Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

OBJECTIVE To explore the effect of fluconazole on proteomics of Trichosporon asahii so as to reveal the responding process of T.asahii to fluconazole stress and the resistance mechanisms to azoles on the protein level.METHODS T.asahii AS 2.2174 was chosen as the research subject,the minimum inhibitory concentration(MIC)of fluconazole was determined by broth microdilution assay.The protein abundance of T.asahii was detec-ted by means of tandem mass tag(TMT)technique combined with liquid chromatography-tandem mass spectrom-etry(LC-MS/MS)before and after the treatment with fluconazole(1× MIC).The differentially expressed pro-teins(DEPs)were identified based on the screening standards of fold change ≥1.20 or ≤0.83 and P＜0.05.Gene ontlogy(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed for the DEPs so as to understand the biological property of the DEPs and the major biological pathways that the DEPs in-volved in.Finally,the targeted validation was carried out for the targeted differentially expressed proteins by using multiple reaction monitoring(MRM).RESULTS The MIC of fluconazole to T.asahii AS 2.2174 was 8 μg/ml.Totally 196 DEPs were identified,including 93 upregulated DEPs and 103 downregulated DEPs.The function en-richment analysis showed that the DEPs mainly participated in synthesis and metabolism of sterols,drug metabo-lism,stress response,energy metabolism and intertranslation.The targeted DEPs showed the consistent expres-sion trends in MRM target validation and TMT-LC-MS/MS.CONCLUSIONS The protein abundance of T.asahii has remarkable change under the fluconazole stress.The bioinformatics analysis reveals the complicated molecular mechanisms of T.asahii in response to the fluconazole stress,which may offer valuable ideas for understanding the drug resistance to azoles and developing new drug targets.

Objective To explore the relationship among sleep quality, fatigue and work-related musculoskeletal disorders (WMSDs) in firefighters, and to examine the mediating effect of fatigue between sleep quality and the risk of WMSDs. Methods A total of 271 firefighters from three prefecture-level cities in Jiangsu Province were selected as the study subjects by a convenient sampling method. The Chinese Musculoskeletal Disorders Questionnaire, Pittsburgh Sleep Quality Index (PSQI), and Fatigue Scale-14 were used to assess WMSDs, sleep quality and fatigue status among the study subjects. The effect of sleep quality and fatigue on WMSDs was analyzed, as well as the mediating role of fatigue between sleep quality and the risk of WMSDs. Results The annual prevalence of WMSDs among the firefighters was 68.6%. The firefighters who had poor and very poor sleep quality accounted for 36.2% and 7.7%, respectively. There were 88.6% of firefighters reported fatigue. The total scores of PSQI and fatigue of firefighters in WMSDs group were higher than those in non-WMSDs group (all P<0.01). Binary logistic regression analysis showed that the higher the total score of PSQI, the worse the sleep quality, and the higher the risk of WMSDs in firefighters (all P<0.01). The higher the total score of fatigue, the higher the risk of WMSDs (P<0.01), and the risk of WMSDs in the fatigue group was higher than that in the non-fatigue group among the firefighters (P<0.01). The direct effect of sleep quality on WMSDs in firefighters was 0.028 [95% confidence interval (CI): 0.012-0.050, P<0.01], and its indirect effect on WMSDs mediated by fatigue was 0.027 (95%CI: 0.018-0.040, P<0.01). Fatigue played a mediating role in sleep quality and WMSDs, with the mediating ratio of 0.491 (95%CI: 0.304-0.740, P<0.01). Conclusion Poor sleep quality and fatigue are related to an increased risk of WMSDs in firefighters in a dose-response manner. Fatigue plays a mediating role between sleep quality and the risk of WMSDs.

Porcine hemagglutinating encephalomyelitis virus(PHEV)is one of the coronaviruses susceptible to swine populations.The non-structural protein 2(NS2)encoded by its genome is fre-quently deleted during the epidemic transmission of the virus,but its biological significance re-mains unclear.In order to explore the structure and function of the NS2 protein,this study utilized platforms such as ProtParam,TMHMM,NetPhos3.1,and ExPASy to analyze its physicochemical properties,spatial structure,genetic evolution,and post-translational modification characteristics.Meanwhile,the NS2 protein was expressed in eukaryotes and transcriptome sequencing was per-formed to clarify the biological processes it participates in.The results showed that the NS2 protein consists of 233 amino acids,with a molecular weight of 26.735 kDa,and a half-life of approximately 30 hours in mammals.It includes 13 phosphorylation sites,2 N-glycosylation sites,and 1 O-glyco-sylation site,with no signal peptide and strong hydrophilicity.The a-helix accounts for the highest proportion in NS2(43.78％),followed by random coils(36.05％).The homology of the NS2 pro-tein between the epidemic strains PHEV-CC14 and PHEV-JL/2008 in Northeast China is 99.57％.The NS2 protein is widely involved in the regulation of nerve-related functions,such as axon guid-ance and synaptic development.This study preliminarily clarified the biological function of the NS2 protein,providing a new perspective for understanding the pathogenic mechanism of PHEV.

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the SPSS 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.
Humans ; Hip Fractures/diagnostic imaging* ; Orthopedic Surgeons ; Algorithms ; Artificial Intelligence

Objective:To observe the clinical effect of urokinase along the pipeline under offline status to dissolve dialyzer microthrombus in patients undergoing continuous renal replacement therapy (CRRT).Methods:A prospective research method was adopted. A total of 248 CRRT patients with dialyzer microthrombus in Sinopharm-Gezhouba Central Hospital from January 2017 to December 2021 were selected. The patients were divided into experimental group (continued CRRT treatment after urokinase along the pipeline under offline status to dissolve dialyzer microthrombus) and control group (continued CRRT treatment after dialyzer replacement) by random number table method with 124 cases in each group. The baseline data were recorded, including gender, age, primary disease, hemoglobin, platelet count, hematocrit, plasma albumin, D-dimer, fibrinogen, anticoagulant method and symptoms associated with dialyzer microthrombus. The blood indexes were detected before and after treatment of microthrombus, and the symptom scores were performed. The blood indexes included creatinine, urea nitrogen, β 2 microglobulin (β 2-MG), international normalized ratio (INR), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); and the symptom scores included acute physiology and chronic health status score Ⅱ (APACHE Ⅱ) and (APACHE Ⅱ) and sequential organ failure score. The initial transmembrane pressure, transmembrane pressure before disembarkation, CRRT treatment extension time and coagulation classification were recorded. In experimental group, the blood coagulation function indexes before and after treatment were detected, including prothrombin time (PT), activated partial prothrombin time (APTT), thrombin time (TT) and fibrinogen (Fib). The adverse reactions were recorded, including black stools, arrhythmias and wound bleeding. Results:There were no statistical differences in baseline data, initial transmembrane pressure, transmembrane pressure before disembarkation, CRRT treatment extension time and coagulation classification between two groups ( P>0.05). There were no statistical differences in creatinine, urea nitrogen, β 2-MG, INR, hs-CRP, IL-6, TNF-α, APACHE Ⅱ and SOFA before treatment between two groups ( P>0.05); after treatment, the indexes in both groups were significantly lower than before treatment, and the indexes in experimental group were significantly lower than those in control group: (179.1 ± 41.2) μmol/L vs. (187.1 ± 53.9) μmol/L, (7.3 ± 2.8) mmol/L vs. (9.3 ± 2.5) mmol/L, (2.5 ± 0.6) mg/L vs. (4.2 ± 0.7) mg/L, 1.0 ± 0.3 vs. 1.8 ± 0.5, (8.7 ± 1.1) mg/L vs. (10.6 ± 2.4) mg/L, (21.5 ± 12.7) ng/L vs. (29.5 ± 10.3) ng/L, (20.2 ± 6.1) ng/L vs. (26.6 ± 7.2) ng/L, (12.1 ± 6.9) scores vs. (17.2 ± 5.2) scores and (5.9 ± 1.8) scores vs. (6.8 ± 1.9) scores, and there were statistical differences ( P<0.05). In experimental group, there were no statistical differences in PT, APTT, TT and Fib between before treatment and after treatment ( P>0.05). The incidence of adverse reactions in experimental group was significantly lower than that in control group: 4.03%(5/124) vs. 12.90%(16/124), and there was statistical difference ( χ2 = 6.30, P<0.05). Conclusions:The urokinase along the pipeline under offline status to dissolve dialyzer microthrombus in patients undergoing CRRT is safer, cheaper and more efficient. It can improve the biocompatibility of tissue with dialyzer and pipe, prolong the use time of the dialyzer, and complete renal replacement therapy.

Objective To carry out quality inspection of the ultrasound soft tissue cutting hemostatic equipment to ensure its safety and effectiveness.Methods Five brands of ultrasound soft tissue cutting hemostatic equipment were selected and noted as test equipment A,test equipment B,test equipment C,test equipment D and test equipment E,which underwent quality inspection in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current based on YY/T 0644-2008 Ultrasonics-surgical systems—Measurement and declaration of the basic output characteristics,YY/T 1750-2020 Ultrasonic surgical equipmetn for soft tissue excision and hemostasia and GB 9706.1-2020 Medical electrical equipment—Part 1:General requirements for basic safety and essential performance.Results The test data of the five brands in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current met the technical requirements of YY/T 0644-2008,YY/T 1750-2020,GB 9706.1-2020.Conclusion The quality inspection of the ultrasound soft tissue cutting hemostatic equipment contributes to enhancing the accuracy and stability of the equipment and decreasing the risk during its clinical application.[Chinese Medical Equipment Journal,2025,46(10):49-53]

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Abstract Prenatal stress is a common, systemic, nonspecific stress response that occurs during pregnancy. The gut microbiota, which is known as the “second genome” of the human body, interacts with all major systems of the body. Changes in the gut microbiota can impact the development and health of infants and young children. Advances in research technology have allowed us to uncover the relationship between prenatal stress and imbalances in offspring intestinal microbiota, as well as the development of multiple systemic diseases. However, the exact mechanisms through which prenatal stress disrupts the gut microbiota of offspring remain incompletely understood. This review summarizes the existing research on diseases caused by prenatal stress disrupting the offspring intestinal flora, and seeks future research directions to expand the understanding of the pathogenesis of infant diseases.