Background Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in prostate cancer (PCa). Although branched-chain amino acid (BCAA) metabolism is implicated in cancer biology, its specific role in PARPi resistance remains unclear. This study aims to investigate how BCAA metabolism contributes to PARPi resistance in PCa.Methods We compared BCAA and Branched-Chain Amino Acid Aminotransferase 2 (BCAT2) levels between PARPi-resistant and PARPi-sensitive cell lines and assessed their clinical relevance. Functional studies were conducted in vitro and in vivo using cell and mouse models. Mechanistic assays, including RNA sequencing, metabolomics, RNA-binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and Cleavage Under Targets and Tagmentation (CUT&Tag), were used to delineate BCAT2-mediated PARPi resistance.Results BCAT2 expression correlated with PARPi resistance in PCa, and increased BCAA/BCAT2 levels in PARPi-resistant tissues were associated with reduced patient survival. Mechanistically, the DNA-binding domain (DBD) of PARP1 directly bound BCAT2 mRNA and regulated its stability; PARPi-induced PARP1 trapping weakened this interaction, increased BCAT2 expression, and promoted resistance. Transcriptomic and energy-metabolism analyses indicated that BCAT2 enhanced ABCG1 transcription by augmenting glycolysis and lactate secretion, thereby increasing histone H3K18la lactylation. These findings support a PARP1-BCAT2-ABCG1 axis in PARPi resistance. Combining a BCAT2 inhibitor with PARPi produced synergistic effects in cell line-derived xenografts (CDXs) and patient-derived organoids (PDOs).Conclusion The PARP1-BCAT2/H3K18la-ABCG1 axis drives PARPi resistance in PCa. Targeted BCAT2 inhibition may enhance the therapeutic efficacy of PARPi.

Hepatocellular carcinoma (HCC) remains a global challenge, with conventional locoregional therapies like transarterial chemoembolization (TACE) lacking tumor specificity and promoting metastasis and inflammation. Cold atmospheric plasma (CAP) offers a tumor-selective ablation strategy but suffers from limited tissue penetration. To overcome this, the FlexiPlasma microcatheter (FPM) is developed, integrating flexible non-metallic microtubes and ring-shaped electrodes for precise CAP delivery to deep tumors. The optimized FPM-generated CAP eliminates cytotoxic UV and ozone while inducing tumor-specific pyroptosis via a ROS/Caspase-8/GSDMC pathway. Gasdermin-C (GSDMC) is highly expressed in liver tumors but absent in normal tissues, ensuring selective targeting with minimal inflammation. FPM is combined with embolic material (EM), PPP@CD hydrogel, enhancing injectability, tumor embolization, and sustained drug release. This FPM-EM strategy potentiates antitumor immunity, particularly CD4+ and CD8+ T-cell responses. These findings establish FPM-EM as a safe, effective, and minimally invasive therapy for HCC, revealing a non-inflammatory pyroptosis mechanism and broadening the potential of CAP-based cancer treatments. The FPM-EM combination offers promising new therapeutic options for HCC, addressing the limitations of TACE. Furthermore, the FPM-EM platform can be extended to the interventional therapy of other tumors and adapted to incorporate various drugs and nano-/micro-materials, highlighting the strong potential for future clinical translation.

BACKGROUND/AIM:The natural killer (NK) cell function of patients with malignant tumours may be suppressed by deficiency, and the poor prognosis of renal cell carcinoma (RCC) patients may be due to escape from NK cell cytotoxicity, especially with respect to natural cytotoxicity receptors (NCRs) on the NK cell surface. However, the specific mechanism remains unclear. Therefore, in this study, we sought to explore the role of NCR, especially NCR3 splice variants, in the process of NK cell deficiency in RCC patients.MATERIALS AND METHODS:We used flow cytometry to analyse the phenotype of NK cells from the peripheral blood and kidney tumour tissue of RCC patients. The NKp30-mediated NK cell killing function was measured by antibody-dependent cell-mediated cytotoxicity (ADCC) in NK and RCC cell coincubation. We extracted RNA from the peripheral blood mononuclear cells (PBMCs) of RCC patients and renal carcinoma tissue and carried out real-time quantitative PCR to detect the mRNA levels of NKp30a, NKp30b and NKp30c. mRNA expression levels of cytokines (IL-6, IL-8, IL-10, IL-18 and TGF-β) based on RNA extracted from renal carcinoma tissue and adjacent normal kidney tissues were also measured by real-time quantitative PCR.RESULTS:Regarding the phenotype of NK cells in RCC patients, the proportion of NK cells in tumour tissue was significantly reduced, with changes in the NK cell proportion being most obvious in NKp30+ NK cells. Furthermore, the results of the ADCC function assay showed limited NKp30+ NK cell-mediated cytotoxicity in RCC patients. Through real-time quantitative PCR, we found lower expression of NKp30a and NKp30b, the immunostimulatory splice variants of NCR3 encoding NKp30, in RCC patients. Moreover, expression of activating cytokines (IL-6 and IL-8) in renal cancer tissue was decreased, though inhibitory cytokine (TGF-β) expression remained unchanged, which may result in an immunosuppressive cytokine microenvironment.CONCLUSION:Decreased expression of immunostimulatory NCR3 splice variants and the inhibitory cytokine microenvironment in RCC patients may contribute to deficient NK cell cytotoxicity and renal carcinoma cell immune escape from NK cell killing, which may provide a theoretical basis for finding new immunotherapeutic targets for RCC.

Metastasis is the greatest clinical challenge for UTUCs, which may have distinct molecular and cellular characteristics from earlier cancers. Herein, we provide single-cell transcriptome profiles of UTUC para cancer normal tissue, primary tumor lesions, and lymphatic metastases to explore possible mechanisms associated with UTUC occurrence and metastasis. From 28,315 cells obtained from normal and tumor tissues of 3 high-grade UTUC patients, we revealed the origin of UTUC tumor cells and the homology between metastatic and primary tumor cells. Unlike the immunomicroenvironment suppression of other tumors, we found no immunosuppression in the tumor microenvironment of UTUC. Moreover, it is imperative to note that stromal cells are pivotal in the advancement of UTUC. This comprehensive single-cell exploration enhances our comprehension of the molecular and cellular dynamics of metastatic UTUCs and discloses promising diagnostic and therapeutic targets in cancer-microenvironment interactions.

Docetaxel is the preferred chemotherapeutic agent in patients with castrate-resistant prostate cancer (CRPC). However, patients eventually develop docetaxel resistance and in the absence of effective treatment options. Consequently, it is essential to investigate the mechanisms generating docetaxel resistance and develop novel alternative therapeutic targets. RNA sequencing was undertaken on docetaxel-sensitive and docetaxel-resistant prostate cancer (PCa) cells. Subsequently, chemoresistance, cancer stemness, and lipid metabolism were investigated. To obtain insight into the precise activities and action mechanisms of NOTCH3 in docetaxel-resistant PCa, immunoprecipitation, mass spectrometry, ChIP, luciferase reporter assay, cell metabolism, and animal experiments were performed. Through RNA sequencing analysis, we found that NOTCH3 expression was markedly higher in docetaxel-resistant cells relative to parental cells, and that this trend was continued in docetaxel-resistant PCa tissues. Experiments in vitro and in vivo revealed that NOTCH3 enhanced stemness, lipid metabolism, and docetaxel resistance in PCa. Mechanistically, NOTCH3 is bound to TUBB3 and activates the MAPK signaling pathway. Moreover, NOTCH3 was directly regulated by MEF2A in docetaxel-resistant cells. Notably, targeting NOTCH3 and the MEF2A/TUBB3 signaling axis was related to docetaxel chemoresistance in PCa. Overall, these results demonstrated that NOTCH3 fostered stemness, lipid metabolism, and docetaxel resistance in PCa via the TUBB3 and MAPK signaling pathways. Therefore, NOTCH3 may be employed as a prognostic biomarker in PCa patients. NOTCH3 could be a therapeutic target for PCa patients, particularly those who have developed docetaxel resistance.

Objective:To compare the efficacy and safety of transurethral thulium laser enucleation of prostate for benign prostatic hyperplasia (BPH) with laser controller and sheath.Methods:The clinical data of 128 BPH patients who underwent transurethral thulium laser enucleation of prostate (THuLEP) in our hospital from January to June 2020 were retrospectively analyzed. Prostatic enucleation by laser controller was performed in 66 patients (LC-THuLEP group). The prostatic urethral mucosa was cut into Ω shape at 0.5 cm in front of the verumontanum to expose the prostate capsule, and then the fiber was retracted into the laser controller. Push the gland directly between the prostate gland and the prostate surgical capsule and expand along the capsule by the laser controller. In case of bleeding or prostate adhesive cord, the fiber was extended to coagulate or cut off, and the prostate was eventually en bloc removed. THuLEP by sheath was performed in 62 cases (THuLEP group). The ages of patients in LC-THuLEP group and THuLEP group were (71.00±8.72) years and (70.32±7.80) years, respectively. The prostate volumes were (74.80±40.88) ml and (73.14±36.31) ml, respectively. Prostate specific antigen (PSA) was (4.67±4.99) ng/ml and (4.89±4.59) ng/ml, International Prostate Symptom Score (IPSS) was (19.48±5.30) points and (18.50±5.05) points, respectively. The quality of life (QOL) scores were (4.17 ± 0.78) points and (4.18± 0.67) points, the maximum urine flow rate (Q max) was (9.82± 2.58) ml /s and (9.98± 2.91) ml/s, respectively. Postvoid residual (PVR) was (60.20±39.19) ml and (61.11±52.83) ml, respectively. The international index of erectile function (IIEF-5) score was (5.58±4.50) and (5.60±4.16), respectively.There was no significant difference in preoperative baseline data between 2 groups ( P>0.05). The operation time, the reduced level of hemoglobin, the weight of removed tissue, The time to postoperative bladder irrigation, the time to indwelling catheter and complications were compared between the two groups. IPSS, QOL score, Q max, PVR, and complications were compared between the two groups at 1, 3 and 6 months after surgery, while IIEF-5 score were compared only at 6 months after surgery. Results:The operative time of LC-THuLEP group and THuLEP group was (71.85±25.68) min and (80.65±29.64) min, respectively, and the decrease of postoperative hemoglobin was (6.42±9.89) g/L and (9.47±10.79) g/L, respectively, the weight of the removed tissue was (56.73±31.21) g and (48.11±24.50) g, respectively, and the time to postoperative bladder irrigation was (14.73±2.71) h and (16.06±2.71) h, respectively, the time to indwelling catheter was (4.41±1.92)d and (4.31±1.66)d, respectively, with no statistically significant differences between the two groups. IPSS scores of LC-THuLEP group were (6.52±2.46) points, (5.83±2.43) points and (5.30±2.49) points at 1, 3 and 6 months after surgery, respectively. QOL scores were (2.36±0.85) points, (2.27±1.02) points and (1.98±0.77) points, Q max were (22.89±2.41) ml/s, (23.61±2.62) ml/s and (23.83±3.53) ml/s, respectively. In THuLEP group, IPSS were (7.60±1.89) points, (6.86±1.81) points and (6.44±1.78) points at 1, 3 and 6 months after surgery, and QOL scores were (2.68±0.67) points, (2.74±1.01) points and (2.35±0.68) points, respectively. Q max were (21.31±2.52) ml/s, (22.13±2.51) ml/s and (22.11±2.49) ml/s, respectively. Those indexes (except Qmax at 6 months)were better in LC-ThuLEP group than THuLEP group, and the differences were statistically significant ( P<0.05). PVR of LC-THuLEP group were (15.95±12.31) ml, (14.83±12.19) ml and (13.67±15.03) ml, respectively, PVR of THuLEP group were (21.89±21.14) ml, (20.03±21.51) ml and (19.69±21.19) ml, respectively, and there were no significant differences. There was no bladder injury, severe bleeding, blood transfusion or secondary operation. The incidence of urinary incontinence 1 month after surgery was 6.1% (4/66) in the LC-THuLEP group and 19.4% (12/62) in the THuLEP group, the difference was statistically significant ( P<0.05). There was no significant difference at 3 months (3/66 vs. 4/62) and 6 months (1/66 vs. 2/62) after surgery ( P>0.05). There were no significant differences in the incidence of epididymitis, urethral stricture and bladder neck contracture between the two groups ( P>0.05). Conclusion:Compared by sheath, THuLEP by laser controller could be a safe and effective surgical method with better curative effect and lower complication rate.

Introduction The classical pathway for diagnosing prostate cancer is systematic 12-core biopsy under the guidance of transrectal ultrasound, which tends to underdiagnose the clinically significant tumour and overdiagnose the insignificant disease. Another pathway named targeted biopsy is using multiparametric MRI to localise the tumour precisely and then obtain the samples from the suspicious lesions. Targeted biopsy, which is mainly divided into cognitive fusion method and software-based fusion method, is getting prevalent for its good performance in detecting significant cancer. However, the preferred targeted biopsy technique in detecting clinically significant prostate cancer between cognitive fusion and software-based fusion is still beyond consensus. Methods and analysis This trial is a prospective, single-centre, randomised controlled and non-inferiority study in which all men suspicious to have clinically significant prostate cancer are included. This study aims to determine whether a novel three-dimensional matrix positioning cognitive fusion-targeted biopsy is non-inferior to software-based fusion-targeted biopsy in the detection rate of clinically significant cancer in men without a prior biopsy. The main inclusion criteria are men with elevated serum prostate-specific antigen above 4–20 ng/mL or with an abnormal digital rectal examination and have never had a biopsy before. A sample size of 602 participants allowing for a 10% loss will be recruited. All patients will undergo a multiparametric MRI examination, and those who fail to be found with a suspicious lesion, with the anticipation of half of the total number, will be dropped. The remaining participants will be randomly allocated to cognitive fusion-targeted biopsy (n=137) and software-based fusion-targeted biopsy (n=137). The primary outcome is the detection rate of clinically significant prostate cancer for cognitive fusion-targeted biopsy and software-based fusion-targeted biopsy in men without a prior biopsy. The clinically significant prostate cancer will be defined as the International Society of Urological Pathology grade group 2 or higher. Ethics and dissemination Ethical approval was obtained from the ethics committee of Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. The results of the study will be disseminated and published in international peer-reviewed journals. Trial registration number ClinicalTrials.gov Registry ( NCT04271527 ).

Objective:To improve the safety of tubeless percutaneous nephrolithotomy by using a kind of innovative hemostatic sheath to electrocoagulate the bleeding in the percutaneous renal channel.Method:The clinical data of 586 patients with tubeless percutaneous nephrolithotomy from July 2015 to June 2020 were retrospectively analyzed. After finishing the process of percutaneous nephrolithotomy, the self-designed innovative hemostatic sheath was used to electrocoagulate the bleeding found in the percutaneous renal channel by routine check. The operation time, hemostasis time, decrease of hemoglobin after operation, blood transfusion rate and renal artery embolism ratio were analyzed.Result:In 586 cases of tubeless percutaneous nephrolithotomy, 103 cases were found to have obvious bleeding in the percutaneous renal channel. The self-designed innovative hemostatic sheath was used to electrocoagulate the bleeding and no nephrostomy tube was left. The operation time of percutaneous nephrolithotomy was 53-105 minutes and the hemostasis time was 7-19 minutes. After operation, hemoglobin decreased 7-21g/L(average 14 g/L) on the next day and decreased 11-32 g/L(average 19 g/L) 2 days later. No blood transfusion or renal artery embolism occurred. The stone removal rate was 94.5%(554/586) 2 weeks after operation. There were 2 cases of renal subcapsular hematoma and 6 cases of pleural effusion, all cured by conservative treatment.Conclusion:Routine channel examination and electrocoagulation by innovative hemostatic sheath can reduce postoperative bleeding, blood transfusion and renal artery embolism, and improve the safety of tubeless percutaneous nephrolithotomy.

Background Recent genomic profiling has identified a subtype of prostate cancer (PCa) characterized by two key genetic alterations: missense mutation of speckle-type POZ protein (SPOP) and homozygous deletion of chromodomain helicase DNA-binding protein 1 (CHD1). Mutually exclusive with E26 transformation-specific (ETS) rearrangements, this subtype displays high genomic instability. Previous studies indicate that deficientSPOPorCHD1alone leads to feeble prostate abnormalities and each protein is involved in DNA damage response (DDR). It remains to be determined whether CHD1 and SPOP cooperate to suppress prostate tumorigenesis and DDR. Methods Prostate-specific single or double knockout ofSpopandChd1was generated with the Cre/loxP system in mice. Wild-type or mutantSPOP(F102C, F133V) overexpression andCHD1knockdown with short hairpin RNA were created in human benign prostatic hyperplasia cell line BPH1. The levels of DNA damage and homologous recombination repair were measured by immunofluorescence staining of gamma H2AX and RAD51, respectively. Results Spop/Chd1double-knockout mice displayed prostatic intraepithelial neoplasia at both young (3 months) and old (12 months) ages and failed to generate prostate adenocarcinoma. Compared with wild-type or single-knockout mice, the double-knockout prostate harbored moderately higher proliferating cells and dramatically augmented the level of gamma H2AX staining, although androgen receptor-positive cells and apoptotic cells remained at a similar level. In BPH1 cell line,SPOPmutant overexpression andCHD1silencing synergistically sensitized the cells to DNA damage by camptothecin, an inducer of double-strand breaks. Conclusions Our results indicate that SPOP and CHD1 can synergistically promote repair of naturally occurring or chemically induced DNA damages in prostate epithelial cells. Regarding the progression of the SPOP/CHD1 subtype of PCa, other functionally complementary drivers warrant further identification. The clinical implication is that this subtype of PCa may be particularly sensitive to poly(ADP-ribose) polymerase inhibitors or DNA-damaging agents.

Targeting mitochondria has always been a challenging goal for therapeutic nanoparticle agents due to their heterotypic features and size, which usually lead to a lysosome/endosome endocytosis pathway. To overcome this limitation, in this work, a portfolio targeting strategy combining a small targeting molecule with a biomembrane was developed. Modification of small targeting molecule H2N-TPP on gold nanoparticles (GNPs) could not only facilitate the mitochondrial targeting but could also induce gold nanoparticle assembly. Therefore, the GNPs were endowed with good absorption and photothermal conversion abilities in the near-infrared (NIR) region. Meanwhile, a biomimetic strategy was adopted by wrapping the gold nanoparticle assembly (GNA) with cancer cell membranes (CCMs), which helped the GNA enter the prostatic cancer cell via a homotypic membrane-fusion process to avoid being trapped in endosomes/lysosomes. Thereafter, the GNA remaining in the cytoplasm could reach mitochondria more efficiently via guidance from H2N-TPP molecules. This "biomembrane-small molecule" combination targeting process was evidenced by fluorescence microscopy, and the highly efficient photothermal ablation of prostatic tumors in vivo was demonstrated. This portfolio targeting strategy could be extended to various nanodrugs/agents to realize an accurate subcellular targeting efficiency for cancer treatments or cell detections.

Myeloid-derived suppressor cells with polymorphonuclear morphology (PMN-MDSCs) contribute to the progression and immune evasion of prostate cancer. However, the spatial distribution of tumor-infiltrating PMN-MDSCs in primary and metastatic prostate cancer, especially in the context of comparison between the epithelial and stromal compartments of the tumor, has not been characterized. Here, we describe a multicolor immunofluorescence staining study of 90 primary tumors, 37 lymph node metastases (all with matched primary tumors) and 35 bone metastases using archived samples. CD11b(+)CD15(+)cells were identified as PMN-MDSCs and pan-cytokeratin(+)cells were identified as prostate epithelial cells. We found that, in both primary tumor and metastases, PMN-MDSCs infiltrate much more readily in the stromal area compared with the epithelial area of the tumor regions. In comparison to the stromal area of primary tumors, the stromal area of either lymph node metastases or bone metastases was infiltrated with more PMN-MDSCs. In primary tumors, stromal PMN-MDSCs were associated with vascularization, segmented neutrophils, patient age and close juxtaposition to neoplastic epithelial cells. These results reveal the stroma rather than the epithelia of prostate cancer as the major hotbed for PMN-MDSCs and support the role of PMN-MDSCs in the metastatic progression of prostate cancer.

目的 探讨前列舒通胶囊联合盐酸坦洛新缓释胶囊、左氧氟沙星治疗慢性骨盆疼痛综合征的临床疗效.方法 160例慢性骨盆疼痛综合征患者随机分成两组,治疗组和对照组,每组80人,治疗组采用前列舒通胶囊2.5 g po tid,盐酸坦洛新缓释胶囊0.2 mg po qn,左氧氟沙星胶囊0.2 g po bid.对照组给予左氧氟沙星胶囊0.2 g po bid,4周为1个疗程,治疗时间为8周.记录治疗过程中的前列腺液常规和NIH-CPSI评分变化.结果 治疗组中80例治愈33例,治愈率41.3％,19例显效及有效,总有效率为65.0％;对照组中80例有17例治愈,治愈率21.25％,21例显效及有效,总有效率为47.0％.两组治愈率及总有效率相比,有明显差异,P<0.05,治疗组优于对照组.结论 前列舒通胶囊联合盐酸坦洛新缓释胶囊和左氧氟沙星治疗慢性骨盆疼痛综合征有效,值得临床应用.

目的 通过研究草酸钙结石小鼠尿液中代谢物的变化，探究草酸钙结晶导致肾损伤的内在机制。 方法 以乙醛酸盐诱导的小鼠草酸钙结晶模型为对象，采用基于超高效液相-四极杆飞行时间串联质谱（UPLC-Q-TOF/MS）的代谢组学方法测定尿液中内源性代谢物的变化，并采用SIMCA-P进行多元统计分析，Metabo Analyst软件进行代谢物通路分析。 结果 与正常组相比，模型组小鼠的肾组织出现明显的钙盐沉积且血清中的肌酐和尿素氮含量异常升高，肾脏出现损伤；从尿液中筛选出尿酸、牛磺酸、苯丙氨酸等21个差异代谢物。 结论 通过代谢物通路分析，差异代谢物主要涉及氨基酸代谢、能量代谢、牛磺酸代谢、嘌呤代谢和VB6代谢，为进行结石疾病机制研究以及早期标志物的筛选提供了重要参考。

The targeted delivery of nanomedicines into solid tumors remains challenging in cancer treatment. Stem cells with tumortropic migration ability are promising as biocarriers to transport nanomedicines. The transportation of nanomedicines into cancer cells is the key step for tumor targeted delivery via stem cells. In this study, we designed a magnetic nanocube (scMNP) loaded in mesenchymal stem cells for magnetic hyperthermia of prostate cancer, and the delivery and transportation pathways into the cancer cells were fully investigated. The MSCs acted as the carrier of the loaded scMNPs along with the upregulation of CXCR4 for the migration to cancer cells. The therapeutic effect was mainly due to scMNPs via magnetic hyperthermia. Stem cell-derived microvesicles containing scMNPs played an essential role in the crosstalk between stem cells and cancer cells for targeted delivery. Both in vitro and in vivo studies demonstrated that the system showed satisfactory therapeutic efficiency under magnetic hyperthermia therapy. Our investigation presents a comprehensive study of magnetic nanoparticles in combination with MSCs and their extracellular microvesicles and is promising as an effective strategy for magnetic hyperthermia therapy of prostate cancer.

Prostate cancer is one of the most common malignancies in men worldwide. Altered expression of ARHGAP10, a member of the Rho GTPase activating protein (RhoGAP) family, has been found in several human cancers. However, its clinical significance in prostate cancer remains unknown. In the current study, we found that mRNA levels of ARHGAP10 were significantly higher in prostate cancer tissues than in the non-cancerous controls. Gene set enrichment analysis (GSEA) revealed that ARHGAP10 expression was negatively correlated with the Wnt signaling pathway. Immunohistochemical staining results showed that 62.2% (56/90) and 65.5% (59/90) of prostate cancer tissues displayed low expression of ARHGAP10 and high expression of β-catenin, respectively. ARHGAP10 protein expression was significantly correlated with histologic grade (P < 0.0001), tumor stage (P = 0.0298), preoperative prostate specific antigen level (P = 0.0261), vital status (P = 0.0017) and β-catenin expression (P < 0.0001). Kaplan-Meier survival analysis indicated that patients with low levels of ARHGAP10 and high levels of β-catenin had poor overall survival. Multivariate analyses revealed that ARHGAP10 and β-catenin expression was independent prognostic factor for prostate cancer. In summary, the current study suggests that ARHGAP10 in association with β-catenin may play a role in the development of prostate cancer and serve as a prognostic factor for this disease.

目的 评价一种腹壁无明显可见瘢痕的腹腔镜精索静脉高位结扎术的安全性与有效性.方法 我院2012年1月至2017年12月收治双侧精索静脉曲张患者27例.患者年龄17～34岁,平均年龄(25.81±5.96)岁.均由同一术者实施经脐隐瘢痕腹腔镜双侧精索静脉高位结扎术.结果 27例手术均获成功,无中转常规腹腔镜或开放手术病例.手术时间37～84min,平均手术时间(56.37±11.91)min.所有患者术后第二日出院,围手术期无严重并发症.术后6个月随访,腹壁无明显手术瘢痕,术后6个月、12个月随访未见复发,未发现睾丸萎缩或睾丸鞘膜积液.结论 经脐隐瘢痕腹腔镜精索静脉高位结扎术治疗双侧精索静脉曲张安全、可行,操作难度与常规腹腔镜手术相当,术后腹壁无明显可见瘢痕,这为腹腔镜手术的更微创化提供了一种可行途径.

目的:探讨软性输尿管镜钬激光碎石术治疗孤立肾结石的安全性及有效性.方法:回顾性分析2015年1月至2018年1月采用软性输尿管镜钬激光碎石术治疗的29例孤立肾结石患者资料.左侧孤立肾18例,右侧孤立肾11例.结石直径0.9 ～2.6 cm,平均1.6 cm.单发结石8例,多发结石21例.结果:29例均顺利进镜并完成钬激光碎石术,一次进镜成功率100％.手术时间25～90 min,平均48 min;术中出血量10～ 40 mL,平均20 mL;住院日3～8天,平均4.5天;2～4周拔除双J管.术后2例患者出现寒战、高热,经积极抗感染治疗后痊愈.其余未见严重并发症.25例行一次手术,4例行两次手术.术后1个月复查,结石总清除率96.55％(28/29).结论:软性输尿管镜下钬激光碎石术治疗孤立肾结石安全、有效,具有创伤小、出血少、并发症少、术后恢复快等优点,对于合适病例和有经验的医师,FURL可成为孤立肾结石的一线治疗选择.

Protein nitration is one of the most important post-translational modifications (PTM) on tyrosine residues and it can be induced by chemical actions of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in eukaryotic cells. Precise identification of nitration sites on proteins is crucial for understanding the physiological and pathological processes related to protein nitration, such as inflammation, aging, and cancer. Since the nitrated proteins are of low abundance in cells even under induced conditions, no universal and efficient methods have been developed for the profiling and identification of protein nitration sites. Here we describe a protocol for nitropeptide enrichment by using a chemical reduction reaction and biotin labeling, followed by high resolution mass spectrometry. In our method, nitropeptide derivatives can be identified with high accuracy. Our method exhibits two advantages compared to the previously reported methods. First, dimethyl labeling is used to block the primary amine on nitropeptides, which can be used to generate quantitative results. Second, a disulfide bond containing NHS-biotin reagent is used for the enrichment, which can be further reduced and alkylated to enhance the detection signal on a mass spectrometer. This protocol has been successfully applied to the model peptide Angiotensin II in the current paper.

Nephrolithiasis is a systemic metabolic disease with a worldwide incidence that is increasing yearly, as well as a high recurrence rate; however, this disease's pathogenesis has not been thoroughly elucidated to date. Several epidemiological studies have shown that the risk for developing kidney stones increases in people with dyslipidemia. To explore the mechanism of lipid-induced kidney stones, we established a mouse model for renal urolithiasis based on intraperitoneal injections of glyoxylate (120 mg/kg/d). Lipidomics based on ultra high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-QTOF-MS/MS) was performed to determine the changes in lipid metabolism in serum and kidneys. We screened 179 and 196 different lipid metabolites in the kidneys and serum, respectively, including fatty acyls, glycerophospholipids, sphingolipids, glycerolipids and prenol lipids. We found that polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic acid, and docosahexoenoic acid, and ceramides and lysophosphocholines mediated inflammatory responses and that the oxidative stress induced by oleylethanolamine and glycerophosphoethanolamine plasmalogens is closely related to the development of kidney stones. These results provide strong evidence for the relationship between lipid metabolism and the development of kidney stones and suggest a clear direction for future research.

OBJECTIVE:To evaluate the effect of cefoxitin prophylactic in reducing the incidence of severe infection after transrectal prostate biopsy (TRPB).METHODS:This retrospective study included 155 cases of TRPB with a 5-day administration of oral levofloxacin at 200 mg bid (the control group) and another 167 cases with a 3-day administration of oral levofloxacin at the same dose plus intravenous cefoxitin at 2.0 g 2 hours before TRPB (the experimental group) according to the distribution characteristics of drug-resistance bacteria in our department. The patients of the control and experimental groups were aged (68.68 ± 8.12) and (68.72 ± 7.51) years, with PSA levels of (19.78 ± 21.57) and (21.15 ± 42.63) μg/L, involving (11.68 ± 1.44) and (11.77±1.02) biopsy cores, respectively. Comparisons were made between the two groups of patients in the incidence rate of severe infection, which was defined as lower urinary track symptoms plus the systemic inflammatory response syndrome (SIRS) within 7 days after TRPB.RESULTS:The incidence rate of postoperative severe infection was significantly lower in the experimental group than in the control (0.6% ［1/167］ vs 5.8% ［9/155］, P < 0.05). Blood cultures revealed positive E-coli strains in 6 cases in the control group, including 5 ESBL-positive and 4 quinolone-resistant and amikacin-sensitive cases, all sensitive to cefoxitin, cefoperazone/sulbactam and imipenem. The only one case of severe infection was shown to be negative in blood culture.CONCLUSIONS:Preoperative intravenous administration of cefoxitin according to the specific distribution characteristics of drug-resistance bacteria can significantly reduce the incidence of severe infection after TRPB.