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 investigate impacts of soy isoflavones(SIF)on alveolar bone resorption and inflammatory response in periodontitis rats based on Slit homologue 2(Slit2)/P38 mitogen-activated protein kinase(MAPK)signaling pathway.Methods:Rats were separated into Control group,Model group,SIF low-dose group(L-SIF,25 mg/kg)and SIF high-dose group(H-SIF,75 mg/kg),with 10 rats per group,and periodontitis model was established by ligating necks of maxillary first molars of rats with silk thread except for control group.Rats in L-SIF group and H-SIF group were given corresponding doses of SIF by gavage,Control group and Model group were given same amount of normal saline by gavage,once a day,for 4 consecutive weeks.After administration,serum Slit2,TNF-α,IL-6 and IL-1β levels were detected by ELISA;Micro-CT scan was performed to detect distance between cemen-tumenamel junction and alveolar ridge crest(CEJ-ABC),bone mineral density(BMD),bone volume fraction(BV/TV),and alveolar bone loss was evaluated;HE staining and tartrate-resistant acid phosphatase(TRAP)staining were performed to evaluate tissue inflam-mation,bone resorption and osteoclast activity;expressions of osteoprotegerin(OPG)and receptor activator of nuclear factor κB ligand(RANKL)in periodontal tissues were detected by immunohistochemistry(IHC);Western blot was performed to detect protein expressions of Slit2,P38 MAPK and p-P38 MAPK in periodontal tissues.Results:Compared with Control group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,protein level of Slit2 and p-P38 MAPK/P38 MAPK were greatly increased in Model group,BMD,BV/TV and positive ex-pression of periodontal tissues OPG were greatly decreased(all P<0.05);compared with Model group,serum levels of Slit2,TNF-α,IL-1β,IL-6,CEJ-ABC distance,periodontal histopathological damage score,osteoclast number,positive expression of RANKL,pro-tein levels of Slit2 and p-P38 MAPK/P38 MAPK were greatly decreased,BMD,BV/TV and OPG positive expression of periodontal tissues were greatly increased in L-SIF group and H-SIF group(P<0.05),the above indicators in H-SIF group changed greatly better than L-SIF group(P<0.05).Conclusion:SIF can inhibit alveolar bone resorption and inflammatory response in periodontitis rats and improve periodontitis,whose mechanism may be related to inhibition of Slit2/P38 MAPK signaling pathway.

Objective To investigate the status quo of pain crisis in advanced lung cancer patients and analyze its influencing factors.Methods From August to November 2023,318 patients with advanced lung cancer were selected from 6 wards of respiratory department of a tertiary A hospital in Zhengzhou.The Numerical Rating Scale,Perceptive Social Support Scale,Self-rating Anxiety Scale and Self-rating Depression Scale were used to investigate the influencing factors of pain crisis in advanced lung cancer patients by Logistic regression.Results Among 318 patients with advanced lung cancer,102 patients had painful crisis,with the incidence rate of 32.08％.0lder age and high level of social support were protective factors for pain crisis,and bone metastasis,anxiety and mild to moderate depression were risk factors for pain crisis.Conclusion The incidence of pain crisis was high in advanced lung cancer patients.Medical staff should pay attention to those with younger age,bone metastasis,low level of social support,high level of anxiety and mild to moderate level of depression,and take timely intervention measures to reduce the occurrence of pain crisis.

Vascular cognitive impairment is a group of disorders characterized by cognitive dysfunction caused by vascular factors. Disruption of the blood-brain barrier is an early pathophysiological mechanism of vascular cognitive impairment. Dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling-based blood-brain barrier imaging techniques can quantitatively assess the integrity of the blood-brain barrier. In recent years, these techniques have gradually been applied to detect the extent of blood-brain barrier dysfunction. This article provides a comprehensive review of the basic principles of relevant magnetic resonance techniques and the progress made in their application to the assessment of the blood-brain barrier in vascular cognitive impairment.

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 ?

Objective The oxidative damage of DNA can be caused by excessive levels of Reactive oxygen species(ROS).Monitoring of DNA oxidative damage enables effective evaluation of ROS damage effects.Although the detection of DNA damage effects based on microbial sensor allows quantitative analysis of oxidative damage,the ROS clearance mechanism existed in bacterial will affect the sensitive of detection.The work of this article is to knockout the key genes of ROS clearance mechanism and construct an antioxidant gene-knock-out microbial sensor.The microbial sensor can realize sensitive monitoring of DNA damage effects and then evaluates the damage effects of cells by ROS.Methods The antioxidant damage genes of bacterial ahpCF,katE and katG were knocked out by λ-Red homologous recombination and antioxidant gene-knockout microbial sensor was constructed.The nalidixic acid sodium salt and UV irradiation were used to characterize the performance for monitoring of DNA damage effects.Results The antioxidant gene-knockout microbial sensors ΔahpC,ΔahpCF/ΔkatEG and ΔahpCF/ΔkatE/ΔkatG were constructed successfully.The results showed that the microbial sensor ΔahpCF/ΔkatE/ΔkatGl had the highest sensitive of damage effects and the limit of detection for nalidixic acid sodium salt was 0.40 μmol/L.In addition,1.80 min of UV irradiation(254 nm)was sufficient to induce a significant fluorescent expression effect in the engineered bacteria.Conclusion In this article,antioxidant gene-knockout microbial sensors had been constructed to realize active and sensitive monitoring of DNA damage effects such as DNA damage reagents and UV irradiation.The sensors could provide an active,effective,and sensitive potential monitoring method for future evaluation of radiation effects in space.

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.