cases were classified as csPCa (ISUP 2-5), and the rest 101 cases were classified as non-csPCa (benign or ISUP 1). Comparison of these microstructural metrics was made between csPCa and non-csPCa groups by independent t-tests or Mann-Whitney U tests, and multivariable logistic regression was used to identify independent predictors. A combined diagnostic model was then constructed based on the independent predictors. The receiver operating characteristic curve analysis was used to evaluate the diagnostic performance. Finally, in PCa, the correlation between microstructural parameters and ISUP grades was investigated by Spearman correlation. Results:The t d-dMRI measurements, including d, f in, cellularity, ADC 33,ADC 17 and ADC 0, were significantly different between csPCa and non-csPCa groups (All P<0.05). But D ex was not significantly different between the two groups ( Z=-1.27, P=0.204). The area under the receiver operating characteristic curve (AUC) for diagnosing csPCa were 0.701 (95% CI 0.628-0.775) for d, 0.869 (95% CI 0.819-0.920) for f in, 0.884 (95% CI 0.835-0.932) for cellularity, 0.777 (95% CI 0.712-0.842) for ADC 33, 0.852 (95% CI 0.799-0.905) for ADC 17, and 0.840 (95% CI 0.786-0.894) for ADC 0. Cellularity ( OR=6.142, 95% CI 2.920-12.929, P<0.001) and ADC 17 ( OR=0.108, 95% CI 0.027-0.429, P=0.002) were identified as the independent predictors, and their combined model achieved an AUC of 0.896 (95% CI 0.852-0.941). In PCa f in and cellularity were positively correlated with ISUP grades ( r=0.490 and 0.397, P<0.001), while ADC 33, ADC 17, and ADC 0 were negatively correlated with ISUP grades ( r=-0.198, -0.345, -0.360; P=0.041,<0.001,<0.001). d and D ex were not correlated with ISUP grades ( P>0.05). Conclusion:t d-dMRI based microstructural mapping correlates with ISUP grades of PCa and may be useful for the differential diagnosis of csPCa.

Objective:To summarize the drug resistance characteristics of clinical pathogen isolates in a tuberculosis specialized hospital from 2017 to 2023，and understand the distribution characterisitics of pathogens and their resistance to antimicrobial agents.Methods:The isolates from January 2017 to December 2023 were identified and subjected to drug susceptibility tests using the VITEK 2-compact system. The susceptibilities of the isolates to antimicrobial agents were determined by the minimum inhibitory concentration（MIC）methods according to the CLSI（2023）guideline. The data of detection of different kinds of bacteria，specimen distribution and the detection rates of major drug-resistant gram-negative bacteria in hospital antimicrobial resistance were analyzed. Chi square test were performed to analyze one or more sets of data related to detection rate or drug resistance rate by SPSS 17.0.Results:A total of 9 993 isolates were detected，among which 9 079（90.9%）were gram-negative bacteria and 914（9.1%）were gram-positive bacteria. From 2017 to 2022，among all gram-negative isolates，the top three most frequently isolated pathogens were Klebsiella pneumonia，followed by Pseudomonas aeruginosa and Acinetobacter baumannii. The overall resistance rates to carbapenems in Acinetobacter baumannii， Pseudomonas aeruginosa， Klebsiella pneumonia，and Escherichia coli were 43.7%（495/1 133），19.4%（276/1 423），8.4%（279/3 304），3.6%（19/521），respectively. The overall detection rates of ceftriaxone/ciprofloxacin-resistant Klebsiella pneumonia（CTX/CRO-R-KPN），or Escherichia coli（CTX/CRO-R-ECO），and quinolone-resistant Escherichia coli（QNR-ECO）were 19.5%（644/3 304），57.6%（300/521），77.4%（403/521），respectively. The difference in resistance rates between imipenem-resistant and imipenem-susceptible Klebsiella pneumoniae was statistically significant（ P<0.05）. Except for CTX/CRO-R-ECO（ χ2=7.9 ，P>0.05），significant differences were observed in the detection rates of other major drug-resistant gram-negative bacteria in hospital（ P<0.05）. The detection of some drug-resistant strains showed an upward trend in recent years. Carbapenem-resistant Acinetobacter baumannii， Pseudomonas aeruginosa，and Escherichia coli exhibited higher resistance rate to other antibiotics. Conclusions:The detection rates of major drug-resistant gram-negative bacteria have increased in the past two years. Carbapenem-resistant strains exhibit relatively high resistance rate to cephalosporin and quinolone antibiotics. Although carbapenem antibiotics remain effective against Enterobacteriaceae，strengthened antimicrobial resistance monitoring and control of multidrug-resistant bacteria spread are necessary.

Objective:To analyze the clinical characteristics of the Chikungunya fever outbreak in Shunde District, Foshan City, Guangdong Province in July 2025 and the risk factors associated with delayed viral RNA clearance.Methods:A total of 562 patients with Chikungunya fever admitted to three designated hospitals in Shunde District from July 10 to 30, 2025 were enrolled. Demographic data, clinical manifestations, and laboratory findings were collected. Patients were categorized into four age groups including minors (<18 years), young adults (18 to 39 years), middle-aged adults (40 to 64 years) and elderly adults (≥65 years). The differences of clinical characteristics among these age groups were analyzed. Intergroup comparisons were performed using chi-square test, one-way analysis of variance, or Kruskal-Wallis H test. Pairwise comparisons between groups were conducted using the Bonferroni or Games-Howell or Dunn method. Binary logistic regression was employed to analyze risk factors associated with delayed viral RNA clearance (>7 days). Results:The mean age of the 562 enrolled Chikungunya fever patients was (44.8±21.3) years. Fever, arthralgia and rash were the three core symptoms, with incidence rates of 87.5% (492/562), 88.4%(497/562) and 69.6%(391/562), respectively. At discharge, only 54.1%(304/562) of patients achieved complete symptom resolution, while 26.5%(149/562) still had arthralgia and 36.1%(203/562) had residual rash. Significant differences were observed among age groups in the incidence of fever ( χ2=9.43, P=0.024), peak body temperature ( F=6.54, P<0.001), incidence of arthralgia ( χ2=26.89, P<0.001), duration of arthralgia ( F=12.68, P=0.001), incidence of rash ( χ2=68.99, P<0.001), rate of residual rash at discharge ( χ2=32.37, P<0.001), lymphocyte count ( F=12.94, P<0.001), platelet count ( F=14.95, P<0.001), and C-reactive protein levels (CRP) ( H=94.18, P<0.001). Further pairwise comparisons revealed that compared to the middle-aged and elderly groups, the minor group had a higher incidence of fever and a lower incidence of arthralgia, and the duration of arthralgia was shorter than the elderly group (all P<0.008 3). Compared with the other three groups, the elderly group had lower incidence and residual rate of rash, and lower platelet counts (all P<0.008 3), and higher levels of CRP (all P<0.05). The elderly group had lower lymphocyte counts compared to the minor and young adult groups (both P<0.05). Significant differences were found among age groups in the time to viral RNA clearance ( F=5.77, P=0.003) and length of hospital stay ( F=11.64, P<0.001), with the elderly group having significantly longer duration for both compared to the other three groups (all P<0.05). Multivariate analysis showed that advanced age (odds ratio ( OR)=1.049, 95% confidence interval ( CI) 1.015 to 1.083), longer duration of fever ( OR=1.529, 95% CI 1.086 to 2.155) and longer duration of arthralgia ( OR=1.927, 95% CI 1.318 to 2.817) were independent risk factors for delayed viral RNA clearance (all P<0.05). Conclusions:Patients with Chikungunya fever in Shunde District primarily present with fever, arthralgia and rash. The incidence and characteristics of these three core symptoms show age-related variations. Elderly patients and those with longer durations of fever or arthralgia are more likely to experience delayed viral clearance.

The early diagnosis rate of esophageal cancer is low, and most of the patients are already in the middle or late stage when diagnosed, making treatment difficult, shortening the survival period and resulting in an extremely poor prognosis. In recent years, the continuous development of targeted therapy and immunotherapy has significantly improved the survival rate and therapeutic effect of esophageal cancer patients. Analyzing the research progress of targeted therapy and immunotherapy for esophageal cancer is of great significance and can provide reference for guiding the treatment of esophageal cancer.

Theory and technology of Medical Immunology are widely used in scientific research.Our teaching and research group uses experimental teaching of Medical Immunology as a platform to carry out practice of scientific research project-based experi-mental system among"5+3"integration students.By completing a mini-project research including experimental design-experimental operation-research article writing,students cultivated scientific research thinking and exercised scientific research practice ability,and generally reported that the course is very difficult,but after completing it,it is very rewarding.

Purpose To investigate the value of automated segmentation technique for quantitative study of the volume of each subregion of medial temporal lobe epilepsy(MTLE)with hippocampal sclerosis(HS).Materials and Methods A total of 37 patients with unilateral HS diagnosed by MRI or pathologically confirmed in General Hospital of Ningxia Medical University from January 2021 to May 2023 were prospectively included,including 24 cases of left-sided HS(L-HS)and 13 cases of right-sided HS(R-HS),and 42 healthy volunteers matched in gender and age during the same period were included as a control group.All subjects underwent T1-weighted equal voxel three-dimensional magnetisation-prepared rapid gradient-echo(3D T1 MP-RAGE)scanning.3D T1 MP-RAGE was post-processed by Freesurfer V7 to obtain volume data of the hippocampus and its subregions.The volume data were normalized and the volume asymmetry index was calculated.Within-group and between-group comparisons were performed for standardized volumes of the hippocampus and its subregions,and between-group comparisons were performed for volume asymmetry index values.The diagnostic efficacy of the two indices was assessed and compared using the subject operating characteristic curve and area under the curve.Results The volumes of the hippocampus and its subregions on the affected side were smaller than those on the contralateral side in both the L-HS and R-HS groups,and the volumes of the left hippocampus and its subregions were smaller than those on the right side in the control group,and the differences were statistically significant(t/Z=-15.159-8.324,all P＜0.05).The volumes of the left side of the hippocampus and its subregions in the L-HS group were smaller than those of the left hippocampus and its subregions in the R-HS group and in the control group,and the volumes of the right side of the hippocampus and its subregions in the R-HS group were smaller than those of the L-HS group and the right hippocampus and its subregions of the control group,and the differences were statistically significant(P＜0.05).The differences in the volumes of the right side of the L-HS group and the left side of the R-HS group and the corresponding side of the control group were not statistically significant(P＞0.05).The differences in the volume asymmetry index values of the L-HS group compared with those of the R-HS group and the control group,and those of the R-HS group compared with those of the control group were all statistically significant(P＜0.05).Except for the diagnostic efficacy of volume asymmetry index values of the hippocampus and subiculum in the L-HS group,which was better than that of the volume,and the difference was statistically significant(Z=2.035,1.989,both P＜0.05),the comparison of the volume and volume asymmetry index values of each volume and volume asymmetry index value of the rest of the hippocampus and subregion was not statistically significant(P＞0.05).Conclusion The automatic segmentation technique is of great value for the quantitative study of hippocampus and its subregion volume in MTLE-HS,which can provide more accurate imaging reference for clinical practice.