[Causal association between depression and stress urinary incontinence: A two-sample bidirectional Mendelian randomization study].

OBJECTIVE: To investigate the causal correlation between depression and stress urinary incontinence (SUI) using Mendelian randomization (MR) analysis. METHODS: We searched the FinnGen Consortium database for genome-wide association studies (GWAS) on depression and obtained 23 424 case samples and 192 220 control samples, with the GWAS data on SUI provided by the UK Biobank, including 4 340 case samples and 458 670 control samples. We investigated the correlation between depression and SUI based on the depression data collected from the Psychiatric Genomics Consortium (PGC). We employed inverse-variance weighting as the main method for the MR study, and performed sensitivity analysis to verify the accuracy and stability of the findings. RESULTS: Analysis of the data from the UK Biobank and FinnGen Consortium showed that depression was significantly correlated with an increased risk of SUI (P=0.005), but not SUI with the risk of depression (P=0.927). And analysis of the PGC data verified the correlation of depression with the increased risk of SUI (P=0.043). CONCLUSION: Depression is associated with an increased risk of SUI, while SUI does not increase the risk of depression.

Integration of bulk RNA-seq and single-cell RNA-seq constructs: a cancer-associated fibroblasts-related signature to predict prognosis and therapeutic response in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a common and aggressive renal cancer with high mortality when metastasized. Cancer-associated fibroblasts (CAFs) are pivotal in ccRCC evolution; however, their significance in forecasting prognosis and guiding therapy is undetermined. METHOD: We used Weighted Correlation Network Analysis to identify modules correlated with CAFs in bulk RNA-seq data. We also screened fibroblast marker genes in single-cell RNA-seq data and upregulated genes in TCGA tumor samples and defined genes identified in all three analyses as CAFs-related genes (CRGs). We extracted a CRG signature using Least Absolute Shrinkage and Selection Operator analysis and investigated its biological mechanisms by combining Gene Set Enrichment Analysis and the AUCell algorithm. The Tumor Immune Dysfunction and Exclusion algorithm and the IMvigor 210 dataset were employed to assess the signature's capability to predict immunotherapeutic responses. Additionally, we analyzed the relationship between the signature and the IC50 of targeted agents. In vitro validation confirmed the relative mRNA expression of the CRGs and the function of CERCAM. RESULTS: The CRG signature was anchored on six genes: CERCAM, TMEM132A, TIMP1, P4HA3, FKBP10, and CEBPB. Kaplan-Meier analysis indicated that patients with high expression of the signature experienced poorer survival than those with low expression. Furthermore, immunotherapy was more effective in patients with low signature expression. In vitro assays revealed CERCAM silencing led to a substantial reduction in the proliferative and migratory capacities of ccRCC cell lines. CONCLUSION: Our CRG signature holds promise in forecasting prognosis and guiding personalized treatment for patients with ccRCC.

Analysis of fatty acid composition and sensitivity to dietary n-3 PUFA intervention of mouse n-3 PUFA-enriched tissues/organs.

PURPOSE: n-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA; C22:6 n3) and eicosapentaenoic acid (EPA; C20:5 n3), are of concern for their health-promoting effects such as anti-inflammatory, but the tissue selectivity for n-3 PUFA (i.e., which tissues and organs are rich in n-3 PUFA) is still not well known. In addition, it is unclear which tissues and organs are more sensitive to n-3 PUFA intervention. These unresolved issues have greatly hindered the exploring of the health benefits of n-3 PUFA. METHODS: Twenty-four 7-week-old male C57BL/6 J mice were assigned to the control, fish oil, DHA, and EPA groups. The last three groups were given a 4-week oral intervention of fatty acids in ethyl ester (400 mg/kg bw). The fatty acid profiles in 27 compartments were determined by gas chromatography. RESULTS: The proportion of long-chain n-3 PUFA (the total relative percentage of EPA, DPA n3, and DHA) was analyzed. Eight tissues and organs, including the brain (cerebral cortex, hippocampus, hypothalamus) and peripheral organs (tongue, quadriceps, gastrocnemius, kidney, and heart) were determined as being n-3 PUFA-enriched tissues and organs, owing to their high n-3 PUFA levels. The highest n-3 PUFA content was observed in the tongue for the first time. Notably, the content of linoleic acid (LA; C18:2 n6c) in peripheral organs was observed to be relatively high compared with that in the brain. Interestingly, the proportions of EPA in the kidney, heart, quadriceps, gastrocnemius, and tongue increased more markedly after the EPA intervention than after the DHA or fish oil intervention. As expected, the levels of proinflammatory arachidonic acid (AA; C20:4 n6) in the kidney, quadriceps, and tongue were markedly decreased after the three dietary interventions. CONCLUSION: Peripheral tissues and organs, including the tongue, quadriceps, gastrocnemius, kidney, and heart, besides the brain, showed obvious tissue selectivity for n-3 PUFA. In the whole body of mice, the tongue exhibits the strongest preference for n-3 PUFA, with the highest proportion of n-3 PUFA. Moreover, these peripheral tissues and organs, especially the kidney, are more sensitive to dietary EPA administration in comparison with the brain.

Effects of fructose from apple and honey on serum uric acid in young Chinese: Randomized crossover trials.

BACKGROUND AND OBJECTIVES: Overconsumption of drinks containing fructose increases the risk for hyperuricemia and gout. Comparative analysis evaluating the indicators of serum uric acid (SUA) load caused by natural food-derived fructose and pure fructose in sweeteners is lacking. We aimed to uncover the effect of fructose from apple and honey and pure fructose powder on the SUA concentration of healthy young Chinese individuals. METHODS AND STUDY DESIGN: Two randomized crossover trials were performed. The participants were randomly assigned to consume apple or honey (test food) or pure fructose powder (reference food); one week later, the groups' dietary intervention was switched. Blood samples were collected at 0, 30, 60, and 120 min after meal to measure the SUA and blood glucose concentrations. RESULTS: At 30 and 60 min, the SUA concentration in participants consuming apple or honey was lower than in those consuming fructose powder. At 120 min, the SUA concentration of participants consuming apple returned to baseline. The areas under the curve (AUC) within 2 h (2h- AUCs) of SUA exhibited the trend of fructose >honey >apple. The 2h-AUC ratio between test food and reference food was determined using the uric acid index to assess the efficiency of food-derived fructose in increasing the SUA concentration. The uric acid index of honey was higher than that of apple. Men had higher postprandial SUA concentration than women. CONCLUSIONS: Food-derived fructose caused a lighter load on uric acid metabolism than pure fructose. Uric acid index can be useful for distinguishing fructose-containing foods.

Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway.

The aim of present study was to examine whether metformin in association with quercetin has any synergistically anti-tumor effects on prostate cancer. Our findings showed that metformin in combination with quercetin synergistically inhibited the growth, migration and invasion of both PC-3 and LNCaP cells. Co-treatment of these two agents induced more apoptosis than single agent treatment. The co-treatment-induced apoptosis was caspase-dependent and accompanied by the down-regulation of Bcl-2 family members. Our data also indicated that co-treatment of metformin and quercetin strongly inhibited the VEGF/Akt/PI3K pathway. Moreover, these two agents acted synergistically to repress the growth of human prostate cancer cell xenograft in vivo in nude mice. In conclusion, our findings indicate that the combination therapy of metformin and quercetin exerted synergistic antitumor effects in prostate cancers via inhibition of VEGF/Akt/PI3K pathway. Thus, combination treatment of metformin and quercetin would be a promising therapeutic strategy for prostate cancer patients.

Modified technique in treating recurrent priapism: a technique report.

Recurrent ischemic priapism is a problem in clinical treatment. Most of the cases require more invasive surgery to shunt the blood stasis. We introduce a modified technique in treating recurrent ischemic priapism. The technique described is applied to acute ischaemic priapic episodes in patients with a history of stuttering priapism. It was carried out by a Winter's shunt combined with a continuous cavernosal irrigation system. Priapism was effectively resolved on the patients without recurrence. The four patients who received this treatment recovered most sexual function after 6 months follow-up.

Formulation and evaluation of PLGA nanoparticles loaded capecitabine for prostate cancer.

The objective of this work is to prepare and evaluate Poly (D, L-Lactide-co-glycolide) (PLGA) Nanoparticles (NPs) of Capecitabine, an anticancer agent loaded by solvent displacement method using stabilizer (poly vinyl alcohol). The prepared NPs were characterized by FT-IR, DSC, drug loading, entrapment efficiency, particle size, surface morphology by Atomic force microscopy (AFM), X-ray diffraction and in-vitro studies. FT-IR and DSC studies indicated that there was no interaction between the drug and polymer. The morphological studies performed by AFM showed uniform and spherical shaped discrete particles without aggregation and smooth in surface morphology with a nano size range of 144 nm. X-ray diffraction was performed to reveal the crystalline nature of the drug after encapsulation. The NPs formed were spherical in shape with zeta potentials (-14.8 mV). In vitro release studies were carried and showed drug release up to 5 days. The drug release followed zero order kinetics and a Fickian transport mechanism. Nanoparticles obtained a high encapsulation efficiency of 88.4% and drug loading of 16.98%. Drug released from Capecitabine loaded PLGA NPs (84.1%) was for 5 days. It is concluded from the present investigation that PLGA NPs of Capecitabine may effectively deliver the drug to the prostate for the treatment of prostate cancer.

The association of fish consumption with bladder cancer risk: a meta-analysis.

BACKGROUND: The association between fish consumption and risk of bladder cancer has not been established yet. The results from epidemiological studies are inconsistent. METHODS: We conducted a meta-analysis of cohort and case-control studies on the relationship between fish intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of relative risk associated to the highest versus the lowest category of fish intake using random effect models. Heterogeneity among studies was examined using Q and I2 statistics. Publication bias was assessed using the Begg's funnel plot. RESULTS: Five cohort and 9 case-control studies were eligible for inclusion. The combined relative risk showed that fish consumption was negatively, but not significantly, associated with a decreased risk of bladder cancer (relative risk, 0.86; 95% confidence interval, 0.61-1.12). In subgroup analyses, there was no evidence that study design, geographical region, case sample size, or exposure assessment substantially influenced the estimate of effects. CONCLUSION: The overall current literature on fish consumption and the risk of bladder cancer suggested no association. Because of the limited number of studies, further well-designed prospective studies are needed to explore the effect of fish on bladder cancer.