Distribution and genotyping of hepatitis C virus (HCV) infection in Gansu province, China.

INTRODUCTION: The distribution of common subtypes of hepatitis C virus (HCV) in Gansu province were analyzed. This information provided a theoretical basis for the selection of appropriate antiviral treatment regimens. METHODOLOGY: We collected data on HCV antibody screening tests from 421,802 outpatients and inpatients at the Second Clinical Hospital of Lanzhou University from January 2018 to June 2022. Ribonucleic acid (RNA) viral load, HCV genotypes, and HCV quantification were analyzed retrospectively. The results of HCV positive detection rate, copy number, and genotype distribution were statistically analysed using SPSS 26.0. RESULTS: A total of 421,802 HCV antibody screenings were performed resulting in 4,558 positive cases (1.081%). In addition, 2,345 cases (1.302%) were positive with quantitative HCV antibodies in 180,157 outpatients and inpatients. Quantitative HCV virus RNA was further measured in 2592 outpatients and inpatients. There were 825 positive cases for HCV, with a positivity rate of 31.83%. High-sensitivity quantification of HCV-RNA was performed in 6538 patients, among which 1336 were HCV-RNA positive infections (positivity rate of 20.43%). Among the 1484 genotype tests, 4 genotypes and 10 subtypes were detected, including 4a, 1b, 2a, 2b, 3a, 3b, 6a, 6n, 1b/2a, and 2a/6a, with the majority of results from 2a (51.89%) and 1b (42.72%). CONCLUSIONS: The most prevalent genetic subtype in HCV-positive patients in Gansu was 2a, followed by 1b. In addition, 8 genotype subtypes appeared: 1a, 2b, 3a, 3b, 6a, 6n, 1b/2a and 2a/6a. Understanding the distribution of HCV genes in Gansu province is of significance for the optimization of virus treatment.

Efficacy and safety of robot-assisted laparoscopic, laparoscopic and open surgery in ureteral reimplantation: a network meta-analysis and systematic review.

To compare the efficacy and safety between open ureteral replantation (OUR), laparoscopic ureteral replantation (LUR) and robot-assisted laparoscopic ureteral replantation (RALUR). This review produced by the R3.5.0 software with "gemtc" program package and JAGS3.4.0 software based on the Bayesian model. A comprehensive search was done in databases including PubMed, Web of Science, Embase, Cochrane library, Cnki, CBM and WANFANG DATA. Studies that compared OUR, LUR OR RALUR were selected. Summary of Conclusions by ranking of Outcomes. A total of 3949 patients from 29 studies were included. The success rate in OUR, LUR and RALUR was 97.72%, 94.68% and 95.82%. The OR (95% CI) of LUR and RALUR was 0.76 (0.42,1.7) and 0.76 (0.30, 2.6), respectively, compared with OUR. The rate of complications in OUR, LUR and RALUR was 12.78%, 7.94% and 16.32%. The OR (95% CI) of LUR and RALUR was 0.28 (0.16, 0.48) and 0.61 (0.24,1.3), respectively, compared with OUR. The MD (95% CI) of LUR and RALUR for operation time was 22 (2,40) and 46 (7.5,84), respectively, compared with OUR. The MD (95% CI) of LUR and RALUR for hospital stay was - 3.6 (- 4.5, - 2.7) and - 1.1 (- 2.9, 0.58), respectively, compared with OUR. There is no significant difference in the success rates of OUR, LUR, and RALUR. RALUR and OUR has similar complication rates and time of hospital stay, while LUR has fewer complications and faster time to discharge compared to RALUR and OUR. The operative time of OUR is significantly less compared to LUR and RALUR.

Association of TERT gene polymorphisms with clinical benign prostatic hyperplasia in a Chinese Han population of the Northwest region.

BACKGROUND: To investigate the association between single nucleotide polymorphisms (rs10078761, rs12696304, rs2853669, rs16847897, rs2736100, rs10069690) of telomerase gene (TERT) and the risk clinical benign prostatic hyperplasia (BPH) in a Chinese Han population of the Northwest region. METHODS: A total of 150 BPH patients and 150 healthy older males from the northwest Chinese Han population were included in this study. The sample size for this unmatched case-control study was estimated by the look-up table method. Meanwhile, the general information and disease data of patients were collected. Age was only collected in healthy control subjects for statistical correction. Genotypes were detected using a multiplex PCR + ligase detection reaction (LDR). Typing results and clinical data were statistically analyzed using multiple linear regression and logistic regression. Pearson correlation was used for Hardy-Weinberg equilibrium. RESULTS: The included population is in Hardy-Weinberg equilibrium. There was no significant association between SNP and the risk of BPH by correlation analysis. However, 4 haplotypes (TCTGGT, TCTGTC, TGCCTC, and TGTGTC) were identified as risk factors of BPH by haplotype analysis. The SNP rs2853669 is an independent risk factor for smooth muscle type of hyperplasia. Besides, rs2736100, rs10078761, and rs10069690 which are in linkage disequilibrium are associated with the severity of BPH. CONCLUSIONS: Polymorphism of the TERT gene determines the different disease development and pathological manifestations of BPH in the Chinese Han population the Northwest region.

Diagnostic and prognostic role of BTA, NMP22, survivin and cytology in urothelial carcinoma.

BACKGROUND: Cytology is a recommended noninvasive urine test for the detection and surveillance of bladder cancer and upper-tract urothelial carcinoma. It is however characterized by poor sensitivity in low-grade tumors. This study aims to determine the diagnostic and prognostic role of BTA, BTA-stat, NMP22, and Survivin. METHODS: Urine samples were collected from a total of 105 patients (bladder cancer (n=61), upper-tract urothelial carcinoma (n=44), and controls (n=52). The samples were directly assessed using cytology, BTA-stat (Qualitative test), BTA (chemiluminescence test), NMP22 (Qualitative test), and Survivin (enzyme-linked immunosorbent assay). Cancer progression and recurrence were assessed after a median follow-up of 32 months (4-47 months). Univariate and multivariate analyses were performed using Kaplan-Meier survival analysis and Cox proportional hazards regression. RESULTS: The triple combination of Survivin + BTA + Cytology was the most promising model for discriminating bladder cancer or upper-tract urothelial carcinoma from controls (UTUC group: the area under the curve value 0.97, sensitivity 86%, specificity 96%; BC group: the area under the curve value 0.86 sensitivity 67%, specificity 96%). Univariate survival analysis, showed Cytology (P=0.02; HR=5.35) and Survivin (HR=3.24; P=0.03) to have a significant association with the progression-free survival, while Survivin (HR=4.15; P=0.04) was statistically associated with cancer-specific survival in the bladder cancer group. The multivariable analysis did not show any of these markers as independent prognostic factors. CONCLUSIONS: These biomarkers showed a higher sensitivity than cytology, but a poorer specificity. All biomarkers exhibited good diagnostic performance in both bladder cancer and upper-tract urothelial carcinoma. Combining Survivin + BTA + Cytology was superior to the use of a single marker or combining other biomarkers.

Pan-cancer analysis of iron metabolic landscape across the Cancer Genome Atlas.

Iron is an essential metal ion in the human body and usually dysregulated in cancers. However, a comprehensive overview of the iron-related genes and their clinical relevance in cancer is lacking. In this study, we utilized the expression profiling, proteomics, and epigenetics from the Cancer Genome Atlas database to systematically characterized the alterations of iron-related genes. There were multiple iron-related genes with dysregulation across 14 cancers and some of these ectopic changes may be associated with aberrant DNA methylation. Meanwhile, a variety of genes were significantly associated with patient survival, especially in kidney renal clear cell carcinoma. Then differentially expressed genes were validated in clinical samples. Finally, we found deferoxamine and erastin could inhibit proliferation in various tumor cells and influence the expression of several iron-related genes. Overall, our study provides a comprehensive analysis of iron metabolism across cancers and highlights the potential treatment of iron targeted therapies for cancers.

Increased expression of TRIP13 drives the tumorigenesis of bladder cancer in association with the EGFR signaling pathway.

Thyroid hormone receptor interactor 13 (TRIP13) is a crucial regulator of the spindle apparatus checkpoint and double-stranded break repair. The abnormal expression of TRIP13 was recently found in several human cancers, whereas the role of TRIP13 in the development of bladder cancer (BCa) has not been fully elucidated. Here, we reported that TRIP13 expression was elevated in BCa tissues compared with normal bladder tissues. Notably, the increased expression of TRIP13 was correlated with advanced tumor stage, lymph node metastasis, distant metastasis and reduced survival in BCa patients. Knockdown of TRIP13 in bladder cancer cells suppressed proliferation, induced cell cycle arrest, promoted apoptosis, and impaired cell motility, ultimately inhibiting tumor xenograft growth. Mechanistic investigations revealed that TRIP13 directly bound to epidermal growth factor receptor (EGFR), modulating the EGFR signaling pathway. Furthermore, TRIP13 expression was positively correlated with EGFR expression in BCa specimens, and the high expression of both TRIP13 and EGFR predicted poor survival. Overall, our results underscore the crucial role of TRIP13 in the tumorigenesis of BCa and provide a novel biomarker and therapeutic target for BCa treatment.

Association of CCL2, CCR2 and CCL5 genetic polymorphisms with the development and progression of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common chronic disease in older males. The pathogenesis of BPH remains elusive but may be associated with chronic inflammation. Chemokines and chemokine receptors have been implicated as critical mediators in the immune response and inflammatory processes. In the present study, the aim was to evaluate the association of three polymorphisms in chemokine genes, namely C­C motif chemokine ligand (CCL)2 rs1024611, CC chemokine receptor 2 (CCR2) rs1799864 and CCL5 rs2107538, with BPH risk. These polymorphisms were genotyped in 109 patients with BPH and 160 control subjects, using the polymerase chain reaction and multiple ligase detection reaction method. The CCL5 rs2107538 polymorphism was identified to be associated with a significantly lower risk of BPH [A/G vs. G/G: odds ratio (OR)=0.37, 95% confidence interval (CI)=0.17­0.78; A/A + A/G vs. G/G: OR=0.39, 95% CI=0.19­0.79; A vs. G: OR=0.58, 95% CI=0.35­0.96). However, this polymorphism was also associated with the development of larger prostate volumes in patients with BPH (A/G vs. G/G: OR=3.02, 95% CI=1.28­7.11; AA + AG vs. GG: OR=2.83, 95% CI=1.28­6.26; A vs. G: OR=1.94, 95% CI=1.08­3.49). The CCR2 rs1799864 polymorphism was associated with lower International Prostate Symptom Score values (A/A + A/G vs. G/G: OR=0.39, 95% CI=0.17­0.91; A vs. G: OR=0.43, 95% CI=0.20­0.90) and low Qmax (A/G vs. G/G: OR=0.38, 95% CI=0.16­0.92; AA + AG vs. GG: OR=0.39, 95% CI=0.17­0.91) in the patients. No association was observed between the CCL2 rs1024611 polymorphism and BPH. These results suggest that the CCR2 and CCL5 genes may contribute to the occurrence and progression of BPH.

Comprehensive analysis of microRNA-messenger RNA regulatory network in gemcitabine-resistant bladder cancer cells.

Chemotherapy is still a standard treatment of unresectable bladder cancer or distant metastases. The chemotherapy resistance always occurs after a period of treatment indicating poor prognosis. The current study aimed to explore the molecular mechanism of chemoresistance in bladder cancer cells. The gene expression profiles of GSE77883, including three untreated T24 cells samples and three gemcitabine-resistant T24 cells samples, was downloaded from Gene Expression Omnibus database. The screening of differentially expressed genes (DEGs), gene function analysis, and interaction prediction between microRNAs (miRNAs) and DEGs were performed by R software. The protein-protein interaction (PPI) and miRNA-DEGs networks were constructed and visualized by Cytoscape software. Then, the small molecules, with potential synergistic or antagonistic effects to gemcitabine resistance, were identified using the Connectivity Map database. Finally, gemcitabine-resistant T24 cell line was established and key genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In total, 536 upregulated and 513 downregulated genes were screened and mainly enriched in oxidative stress response and signaling pathways related to extracellular matrix-receptor interaction and focal adhesion. PPI network showed interleukin 6, tumor necrosis factor, kinesin family member 11, and BUB1 mitotic checkpoint serine/threonine kinase B were key genes. The miRNA-DEGs regulatory networks included 18 miRNAs and 185 DEGs, including miR-182-5p, miR-590-3p, miR-320a and serum- and glucocorticoid-regulated kinase 1 (SGK1). Then, the related key genes and miRNAs were confirmed by qRT-PCR. Furthermore, 81 small molecules with antagonistic or synergistic effect to GEM were screened. We have investigated the molecular mechanisms driving GEM-resistance in bladder cancer cells that would contribute to the development of chemotherapy for advanced bladder cancer.

Modified Mechanical Percussion for Upper Urinary Tract Stone Fragments After Extracorporeal Shock Wave Lithotripsy: A Prospective Multicenter Randomized Controlled Trial.

OBJECTIVE: To investigate the effectiveness of modified mechanical percussion for eliminating upper urinary tract stone fragments after extracorporeal shock wave lithotripsy. MATERIALS AND METHODS: We assigned patients aged 18-60 years with upper urinary tract calculi to the modified mechanical percussion (trial) or observation (control) group. Kidney-ureter-bladder radiography and ultrasound were used for diagnostic evaluation. The primary outcome was the stone-expulsion rate (SER) at 6 hours. The first stone-expulsion time, the SER at 3, 12, and 24 hours, the stone-free rate, additional interventions, and adverse events (AEs) were recorded. RESULTS: A total of 120 patients underwent randomization: 60 for each group. The mean first stone-expulsion time in the trial and control groups was 6.75 and 13.58 hours, respectively (P = .001). The SERs at 3, 6, and 12 hours in the trial group were 51.8%, 75.4%, and 76.8%, respectively, which were higher than the control group (all P <.05). Among patients who expelled fragments within 6 hours, the stone-free rates were improved at 1 week (P = .002) and at 2 weeks (P = .000). Patients needed fewer additional interventions in the trial group (P = .035). AEs occurred in 42.9% (24 of 56) and 67.9% (38 of 56) of the patients in the trial and control groups, respectively (P = .008). Age, gender, stone size and location, and SER at 24 hours did not differ significantly among the groups. CONCLUSION: Modified mechanical percussion significantly improved SERs and accelerated stone passage after shock wave lithotripsy, resulting in a stone-free status with a lower risk of AEs and reduced need for additional interventions.

Human hemokinin-1 and human hemokinin-1(4-11), mammalian tachykinin peptides, suppress proliferation and induce differentiation in HL-60 cells.

Human hemokinin-1 (h HK-1) and its truncated form h HK-1(4-11) are mammalian tachykinin peptides encoded by the TAC4 gene identified in human, and the biological functions of these peptides have not been well investigated. The tachykinins have shown immuno-regulatory activities in humans. In the present study, we investigated the effects of h HK-1 and h HK-1(4-11) on the proliferation and differentiation of a human promyelocyte leukemia cell line, HL-60. It is noteworthy that h HK-1 (1-300muM) displayed inhibitory effects on the proliferation of HL-60 cells in a dose- and time-dependent manner. The effect of suppressing proliferation induced by these peptides was accompanied by an accumulation of cell cycle in the S phase. Moreover, this peptide induced differentiation of HL-60 cells by significantly increasing the NBT-reduction activity. The effects induced by h HK-1(4-11) on HL-60 cells were similar to that of h HK-1, indicating that it is the active fragment of h HK-1. However these effects induced by h HK-1 or h HK-1(4-11) were not antagonized by the NK(1) receptor antagonist SR140333 or the NK(2) receptor antagonist SR48968. All the results indicated that h HK-1 and h HK-1(4-11) were able to significantly inhibit proliferation and induce differentiation and S phase arrest of a human promyelocyte leukemia cell line HL-60, which may not be mediated through the activation of classical tachykinin NK(1) receptors and tachykinin NK(2) receptors. Our observations also implied that h HK-1 and h HK-1(4-11) could act as immunomodulatory factors in cancer chemotherapy.

In vitro characterization of the effects of rat/mouse hemokinin-1 on mouse colonic contractile activity: a comparison with substance P.

Rat/mouse hemokinin-1 (r/m HK-1) has been identified as a member of the tachykinin family and its effect in colonic contractile activity remains unknown. We investigated the effects and mechanisms of actions of r/m HK-1 on the mouse colonic contractile activity in vitro by comparing it with that of substance P (SP). R/m HK-1 induced substantial contractions on the circular muscle of mouse colon. The maximal contractile responses to r/m HK-1 varied significantly among proximal-, mid- and distal-colon, suggesting that the action of r/m HK-1 was region-specific in mouse colon. The contractile response induced by r/m HK-1 is primarily via activation of tachykinin NK(1) receptors leading to activation of cholinergic excitatory pathways and with a minor contribution of NK(2) receptors, which may be on the smooth muscle itself. A direct action on colonic smooth muscles may be also involved. In contrast, SP induced biphasic colonic responses (contractile and relaxant responses) on the circular muscle, in which the contractile action of SP was equieffective with r/m HK-1. SP exerted its contractile effect predominantly through neural and muscular tachykinin NK(1) receptors, but unlike r/m HK-1 did not appear to act via NK(2) receptors. The relaxation induced by SP was largely due to release of nitric oxide (NO) produced via an action on neural NK(1) receptors. These results indicate that the receptors and the activation properties involved in r/m HK-1-induced mouse colonic contractile activity are different from those of SP.