ObjectiveTo investigate the effectiveness and safety of drug-loaded microsphere interventional embolization (D-TAE) in conjunction with sorafenib and envafolimab in the management of intermediate and advanced renal carcinoma.Methods120 cases of intermediate and advanced renal cell carcinoma cured in the Oncology Department of our hospital from January 2022 to December 2023 were selected. Individuals in the combination group received D-TAE paired with sorafenib and envafolimab. Individuals in the D-TAE group received only D-TAE. The clinical data, clinical efficacy, vascular endothelial growth factor (VEGF), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), mortality, progression-free survival time (PFS), objective tumor response rate (ORR) and tumor control rate (DCR) and adverse reactions were compared in both groups.ResultsThe proportion of individuals with ORR and DCR in the combination group was greatly increased compared to that in the D-TAE group (P <0.05). After 1 week and 1 month of treatment, the serum VEGF levels in both groups showed a great decrease compared to pre-treatment levels (P<0.05), with the combination group demonstrating notably lower serum VEGF levels than the D-TAE group (P<0.05). Following treatment, serum CA125 and CEA levels in both groups experienced a great decrease compared to pre-treatment levels, with the combination group showing notably lower levels than the D-TAE group (P<0.05). Additionally, the mortality rate in the combination group was greatly lower than that in the D-TAE group, and the PFS was greatly increased in the combination group compared to the D-TAE group (P<0.05). In addition, the observed adverse reactions included gastrointestinal reactions, liver and kidney damage, myelosuppression and rash. Overall, the incidence of adverse reactions in the combination group was greatly decreased than that in the D-TAE group (P<0.05).ConclusionDrug-loaded microsphere interventional embolization combined with sorafenib and envafolimab has certain efficacy and acceptable safety in treating intermediate and late-stage renal tumor, providing a new treatment option for patients with renal cell carcinoma.

[This retracts the article DOI: 10.3892/ol.2021.13034.].

BACKGROUND:The combined treatment of transcatheter arterial chemoembolization (TACE) and apatinib had beneficial effects on the survival of patients with advanced hepatocellular carcinoma (HCC), but the efficacy of this regimen is still controversial and needs further investigation. MATERIALS AND METHODS:The clinical records of advanced HCC patients between May 2015 and December 2016 were collected from our hospital. They were categorized into the TACE monotherapy group and the combination of TACE and apatinib group. After propensity score matching (PSM) analysis, the disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and occurrence of adverse events were compared between the two treatments. RESULTS:There were 115 HCC patients included in the study. Among them, 53 received TACE monotherapy and 62 were treated with TACE plus apatinib. After PSM analysis, 50 pairs of patients were compared. The DCR of the TACE group was significantly lower than that of the combination of TACE and apatinib group (35 [70%] versus 45 [90%], P < 0.05). The ORR of the TACE group was also significantly lower than that of the combination of TACE and apatinib group (22 [44%] versus 34 [68%], P < 0.05). Patients who received the combined treatment of TACE and apatinib had longer PFS compared with those in the TACE monotherapy group ( P < 0.001). Moreover, hypertension, hand-foot syndrome, and albuminuria were more common in the combination of TACE and apatinib group ( P < 0.05), although all adverse events were well tolerated. CONCLUSIONS:The combined treatment of TACE and apatinib showed beneficial effects on tumor response, survival outcomes, and tolerance to treatment, which may be used as a routine regimen for advanced HCC patients.

The renal interstitial fibrosis contributes to the progression and deterioration of diabetic nephropathy (DN). Long noncoding RNA taurine-up-regulated gene 1 (TUG1) in kidneys may be down-regulated by hyperglycemia. We aim to explore its role in tubular fibrosis caused by high glucose and the possible target genes of TUG1. In this study, a streptozocin-induced accelerated DN mouse model and a high glucose-stimulated HK-2 cells model was established to evaluate TUG1 expression. Potential targets of TUG1 were analyzed by online tools and confirmed by luciferase assay. A rescue experiment and gene silencing assay were used to investigate whether TUG1 plays its regulation role via miR-145-5p/dual-specificity phosphatase 6 (DUSP6) in HK2 cells. The effects of TUG1 on inflammation and fibrosis in high glucose treated tubular cells were evaluated by in vitro study, as well as in vivo DN mice model through AAV-TUG1 delivery. Results showed TUG1was downregulated in HK2 cells incubated with high glucose while miR-145-5p was upregulated. Overexpression of TUG1 alleviated renal injury by suppressing inflammation and fibrosis in vivo. Overexpression of TUG1 inhibited HK-2 cell fibrosis and relieved the inflammation. A mechanism study demonstrated that TUG1 directly sponged to miR-145-5p, and DUSP6 was identified as a target downstream of miR-145-5p. In addition, miR-145-5 overexpression and DUSP6 inhibition countervailed the impacts of TUG1. Our findings revealed that TUG1 overexpression alleviates kidney injury in DN mice and decreases the inflammatory response and fibrosis of high glucose-stimulated HK-2 cells via miR-145-5p/DUSP6 axis.

Background Diabetic nephropathy (DN) is a prevalent complication of diabetes, in which inflammation and fibrosis are the significant pathogenesis. Periostin is a matricellular protein that functions on stabilizing the extracellular matrix by binding to integrins during development. This study aimed to explored the role of periostin in DN. Methods The animal and cell models of DN were constructed in streptozocin (STZ)-induced mice and high glucose-challenged human mesangial cells (HMCs). The role of periostin in pathological changes, inflammation and fibrosis in DN was investigated through biochemical detection, HE and Masson staining and scores, western blot, enzyme‑linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) assays. Results Knockdown of periostin counteracted the STZ-induced the ratio of kidney weight and body weight, and the concentrations of urine albumin excretion (UAE), serum creatinine (Scr), urine albumin/creatinine ratio (UACR) and blood urea nitrogen (BUN) in mice. Moreover, silencing of periostin alleviated the pathological manifestations and reduced the concentrations of IL-6, TNF-α and IL-1β in mice kidney tissues and sera. Also, downregulation of periostin decreased the relative protein expression of fibronectin, collagen IV and α-SMA in kidney tissues. Meanwhile, interference of periostin attenuated the levels of pro-inflammation factors and the expressions of fibrosis markers in HG-induced HMCs. Conclusion Interference of periostin resisted DN via attenuating the pro-inflammatory cytokines release and renal fibrosis in diabetic kidney injury. Our study establishes a basis for its further study and underlying application in clinical practice in diagnosing and treating diabetic kidney injury or other relevant diseases.

BACKGROUND:Diabetic nephropathy (hereinafter referred to as DN) is one of the important causes of chronic renal failure, with great harm. We aimed to elucidate the role of transgelin-2, a key early detection for diabetic ne-phropathy.METHOD:The serum samples of 12 DN patients and 12 normal volunteers were collected for this experiment. Mice of the model group were injected intraperitoneally with streptozotocin following a high fat diet. Mouse podocyte (MPC5) cells were induced with 20 mmol/L d-glucose.RESULT:Transgelin-2 was highly expressed in DN patients with diabetic nephropathy both at the expression levels of mRNA and protein. Transgelin-2 expression was correlated with blood sugar in patients with DN. Transgelin-2 gene up-regulation enhanced inflammation and periostin levels, and reduced E-cadherin activity level in mice with DN. Over-expression of transgelin-2 increased inflammation and periostin levels, and reduced E-cadherin activity level in the in vitro model. Down-regulation of Transgelin-2 reduced inflammation and periostin levels and induced E-cadherin activity level in the in vitro model. Transgelin-2 induced ANXA2/ STAT3 signaling in a mouse model or an in vitro model. ANXA2 was one of the regulatory factors for the effects of transgelin-2 with inflammation, periostin, and E-cadherin in a model of DN.CONCLUSIONS:Taken together, these findings demonstrated that transgelin-2 promoted inflammation and periostin levels, and suppressed E-cadherin levels in DN by STAT3 signaling through ANXA2.

Neutrophil gelatinase-associated lipocalin (NGAL), also called lipocalin 2, is considered a promising biomarker for acute and chronic kidney injuries. Several studies have demonstrated that its levels increase in plasma and urine in diabetic nephropathy (DN), and its urine concentration increases upon kidney function deterioration. However, its role in DN progression remains unclear. The current study used in vitro gene expression knockdown in human proximal tubular cell line human kidney (HK)2 to investigate the role of NGAL in oxidation and extracellular matrix secretion under high-glucose (HG) incubation. In addition, type 1 diabetes was induced in vivo in knockout NGAL-/- and wild-type mice in order to investigate role of NGAL in the progression of DN. The results demonstrated that NGAL knockdown in HK2 cells significantly increased oxidative stress under HG stimulation tested by flow cytometry, and increased the secretion of interleukin-6, fibronectin (FN) and collagen IV examined by ELISA. Western blotting demonstrated that the phosphorylation of Smad2/3 also increased in HK2 cells under transforming growth factor-β1 stimulation. In vivo experiments demonstrated that diabetic NGAL-/- mice showed deteriorated renal function compared with that of diabetic wild-type mice. Histopathological analysis suggests that diabetic NGAL-/- mice had more serious glomerulosclerosis and tubular vascular degeneration than wild-type mice. Immunohistochemistry suggested that the absence of NGAL lead to increased FN deposition in glomeruli in a mouse model of DN. In conclusion, NGAL appears to have renal protective effects by slowing down the progression of DN, and its effect may be associated with a reduction in oxidation, fibrosis and inflammation.

Long non-coding RNA transmembrane and coiled-coil domain family 1 antisense RNA 1 (TMCC1-AS1) has been frequently reported to be associated with prognosis in patients with liver cancer (LC). However, the biological role of TMCC1-AS1 in LC in vitro remains unclear. The expression levels of TMCC1-AS1 in primary tumor tissues and LC cell lines were determined using reverse transcription-quantitative PCR. The associations between TMCC1-AS1 expression and the clinicopathological factors of patients with LC were statistically analyzed using the χ2 test. The role of TMCC1-AS1 in LC prognosis was assessed using Kaplan-Meier curves and proportional hazards model (Cox) analysis. Cell proliferation was determined by Cell Counting Kit-8 and colony formation assays. Transwell assays were performed to determine migration and invasion. TMCC1-AS1 expression was found to be significantly upregulated in LC tissues and cell lines compared with the corresponding controls. High TMCC1-AS1 expression was associated with advanced TNM stage and lymph node metastasis. Furthermore, high TMCC1-AS1 expression predicted poor survival in patients with LC. Knockdown of TMCC1-AS1 significantly inhibited the proliferation, migration and invasion of HepG2 and SNU-182 cells, while overexpression of TMCC1-AS1 had the opposite effect in HepG2 and SNU-182 cells. At the molecular level, downregulation of TMCC1-AS1 expression resulted in increased E-cadherin expression and decreased proliferating cell nuclear antigen, Ki67, N-cadherin and Vimentin expression in HepG2 cells. Overexpression of TMCC1-AS1 had the opposite effects on these factors in SNU-182 cells. In conclusion, the present findings indicated that TMCC1-AS1 might be considered as a novel oncogene, which promotes cell proliferation and migration, and may be a potential therapeutic target for LC.

目的 评价阿帕替尼联合经导管动脉化疗栓塞术(TACE)治疗原发性肝癌(PLC)的有效性和安全性.方法 计算机检索2015年1月1日至2019年5月1日PubMed、Cochrane library、NCKI、万方、维普(VIP)数据库中阿帕替尼联合TACE(实验组)和单纯TACE(对照组)治疗PLC的随机对照研究文献,并分别按照Cochrane系统评价手册中随机对照试验质量评价标准筛选文献,提取相关资料,采用RevMan 5.3软件对有效数据进行meta分析.结果 共纳入11篇文献,均为实验组与对照组对比研究,其中随机对照文献6篇、回顾性分析文献3篇,未描述文献2篇;累积720例患者,实验组、对照组分别为363例、357例.与对照组相比,实验组客观缓解率(ORR)(OR=3.26,95％CI=2.22～4.79,P＜0.001)和疾病控制率(DCR)(OR=3.72,95％CI:2.51～5.52,P＜0.001)显著提高,尤其是3个月后;患者6个月(OR=2.89,95％CI=1.36～6.15,P=0.006)、12个月(OR=3.06,95％CI=1.69～5.53,P=0.002)生存率显著提高;血清中基质金属蛋白酶(MMP)(OR=-2.56,95％CI=-3.05～2.06,P＜0.001)、血管内皮细胞生长因子(VEGF)(OR=-3.59,95％CI=-6.0～ 1.14,P--0.004)及甲胎蛋白(AFP)(OR=-0.69,95％CI=-0.99～-0.40,P＜0.001)表达水平降低.但在3个月内,两组间ORR(OR=1.37,95％CI:0.63～3.02,P=0.43)和DCR(OR=1.52,95％CI:0.49～4.68,P=0.47)差异均无统计学意义.与对照组相比,实验组栓塞后综合征(肝区疼痛、食欲下降、发热、恶心呕吐)无明显增加(P＞0.05),但药物不良反应(手足综合征、高血压、蛋白尿、腹泻、皮疹)显著增加(P＜0.05),无乏力、口腔黏膜炎、血细胞减少不良反应(P＞0.05).结论 阿帕替尼联合TACE治疗PLC比单纯TACE更能提高远期临床疗效、延长生存时间,且未增加栓塞后综合征.但也应注意手足综合征、高血压、蛋白尿、皮疹等药物不良反应发生.

目的 探讨早期尿激酶应用对慢性肾衰竭静脉置管长期血液透析患者导管纤维蛋白鞘形成的防治作用.方法 选取我院2017年3月—2018年10月收治的慢性肾衰竭静脉置管长期血液透析患者85例,根据防治导管纤维蛋白鞘形成方法的不同分为观察组44例和对照组41例.观察组置管首次透析后即开始采用尿激酶封管法和滴注法防治导管纤维蛋白鞘形成;对照组置管首次透析后先采用常规肝素封管,待出现导管功能不良时再开始采用尿激酶封管法和滴注法防治导管纤维蛋白鞘形成.观察比较两组透析6个月后导管功能不良发生次数和首次导管功能不良出现时间;两组透析1、3及6个月时的血流量及静脉压;两组透析前及透析6个月时凝血酶原时间(PT)、凝血酶时间、纤维蛋白原、部分凝血酶时间;两组治疗期间不良反应发生情况.结果 观察组导管功能不良发生次数明显少于对照组,首次导管功能不良出现时间明显晚于对照组,差异均有统计学意义(P<0.05或P<0.01).透析3、6个月时观察组血流量明显大于对照组,静脉压明显低于对照组,差异均有统计学意义(P<0.05).透析6个月时两组组内治疗前后比较,仅对照组PT降低(P<0.05);观察组透析6个月时PT明显长于对照组(P<0.05).两组治疗期间均无严重不良反应发生.结论 早期应用尿激酶可有效防治慢性肾衰竭静脉置管长期血液透析患者导管纤维蛋白鞘形成,且安全性良好,是一种防治长期血液透析留置导管功能不良的有效手段.

Objective: To explore the correlation of FGF-23 and OPG with vascular calcification in chronic kidney disease (CKD). Methods: Altogether 154 patients with CKD admitted to Affiliated Hospital of Hebei University of Engineering were selected. Among them, 83 patients with vascular calcification were regarded as the research group (RG). Another 71 patients without vascular calcification were regarded as the control group (CG). The expression of FGF-23 and OPG before operation in RG and CG, the correlation between FGF-23 and OPG in RG, the predictive value of FGF-23 and OPG on vascular calcification, the changes of FGF-23 and OPG expression during treatment, and the risk factors affecting vascular calcification were observed. Results: FGF-23 in RG was higher than that in CG before operation, while OPG was lower than that in CG before operation (P < 0.05). FGF-23 was negatively related to OPG before operation in RG (r = -0.608, P < 0.001). The sensitivity and specificity of FGF-23 for predicting vascular calcification were 74.65% and 83.13%, respectively. OPG had a predictive sensitivity of 66.20% and specificity of 78.31% for vascular calcification. The sensitivity and specificity of FGF-23 combined with OPG for predicting vascular calcification were 84.51% and 83.13%, respectively. FGF 23 in RG was higher than that CG at T0, T1, T2, T3 and T4. FGF-23 was highest at T0, began to decline at T1, and was lowest at T4 (P < 0.05). OPG in RG was lower than that CG at T0, T1, 12, T3 and T4. OPG was lowest at TO, began to rise at T1 and was highest at T4 (P < 0.05). Blood glucose, blood lipids, FGF-23 and OPG were independent risk factors for vascular calcification (P < 0.05). Conclusion: FGF 23 is increased in CKD patients with vascular calcification, while OPG is decreased. Both of them are related to CKD vascular calcification, and may be important observation indicators of vascular calcification in CKD patients.

目的 研究膀肌癌O6-甲基鸟嘌吟-DNA转移酶(MGMT)基因启动子甲基化情况,探讨其与临床病理特征间的关系及临床意义.方法 选取2010年1月~2012年1月于河北工程大学附属医院就诊并行手术切除治疗的膀肌癌患者93例,选取同期就诊且经膀肌镜检查证实无膀肌肿瘤的47例患者作为对照.应用甲基化特异聚合酶链式反应(PCR)检测膀肌癌组织和正常膀肌黏膜组织中MGMT基因甲基化状况.统计分析MGMT甲基化与临床病理特点关系,Kaplan-Meier分析MGMT甲基化与患者预后间的关系.结果 膀肌癌组织中MGMT相对甲基化程度明显高于正常膀肌组织,差异有统计学意义(P＜0.01). MGMT甲基化与分期、分级相关(均P＜0.01),与年龄、性别、肿瘤大小、数目、形态及复发频率无关(均P＞0.05). Kaplan-Meier生存分析发现甲基化组患者5年总体生存率明显低于非甲基化组(均P＞0.05).结论 膀肌癌组织中MGMT基因甲基化水平明显增高,MGMT甲基化与肿瘤分期、分级及不良预后有关,可作为判断膀肌癌病情判断及预后的分子生物学标志,值得临床关注.