Background: Immunotherapy is a new and powerful weapon against tumors, represented by inhibitors of programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated protein-4 (CTLA-4). This study aimed to determine the similarities and differences between PD-1 and CTLA-4 in 33 cancers in The Cancer Genome Atlas (TCGA) and the impact of subtypes of the immune environment on tumor production and treatment.Methods: From the Xena browser, we downloaded TNM stage, immune subtypes, and tumor microenvironment scores for 33 tumors from TCGA. Expression of CTLA-4 and PD-1 in normal and tumor samples were compared for various tumors with normal tissue sample sizes greater than five. The relationship between expression and overall survival was investigated using one-way Cox analysis. The immune scores of 33 tumors were assessed using ESTIMATE prediction software to predict the degree of immune cell infiltration across tumors and calculate the correlation between PD-1 and CTLA-4 expression with the tumor microenvironment and tumor stem cells. We also examined the correlation between genes and drug sensitivity.Results: PD-1 and CTLA-4 were highly expressed in breast invasive carcinoma (BRCA), cholangiocarcinoma (CHOL), esophageal carcinoma (ESCA), and kidney renal clear cell carcinoma (KIRC) (P<0.05), highly correlated with immune subtypes C2 (IFN-γ-dominant) and C6 (TGF-β-dominant), and positively correlated with tumor microenvironmental immune scores (P<0.05). In renal clear cell carcinoma, PD-1 and CTLA-4 expression was positively correlated with clinical stage and microenvironmental score (r>0.7, P<0.05). Conclusions:The finding that PD1 and CTLA-4 are associated with the prognosis of most tumour patients and are closely related to the tumour microenvironment is of great value and provides a research direction for the screening of populations benefiting from immunotherapy.

Purpose This study aimed to combine plasma netrin-1 and clinical parameters to construct a diagnostic model for bladder pain syndrome/interstitial cystitis (BPS/IC). Methods We analyzed the independent diagnostic value of netrin-1 and the correlation with clinical symptom scores of BPS/IC. Clinical parameters were selected using LASSO regression, and a multivariate logistic regression model based on netrin-1 was established, and then a nomogram of BPS/IC prevalence was constructed. The nomogram was evaluated using calibration curves, the C-index, and decision curve analysis (DCA). Finally, the model was validated using an internal validation method. Results The area under the curve for the ability of netrin-1 to independently predict BPS/IC diagnosis was 0.858 (p < 0.001), with a sensitivity of 85% and specificity of 82%. The predicted nomogram included three variables: age, CD3 + /CD4 + T lymphocyte ratio, and netrin-1. The C-index of this nomogram was 0.882, and the predicted values were highly consistent with the actual results in the calibration curve. In addition, the internally validated C-index of 0.870 confirms the high reliability of the model. DCA results show that the net patient benefit of the netrin-1 combined with other clinical parameters was higher than that of the single netrin-1 model. Conclusion Netrin-1 can be used as a diagnostic marker for BPS/IC and is associated with pain. The nomogram constructed by combining netrin-1 and clinical parameters was able to predict BPS/IC with great accuracy. In addition, Netrin-1 may also serve as a novel therapeutic target for BPS/IC.

This study explored a new model of Prostate Imaging Reporting and Data System (PIRADS) and adjusted prostate-specific antigen density of peripheral zone (aPSADPZ) for predicting the occurrence of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The demographic and clinical characteristics of 853 patients were recorded. Prostate-specific antigen (PSA), PSA density (PSAD), PSAD of peripheral zone (PSADPZ), aPSADPZ, and peripheral zone volume ratio (PZ-ratio) were calculated and subjected to receiver operating characteristic (ROC) curve analysis. The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve (AUC). The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves. The AUCs of PSA, PSAD, PSADPZ, aPSADPZ, and PZ-ratio were 0.669, 0.762, 0.659, 0.812, and 0.748 for PCa diagnosis, while 0.713, 0.788, 0.694, 0.828, and 0.735 for csPCa diagnosis, respectively. All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa. The new model significantly improved the diagnostic accuracy of PCa (0.945 vs 0.830, P < 0.01) and csPCa (0.937 vs 0.845, P < 0.01) compared with the base model. In addition, the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold. This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators. Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

Objective: The primary purpose of this study is to evaluate the efficacy and safety of low-dose amitriptyline therapy on symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). Patients and Methods: Between September 2015 and December 2016, 102 patients with IC/BPS received low-dose amitriptyline therapy (25 mg/d, before bedtime) at a 12-week course. The outcome measures used were IC symptom index and IC problem index (ICSI/ICPI), 24-h frequencyvolume chart, and visual analog scale (VAS), which were completed before and 4 and 12 weeks after amitriptyline treatment. Results: A total of 89 patients (mean age of 61.9 years) with IC/BPS were recruited in this low-dose amitriptyline therapy study. The response rate was 66.3% (89 patients). Compared with baseline, the various IC symptoms improved significantly. Comparing values before treatment and 4 and 12 weeks after treatment (baseline vs. 4 weeks-baseline vs. 12 weeks), the rates of improvement were as follows: ICSI -38.42%-49.61%, ICPI -45.04%-53.20%, 24-h frequency -45.54%-50.83%, VAS -41.18%-70.01%, and function bladder volume -+139 ml-+122 ml, which showed statistically significant differences (P < 0.05). However, comparing values at 4 and 12 weeks after treatment (4 weeks vs. 12 weeks), only VAS and urgency showed a statistically significant decrease (P < 0.05). Side effects occurred in 72 patients (80.90%), primarily including mouth dryness (66.30%) and drowsiness (49.44%). Conclusion: Low-dose amitriptyline therapy is a feasible, effective, and safe treatment for the subgroup of patients with IC/BPS in a short term.