Gleason score 7 prostate cancer comprises two biologically distinct subgroups—Gleason 3 + 4 and Gleason 4 + 3—with differing prognoses and therapeutic implications. However, reliable non-invasive methods to distinguish these subtypes prior to treatment remain limited. This exploratory study evaluated whether systemic inflammatory markers and prostate volume (PV) provide preliminary signals differentiating Gleason 3 + 4 from 4 + 3 disease. We analyzed 26 patients with biopsy-confirmed Gleason score 7 prostate cancer (3 + 4, n = 15; 4 + 3, n = 11). Pre-biopsy complete blood counts were used to calculate inflammation-based indices, including neutrophil-to-lymphocyte-to-platelet ratio (NLPR), systemic immune-inflammation index (SII), and others. Prostate volume (PV) was measured by a transrectal ultrasonography. Group comparisons used non-parametric tests, and receiver operating characteristic (ROC) analyses were performed. NLPR and PV showed modest separation between groups (NLPR AUC = 0.715; PV AUC = 0.709). Most other inflammatory markers-including NLR, PLR, MLR, AISI and SIRI-showed limited discriminatory performance. A multivariable combining NLPR and PV yielded an AUC of 0.776, which improved to 0.82 after adding SII. Given the very small cohort size (n = 26), these findings should be regarded strictly as preliminary and hypothesis-generating. This exploratory analysis suggests that NLPR and PV may reflect biological difference between Gleason 3 + 4 and 4 + 3 tumors. These observations require validation in larger, prospective, multi-institutional cohorts before any clinical interpretation or application can be considered.

Objective Prostate-specific antigen (PSA) testing is widely used for prostate cancer (PCa) screening; however, its limited specificity remains a major challenge, as elevated PSA levels also occur in benign prostatic hyperplasia (BPH). Systemic inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII), have been proposed as adjunctive diagnostic tools. Method This retrospective study included 100 patients (50 PCa and 50 BPH) who underwent transrectal ultrasound-guided prostate biopsy between October 2018 and October 2021. Clinical data, including PSA, prostate volume (PV), and complete blood counts, were collected. Inflammatory indices were calculated and evaluated using receiver operating characteristic (ROC) analysis. Results NLR, MLR, RLR, and SII were significantly elevated in PCa patients (p < 0.05). However, their individual diagnostic performance was modest (AUC range: 0.624–0.656). The combined inflammatory model showed limited improvement (AUC = 0.662). In contrast, PV demonstrated superior diagnostic accuracy (AUC = 0.774) with high specificity. When combined with inflammatory markers, PV further improved predictive performance, achieving a positive predictive value of 70.3% and a negative predictive value of 73.9%. Conclusion Systemic inflammatory markers alone have limited diagnostic value in distinguishing PCa from BPH. However, their combination with prostate volume may enhance diagnostic accuracy and provide a simple, non-invasive approach for risk stratification in clinical practice.

Introduction:Evidence on the impact of different stent sizes on stone-free rate (SFR) and ureteral stent-related symptom questionnaire (USSQ) scores in endoscopic lithotripsy remains limited. This study aimed to evaluate the effects of 2 commonly used double-J stents of different diameters on these outcomes. Material and methods:We retrospectively reviewed 108 patients with upper urinary tract stones who underwent lithotripsy between January 2022 and December 2023. Patients were stratified into 4.7F and 6F groups based on stent diameter. Primary outcomes were SFR at 24 h and 30 days. USSQ scores and complications were compared between groups. Results:SFR was similar between groups at 24 h (52.5% vs 55.1%; p = 0.791) and 30 days (74.6% vs 77.6%; p = 0.719). USSQ scores were comparable (Urinary Symptoms: 29 vs 29, p = 0.473; Body Pain: 12 vs 12.5, p = 0.347; General Health: 13 vs 13, p = 0.706; Work Performance: 8 vs 8, p = 0.072; Sexual Matters: 4 vs 3, p = 0.242; Additional Problems: 12 vs 12, p = 0.485). More patients in the 4.7F group reported hematuria (83.1% vs 69.4%; p = 0.094) and changes in daily work activities. Many experienced body pain (76.9%) and absence of sexual activity (88.9%). No complications exceeded grade II. Conclusions:Both 4.7F and 6F stents showed similar efficacy and safety. Stent size did not significantly impact USSQ scores or SFR.

The incidence of prostate cancer (PCa) is increasing annually, making it the leading cause of tumor-related mortality in males. The available treatment options for metastatic PCa are limited. Vasculogenic mimicry (VM), an emerging phenomenon involving aggressive tumor cells, has a significant impact on patient survival. Misregulation of Wnt5a expression is commonly observed during cancer progression. However, there is a lack of comprehensive studies investigating the effects of Wnt5a on tumor VM formation. In this study, we demonstrate that alterations in wnt5a expression, either through gain or loss, have a significant influence on the formation of VM in tumor cells mediated by cell stemness and EMT progression. Further research has demonstrated that Wnt5a regulates the formation of VM through the PI3K/JNK signaling pathway. These experimental findings offer a novel avenue for the clinical management of prostate cancer.

Prostate cancer (PCa) is the most prevalent cancer in men and the leading cause of cancer-related mortality. Recent studies have highlighted the pivotal role of glycolysis in tumor progression. This study aimed to investigate the involvement of the EDNRB gene and its ligand endothelin 3 (EDN3) in glycolysis in PCa and to elucidate its underlying molecular mechanism. Quantitative reverse transcription PCR (RT-qPCR) and methylation-specific PCR (MSP) were used to probe EDNRB expression and methylation in PCa tissues. Cell proliferation and glycolysis in PCa cells were evaluated using Cell Counting Kit-8 (CCK-8), EDU staining, Seahorse assay, and biochemical kits to analyze the effects of EDN3/EDNRB. The underlying molecular mechanism was further explored through Western blotting. The in vivo effect of EDNRB on tumor growth was examined using a xenograft tumor model. Our findings revealed that EDNRB was hypermethylated and downregulated in PCa tissues and cell lines. Overexpression of EDNRB or EDN3 led to reduced cell proliferation and downregulation of glycolytic markers. EDNRB also decreased the extracellular acidification rate (ECAR) baseline and increased the oxygen consumption rate (OCR) baseline, indicating a shift away from glycolysis. Additionally, the anticancer effects of EDNRB or EDN3 was reversed upon inhibition of the cGMP/PKG pathway. In vivo, enhanced EDNRB expression significantly suppressed tumor growth. Therefore, EDNRB or EDN3 possess anticancer potential in PCa, primarily through the regulation of glycolysis via the cGMP/PKG pathway.

BACKGROUND:Pheochromocytoma (Pheo) represents a potential metastatic neuroendocrine tumor. As a tumor suppressor gene, LRP1B is involved in the regulation of tumor progression. However, the precise regulatory mechanism of LRP1B in Pheo remains elusive. METHODS:RT-QPCR, western blot and immunohistochemistry (IHC) were used to identify the expression levels of DNMT3B and LRP1B. Biochemistry assays including luciferase and ChIP were utilized to detect the interaction between the methyltransferase DNMT3B and LRP1B promoter. LRP1B or DNMT3B were knock-down in Pheo cell line by shRNAs. Functional experiments including clonal formation, migration, and in vivo transplantation were performed to evaluate the regulation of LRP1B or DNMT3B on tumor growth. RESULTS:LRP1B was down-regulated, while DNMT3B was up-regulated in Pheo.Overexpression of LRP1B or inhibition of DNMT3B inhibited the progress of Pheo. DNMT3B was responsible for the hypermethylation of LRP1B promoter in Pheo. At the same time, overexpression of DNMT3B reversed the inhibitory effect of overexpression of LRP1B on Pheo progression. CONCLUSION:DNMT3B mediated the hypermethylation of the tumor suppressive gene LRP1B and promotes Pheo progression.

BackgroundErectile dysfunction (ED) is a common complication of diabetes mellitus (DM), and because of its complex neurovascular etiology, the associated molecular pathogenic mechanisms are not fully understood. This study investigated the important functions and potential molecular regulatory roles of CELF2 in DMED.MethodsAn in vitro HUVEC model with CELF2 overexpression was successfully established via transfection with a CELF2-overexpressing lentiviral vector. The effects of CELF2 overexpression on cell proliferation and angiogenesis were assessed via CCK-8 and angiogenesis assays. RNA sequencing was employed to evaluate the gene expression profiles and alternative splicing events regulated by CELF2. An RNA-sequencing assay was performed to evaluate gene expression profiles and alternative splicing genes in HUVECs overexpressing CELF2, and an integration analysis was combined with GSE146078 data to detect potential target genes related to DMED.ResultsThe expression of genes related to angiogenesis and the immune response significantly increased with CELF2 overexpression, and the four hub genes associated with alternative splicing in aging and angiogenesis were CXCL2, CXCL10, IL-1A and IL-6.ConclusionCELF2 appears to be a key factor in DMED, influencing gene expression and alternative splicing related to angiogenesis and immune responses. The identified hub genes (CXCL2, CXCL10, IL-1A, and IL-6) are closely related to DMED and warrant further investigation to understand the underlying mechanisms and potential therapeutic implications.

Prostate-specific antigen (PSA) is used to screen for prostate cancer for decades. However, PSA has poor specificity in prostate cancer screening within the 4.0- to 10.0-ng/mL range. This study aimed to develop a new prediction model for PCa in patients with a PSA level of 2.5–20 ng/mL. The clinical data of 80 patients with PSA 4–22 ng/mL from 2016 to 2022 were selected for retrospective analysis. Prostate volume was estimated by suprapubic ultrasonography. PSA and the inflammatory markers like neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) in peripheral blood were analyyzed to assess their value in PCa. The diagnostic performance of PSA, PSA density (PSAD), and inflammatory markers, respectively, was estimated by ROC curve. The areas under the ROC curve for f/t PSA, PV, PSAD, MLR, NLR, and PLR for predicting PCa in patients with a PSA level of 4.0–22.0 ng/mL were 0.7375, 0.7774, 0.8294, 0.5945, 0.5571, and 0.5437, respectively. The PSAD performed better than f/t PSA and PV in the diagnosis of PCa. The specificity of PSAD was higher than that of f/tPSA when tPSA was in the gray zone (between 4 and 10 ng/mL). The area under the curve (AUC) increased when PSAD was combined with MLR in patients with PSA 4–10 ng/mL and patients with PSA 10–22 ng/mL, and the positive predictive values were 81.81% and 90.91%, respectively (P = 0.0008 and P = 0.0002). PSAD has a moderate diagnostic value for PCa detection. The combination of PSAD and MLR could improve the diagnostic accuracy in PCa diagnosis.

Objective To investigate the correlation of Wnt5a expression and vasculogenic mimicry(VM)in prostate cancer tissues,and analyze their relationships with cancer stem cells(CSCs)characteristics and epithelial-mesenchymal transition(EMT).Methods Immunohistochemistry was conducted to detect the expression of Wnt5a in 50 prostate cancer tissues and 50 benign prostatic hyperplasia tissues.The expression levels of CD133,vimentin,and E-cadherin were detected in the prostate cancer tissues,and CD34/PAS double staining was used to detect VM structures.We analyzed the difference in Wnt5a level between prostate cancer and benign prostatic hyperplasia tissues,the clinical significance of Wnt5a and VM,the relationship of Wnt5a expression and VM,and the relationships of Wnt5a expression and VM with CD133,Vimentin,E-cadherin.Results The expression of Wnt5a was significantly higher in prostate cancer tissues than in benign prostatic hyperplasia(P<0.05).A positive correlation was observed between Wnt5a expression and VM(P<0.05).The expression levels of Wnt5a and VM were positively correlated with those of CD133 and vimentin(P<0.05).Wnt5a expression and VM were positively correlated with Gleason score,vas deferens invasion and lymphatic metastasis(P<0.05)of prostate cancer,and VM was also positively correlated with T stage of prostate cancer(P<0.05).Conclusion The expression level of Wnt5a in prostate cancer tissues is elevated and positively related with VM formation.Wnt5a expression and VM are correlated with cancer stem cells characteristics and the expression of epithelial-mesenchymal transition marker proteins.

OBJECTIVE:To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis. METHODS:A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group (n = 68) and a control group (n = 64), the former following the Mediterranean dietary pattern, the latter adhering to their own dietary habits, and meanwhile both receiving lifestyle guidance, psychological counseling, symptomatic medication and physiotherapy according to their specific symptoms. The patients were followed up for 4 weeks, therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment. RESULTS:Compared with the baseline, the quality of life (QOL) scores, pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment (P < 0.05), even more decreased in the former than in the latter, but with no statistically significant difference between the two (P > 0.05). The rate of therapeutic effectiveness was higher in the observation group than in the control (87.1% vs 79.7%, but showed no statistically significant difference between the two groups (P > 0.05). CONCLUSION:Multimodal therapy is suitable for the management of different clinical manifestations of individual patients, while dietary habits vary from person to person as well as from region to region. Therefore, scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.

Prostate cancer (PCa) represents a substantial global health concern and a prominent contributor to male cancer-related mortality. The aim of this study is to explore the role of B-type endothelin receptor (EDNRB) in PCa and evaluate its therapeutic potential. The investigation employed predictive methodologies encompassing data acquisition from the GEO and TCGA databases, gene screening, enrichment analysis, in vitro experiments involving PCR, Western blotting, wound healing, and Transwell assays, as well as animal experiments. Analysis revealed a significant downregulation of EDNRB expression in PCa cells. Overexpression of EDNRB demonstrated inhibitory effects on tumor cell growth, migration, and invasion, likely mediated through activation of the cGMP-Protein Kinase G pathway. In vivo experiments further confirmed the tumor-suppressive properties of EDNRB overexpression. These findings underscore the prospect of EDNRB as a therapeutic target for PCa, offering novel avenues for PCa treatment strategies.

BACKGROUND:Docetaxel (DTX) resistance attenuates anti-tumor effects of DTX on prostate cancer (mCRPC) and drug resistance was related to Treg expansion in tumors. ZNF667-AS1 played a suppressing role in various tumors and tumor-derived exosomes carry lncRNAs to participate in tumor progression. Here, the effects of ZNF667-AS1 on malignant characteristics and DTX resistance in PC and the effect and its underlying molecular mechanism of tumor-derived exosomes carrying ZNF667-AS1 on Treg expansion were investigated. METHODS:The identification of exosomes were determined using TEM, NTA and western blot. The abundance of genes and proteins were evaluated using IHC, RT-qPCR, western blot and FISH. Malignant phenotypes of PC cells were evaluated by means of Edu, scratch test, transwell, CCK-8 and flow cytometry. The percentage of CD4+CD25+Foxp3+ Tregs was detected using flow cytometry. The location of ZNF667-AS1 was detected using nuclear-cytoplasmic fractionation. The co-location of ZNF667-AS1 and U2AF1 protein was detected using IF-FISH assay. The interactions among ZNF667-AS1, TGFBR1 and U2AF1 were verified using RNA pull-down, RIP and dual luciferase activity. RESULTS:ZNF667-AS1 expression in PC samples was lowered, which was negatively relative to poor prognosis and DTX resistance. ZNF667-AS1 overexpression inhibited malignant phenotypes of PC cells, tumor growth and DTX resistance. Besides, DTX resistant cell-derived exosomes expressed lower ZNF667-AS1 expression. Exosomes carrying exogenously high ZNF667-AS1 expression derived PC cells or serum of mice suppressed Treg expansion. On the mechanism, ZNF667-AS1 interacted with U2AF1 to destabilize TGFBR1 mRNA and reduce TGFBR1 expression in CD4+T cells. CONCLUSION:ZNF667-AS1 suppressed cell growth of PC cells, tumor growth of mice and DTX resistance to PC cells and exogenously high ZNF667-AS1 expression in tumor-derived exosomes destabilized TGFBR1 mRNA and reduce TGFBR1 expression through interacting with U2AF1, thus resulting in attenuated Treg expansion, which was related to DTX resistance.

OBJECTIVE:To investigate the selection of the modality of transperineal surgery and its effect in the treatment of pelvic fracture-induced posterior urethral atresia (PUA). METHODS:This study included 116 cases of PUA caused by pelvic fractures treated in our hospital from January 2012 to December 2021. We used transperineal resection of the urethral stricture and end-to-end urethral anastomosis (EEUA) as the first choice in the treatment of 79 cases. For the patients with the urethral atresia segment longer than 3 cm and evident urethral involution tension, we incised the penile septum, separated and removed the muscle tendon and scar tissue attached to the lower border of the pubis, and anastomosed with 4-0 absorbable thread for 8 stitches. For the other 37 cases for which we were not sure of effective suture of the membrane due to obvious scarring of the proximal urethra, the remaining urethra shorter than 5 mm or incomplete urethral mucosa, we selected conventional urethral pull-through operation (UPTO). We followed up the patients for 3－24 months postoperatively. RESULTS:The total success rate of surgery was 78.4% (91/116), 81.1% (30/37) in the UPTO and 77.2% (61/79) in the EEUA group, significantly higher in the former than in the latter (P= 0.05). The rate of postoperative dysuria was remarkably lower in the UPTO than in the EEUA group (13.5% ［5/37］ vs 16.5% ［13/79］, P= 0.05), and so was that of surgical failure (5.4% ［2/37］ vs 6.3% ［5/79］, P= 0.05 ). The main causes of postoperative dysuria in the EEUA group included restenosis resulting from incomplete scar resection and the two sides of the anastomosed urethral segment not being at the coaxial level, while those in the UPTO group included the formation of mucosal flaps in the pulled-through urethra, and re-scarring leading to stricture or the pulled-through urethra not being at the coaxial level. Among the 7 cases of surgical failure due to recurrence, 1 refused reoperation and opted for cystostomy tube drainage, and the other 6 underwent EEUA again 6 months later. CONCLUSION:EEUA is preferred as the first-choice surgery for PUA, while UPTO remains an effective treatment option in hospitals with preliminary skills and less experience in the management of PUA.

Self-oscillating polymer brushes have unique applications in enclosed spaces,but there has been a lack of theoretical model to reveal their physical mechanisms systematically and profoundly and predict new structures.Based on diffusion dynamics,we establish a new theoretical model to study the self-oscillation of switching for polymer brushes.Firstly,we quantitatively determine the dynamic characteristics of self-oscillation switching of polymer brush as well as the important role of the Belousov Zhabotinsky(BZ)reaction of polymer monomers in inducing polymer brush self-oscillation.Then,the chemical wave characteristics of the conformational transition of the polymer brush are obtained,revealing that this chemical wave largely originated from the BZ reaction.The theoretical results reveal that the BZ reaction lead to chemical oscillations,and the diffusion within the polymer brush also propagates in the form of chemical waves.Moreover,the self-oscillating polymer brush can also change the reaction mode of BZ.The research results confirm that the self-oscillating characteristics of the conformational transition of the polymer brush follow diffusion dynamics.Based on the model,it can be predicted that the spatial fluctuation of the volume fraction of polymer brushes will lead to the spatial non-uniformity of volume distribution of polymer monomers in the brushes,and then a nodular structure will appear in the polymer brushes.The results of this paper can provide useful reference for designing intelligent polymer surface materials.

本文基于Hill动力学与Michaelis-Menten方程,建立理论模型研究胰岛素通过环磷腺苷效应元件结合蛋白(CREB)调节肝糖异生的物理机制.理论模型考虑胰岛素通过CREB调节过氧化物酶体增活化受体γ辅助活化因子(PGC)联级信号,进而调控肝脏糖异生,影响糖代谢信号通路特性.研究发现,在异常胰岛素(Ginsulin)作用下CREB表达提升,进一步刺激了磷酸烯醇式丙酮酸羧激酶1(Pck1)表达.通过Pck1的调控,柠檬酸盐酯(citrate)、α-酮戊二酸(α-keto glutarate)、苹果酸酯(Malate)、草酰乙酸盐(Oxaloacetate)出现了不同的代谢水平.高表达的CREB会上调Pck1的表达水平,通过CREB、Pck1的调节作用,磷酸烯醇式丙酮酸羧化酶(phosphoenolpyruvate)转化为白藜芦醇(Pyruvate)的水平提升,进而促使citrate、α-keto glutarate、Malate、Oxaloacetate大幅度升高,最终影响细胞葡萄糖代谢.在糖异生基因的调控作用下,较高浓度的葡萄糖(Glocose),使得phosphoenolpyruvate浓度提升,并且在Pck1的调控作用下,phosphoenolpyruvate转化为Pyruvate的量增多,也会使得citrate、α-keto glutarate、Malate、Oxaloacetate大幅度提升.理论结果进一步深刻揭示了胰岛素、CREB蛋白,以及糖异生基因对细胞糖代谢新的调控机理,可为设计阻断糖尿病转变通路的治疗方案提供理论依据.

Objective To investigate the role of urotoxin Indoxyl sulfate(IS)in inducing oxidative stress and fibro-sis factors in HK-2 cells through organic anion transporter-3(OAT-3).Methods Human normal renal tubular epithelial(HK-2)cells were subcultured.After cells grown with 80%～90%density,the experiment was divided into control group(Control)and IS treatment group(IS)cultured with 250 μmol of IS for 24h.At the same time,the expression of OAT-3 was further silenced with small interfering RNA(siRNA).RT-PCR and western blot was performed to analyze the mRNA and protein levels of oxidative stress(Nox-4)and fibrosis factors(CollagenI,TGF-β1,Smad-3,α-SMA).Fi-nally,HK-2 cells were pre-treated with antioxidant N-acetylcysteine(NAC)and stimulated with 250 μmol of IS for 24 h.Results RT-PCR results showed that after HK-2 cells were stimulated with IS of 250 μ mol for 24h,IS significantly increased oxidative stress(Nox-4)and fibrosis factors(Collagen I,TGF-β1,Smad-3,α-SMA)in HK-2 cells(P<0.01).After OAT-3 silenced by siRNA in HK-2 cells,the mRNA and protein expression levels of oxidative stress and fibrosis factors induced by IS were significantly decreased(P<0.001).It is suggested that IS can induce their high expression through OAT-3.After HK-2 cells were pretreated with N-acetylcysteine(NAC)and stimulated with IS for 24h,it was found that NAC effectively inhibited IS induced mRNA and protein high expressions of Nox-4,Collagen I,TGF-β1,Smad-3,and α-SMA(p<0.01),showed that IS promoted the high expression of fibrosis factors in HK-2 cells through the high expression of oxidative stress.Conclusion IS uptaken by OAT-3 in HK-2 cells induces high expressions of oxi-dative stress and fibrosis factors.

目的 研究输尿管软镜碎石术教学中采用操作技能直接观察(DOPS)评估效果.方法 选择2021—2023年本院泌尿外科带教的学生56名,按照带教形式与评估方式的不同,分为试验组和对照组,分析带教效果.结果 试验组学生末期SOAP量表评分明显高于中期SOAP量表评分,P<0.05,但初期、中期SOAP量表评分组间对比,差异无显著性,P>0.05;试验组学生综合能力、学生对带教老师满意度、学生批判性思维评分高于对照组,P<0.05.结论 DOPS评估作为高效的一种教学和评估形式,可明显提升教学的效果.

Prostate cancer (PCa) is one of the leading causes of cancer-related death in males worldwide and exploring more reliable biomarkers for PCa is essential for the diagnosis and therapeutics for the disease. Although the functions of miR-141-3p and AlkB homolog 5 (ALKBH5) were identified in some cancers, whether they were involved in the development of PCa remains unclear. In this study, reverse transcription-quantitative polymerase chain reaction unveiled that the expression of ALKBH5 was reduced in PCa tissues and was negatively correlated with miR-141-3p. ALKBH5 attenuated the malignant development of PCa through suppressing the growth, migration, invasion, and sphere formation abilities of PCa cells. In addition, the luciferase activity assay identified that ALKBH5 was corroborated as a downstream target of miR-141-3p. Moreover, miR-141-3p expression was boosted in PCa tissues and cells and inhibition of miR-141-3p suppressed the tumor growth of PCa in vivo. Moreover, ALKBH5 was confirmed to suppress protein arginine methyltransferase 6 (PRMT6) expression through N6-methyladenosine (m6A) modification. We further identified that miR-141-3p-modulated PRMT6 level through mediating ALKBH5. Furthermore, PRMT6 level was positively correlated with miR-141-3p level and negatively associated with ALKBH5 level. Finally, rescue assays also uncovered that miR-141-3p aggravated PCa development by regulating PRMT6. In conclusion, miR-141-3p accelerated the malignant progression of PCa through ALKBH5-mediated m6A modification of PRMT6, which might offer a novel insight into the role of miR-141-3p and ALKBH5 in the treatments of PCa patients.

Objective To explore the inhibition effect and mechanism of miR-146a-5p on proliferation and invasion of prostate cancer (PCa) cell line PC-3 by targeting SMAD4. Methods RT-qPCR was used to detect the expression of miR-146a-5p in PCa tissues and cell lines. The relevance of miR-146a-5p expression with Gleason score was also analyzed. MTT, BrdU experiment, cell colony formation experiment, scratch experiment, Transwell assay and nude mouse xenograft model experiment were conducted to detect the effect of miR-146a-5p on cell proliferation, tumorigenicity, migration and invasion. The expression of SMAD4 in PCa tissues was detected by RT-qPCR, and the targeting relationship of SMAD4 and miR-146a-5p was confirmed by double luciferase reporter gene assay and rescue experiment. Western blot was used to detect the expression of SMAD2/SMAD3 complex in nucleus affected by miR-146a-5p and SMAD4. Finally, double luciferase reporter gene assay and ChIP experiment were performed to examine the targeting regulation of TIM3 by miR-146a-5p/SMAD4/SMAD2/SMAD3 signaling axis. Results miR-146a-5p was low expressed in PCa tissues and cell lines; its expression was negatively correlated to Gleason score and had the lowest expression in PC-3 cells. miR-146a-5p inhibited the proliferation and invasion of PC-3 cells by targeting SMAD4. SMAD2/SMAD3/TIM3 axis seemed to be the downstream mechanism of miR-146a-5p/SMAD4 signaling pathway. Conclusions miR-146a-5p can inhibit the proliferation and invasion of PC-3 cells by targeting SMAD4, and the downstream mechanism might be related to the SMAD2/SMAD3/TIM3 signaling pathway.

目的:分析上尿路结石梗阻所致脓毒血症患者的菌群分布及抗生素敏感谱特点.方法:回顾性分析2004年1月至2021年9月在新疆维吾尔自治区人民医院住院治疗的上尿路结石梗阻所致脓毒血症患者的病历资料,收集其性别、年龄、合并症、病原菌培养及药敏试验结果,并进行统计学分析,探讨其病原菌分布及抗生素敏感谱的特点.结果:本研究共纳入215例患者,男性76例,女性139例,其中病原菌培养阳性结果为151例(70.2％),阴性结果为64例(29.8％).在阳性结果患者中,共分离出菌株154株,其中革兰阴性菌125株(81.2％),革兰阳性菌25株(16.2％),真菌4株(2.6％).最常见的病原菌为大肠埃希菌,共98株(63.6％),其在革兰阴性菌中占比高达78.4％.在性别方面,女性感染大肠埃希菌的比例(74.0％)与男性(51.0％)有明显的统计学差异(P<0.05).革兰阳性菌中最常见的病原菌为屎肠球菌,共6株(3.9％).本研究中,革兰阴性菌对亚胺培南的敏感率最高,达99.2％.大肠埃希菌对碳青霉烯类抗生素(亚胺培南和美洛培南)的敏感率为100.0％.除亚胺培南和美洛培南外,大肠埃希菌对阿米卡星、呋喃妥因、哌拉西林/他唑巴坦、头孢哌酮/舒巴坦的敏感率也较高.革兰阳性菌对万古霉素、利奈唑烷、替拉考宁的敏感率最高,均为100.0％.在治疗大肠埃希菌感染时,女性对头孢他啶的敏感率(70.8％)明显高于男性(47.8％),差异具有统计学意义(P<0.05).结论:引起上尿路结石梗阻所致脓毒血症的主要病原菌为革兰阴性菌中的大肠埃希菌,女性更易感染大肠埃希菌,且女性大肠埃希菌感染者对头孢他啶的敏感性更高.临床可选用碳青霉烯类抗菌药物、头孢他啶等治疗上尿路结石梗阻所致脓毒血症.