BACKGROUND:Chemotherapy remains the most effective systemic treatment for bladder cancer (BLCA), with cisplatin as the primary agent. However, the frequent development of cisplatin resistance limits its clinical efficacy. Forkhead box D1 (FOXD1) is implicated in BLCA progression, yet its role in mediating cisplatin resistance remains unexplored. METHODS:FOXD1 expression and its correlation with patient prognosis in BLCA were analyzed using the TCGA database. Cisplatin-resistant BLCA cell lines (T24-R and HT-1376-R) were established by treatment with gradient concentrations of cisplatin. qRT-PCR and Western blot were performed to detect the expression levels of FOXD1, β-catenin, and Aspartyl-tRNA Synthetase 2 (DARS2). Cell viability, proliferation, cell cycle, and apoptosis were assessed using CCK-8, colony formation assays, and flow cytometry. Co-IP was performed to examine the interaction between FOXD1 and β-catenin. Glycolysis levels in BLCA cells were determined using specific assay kits. RESULTS:FOXD1 was highly expressed in BLCA tissues and correlated with poor prognosis. Knockdown of FOXD1 inhibited proliferation and cell cycle progression, promoted apoptosis, and enhanced cisplatin sensitivity in T24-R cells, while reducing β-catenin nuclear translocation and DARS2 expression. Overexpression of FOXD1 exerted the opposite effects on HT-1376-R cells and increased DARS2 expression, which were reversed by β-catenin knockdown. Moreover, knockdown of TCFs/LEF suppressed DARS2 expression. DARS2 was enriched in the glycolysis pathway. Its overexpression promoted glycolysis, proliferation, and cell cycle progression, while inhibiting apoptosis and cisplatin sensitivity in HT-1376-R cells-effects were reversed by 2-DG. CONCLUSION:FOXD1 facilitates β-catenin nuclear translocation and upregulates DARS2 to enhance glycolysis, thereby promoting cisplatin resistance in BLCA. These findings identify the FOXD1/β-catenin/DARS2 axis as a potential therapeutic target for overcoming cisplatin resistance in BLCA clinically.

Traditional clinicopathological features often inadequately reflect systemic host-tumor dynamics, compromising the predictive accuracy of biochemical recurrence (BCR) in prostate cancer, particularly with respect to early oncological failure. This study sought to evaluate the SII-HALP combined score—integrating the Systemic Immune-Inflammation Index (SII) and Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score—and assess its time-dependent prognostic value in patients undergoing radical prostatectomy. Clinicopathological data from patients with localized prostate cancer were retrospectively analyzed. Maximally selected rank statistics identified optimal threshold values for SII and HALP. A prognostic nomogram incorporating the combined score was then constructed. Model performance was assessed using time-dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). The incremental predictive value was quantified via integrated discrimination improvement (IDI) and net reclassification improvement (NRI). Multivariable Cox regression established the SII-HALP combined score as an independent predictor of BCR. The nomogram exhibited an improved predictive performance for 1-year recurrence (AUC 0.866 vs. 0.821 in the base model; P = 0.002). This incremental gain was confirmed by an IDI of 0.067 (P < 0.001) and an NRI of 0.532 (P = 0.040). While the incremental benefit diminished at exploratory 3- and 5-year timepoints as anatomical factors became predominant, DCA indicated a superior net benefit at 1 year across most threshold probabilities, and tentatively at higher thresholds (> 50

Background: Clear cell renal cell carcinoma (ccRCC) accounts for 70 % of all renal cell carcinoma (RCC) types, and 30 % of patients with ccRCC present with metastasis at the time of initial diagnosis. Given the high prevalence of metastasis, basic research into potential therapeutic targets for unresectable and metastatic ccRCC is crucial. Our study aims to explore the regulatory mechanism of targeting protein for Xklp2 (TPX2) in ccRCC, which may provide novel insights for the treatment of this disease. Methods: Reverse-transcription polymerase chain reaction (RT-qPCR) was performed to analyze mRNA expression, whereas Western blot (WB) was used to detect protein expression. The abilities of colony formation and proliferation, as well as the proportion of apoptosis in treated RCC cells, were assessed using colony formation, 5-Ethynyl-2 '-deoxyuridine (EdU), and flow cytometry assays, respectively. The intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and ferrous ion (Fe2+) in treated RCC cells were examined by corresponding kits. A tumor cell-derived xenograft model was utilized to verify the regulatory function of TPX2 in vivo. The RBPsuite website and methylated RNA immunoprecipitation (MeRIP)-qPCR assay were employed to verify the N6-methyladenosine (m6A) modification level on TPX2 mRNA, mediated by methyltransferase-like 14 (METTL14). The stability of TPX2 mRNA triggered by METTL14 was evaluated by RNA decay assay. Results: The expression of TPX2 was elevated in ccRCC tissues and cell lines. TPX2 knockdown in RCC cells inhibited the abilities of cell colony formation and proliferation and boosted cell apoptosis, and its knockdown facilitated cell ferroptosis by hindering the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). The tumor cell-derived xenograft tumor model exhibited that TPX2 silence inhibited tumor growth in vivo. RCC cells with METTL14 overexpression showed higher levels of m6A-modifying sites compared to those without overexpression. METTL14 overexpression in RCC cells boosted TPX2 mRNA degradation and impeded its protein expression in a YTHDF2-dependent manner. In addition, RCC cells overexpressing METTL14 displayed impaired abilities for colony formation and proliferation, as well as an increased proportion of apoptotic cells. However, these effects were mitigated by the overexpression of TPX2. TPX2 overexpression also reversed the promotion of ferroptosis induced by METTL14 upregulation. Conclusion: METTL14-mediated m6A modification on TPX2 mRNA inhibited tumor progression by repressing the expression of SLC7A11 and GPX4 in ccRCC.

BACKGROUND:Mal, T cell differentiation protein 2 (MAL2) has emerged as a potential regulator in the progression of bladder cancer (BCa). Therapeutic resistance to sunitinib poses a significant challenge in BCa treatment. This study investigates the role of MAL2 in modulating BCa malignant development and its influence on sunitinib sensitivity. METHODS:The mRNA levels of MAL2 and E2F transcription factor 1 (E2F1) were analyzed by quantitative real-time polymerase chain reaction, whereas their protein expression was detected by western blotting. Cell proliferation was analyzed by 5-Ethynyl-2'-deoxyuridine assay. Cell apoptotic rate was quantified by flow cytometry. Cell migration and invasion were analyzed through transwell assays. The sensitivity of BCa cells to sunitinib was analyzed by cell counting kit-8 assay. Fe2+ and malondialdehyde levels were analyzed through colorimetric assays. Reactive oxygen species levels were analyzed through fluorometric assay. The molecular interactions between E2F1 and MAL2 were explored using chromatin immunoprecipitation and dual-luciferase reporter assays. The in vitro findings regarding the effects of E2F1 and MAL2 on the malignant progression of BCa cells were further corroborated in vivo using xenograft mouse models. RESULTS:The expression of MAL2 was elevated in both BCa tissues and cells. Silencing MAL2 expression led to a suppression of BCa cell proliferation, migration, and invasion, while simultaneously enhancing cell apoptosis and ferroptosis, and increasing sensitivity to sunitinib. E2F1 was identified as a transcriptional activator of MAL2 in T24 and J82 BCa cells, and its overexpression fostered the malignant progression of BCa cells and reduced their responsiveness to sunitinib. Additionally, the adverse effects of E2F1 silencing on BCa cell behavior were mitigated by the overexpression of MAL2 in vitro and in vivo. CONCLUSION:E2F1-induced transcriptional activation of MAL2 promoted the progression of BCa and inhibited sunitinib sensitivity, offering a potential novel therapeutic approach for BCa patients.

BACKGROUND:The response of prostate cancer (PCa) to immunotherapy remains suboptimal. Although MEIS homeobox 2 (MEIS2) has been shown to delay the malignant progression of PCa by inhibiting cancer cell proliferation, promoting DNA damage, and affecting CD8+ T cell immune surveillance, its role in immune regulation and the underlying mechanisms remain elusive. METHODS:MEIS2 expression in PCa and its correlation with CD8+ T cells were characterized using bioinformatics analysis and cell experiments. Using qPCR, flow cytometry, and ELISA, the impact of MEIS2 on CD8+ T cell antitumor immunity was assessed. To delineate the role of MEIS2 in oxidative phosphorylation and ROS generation, OCR, ATP, and ROS measurements were collected. Finally, the oxidative phosphorylation inhibitor MCH32 was introduced and rescue experiments were conducted to elucidate the mechanism by which MEIS2 regulated CD8+ T cell cytotoxicity. RESULTS:MEIS2 expression in PCa was found to be downregulated, positively correlating with CD8+ T cell infiltration. Functionally, MEIS2 overexpression enhanced the cytotoxicity of CD8+ T cells. Mechanistically, MEIS2 was notably enriched in oxidative phosphorylation and ROS pathways. Knockdown of MEIS2 in cancer cells stimulated oxidative phosphorylation and ROS production, which impaired CD8+ T cell antitumor immunity. Treatment with the oxidative phosphorylation inhibitor MCH32 reversed these effects induced by MEIS2 knockdown. CONCLUSION:Targeting MEIS2 could represent a clinically relevant approach to enhancing CD8+ T cell antitumor efficacy in PCa, our findings indicate.

INTRODUCTION:Vesicular transport (VT) has a complex relationship with tumor progression and immunity. But prognostic significance of VT in clear cell renal cell carcinoma (ccRCC) is unclear. Thus, we aimed to establish a prognostic model according to VT to predict overall survival of ccRCC patients.METHODS:We used patient data from TCGA database and built a prognostic model with 13 VT-related genes (VTRGs) by differential expression analysis, LASSO regression, and univariate/multivariate Cox analysis. The model was validated internally and externally, and survival analysis and ROC curves depicted excellent predictive ability. Furthermore, higher modeled riskscores corresponded to more advanced tumor progression. To further understand the potential reasons for different prognoses in patients, we did enrichment analysis on differentially expressed genes identified by the model in risk groups. The expression levels and roles of SAA1 and KIF18B in ccRCC were verified by qRT-PCR and cell function experiments.RESULTS:Humoral immune response and cAMP signaling pathway may be the biological processes and pathways leading to poor prognosis. Further analysis of immune microenvironment presented that ccRCC patients with poor prognoses had highly immune-infiltrated characteristics. We compared the drug response data of samples from different prognostic patients in the GDSC database and identified drug sensitivity differences associated with prognosis. Finally, we demonstrated that SAA1 and KIF18B could increase the proliferation, migration, and invasion ability of ccRCC cells using cellular experiments.CONCLUSION:In summary, we further revealed the importance of VTRGs in ccRCC prognosis.

兰新(张)三四线甘肃牵引站 330 千伏外部供电工程对于甘肃省河西经济走廊的重要客运通道贯通具有重要保障作用,甘肃祁连山国家级自然保护区生物多样性可能会因为工程的开工建设和后期的运行阶段受到影响.根据工程性质及影响对象的特点,通过野外调查,结合内业数据分析处理,建设工程对保护区的生物多样性影响指数值为 51.67＜60,属中低度影响,不会威胁到甘肃祁连山国家级自然保护区主体的生态价值功能和自然资源现状.

As a widely used first-line agent for prostate cancer treatment, cisplatin is facing drug resistance which has resulted in chemotherapy failure in many prostate cancer patients, while the related molecular mechanisms remain unclear. In this study, we discovered that MEIS homeobox 2 (MEIS2) was lowly expressed in prostate cancer tissues by bioinformatics analysis, which had a close connection with the T stage and N stage of the tumor. Cell function experiments demonstrated that MEIS2 overexpression was capable of significantly suppressing proliferation of tumor cells, arresting prostate cancer cells in G0/G1 phase, and promoting DNA damage, thereby enhancing the sensitivity of prostate cancer to cisplatin. Dual-luciferase assay and chromatin co-immunoprecipitation (ChIP) assays confirmed the binding relationship between MEIS2 and ELF1. The results of rescue assay showed that ELF1 could promote DNA damage and enhance the sensitivity of tumor cells to cisplatin by activating MEIS2. In conclusion, the results of this study demonstrated that ELF1 could modulate DNA damage through activating MEIS2 and thus enhance cisplatin sensitivity in prostate cancer. This study suggested that the ELF1/MEIS2 axis may be a therapeutic target to strengthen cisplatin sensitivity in prostate cancer.

Background:Neoadjuvant endocrine therapy (NET) of prostate cancer (PCa) may alter the tissue acoustic environment (AET). The structure of tissue is an important factor affecting AET. The aim is to analyze changes in tissue structures after NET in PCa, focusing on calcifications, smooth muscle cells, and blood vessels.Methods:We collected 40 patients diagnosed with PCa by pathological examination between October 2020 and December 2022. Twenty patients who underwent radical prostatectomy (RP) after NET were designed as the test group. Twenty patients without NET were assigned to the control group. Calcifications, smooth muscle cells and blood vessels were observed by hematoxylin-eosin (HE) staining and Van Gieson (VG)-special staining respectively. Then the amount and acreage of calcified tissue, the number of smooth muscle cells and different types of blood vessels were quantitatively analyzed.Results:There was a subtle increase in the number (P=0.001) and the area (P<0.001) of calcification after NET. The total number of smooth muscle cells was significantly higher than that without NET (P<0.001). NET resulted in significantly fewer veins compared to those without NET (P<0.001). There was a little increase in the number of arteries after NET (P=0.001). The number of veins decreased was much greater than the number of arteries increased resulting in significantly fewer total vessels after NET (P<0.001).Conclusions:NET can lead to changes in calcifications, smooth muscle cells, and blood vessels within PCa tissues, which may cause alterations in AET.

目的 观察甲基转移酶3(METTL3)基因对前列腺癌细胞系PC-3、DU145中肿瘤相关蛋白c-Myc、EGFR、Bcl-2表达的影响,并探讨相关作用机制.方法 运用RNA干扰技术合成METTL3 siRNA-1400、阴性siRNA.将PC-3、DU145细胞分别分为空白对照组、阴性对照组、实验组,空白对照组不做特殊处理,阴性对照组转染阴性对照siRNA,实验组转染METTL3 siRNA-1400.采用Western blotting法检测各组细胞中的肿瘤相关蛋白c-Myc、EGFR、Bcl-2,Dolt blotting法检测各组细胞RNA的N6-甲基腺苷(m6A)修饰水平.结果 PC-3细胞、DU145细胞的实验组c-Myc、EGFR、Bcl-2蛋白表达均低于空白对照组、阴性对照组(P均<0.01).PC-3细胞、DU145细胞的实验组RNA m6A修饰水平均低于空白对照组和阴性对照组(P均<0.01).结论 沉默前列腺癌PC-3、DU145细胞中METTL3基因可抑制肿瘤相关蛋白c-Myc、EGFR、Bcl-2的表达,其机制可能与METTL3参与RNA的m6 A修饰有关.

通过对甘肃省武威市湿地类型特征和分布规律进行的分析,总结了武威市湿地保护管理存在的生态用水匮乏、保护与开发矛盾突出、管理体系与法律体系不完善等主要问题,提出了增加湿地生态用水优先发展新型节能环保项目、加大湿地自然保护区建设力度、加强湿地管理体系、执法体系建设等建议和对策.

目的:探讨医护一体化"泌联APP"在泌尿外科留置双J管后延续护理中的应用效果.方法:选取2018年7月至12月在我院泌尿外科因上尿路结石行输尿管软镜碎石手术,且术后留置双J管的320例出院患者作为研究对象,通过动态随机化法分为干预组160例,对照组160例.对照组患者给予常规健康教育和出院指导;干预组患者采用医护一体化"泌联APP"实施延续护理.比较2组患者院外留置双J管期间的并发症发生情况,应用自我感受负担量表(SPB)、焦虑自评量表(SAS)对患者负担感、焦虑感进行评价.结果:干预组发生尿频、尿急、尿路感染、血尿、腰部胀痛、延迟拔管及双J管移位等发生率均明显低于对照组(P<0.05);拔管前干预组SPB评分和SAS评分均低于对照组(P<0.05).结论:与院外采用常规健康教育和出院指导进行延续护理相比,外院留置双J管患者采用医护一体化"泌联APP"实施延续护理能显著减少并发症,改善患者的负担感和焦虑感.

BACKGROUND The role of lateral retroperitoneoscopic adrenalectomy (LRA) for complicated tumor with large diameter remains controversial, this study aimed to evaluate the effectiveness of this procedure on the management of tumor larger than 5cm in diameter. METHODS A retrospective comparison was conducted of 67 patients with large complicated adrenal tumor (>5cm). 41 patients received LRA, and 26 received open adrenalectomy (OA) in our hospital between January 2011 and June 2015. Basic characteristics regarding mean age, gender, body mass index (BMI), tumor size, tumor side, previous abdominal surgery, resection method, pathology were preferentially analyzed. Operative indicators regarding operation time, estimated blood loss (EBL), conversion to ICU, complications, post-operative hospitalization, duration of drain, time to first oral intake and ambulation were compared between groups. RESULTS There were no significant differences between the two groups in the basic characteristics. The mean operation time for LRA was shorter than OA (98.7±32.3 min vs 152.7±72.3 min, P = 0.001). EBL was 31.9±20.0 ml for LRA and 590.0±1181.1 ml for OA (P = 0.03). There was no complication in LRA group and one patient in OA group had complications, but this difference was not significant (P = NS). The post-operative hospitalization in LRA was 7.4±2.8 days, and shorter than 9.8±2.7 days in OA group (P = 0.00). The time to first oral intake and ambulation for LRA was shorter than OA (first oral intake, 1.9±0.8 days vs 3.1±1.3 days, P = 0.00; time to ambulation, 2.6±1.4 days vs 4.2±1.6 days, P = 0.00). While the difference between groups were not significant in terms of ICU conversion (3/41 vs 4/26, P = NS) and duration of drain (3.9±2.2 days vs 4.7±1.9 days, P = NS). CONCLUSION Our study shows that LRA can be performed safely and effectively for complicated adrenal tumors larger than 5 cm in diameter, but it remains technically demanding.

Objective To investigate the effect of preoperative placement of double-J ureteral catheter on complications of flexible ureteroscopic lithotripsy for kidney stones.Methods A total of 218 patients with kidney stones who underwent flexible ureteroscopic lithotripsy were enrolled.According to whether a double-J ureteral catheter was placed before surgery,these patients were divided into preoperative placement group (131 patients) and conventional group (87 patients).The two groups were compared in terms of time of operation,length of postoperative hospital stay,and complications.Results There were significant differences between the two groups in time of operation,length of postoperative hospital stay,success rate of ureteral sheath placement,ureteral injuries,intraoperative bleeding,postoperative hematuria,urinary-derived sepsis,formation of steinstrasse,and incidence of residual stones in kidney (t=7.19,6.18;x2 =4.26-9.39;P＜0.05).Conclusion Preoperative placement of double-J ureteral catheter before flexible ureteroscopic lithotripsy can significantly reduce time of operation,length of postoperative hospital stay,and number of complications.

目的：探讨不同类型慢性前列腺炎（CP）对男性精液质量参数变化的影响。方法检测98例不同类型的CP患者，其中Ⅱ型21例，ⅢA型40例，ⅢB型37例，另选取31例健康男性对照组精液参数，比较C P患者和对照者精液质量变化差异有统计学意义。结果各型CP患者精液精子浓度及精液量与对照组比较差异无统计学意义（P＞0．05），ⅢA型及ⅢB型CP患者与对照者比较液化时间更长，畸形率更高，差异有统计学意义（P＜0．05），CP各组与对照组比较精子活率及精子活动力更低，差异有统计学意义（P＜0．05）。结论 CP影响患者精液液化时间、精子存活率、精子活动力，对男性生育力也有一定影响。

To elucidate the association between nerve growth factor (NGF) level and bladder pain syndrome/interstitial cystitis (BPS/IC) by conducting a meta-analysis.

Prostate sarcoma, particularly the pathological type of leiomyosarcoma, is a rare carcinoma, which originated from the interstitial tissue of the prostate. This sarcoma type has a poor prognosis. This disease accounts for ~0.1% of all prostate cancer and it usually occurrs in patients aged between 40 and 78-years-old. Although prostate leiomyosarcoma has a poor prognosis, early treatment of post-operative recurrence and metastases via a whole-body examination and closer follow-up was possible. These measurements may significantly prolong the survival time and improve the quality of life. The present study reported a successful case of surgical management for prostate leiomyosarcoma in the Zigong No. 4 People's Hospital (Sichuan, China) during 1995 until 2015, with post-operative follow-up for 20 years.

目的：探讨经皮肾镜碎石术（PCNL）并发症发生的原因及处理方法。方法回顾性分析2011年5月至2013年2月265例PC N L患者中发生并发症的临床资料，总结出现的并发症及采取的治疗方法。结果术中并发大出血4例（1．51％），肾实质损伤11例（4．15％），冲洗液严重外渗2例（0．75％），穿刺建立操作通道发现进入肾囊肿1例（0．38％）；扩张器外鞘脱出肾盂5例（1．87％），输尿管下段穿孔1例（0．38％），术中寒战3例（1．13％），肾结石残留17例（6．42％），输尿管结石残留5例（1．87％），术后持续性血尿1例（0．38％），术后发生肾周积脓1例（0．38％）、败血症8例（3．02％）、尿路感染25例（9．43％），肾功能一过性下降6例（2．26％），肾造瘘管1 d不慎扯落1例（0．38％）。全部患者均治愈出院，无一例死亡。结论经皮肾镜碎石术虽然有可能会出现各种并发症，但只要通过有效处理，并发症是可以控制的。

Objective To investigate the abnormal expression of Skp2 in human testicular germ cell tumours.Methods The expression of Skp2 in the tissues of human testicular germ cell tumours,normal testicular tissues,and chronic orchitis tissues were studied by immunohistochemistry(S-P method).Results The positive rate of Skp2 was 74.5% in testicular germ cell tumours,20.0% in normal testicular tissues,and 40.0% in chronic orchitis tissues respectively.There was a higher expression of Skp2 in testicular germ cell tumour tissues(P0.05),and the Skp2 expression was not associated with histological subtype(P0.05).Though the positive expression rate of Skp2 increased with rising clinical stage of testicular germ cell tumours,there was no relationship between the expression of Skp2 and clinical stage of testicular germ cell tumours(P0.05).Conclusion Difference of Skp2 protein expression in testicular germ cell tumours and normal testicles or chronic orchitis tissues indicates that abnormal regulation of cell cycle plays an important role in testicular germ cell tumours development and differentiation.

Objective To observe symptoms and urodynamic changes of patients with benign prostatic hyperplasia(BPH) before and after the combined treatment of Epristeride and Harold,and to investigate clinical significance of the combined treatment.Methods 38 outpatients with BPH underwent Epristeride and Harold received treatment in the 12 weeks,and the changes of urodynamic,residual urine and the symptoms were analyzed before and after the treatment.Results IPSS decreased from 21.4±5.1 to 13.2±3.9(P0.05),and the maximum urinary flow rate increased from(7.6±1.3)mL/s to(18.3±2.2)mL/s(P0.05)after treatment,the residual urine decreased from(75±7.1)mL to(36±5.2)mL(P0.05)after treatment,symptoms improved significantly in 32 cases,with an effective rate of 84%.Conclusion The combined treatment of Epristeride and Harold can improve urinary flow rate and reduce the IPSS score,and reduce the residual urine volume,with fewer side-effects and it is ideal clinical treatment of BPH.