Effect of chemotherapy on prognosis in patients with primary pancreatic signet ring cell carcinoma: A large real-world study based on machine learning.

BACKGROUND: Primary pancreatic signet ring cell carcinoma (PSRCC), an extremely rare histologic variant of pancreatic cancer, has a poor prognosis. This study aimed to investigate the prognostic value of chemotherapy in PSRCC. METHODS: Patients with PSRCC between 2000 and 2019 were identified using the Surveillance Epidemiology and End Results (SEER) database. The main outcomes in this study were cancer-specific survival (CSS) and overall survival (OS). The baseline characteristics of patients were compared using Pearson's Chi-square test. Kaplan-Meier analysis was used to generate the survival curves. Least absolute shrinkage and selection operator (LASSO), univariate and multivariate Cox regression models, and Random Survival Forest model were used to analyze the prognostic variables for OS and CSS. The variance inflation factors (VIFs) were used to analyze whether there was an overfitting problem. RESULTS: A total of 588 patients were identified. Chemotherapy was an independent prognostic factor for OS and CSS, and significantly associated with OS (HR = 0.33, 95% CI = 0.27-0.40, P <0.001) and CSS (HR = 0.32, 95% CI = 0.26-0.39, P <0.001). CONCLUSIONS: Chemotherapy showed beneficial effects on OS and CSS in patients with PSRCC and should be recommended in clinical practice.

LncRNA TYMSOS is a novel prognostic biomarker associated with immune infiltration in prostate cancer.

The long noncoding RNA thymidylate synthetase opposite strand (lncRNA TYMSOS) plays an important role in cancers; however, its impact on prostate cancer (PCa) is still unclear. By analyzing the online data, we found that lncRNA TYMSOS was highly expressed in PCa and associated with T stage, Gleason score, age, and primary therapy outcome. The results of the ROC curve showed that lncRNA TYMSOS has a significant diagnostic ability. Furthermore, Kaplan-Meier analyses suggested that lncRNA TYMSOS plays an important role in progression-free survival (PFS). Increased lncRNA TYMSOS expression was an independent risk factor correlated with PFS in PCa patients. GSEA and GSVA indicated that the lncRNA TYMSOS was involved in the cell cycle, neurodegenerative diseases, oxidative phosphorylation, spliceosomes, and adaptive immune system pathways. Additionally, lncRNA TYMSOS expression was also associated with immune cell infiltrates and tumor mutational burden in PCa. Functional experiments were further conducted, and we verified that lncRNA TYMSOS played an oncogenic role in regulating PCa aggressiveness. Specifically, silencing of lncRNA TYMSOS suppressed cell proliferation, division and epithelial-mesenchymal transition (EMT) but promoted cell apoptosis in PCa cells, and conversely, lncRNA TYMSOS overexpression had the opposite effects. In summary, our study revealed that the lncRNA TYMSOS could be a biomarker and therapeutic target in PCa and participate in tumor-immune cell infiltration.

Chrysophanol ameliorates oxidative stress and pyroptosis in mice with diabetic nephropathy through the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling pathway.

Diabetic nephropathy (DN), a microvascular complication of diabetes, increases the risk of all-cause diabetes and cardiovascular mortalities. Moreover, oxidative stress and pyroptosis play important roles in the pathogenesis of DN. Rhubarb is widely used in traditional medicine, and chrysophanol (Chr), a free anthraquinone compound abundant in rhubarb, exhibits potent antioxidant properties and ameliorates renal fibrosis. Therefore, this study aimed to investigate the effects of Chr on renal injury, oxidative stress, and pyroptosis in mice with DN. A DN model was established by feeding the mice a high-sugar and fat diet and injecting them with 50 mg/kg streptozotocin as a positive control. The DN mice had significantly impaired renal function, thickened glomerular thylakoids and basement membranes, increased fibrous tissue, and inflammatory cell infiltration. Superoxide dismutase (SOD) levels were reduced, malondialdehyde (MDA) levels were increased, interleukin (IL)-1ß and IL-18 increased, and cleaved caspase-1, caspase-1, and gasdermin D (GSDMD) involved in the process of pyroptosis were upregulated in DN. Kelch-like ECH-associated protein 1 (Keap1) expression was upregulated, and nuclear factor erythroid 2-related factor 2 (Nrf2) expression was downregulated. Compared to those in the DN group, the Chr-treated mice with DN had improved renal dysfunction, weakened glomerular thylakoid and basement membrane thickening, and reduced fibrous tissue proliferation and inflammatory cell infiltration. Additionally, Chr increased SOD levels, decreased MDA, IL-1ß, and IL-18, down-regulated caspase-1, cleaved caspase-1, GSDMD, and Keap1 expression, and upregulated Nrf2 expression, which reversed the DN. Therefore, Chr reduced oxidative stress and pyroptosis in DNmice by activating the Keap1/Nrf2 pathway.

Development and validation of a multivariate model for predicting heart failure hospitalization and mortality in patients receiving maintenance hemodialysis.

BACKGROUND: Heart failure (HF) in patients undergoing maintenance hemodialysis (MHD) increases their hospitalization rates, mortality, and economic burden significantly. We aimed to develop and validate a predictive model utilizing contemporary deep phenotyping for individual risk assessment of all-cause mortality or HF hospitalization in patients on MHD. MATERIALS AND METHODS: A retrospective review was conducted from January 2017 to October 2022, including 348 patients receiving MHD from four centers. The variables were adjusted by Cox regression analysis, and the clinical prediction model was constructed and verified. RESULTS: The median follow-up durations were 14 months (interquartile range [IQR] 9-21) for the modeling set and 14 months (9-20) for the validation set. The composite outcome occurred in 72 (29.63%) of 243 patients in the modeling set and 39 (37.14%) of 105 patients in the validation set. The model predictors included age, albumin, history of cerebral hemorrhage, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/"sacubitril/valsartan", left ventricular ejection fraction, urea reduction ratio, N-terminal prohormone of brain natriuretic peptide, and right atrial size. The C-index was 0.834 (95% CI 0.784-0.883) for the modeling set and 0.853 (0.798, 0.908) for the validation set. The model exhibited excellent calibration across the complete risk profile, and the decision curve analysis (DCA) suggested its ability to maximize patient benefits. CONCLUSION: The developed prediction model offered an accurate and personalized assessment of HF hospitalization risk and all-cause mortality in patients with MHD. It can be employed to identify high-risk patients and guide treatment and follow-up.

Application of robot-assisted radical prostatectomy in men over 75 years: an analysis of comparative outcomes.

OBJECTIVE: This study aimed to summarize the current evidence regarding the feasibility of robot-assisted radical prostatectomy (RARP) in men aged over 75 years. METHOD: A comprehensive search of four electronic databases (China National Knowledge Infrastructure, PubMed, Web of Science, and Cochrane Library) was performed to identify eligible comparative studies as of April 2022. Parameters, including perioperative results and oncological and functional outcomes, were evaluated. RESULTS: Seven articles with 7575 patients undergoing RARP were included in this study. Patients with prostate cancer were grouped by age ≥ 75 years versus < 75 years. Our results demonstrated that compared with the older group, the younger group had better potency (p < .00001). However, there were no significant differences in operation time (p = .29), estimated blood loss (p = .13), length of hospital stay (p = .48), complications (p = .22), continence (p = .21), positive surgical margin (p = .28), and biochemical recurrence (p = .74) between the groups. CONCLUSION: Our study revealed that the perioperative, oncological, and functional outcomes in men aged over 75 years undergoing RARP were not significantly different from those of their younger counterparts. RARP is feasible in men aged over 75 years.

Serum albumin to globulin ratio prior to treatment as a potential non-invasive prognostic indicator for urological cancers.

Background: Numerous clinical studies have reported an association between the pretreatment albumin to globulin ratio (AGR) and survival outcomes of urological cancers. However, these conclusions remain controversial. Therefore, we performed a meta-analysis to explore the prognostic value of the AGR in urinary system tumors. Methods: We retrieved eligible studies published up to June 2022 through a comprehensive search of multiple databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), progression-free survival (PFS), and biochemical recurrence-free survival (BRFS) were used to evaluated the predictive effect of the AGR before treatment in urinary system tumors. Heterogeneity test, random-effects models, fixed-effects models and sensitivity tests were used for analyses. Results: A total of 21 studies with 18,269 patients were enrolled in our meta-analysis. We found that patients with urinary system cancer with low AGR prior to treatment had poor OS [HR = 1.93, 95% CI (1.56-2.39), p < 0.001], CSS [HR = 2.22, 95% CI (1.67-2.96), p < 0.001], RFS [HR = 1.69, 95% CI (1.29-2.22), p < 0.001], and PFS [HR = 1.29, 95% CI (0.54-3.07), p < 0.001]. For prostate cancer (PCa), a low pretreatment AGR was associated with poor BRFS [HR = 1.46, 95% CI (1.28-1.67), p < 0.001]. Also, a subgroup analysis, stratified by ethnicity, cancer type, cutoff value, sample size and publication year, was conducted. The results showed that worse OS and CSS were significantly associated with these factors. Conclusion: Our meta-analysis revealed that the AGR before treatment could be used as a non-invasive predictive biomarker to evaluate the prognosis of urological cancer patients in clinical practice.

Prognostic value of pretreatment serum albumin-globulin ratio in urothelial carcinoma: A systematic review and meta-analysis.

Objective: To evaluate whether pretreatment albumin-globulin ratio (AGR) can be used as a biomarker for predicting the prognosis of patients with urothelial carcinoma (UC). Methods: We systematically searched PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Google Scholar and Cochrane Library; the search time was up to May 2022. Stata 16.0 was used for data processing and statistical analysis. Results: We identified 12 studies with 5,727 patients from 317 unique citations during the meta-analysis. Our results suggested that a low AGR before treatment was significantly associated with poor overall survival (OS) [hazard ratio (HR) = 1.99, 95% confidence interval (CI) = 1.45-2.75, P < 0.001], cancer-specific survival (CSS) [HR=2.01, 95% CI = 1.50-2.69, P < 0.001] and recurrence-free survival (RFS) [HR=1.39, 95% CI = 1.12-1.72, P = 0.002]. Furthermore, we defined different subgroups according to ethnicity, cancer type, cut-off value, sample size and stage. Similar prognostic outcomes for OS and CSS were observed in most subgroups. However, for subgroup of stage, the low pretreatment AGR only predicted the poor survival of patients with non-metastatic UC. Conclusion: Our meta-analysis revealed that the AGR before treatment could be used as a predictive biomarker to indicate the prognosis of UC patients during clinical practice, especially in patients with non-metastatic UC.

[Regulation of Chrysophanol-mediated TLR4/NF-κB Pathway on Renal Injury and Immune Response in IgA Nephropathy Rats].

OBJECTIVE: To investigate the regulatory effect and its mechanism of chrysophanol (CP) on renal injury and immune response in immunoglobin A (IgA) nephropathy rats. METHODS: IgA nephropathy rat model was established by the method of lipopolysaccharide + bovine serum protein + carbon tetrachloride. Then the rats were randomly divided into 5 groups: control group, IgA group, IgA+low, medium and high dose of CP groups(2.5, 5 and 10 mg/kg for each group respectively). IgA+CP groups were intraperitoneally injected with different doses of chrysophanol once a day for 4 weeks, and the control group and IgA group were given isovolumetric saline. Urine protein content, serum creatinine and urea nitrogen were detected at 24 h after the administration of drugs. Kidney histopathological damage and apoptosis were measured by HE and TUNEL staining. The expression levels of Caspase-3 and Caspase-9 were detected by RT-PCR and Western blot; The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and (glutathione peroxidase, Gpx) were detected by enzyme-linked immunosorbent assay (ELISA). The expression of interleukin-1ß, -6 (IL-1ß, IL-6) and tumor necrosis factor (TNF-α) in serum and kidney tissue were measured by ELISA and Western blot, respectively. The mRNA and protein expression levels of toll-like receptro 4 (TLR4), nuclear factor-κB P65 (NF-κB P65) were also detected by RT-PCR and Western blot, and vascular cell adherin molecule (VCAM-1) protein level was deteted by Western blot. RESULTS: In IgA nephropathy rats, the administration of CP reduced proteinuria, serum creatinine and urea nitrogen in a dose-dependent manner (P < 0.01). It also improved the pathological damage of kidney tissue, reduced the apoptosis rate (P < 0.01), and decreased the mRNA and protein expression levels of apoptosis-related proteins Caspase-3 and Caspase-9 (P < 0.01). CP inhibited MDA production while increased the activities of antioxidant enzymes Gpx and SOD (P < 0.01), and decreased the levels of serum and protein expression of IL-1ß, IL-6 and TNF-α (P < 0.01), as well as the expression levels of TLR4, NF-κB P65 and VCAM-1 (P < 0.01). CONCLUSION: Chrysophanol could play a protective role in IgA nephropathy rats, and its mechanism may be related to alleviating kidney injury and regulating immune response.

Controlling the Self-Assembly of Biomolecules into Functional Nanomaterials through Internal Interactions and External Stimulations: A Review.

Biomolecular self-assembly provides a facile way to synthesize functional nanomaterials. Due to the unique structure and functions of biomolecules, the created biological nanomaterials via biomolecular self-assembly have a wide range of applications, from materials science to biomedical engineering, tissue engineering, nanotechnology, and analytical science. In this review, we present recent advances in the synthesis of biological nanomaterials by controlling the biomolecular self-assembly from adjusting internal interactions and external stimulations. The self-assembly mechanisms of biomolecules (DNA, protein, peptide, virus, enzyme, metabolites, lipid, cholesterol, and others) related to various internal interactions, including hydrogen bonds, electrostatic interactions, hydrophobic interactions, π⁻π stacking, DNA base pairing, and ligand⁻receptor binding, are discussed by analyzing some recent studies. In addition, some strategies for promoting biomolecular self-assembly via external stimulations, such as adjusting the solution conditions (pH, temperature, ionic strength), adding organics, nanoparticles, or enzymes, and applying external light stimulation to the self-assembly systems, are demonstrated. We hope that this overview will be helpful for readers to understand the self-assembly mechanisms and strategies of biomolecules and to design and develop new biological nanostructures or nanomaterials for desired applications.