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SUMOylation is an important part of post-translational protein modifications and regulates thousands of proteins in a dynamic manner. The dysregulation of SUMOylation is detected in many cancers. However, the comprehensive role of SUMOylation in prostate cancer (PCa) remains unclear. Using 174 SUMOylation-related genes (SRGs) from the MigDSB database and the transcript data of PCa from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we constructed a SUMOylation-related risk score and correlated it with prognosis, tumor mutation burden (TMB), tumor microenvironment (TME) infiltration, and response to chemotherapy and immunotherapy. Moreover, we validated two vital SRGs by RT-qPCR, western blotting, and immunohistochemistry. Two vital SRGs (DNMT3B and NUP210) were finally selected. The risk score based on these genes exhibited excellent predictive efficacy in predicting the biochemical recurrence (BCR) of PCa. A nomogram involving the risk score and T stage was established to further explore the clinical value of the risk score. We found the high-score group was correlated with worse prognosis, higher TMB, a more suppressive immune microenvironment, and a better response to Docetaxel but worse to PD-1/CTLA-4 blockade. Meanwhile, we validated the significantly higher expression level of NUP210 in PCa at mRNA and protein levels. This study elucidated the comprehensive role of SUMOylation-related genes in PCa. Importantly, we highlighted the role of an important SRG, NUP210, in PCa, which might be a promising target in PCa treatment. A better understanding of SUMOylation and utilizing the SUMOylation risk score could aid in precision medicine and improve the prognosis of PCa. [ABSTRACT FROM AUTHOR]

Background. With the growth and aging of population, the incidence of prostate cancer will increase year by year, which is bound to bring greater economic burden to the society. There has been greater interest in the anticancer effects of statin in recent years. It is controversial whether statin use is associated with the risk of prostate cancer (PCa). Thus, we conducted a meta-analysis and systematic review to explore the effects of statin use and their duration and cumulative dose on the overall incidence of PCa. Method. The study was conducted according to the latest guidelines for PRISMA 2020. We searched PubMed and other databases for studies about the association of statin use with the risk of incident prostate cancer between January 1, 1990, and April 11, 2022. Two independent researchers extracted data and evaluated the quality of the studies. R x64 4.1.2 and random-effects model were used for data statistics. Relative risk (RR) and odds ratio (OR) effective values with a 95% confidence interval (95% CI) were used to assess the main results. Results. The results of 6 RCT and 26 cohort studies showed that statins did not significantly associate with the incidence of PCa (RR = 0.94, 95% CI: 0.82–1.08). The similar results were obtained from 9 case-control studies (OR = 1.03, 95% CI: 0.99–1.07). However, statins were associated with a lower risk of Pca (RR = 0.44, 95% CI: 0.28–0.70) when the cumulative defined daily dose (cDDD) was high. Using statins for more than five years could be associated with a reduced incidence of Pca (RR = 0.47, 95% CI: 0.23–0.97). There was a significant heterogeneity in these studies (RCT and cohort study: I2 = 98%, P < 0.01; case-control study: I2 = 72%, P < 0.01). Conclusion. We concluded that statins had a neutral association with the overall risk of PCa. High cDDD and long duration were associated with a lower risk of PCa. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) is the 10th most commonly diagnosed cancer worldwide, and cellular senescence is defined as a state of permanent cell cycle arrest and considered to play important roles in the development and progression of tumor. However, the comprehensive effect of senescence in BCa has not ever been systematically evaluated. Using the genome-wide CRISPR screening data acquired from DepMap (Cancer Dependency Map), senescence genes from the CellAge database, and gene expression data from The Cancer Genome Atlas (TCGA), we screened out 12 senescence genes which might play critical roles in BCa. A four-cell-senescence-regulator-gene prognostic index was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression model. The transcriptomic data and clinical information of BCa patients were downloaded from TCGA and Gene Expression Omnibus (GEO). We randomly divided the patients in TCGA cohort into training and testing cohorts and calculated the risk score according to the expression of the four senescence genes. The validity of this risk score was validated in the testing cohort (TCGA) and validation cohort (GSE13507). The Kaplan–Meier curves revealed a significant difference in the survival outcome between the high- and low-risk score groups. A nomogram including the risk score and other clinical factors (age, gender, stage, and grade) was established with better predictive capacity of OS in 1, 3, and 5 years. Besides, we found that patients in the high-risk group had higher tumor mutation burden (TMB); lower immune, stroma, and ESTIMATE scores; higher tumor purity; aberrant immune functions; and lower expression of immune checkpoints. We also performed gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) to investigate the interaction between risk score and hallmark pathways and found that a high risk score was connected with activation of senescence-related pathways. Furthermore, we found that a high risk score was related to better response to immunotherapy and chemotherapy. In conclusion, we identified a four-cell-senescence-regulator-gene prognostic index in BCa and investigated its relationship with TMB, the immune landscape of tumor microenvironment (TME), and response to immunotherapy and chemotherapy, and we also established a nomogram to predict the prognosis of patients with BCa. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have reported the role of statins on biochemical recurrence (BCR) among patients with prostate cancer (PCa) after definite treatment. However, the conclusions of these studies are contradictory. We aimed to determine the effect of statins on BCR of PCa using a systematic review and meta-analysis. Methods: We searched PubMed (Medline) and other databases for cohort studies evaluating the effect of statins on the BCR of patients with PCa between January 1, 2000, and December 31, 2021. The random effects (RE) model and quality effects (QE) model were used to calculate the pooled hazard ratio (pHR) and pooled risk ratio (pRR) and their 95% confidence interval (95% CI). Results: A total of 33 cohort studies were finally selected and included in this systematic review and meta-analysis. Statin use was significantly associated with a 14% reduction in the HR of BCR (pHR: 0.86, 95% CI: 0.78 to 0.95, I2 = 64%, random effects model, 31 studies) and a 26% reduction in the RR of BCR (pRR: 0.74, 95% CI: 0.57 to 0.94, 24,591 patients, I2 = 88%, random effects model, 15 studies) among patients with PCa. The subgroup analyses showed that statins could result in 22% reduction in the HR of BCR (pHR: 0.78, 95% CI: 0.61 to 0.98, I2 = 57%, random effects model) among patients accepting radiotherapy (RT). Conclusions: Our study suggests that statins have a unique role in the reduction of BCR in patients with PCa after definite treatment, especially RT. In the future, more clinical trials and in vitro and animal experiments are needed to further verify the effects of statins in PCa and the potential mechanisms. [ABSTRACT FROM AUTHOR]

Background. Sepsis is a potentially lethal complication for both flexible ureteroscopy (fURS) and percutaneous nephrolithotomy (PCNL). This study is aimed at comparing the sepsis rate after fURS and PCNL and the risk factors for sepsis in patients with solitary proximal ureteral stone. Methods. We reviewed the data of patients with calculi between 10 mm to 20 mm who underwent fURS or PCNL surgery from Tongji Hospital's database. A total of 910 patients were eligible with 412 fURS cases and 498 PCNL cases. We used univariate analysis and multivariate logistic regression analysis to identify the risk factors for sepsis. Subgroup analysis was performed using logistic regression analysis. Results. In the cohort, 27 (6.6%) and 19 (3.8%) patients developed sepsis after fURS and PCNL, respectively. Multivariate analysis shows that the risk factors for sepsis are fURS (OR = 3.160 , P = 0.004), serum WBC ≥ 10,000 cells/μL (OR = 3.490 , P = 0.008), albumin − globulin ratio < 1.2 (OR = 2.192 , P = 0.029), positive urine culture (OR = 6.145 , P < 0.001), and prolonged operation time (OR = 1.010 , P = 0.046). Subgroup analysis was conducted using potential risk factors: stone size, serum WBC, urine culture, and albumin-globulin ratio (AGR). In subgroup of positive urine culture, patients were more likely to develop sepsis after fURS than PCNL. Conclusions. PCNL may be a better choice than fURS to reduce postoperative sepsis, especially for patients with positive urine culture. [ABSTRACT FROM AUTHOR]

Background. Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of any detectable organic illnesses. Interest in the effect of dietary opponents to the IBS pathogenesis has been increased in recent years. This study aims to review previous studies to determine the relationship between IBS prevalence in community and dietary energy and macronutrients intakes according to the national nutrition surveys. Methods. A literature search was conducted in PubMed and EMBASE to September, 2018, to identify population-based studies that reported the prevalence of IBS. Daily energy intake, daily carbohydrates, and protein and fat percent contribution to energy intake (%) were obtained from study population-based national nutrition survey. The correlations of prevalence of IBS and dietary intakes were obtained by Spearman coefficient or Pearson coefficient. Results. Global prevalence of IBS was 11.7%. There was no correlation between overall prevalence of IBS of individual countries and national energy intake (P = 0.785), protein proportion (P = 0.063), carbohydrates proportion (P = 0.505), or fat proportion (P = 0.384) according to the years when the studies were conducted. No correlations were detected between dietary intake and male or female IBS prevalence. Interestingly, protein proportion was positively correlated with the prevalence of IBS in Rome III criteria (r = 0.569). Conclusion. Our findings demonstrate that dietary energy and macronutrients intake do not play a direct role in prevalence of IBS. However, IBS diagnostic criteria seem to have a bias on the correlation between prevalence of IBS and dietary intake. Further studies are needed to confirm the correlation between prevalence of IBS and specific dietary intake. [ABSTRACT FROM AUTHOR]

Background/Aims: The biological heterogeneity of hepatocellular carcinoma (HCC) makes prognosis difficult. Although many molecular tools have been developed to assist in stratification and prediction of patients by using microarray analysis, the classification and prediction are still improvable because the high-through microarray contains a large amount of information. Meanwhile, gene expression patterns and their prognostic value for HCC have not been systematically investigated. In order to explore new molecular diagnostic and prognostic biomarkers, the gene expression profiles between HCCs and adjacent nontumor tissues were systematically analyzed in the present study. Materials and Methods: In this study, gene expression profiles were obtained by repurposing five Gene Expression Omnibus databases. Differentially expressed genes were identified by using robust rank aggregation method. Three datasets (GSE14520, GSE36376, and GSE54236) were used to validate the associations between cytochrome P450 (CYP) family genes and HCC. GSE14520 was used as the training set. GSE36376 and GSE54236 were considered as the testing sets. Results: From the training set, a four-CYP gene signature was constructed to discriminate between HCC and nontumor tissues with an area under curve (AUC) of 0.991. Accuracy of this four-gene signature was validated in two testing sets (AUCs for them were 0.973 and 0.852, respectively). Moreover, this gene signature had a good performance to make a distinction between fast-growing HCC and slow-growing HCC (AUC = 0.898), especially for its high sensitivity of 95%. At last, CYP2C8 was identified as an independent risk factor of recurrence-free survival (hazard ratio [HR] =0.865, 95% confidence interval [CI], 0.754-0.992, P = 0.038) and overall survival (HR = 0.849; 95% CI, 0.716-0.995, P = 0.033). Conclusions: In summary, our results confirmed for the first time that a four-CYP gene (CYP1A2, CYP2E1, CYP2A7, and PTGIS) signature is associated with fast-growing HCC, and CYP2C8 is associated with patient survival. Our findings could help to identify HCC patients at high risk of rapid growth and recurrence. [ABSTRACT FROM AUTHOR]

Objective: Clinical and basic research increasingly suggests a correlation between migraine and irritable bowel syndrome (IBS). In this study, we aimed to explore the clinical features and risk factors for IBS in migraine patients. Methods: This was a retrospective, cross-sectional study. A total of 1,112 consecutive patients from the internal medicine and emergency departments of three hospitals from June 2014 through 2016. A comprehensive interviewer-administered questionnaire was designed based on the International Classification of Headache Disorders, 3rd edition (beta version). Results: The response rate was 94.6%. Among 1,052 participants, 287 suffered from migraine (27.3%) and 312 suffered from IBS (29.7%). A total of 79 patients suffered from both migraine and IBS (comorbidity rate: 7.5%). The migraine cohort exhibited a higher frequency of IBS than did the comparison cohort at baseline (P<0.05). Migraine patients with higher headache frequency, longer length of headache history and anxiety disorders were more likely to also suffer from IBS (P=0.015). There were no significant differences between the two groups in age, sex, family history, duration of headache attack, migraine aura, headache intensity, or depression disorders (P>0.05). Multiple regression analysis indicated length of headache history and headache frequency were associated with IBS. Conclusion: Migraine patients with a long headache history, recurrent episodic headache attacks and anxiety were more likely to have IBS. [ABSTRACT FROM AUTHOR]

Background and purpose: Lacunar infarct (LI) is well known as a heterogeneous primary disorder of cerebral small vessel. Compelling results have demonstrated that age is a risk factor to the prevalence of LI. However, the relationship between age and the prevalence of LI remains obscure. It is essential to note the relationship between age and the prevalence of LI through more clinical data. Methods: A total of 3,500 patients were included in the case-controlled study. All data were collected from the Examination Center of Magnetic Resonance Imaging, Lu'an People's Hospital from January 2014 to December 2015. A primary discharge diagnosis of LI was done, and all subjects were evaluated as retrospective data. The relationship between the risk factors and the prevalence of diabetes and the relationship between age and the prevalence of diabetes was analyzed. A chi-square test was used to analyze the associations between different variables. A one-way analysis of variance was used to test the equality of three or more means at one time by using variances. Statistical significance was defined as a P-value of <0.05. Results: The one-way analysis of variance demonstrated that the prevalence of LI increased with age before 60 years and decreased with age after 69 years. The same results were found in both the male and the female subjects. These results showed that the age-related risk factors (hypertension, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking) have no relationship with the prevalence of LI on the basis of age. There is a significant difference among the different age ranges (P=0.0006). Two-tailed P-value (unpaired t-test) showed the mean significant difference between 30-39 years and 40-49 years (P=0.009) and between 70-79 years and 80-100 years (P=0.0196). F-test (to compare variances) demonstrated that the variances of the different age ranges are significantly different between 30-39 years and 40-49 years (P=0.0002), between 40-49 years and 50-59 years (P=0.0424), and between 70-79 years and 80-100 years (P=0.0003). Conclusion: The age-related risk factors (hypertension, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking) have no relationship with the prevalence of LI on the basis of age. A decreasing prevalence of LI with aging occurs in the elderly, while the prevalence of LI increases with aging in the young and in adults. This investigation implicates that age is not a risk factor for LI in the elderly. [ABSTRACT FROM AUTHOR]

Previous studies have highlighted that the transforming growth factor-β1 (TGF-β1) pathway may be activated by hypoxic conditions. TGF-β1 also participates in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. Furthermore, TGF-β1 has been reported to participate in the regulation of the progression of pulmonary arterial hypertension (PAH). However, the effect of TGF-β1 on pulmonary arterial smooth muscle cells (PASMCs) and the corresponding molecular mechanisms remain unclear. The present study aimed to determine whether TGF-β1 protects against cell apoptosis in PASMCs, and identify the underlying molecular mechanisms. Western blotting, MTT and lactate dehydrogenase activity assays were performed, and the activity of caspase-3 and caspase-9 was detected in order to investigate the hypothesis. It was determined that TGF-β1 may facilitate cell growth in a dose-dependent manner in serum-starved PASMCs. Furthermore, it was observed that apoptosis in serum-starved PASMCs was inhibited by TGF-β1 via regulation of the expression levels of mitochondrial membrane proteins. Additionally, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway was found to be activated by TGF-β1 in PASMCs, while the inhibition of PI3K/Akt signaling also prevented the apoptosis-limiting effects of TGF-β1. These observations suggest that TGF-β1 protects PASMCs from apoptosis and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Background Vascular mild cognitive impairment (VaMCI) is the prodromal syndrome of vascular dementia (VaD) and key target for drug treatment. There is controversy over the diagnostic criteria and screening tools of VaMCI, which affects its clinical diagnosis. This paper aims to explore the clinical features, diagnostic criteria and screening technique of VaMCI. Methods Taking "vascular mild cognitive impairment OR vascular cognitive impairment no dementia" as retrieval terms, search in PubMed database from January 1997 to March 2015 and screen relevant literatures concerning VaMCI. According to Guidance for the Preparation of Neurological Management Guidelines revised by European Federation of Neurological Societies (EFNS) in 2004, evidence grading was performed on literatures. Results A total of 32 literatures in English were selected according to inclusion and exclusion criteria, including 3 guidelines and consensus and 29 clinical studies. Seven literatures (2 on Level I, 5 on Level II) studied on neuropsychological features in VaMCI patients and found reduced processing speed and executive function impairment were main features. Two literatures reported the diagnostic criteria of VaMCI, including VaMCI criteria published by American Heart Association (AHA)/American Stroke Association (ASA) in 2011 and "Diagnostic Criteria for Vascular Cognitive Disorders" published by International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2014. Fifteen literatures (4 on Level I, II on Level II) described the diagnostic criteria of VaMCI used in clinical research, from which 6 operational diagnostic items were extracted. Fourteen literatures (4 on Level I, 10 on Level II) described neuropsychological assessment tools for VaMCI screening, and found the 5-minute protocol recommended by National Institute of Neurological Disorders and Stroke - Canadian Stroke Network (NINDS- CSN) was being good consistency with other neuropsychological assessment tools. Conclusions The neuropsychological features of VaMCI have guiding significance for diagnosis. VASCOG diagnostic criteria for VaMCI is practical in clinical practice, and 5-minute protocol is suitable for clinical rapid screening of VaMCI. [ABSTRACT FROM AUTHOR]

Coal combustion can release large amounts of polycyclic aromatic hydrocarbons (PAHs), which persist in various environment matrices (e.g., road dust) and hence cause the carcinogenic risk to human health. In this study, an exhaustive characterization of road dust samples coupling their physicochemical characteristics and stable isotope compositions (δ13C and δ15N) was conducted to evaluate the source, level, spatial distribution, and carcinogenic risk of PAHs in a typical coal-utilization city. Concentrations of Σ 16 PAHs ranged from 605.5 to 25,374.3 ng/g with a mean concentration of 4083.0 ng/g. Pollution levels of sites around the coal-fired power plant (Zone 1) were significantly higher than those in other zones (p < 0.05). PAH concentration showed significant correlations with both C and N fractions (p < 0.01). Compositions of δ13C and δ15N in road dust coupled to principal component analysis and the partitions and diagnostic ratios of PAHs contributed to associating road dust to several local sources of contamination. Coal combustion and vehicular exhaust were major sources of PAHs around the power plant and urban area. Results of incremental lifetime cancer risk showed 81.5% of all sampling sites suffered potential risk (>10−6) for both adults and children, while children around the power plant suffered the highest risk. Despite the estimation of only potential risk being posed by PAHs in road dust, human exposure to the various environmental matrices, scientific and systematic assessment of carcinogenic risks by PAHs in the total environment warrants further investigations. [Display omitted] • Total PAH levels were significantly higher in Zone 1 than Zones 2 and 3. • PAH level in road dust was significantly correlated with organic carbon fractions. • Coal combustion, vehicular and industrial emission were the main sources for PAH. • Road dust was from various sources in different zones. • The potential cancer risk was posed by PAHs in road dust to local residents. [ABSTRACT FROM AUTHOR]