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 safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

Traditional Chinese medicine (TCM) represents a paradigmatic approach to personalized medicine, developed through the systematic accumulation and refinement of clinical empirical data over more than 2000 years, and now encompasses large-scale electronic medical records (EMR) and experimental molecular data. Artificial intelligence (AI) has demonstrated its utility in medicine through the development of various expert systems (e.g., MYCIN) since the 1970s. With the emergence of deep learning and large language models (LLMs), AI's potential in medicine shows considerable promise. Consequently, the integration of AI and TCM from both clinical and scientific perspectives presents a fundamental and promising research direction. This survey provides an insightful overview of TCM AI research, summarizing related research tasks from three perspectives: systems-level biological mechanism elucidation, real-world clinical evidence inference, and personalized clinical decision support. The review highlights representative AI methodologies alongside their applications in both TCM scientific inquiry and clinical practice. To critically assess the current state of the field, this work identifies major challenges and opportunities that constrain the development of robust research capabilities-particularly in the mechanistic understanding of TCM syndromes and herbal formulations, novel drug discovery, and the delivery of high-quality, patient-centered clinical care. The findings underscore that future advancements in AI-driven TCM research will rely on the development of high-quality, large-scale data repositories; the construction of comprehensive and domain-specific knowledge graphs (KGs); deeper insights into the biological mechanisms underpinning clinical efficacy; rigorous causal inference frameworks; and intelligent, personalized decision support systems.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Humans ; Precision Medicine ; Decision Support Systems, Clinical

Objective:To compare the diagnostic efficacy of ultrasound and MRI in fibro-adipose vascular anomaly (FAVA).Methods:The clinical data of patients with suspected FAVA who underwent ultrasound and MRI examinations at Henan Provincial People’s Hospital from January 2011 to October 2021 were retrospectively analyzed. The imaging findings from ultrasound and MRI were analyzed, and then compared with the pathological findings. To evaluate the diagnostic efficacy of ultrasound and MRI in diagnosing FAVA by assessing sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate. Paired χ2 test (McNemar test) was used to compare the coincidence rate of ultrasound and MRI, as well as their combined diagnosis. A significance level of P < 0.05 was considered statistically significant. Results:A total of 50 patients were included in the study, comprising 24 males and 26 females, with their ages ranging from 1 to 50 years and an average age of (16.2 ± 10.5) years. Pathology confirmed 43 FAVA patients and 7 non-FAVA patients. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of ultrasound in the diagnosis of FAVA were 83.7%, 71.4%, 94.7%, 41.7%, and 82.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of MRI in the diagnosis of FAVA were 69.8%, 85.7%, 96.8%, 31.6%, and 72.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of FAVA were 90.7%, 71.4%, 95.1%, 55.6%, and 88.0%, respectively. The diagnostic accuracy of ultrasound was higher than that of MRI, but the difference was not statistically significant ( χ2 = 1.41, P = 0.235). The coincidence rate of combined diagnosis was higher than that of ultrasound ( χ2= 0.71, P = 0.401) and MRI ( χ2= 4.00, P = 0.039), with a statistically significant difference. Conclusion:Both ultrasound and MRI are highly valuable in diagnosing FAVA. The combined usage of ultrasound and MRI can enhance the accuracy of preoperative FAVA diagnosis.

Objective:To compare the diagnostic efficacy of ultrasound and MRI in fibro-adipose vascular anomaly (FAVA).Methods:The clinical data of patients with suspected FAVA who underwent ultrasound and MRI examinations at Henan Provincial People’s Hospital from January 2011 to October 2021 were retrospectively analyzed. The imaging findings from ultrasound and MRI were analyzed, and then compared with the pathological findings. To evaluate the diagnostic efficacy of ultrasound and MRI in diagnosing FAVA by assessing sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate. Paired χ2 test (McNemar test) was used to compare the coincidence rate of ultrasound and MRI, as well as their combined diagnosis. A significance level of P < 0.05 was considered statistically significant. Results:A total of 50 patients were included in the study, comprising 24 males and 26 females, with their ages ranging from 1 to 50 years and an average age of (16.2 ± 10.5) years. Pathology confirmed 43 FAVA patients and 7 non-FAVA patients. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of ultrasound in the diagnosis of FAVA were 83.7%, 71.4%, 94.7%, 41.7%, and 82.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of MRI in the diagnosis of FAVA were 69.8%, 85.7%, 96.8%, 31.6%, and 72.0%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and coincidence rate of FAVA were 90.7%, 71.4%, 95.1%, 55.6%, and 88.0%, respectively. The diagnostic accuracy of ultrasound was higher than that of MRI, but the difference was not statistically significant ( χ2 = 1.41, P = 0.235). The coincidence rate of combined diagnosis was higher than that of ultrasound ( χ2= 0.71, P = 0.401) and MRI ( χ2= 4.00, P = 0.039), with a statistically significant difference. Conclusion:Both ultrasound and MRI are highly valuable in diagnosing FAVA. The combined usage of ultrasound and MRI can enhance the accuracy of preoperative FAVA diagnosis.

Objective:To investigate the impact of early blood glucose fluctuations after acute multiple injuries on post-traumatic stress disorder (PTSD).Methods:This study was a case-control study. From March 2022 to March 2023, patients with acute multiple injuries who were admitted to the ICU of the Affiliated Hospital of Xuzhou Medical University were selected. According to whether complicated with traumatic brain injury (TBI), the patients were divided into TBI group and non-TBI group. Early post-traumatic blood glucose fluctuations were observed, including stress-induced hyperglycemia (SIH), initial blood glucose value on admission, blood glucose extreme, short-term glycemic variability (GV) and other related indicators. The 72-hour glucose coefficient of variation (Glu-CV) was used to reflect short-term GV. After 1 month, the PTSD checklist for DSM-5 (PCL-5) was used to assess the patient's symptoms of PTSD. The patients were divided into PTSD group and non-PTSD group according to PCL-5 score ≥38. The differences in short-term glucose fluctuations in each groups were compared; the risk factors of PTSD were analyzed by logistic regression; the receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of related indicators on the incidence of PTSD.Results:159 patients with acute multiple injuries were selected and defined as the TBI group ( n=94) and non-TBI group ( n=65). The incidence of PTSD, PCL-5 scale scores, the incidence of SIH and 72 h Glu-CV in the TBI group were significantly higher than the non-TBI group (all P<0.05). The incidence of SIH and 72 h Glu-CV in the PTSD group were significantly higher than the non-PTSD group (both P<0.05). Multivariate logistic regression analysis showed that 72 h Glu-CV ( OR=1.333, 95% CI: 1.028-1.727, P=0.030) was the independent risk factor for PTSD after acute multiple injuries, and the area under the ROC curve was 0.861 (95% CI: 0.789-0.933, P<0.001), the sensitivity was 62.9% and the specificity was 93.5%. Conclusion:Patients with acute multiple injuries with TBI are more likely to have early glucose fluctuations and develop PTSD, and increased short-term glucose variability is the independent risk factor for PTSD after acute multiple injuries.

Objective To investigate the value of tranexamic acid combined with aspirin,low molecular weight heparin calcium in regulating inflammatory mediators and TEG in blood management of Total knee arthroplast(TKA).Methods 120 elderly patients with TKA in our hospital from January 2020 to October 2022 were randomly divided into group A(n=60)and group B(n=60).They were given tranexamic acid+aspirin and tranexamic acid+low molecular weight heparin calcium,respectively,for 2 weeks.Perioperative indexes,complications[lower limb deep vein thrombosis(DVT),intermuscular vein thrombosis(MCVT),incision infection],blood transfusion rate,adverse reactions(gastrointestinal discomfort,subcutaneous ecchymosis),TEG parameters[coagulation reaction time(R),blood coagulation time(K),maximum amplitude(MA),coagulation angle(α)],inflammatory mediators[soluble CD40 ligand(sCD40L),Toll-like receptor 4(TLR4),tumor necrosis factor(TNF-α)],vascular endothelial injury factors[soluble thromboregulatory protein(sTM),vascular endothelial cell growth factor(VEGF),E-selectin]were compared between the two groups.Results There was no significant difference in the 24 h postoperative drainage volume,latent blood loss,total blood loss,intraoperative blood loss,Hb and HCT levels 72 h after surgery between the two groups(P＞0.05).There was no statistically significant difference in TEG parameters between the two groups,at different time points,and between groups at different time points(P＞0.05);The serum levels of TLR4,sCD40L and TNF-α in group A were lower than those in group B 2 weeks after surgery(P＜0.05).The levels of plasma sTM and serum VEGF and E-selectin in group A were lower than those in group B 2 weeks after surgery(P＜0.05).There was no significant difference in the incidence of deep vein thrombosis(DVT),intermuscular vein thrombosis(MCVT),incision infection and blood transfusion rate between group A and group B(P＞0.05).There was no significant difference in the total incidence of adverse reactions between group A and group B(P＞0.05).Conclusion Compared with the combination of low molecular weight heparin calcium,the combination of tranexamic acid and aspirin can protect vascular endothelium and inhibit inflammatory response.However,both can maintain the patient's coagulation function and avoid massive blood loss or thrombosis.There is no significant difference in safety and effectiveness.

Objective:To evaluate the long-term efficacy of percutaneous microwave ablation (MWA) therapy for hepatocellular carcinoma.Methods:2054 cases with Barcelona Clinic Liver Cancer (BCLC) stage 0~B at the Fifth Medical Center of the Chinese People's Liberation Army General Hospital from January 2006 to September 2020 were retrospectively collected. All patients were followed up for at least 2 years. The primary endpoint of overall survival and secondary endpoints (tumor-related survival, disease-free survival, and postoperative complications) of patients treated with ultrasound-guided percutaneous MWA were analyzed. Kaplan-Meier method was used for stratified survival rate analysis. Fine-and-Gray competing risk model was used to analyze overall survival.Results:A total of 5 503 HCC nodules [mean tumor diameter (2.6±1.6) cm] underwent 3 908 MWAs between January 2006 and September 2020, with a median follow-up time of 45.6 (24.0 -79.2) months.The technical effectiveness rate of 5 375 tumor nodules was 97.5%. The overall survival rates at 5, 10, and 15-years were 61.6%, 38.8%, and 27.0%, respectively. The tumor-specific survival rates were 67.1%, 47.2%, and 37.7%, respectively. The free tumor survival rates were 25.8%, 15.7%, and 9.9%, respectively. The incidence rate of severe complications was 2.8% (108/3 908). Further analysis showed that the technical effectiveness and survival rate over the passing three time periods from January 2006-2010, 2011-2015, and 2016-September 2020 were significantly increased, with P ?

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.