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: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Objective To evaluate the efficacy and safety of modified pelvic floor reconstruction in non-nerve-sparing robot-assisted radical prostatectomy (NNS RARP) for improving postoperative urinary control. Methods A retrospective analysis was conducted on the clinical data of 79 prostate cancer patients who underwent NNS RARP at Tangdu Hospital during Jan.2020 and Dec.2023, including 29 in the reconstruction group, and 50 in the non-reconstruction group. The baseline characteristics including age, body mass index, prostate-specific antigen (PSA) level, clinical stage, prostate volume, and biopsy Gleason score, and perioperative indexes including operation time, intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins were compared between the two groups. Additionally, urinary continence function was assessed before operation and 1,3,6, and 12 months after operation using the international consultation on incontinence questionnaire-short form (ICIQ-SF) and the incontinence quality of life questionnaire score (I-QoL). Results No statistically significant differences were observed in the baseline characteristics between the two groups (P>0.05). The operation time was significantly longer in the reconstruction group than in the non-reconstruction group [ (110.24±15.08) min vs. (101.80±9.89) min, P=0.010]. There were no significant differences in intraoperative blood loss, catheter indwelling time, complication rate, and positive rate of surgical margins between the two groups (P>0.05). The reconstruction group demonstrated significantly lower ICIQ-SF scores at 1 month [ (10.17±2.16) vs. (11.56±1.66), P=0.002],3 months [ (7.62±1.29) vs. (9.52±1.80), P<0.001], and 6 months postoperatively [ (4.93±1.22) vs. (6.18± 1.67), P=0.001]compared to the non-reconstruction group (adjusted P<0.0125). Conversely, the I-QoL scores were significantly higher in the reconstruction group at 1 month [ (73.32±10.30) vs. (63.88±9.55), P<0.001]and 3 months postoperatively [ (78.91±4.82) vs. (75.66±5.17), P=0.007] (adjusted P<0.0125). However, no significant differences were found in ICIQ-SF or I-QoL scores between the two groups preoperatively and 12 months postoperatively (adjusted P>0.0125). Conclusion The application of modified pelvic floor reconstruction technique in NNS RARP is safe and feasible. Although it slightly prolongs the operation time, it does not increase surgical risks; instead, it effectively promotes early recovery of postoperative urinary continence, thereby significantly enhancing patients'quality of life.

Renal tumor scoring systems can describe the anatomical characteristics of renal tumors. It is an important standard to evaluate the surgical complexity and to evaluate the surgical complexity and feasibility of partial nephrectomy. Scholars at home and abroad have established various scoring systems based on different anatomical parameters，such as R.E.N.A.L.，PADUA，C-Index，which are used to guide the clinical selection of surgical modalities，and predict perioperative complications and prognosis. In this paper，various scoring systems are grouped into three major categories according to their functions：prediction of surgical complexity，prediction of complications，and prediction of prognosis. The contents，characteristics and clinical application value of various renal tumor scoring systems are introduced in detail to guide urologists，enhance their surgical decision-making ability，and improve the clinical outcomes.

Objective To develop models for predicting response to chemotherapy combined with immunotherapy in patients with esophageal squamous carcinoma with various machine learning algorithms,and then select the optimal model.Methods A retrospective study was performed for 174 patients with esophageal squamous cell carcinoma undergoing chemotherapy combined with immunotherapy admitted in Department of Thoracic Surgery of the First Affiliated Hospital of Army Medical University from January 2022 to December 2023.The CT scans and clinical information were collected before treatment.They were randomly divided into a training set(n=122)and a testing set(n=52)in a ratio of 7∶3.CT radiomic features were extracted and selected,and then 5 machine-learning algorithms were employed to establish the prediction models,including radiomics model and clinical-radiomics model.Five-fold cross-validation was conducted on the training set,and the performance of the prediction models was evaluated on the testing set using receiver operating characteristic(ROC)curve and the F1 score.The best-performing model was further explained using local interpretable model-agnostic explanations(LIME)algorithm.Results Among the 174 patients,115(66.1%)achieved clinical remission.From the clinical information and CT images,1 clinical features and 10 radiomic features were identified.The area under of ROC curve(AUC)for the radiomics and clinical-radiomics models was 0.750(95%CI:0.616～0.883),and 0.766(95%CI:0.637～0.895),respectively.The F1 score of the optimal clinical-radiomics model was 0.829.LIME algorithm indicated that this best model demonstrated reliability in predicting individual samples.Conclusion The clinical-radiomics prediction model based on machine learning algorithm performs well,and can provide a reference for doctors'clinical decision-making by predicting the response to chemotherapy combined with immunotherapy in patients with esophageal squamous cell carcinoma.

Objective To evaluate the efficacy of transcatheter arterial chemoembolization(TACE)combined with argon-helium cryoablation(AHC)in the treatment of hypervascular small hepatocellular carcinoma(sHCC).Methods The clinical data of 35 patients with hypervascular sHCC,who received TACE combined with AHC at the Affiliated Cancer Hospital of Zhengzhou University of China from March 2018 to February 2019,were retrospectively analyzed.All patients were treated with TACE treatment first,after 3-7 days the patients received AHC therapy.The postoperative 1-,3-,and 6-month curative effect were evaluated,and the postoperative 1-,3-,and 5-year survival rates were calculated.The liver function and immune function indicators,as well as the serum tumor markers were detected.The adverse reactions during treatment were recorded.Results The postoperative 1-,3-,and 6-month objective remission rate(ORR)were 100.00％,94.29％and 91.43％respectively,and the disease control rate(DCR)were 100.00％,100.00％and 97.14％ respectively.The overall survival(OS)was(46.54±2.88)months,and the postoperative 1-,3-,and 5-year survival rates were 94.29％(33/35),65.71％(23/35)and 48.57％(17/35)respectively.The postoperative 3-day serum levels of ALT,AST and TBIL were significantly elevated when compared with their preoperative baseline levels(all P＜0.05),which returned to preoperative levels in 2 weeks after treatment(P＞0.05).The postoperative 2-week CD4+％and CD4+％/CD8+％ratio were remarkably increased when compared with their preoperative values(both P＜0.05),while the postoperative 2-week AFP,AFP-L3％,DCP and GPC3 levels were strikingly decreased when compared with their preoperative values(all P＜0.001).None of the patients developed procedure-related severe complications after treatment.Conclusion For the treatment of hypervascular sHCC,TACE combined with AHC has satisfactory clinical efficacy and safety.

Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P＜0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P＜0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P＜0.05).α-SMA expression was also increased,while OPN expression was reduced(P＜0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P＜0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P＜0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.

Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P＜0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P＜0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P＜0.05).α-SMA expression was also increased,while OPN expression was reduced(P＜0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P＜0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P＜0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.