Predicting estimated glomerular filtration rate after partial and radical nephrectomy based on split renal function measured by radionuclide: a large-scale retrospective study.

PURPOSE: The purpose of this study was to develop predictive models for postoperative estimated glomerular filtration rate (eGFR) based on the split glomerular filtration rate measured by radionuclide (rGFR), as choosing radical nephrectomy (RN) or partial nephrectomy (PN) for complex renal masses requires accurate prediction of postoperative eGFR. METHODS: Patients who underwent RN or PN for a single renal mass at Xijing Hospital between 2008 and 2022 were retrospectively included. Preoperative split rGFR was evaluated using technetium-99 m-diethylenetriaminepentaacetic acid (Tc-99 m DTPA) renal dynamic imaging, and the postoperative short-term (< 7 days) and long-term (3 months to 5 years) eGFRs were assessed. Linear mixed-effect models were used to predict eGFRs, with marginal R2 reflecting predictive ability. RESULTS: After excluding patients with missing follow-up eGFRs, the data of 2251 (RN: 1286, PN: 965) and 2447 (RN: 1417, PN: 1030) patients were respectively included in the long-term and short-term models. Two models were established to predict long-term eGFRs after RN (marginal R2 = 0.554) and PN (marginal R2 = 0.630), respectively. Two other models were established to predict short-term eGFRs after RN (marginal R2 = 0.692) and PN (marginal R2 = 0.656), respectively. In terms of long-term eGFRs, laparoscopic and robotic surgery were superior to open surgery in both PN and RN. CONCLUSIONS: We developed novel tools for predicting short-term and long-term eGFRs after RN and PN based on split rGFR that can help in preoperative decision-making.

Construction and validation of a novel prognostic nomogram for patients with sarcomatoid renal cell carcinoma: a SEER-based study.

OBJECTIVE: The only one established prognostic nomogram for patients with sarcomatoid renal cell carcinoma (sRCC) was based on a small sample-sized study without external validation, and a nomogram can be applied to western sRCC patients has not yet been developed. Therefore, our study aimed to construct and validate an effective nomogram to predict overall survival (OS) for these patients. METHODS: The independent predictors for OS were identified and the nomogram was constructed on the basis of a retrospective study of a training cohort consisted of 428 non-Hispanic white sRCC patients registered in the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015. Then, the discriminative performance of the nomogram was assessed by the concordance index (C-index). OS calibrations of the nomogram were also performed by comparing the nomogram-predicted probability to the observed survival rate. Furthermore, our nomogram was externally validated using two independent cohorts consisted of 71 non-Hispanic black patients and 82 Hispanic patients, respectively. RESULTS: Age at diagnosis, T stage, N stage, bone metastases, liver metastases, lung metastases and nephrectomy were identified as independent predictors for OS. In the training cohort and two validation cohorts, the C-indexes of the nomogram were 0.737, 0.801 and 0.764, respectively. Besides, excellent agreements between the nomogram prediction and the actual observation were achieved in all cohorts. CONCLUSIONS: The current study constructed and validated an effective prognostic nomogram for patients with sRCC, which can be used to perform accurate predictions of the 0.5-, 1-, and 2-year possibilities of OS.

Landscape of targeted therapies for advanced urothelial carcinoma.

Bladder cancer (BC) is the tenth most common malignancy globally. Urothelial carcinoma (UC) is a major type of BC, and advanced UC (aUC) is associated with poor clinical outcomes and limited survival rates. Current options for aUC treatment mainly include chemotherapy and immunotherapy. These options have moderate efficacy and modest impact on overall survival and thus highlight the need for novel therapeutic approaches. aUC patients harbor a high tumor mutation burden and abundant molecular alterations, which are the basis for targeted therapies. Erdafitinib is currently the only Food and Drug Administration (FDA)-approved targeted therapy for aUC. Many potential targeted therapeutics aiming at other molecular alterations are under investigation. This review summarizes the current understanding of molecular alterations associated with aUC targeted therapy. It also comprehensively discusses the related interventions for treatment in clinical research and the potential of using novel targeted drugs in combination therapy.

Enhancing anti-tumor immune responses through combination therapies: epigenetic drugs and immune checkpoint inhibitors.

Epigenetic mechanisms are processes that affect gene expression and cellular functions without involving changes in the DNA sequence. This abnormal or unstable expression of genes regulated by epigenetics can trigger cancer and other various diseases. The immune cells involved in anti-tumor responses and the immunogenicity of tumors may also be affected by epigenomic changes. This holds significant implications for the development and application of cancer immunotherapy, epigenetic therapy, and their combined treatments in the fight against cancer. We provide an overview of recent research literature focusing on how epigenomic changes in immune cells influence immune cell behavior and function, as well as the immunogenicity of cancer cells. And the combined utilization of epigenetic medications with immune checkpoint inhibitors that focus on immune checkpoint molecules [e.g., Programmed Death 1 (PD-1), Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4), T cell Immunoglobulin and Mucin Domain (TIM-3), Lymphocyte Activation Gene-3 (LAG-3)] present in immune cells and stromal cells associated with tumors. We highlight the potential of small-molecule inhibitors targeting epigenetic regulators to amplify anti-tumor immune responses. Moreover, we discuss how to leverage the intricate relationship between cancer epigenetics and cancer immunology to create treatment regimens that integrate epigenetic therapies with immunotherapies.

Natural Shikonin Potentially Alters Intestinal Flora to Alleviate Acute Inflammation.

Shikonin, derived from the herb Lithospermum erythrorhizon (Purple Cromwell), is extensively utilized in traditional Chinese medicine as an anti-inflammatory agent; however, its effect on the intestinal flora is not yet known. Herein, we demonstrate that, compared to a blank control group, the intragastric administration of shikonin suppressed the swelling rate of ears in a mouse model of acute inflammation in a dose-dependent manner via animal experiments; furthermore, the 20 mg/kg shikonin treatment exhibited the highest inhibitory effect. In formal animal experimentation, we discovered that the inhibitory effect of shikonin with 20 mg/kg on inflammation was closely linked to the intestinal flora, whereby the microbiota phylum was altered in feces through a 16S rDNA sequencing analysis, implying that shikonin improves gut microbiota structures and compositions to counteract inflammation. Notably, using a real-time quantitative polymerase chain reaction (RT-qPCR), a Western blotting assay, and an immunohistochemistry (IHC) assay, we found that inflammatory cytokines such as TNF-α, IL-6, and IL-1ß reduced in both the shikonin-administration group and the positive control group than those in the blank control group, as expected. To the best of our knowledge, this is the first study to outline the underlying mechanism through which shikonin acts on gut microbes to alleviate acute inflammation, providing an alternative mechanism for shikonin to become a preventive agent in countering inflammation.

FBP1 /miR-24-1/enhancer axis activation blocks renal cell carcinoma progression via Warburg effect.

Warburg effect is a pivotal hallmark of cancers and appears prevalently in renal cell carcinoma (RCC). FBP1 plays a negative role in Warburg effect as a rate-limiting enzyme in gluconeogenesis, yet its mechanism in RCC remains to be further characterized. Herein, we revealed that FBP1 was downregulated in RCC tissue samples and was related to the poor survival rate of RCC. Strikingly, miR-24-1 whose DNA locus is overlapped with enhancer region chr9:95084940-95087024 was closely linked with the depletion of FBP1 in RCC. Of note, miRNAs like miR-24-1 whose DNA loci are enriched with H3K27ac and H3K4me1 modifications are belonging to nuclear activating miRNAs (NamiRNAs), which surprisingly upregulate target genes in RCC through enhancer beyond the conventional role of repressing target gene expression. Moreover, miR-24-1 reactivated the expression of FBP1 to suppress Warburg effect in RCC cells, and subsequently inhibited proliferation and metastasis of RCC cells. In mechanism, the activating role of miR-24-1 was dependent on enhancer integrity by dual luciferase reporter assay and CRISPR/Cas9 system. Ultimately, animal assay in vivo validated the suppressive function of FBP1 on 786-O and ACHN cells. Collectively, the current study highlighted that activation of FBP1 by enhancer-overlapped miR-24-1 is capable of contributing to Warburg effect repression through which RCC progression is robustly blocked, providing an alternative mechanism for RCC development and as well implying a potential clue for RCC treatment strategy.

Construction and internal validation of a prediction nomogram for acquired premature ejaculation (APE) in PE patients.

BACKGROUND: A predictive model for acquired premature ejaculation (APE) in PE patients has not yet been established. OBJECTIVES: This study was aimed at determining which factors were independently associated with the possibility of predicting APE in PE patients, and whether an effective pre-treatment nomogram for predicting their individual chances of being APE in PE patients can be developed. MATERIALS AND METHODS: We analyzed the medical histories of 915 PE patients diagnosed at Xijing Hospital (Xi'an, China) and Northwest Women's and Children's Hospital (Xi'an, China) between May 2019 and May 2020. The diagnostic nomogram was developed using a multivariate logistic regression model by integrating selected significant variables determined through univariate analysis. Receiver operating characteristic curves were used to measure the predictive accuracy of the nomogram and its constituted variables, and calibrations were performed by making a comparison of nomogram-predicted probability with actual rate of APE. RESULTS: The independent predictors for APE that were identified include Age, Intra-vaginal Ejaculation Latency Time (IELT), Frequency of sexual desire (FSD), and Eysenck Personality Questionnaire-Revised Short Scale for Chinese (psychoticism) [EPQ-RSC(P)] scores. The predictive accuracy of the nomogram was 0.782 (95% CI: 0.723-0.841). Also, excellent agreement was demonstrated between the nomogram-predicted probability and the actual rate of APE. DISCUSSION AND CONCLUSION: We identified 4 independent predictors for APE and demonstrated the potential significant differences in psychoticism between LPE and APE patients. This was the first internally validated predictive APE nomogram where good discrimination and calibration were applied, and it offers a promising role in clinical practice. More studies are necessary for verification of its universal applicability.

A novel nomogram predicting the risk of positive biopsy for patients in the diagnostic gray area of prostate cancer.

The roles played by several inflammatory factors in screening for prostate cancer (PCa) among gray area patients, namely those with serum prostate-specific antigen (PSA) levels between 4 and 10 ng/ml, have not been completely identified, and few effective diagnostic nomograms have been developed exclusively for these patients. We aimed to investigate new independent predictors of positive biopsy (PB) results and develop a novel diagnostic nomogram for this group of patients. The independent predictors of PB results were identified, and a nomogram was constructed using multivariate logistic regression analysis based on a cohort comprising 401 Gy area patients diagnosed at Xijing Hospital (Xi'an, China) between January 2016 and December 2019. The predictive accuracy of the nomogram was assessed using the receiver operating characteristic curve, and the nomogram was calibrated by comparing the prediction with the observation. The performance of the nomogram was further validated using an independent cohort. Finally, lymphocyte-to-monocyte ratio (LMR) > 4.11 and red blood cell distribution width (RDW)-standard deviation (SD) > 42.9 fl were identified as independent protective predictors of PB results, whereas PSA density (PSAD) > 0.141 was identified as an independent risk predictor. The nomogram established using PSAD, LMR, and RDW-SD was perfectly calibrated, and its predictive accuracy was superior to that of PSAD in both internal and external validations (0.827 vs 0.769 and 0.765 vs 0.713, respectively). This study is the first to report the importance of LMR and RDW-SD in screening for PCa among gray area patients and to construct an exclusive nomogram to predict the individual risk of positive 13-core biopsy results in this group of patients. With superior performance over PSAD, our nomogram will help increase the accuracy of PCa screening, thereby avoiding unnecessary biopsy.

Novel survival nomograms for patients with lung metastatic clear cell renal cell carcinoma: A population-based study.

ABSTRACT: Survival heterogeneity is observed among renal cell carcinoma (RCC) patients with metastases in different organs. Moreover, almost all previous prognostic nomograms based on data from metastatic RCC patients did not take competing events, such as death from cerebrovascular and heart diseases, into account. We aimed to construct novel prognostic nomograms for patients with lung metastatic clear cell RCC (LMCCRCC).Data of 712 non-Hispanic white LMCCRCC patients registered in the Surveillance, Epidemiology, and End Results database were retrospectively analyzed. Nomograms for predicting overall survival (OS) and disease-specific survival (DSS) were established using the Cox approach and Fine and Gray approach, respectively, and their performances were assessed using the concordance index (C-index), calibration plots, and an independent cohort comprising 181 Hispanic patients.Sex, tumor grade, T stage, N stage, presence or absence of bone metastases, and presence or absence of brain metastases were independent predictors for both OS and DSS. Additionally, presence or absence of liver metastases was an independent predictor only for DSS. Meanwhile, age at diagnosis was independently associated with OS. The C-indexes of the nomograms were 0.702 for OS and 0.723 for DSS in internal validation. In external validation, the C-indexes were 0.700 for OS and 0.708 for DSS. Both internal and external calibration plots showed excellent consistency between the prediction and the observation.The current study developed a novel nomogram for predicting individual OS in LMCCRCC patients. Moreover, we constructed an effective competing risk nomogram for predicting their individual DSS for the first time.