Survival Analysis of Tunneled Cuffed Central Venous Catheters in Maintenance Hemodialysis Patients: A Retrospective Study in China.

Aim: The study aimed to investigate the clinical epidemiological data and the survival rate of maintenance hemodialysis patients with tunneled cuffed central venous catheters (TCCs) in a single hemodialysis center in China. Methods: We retrospectively investigated the general clinical characteristics (including sex, age, primary causes, and catheter outcome) of 316 patients undergoing maintenance hemodialysis (MHD) via TCC for >3 months at Wannan Medical College Affiliated Yijishan Hospital, Wuhu, China, from July 2011 to June 2021. The long-term survival rate of the catheters was determined by Kaplan-Meier survival analyses. Results: A total of 316 patients (137 males, 179 females) were included, with a mean age of 65.0 ± 15.5 years. The right internal jugular vein was the most commonly used central vein, accounting for 89.1% of catheterizations. After censoring for noncatheter-related events leading to the removal of the catheter, the mean survival time of the TCCs was 26.2 ± 19.8 smonths and the median survival time was 58.0 (95% CI, 54.0-62.0) months. Seventy patients had catheter loss-of-function events, with an incidence of 22.2%. Moreover, 97.3% of TCCs survived 1 year and 43.3% survived 5 years, respectively. The sex and age of the patients were not related to the survival rate (p > 0.05). There were also no statistical differences between the primary diseases of patients and the survival rate of TCCs (p > 0.05). Conclusion: In this study, we provide evidence of the mean TCC survival time beyond 2 years. We found that TCC is an effective alternative for MHD patients with poor vessel status or limited survival time or become a bridge waiting for arteriovenous fistula to mature, regardless of age, sex, and primary diseases.

Protective Effects of Shorea roxburghii Phenolic Extract on Nephrotoxicity Induced by Cyclophosphamide: Impact on Oxidative Stress, Biochemical and Histopathological Alterations.

Cyclophosphamide (CTX) is one of the most commonly used alkylating agents for the treatment of various cancers; however, CTX-induced nephrotoxicity is one of the most prevailing side effects of the drug. Shorea roxburghii is a plant with diverse bioactivities including antioxidant, anti-inflammatory and renoprotective effects. This study investigated the nephroprotective effect of Shorea roxburghii phenolic extract (SRPF) against CTX-induced nephrotoxicity in rats. The rats were treated with SRPF (100 and 400 mg/kg) for 5 weeks and were concomitantly administered with CTX. The results indicated that treatment with SRPF significantly decreased serum creatinine, blood urea nitrogen (BUN), uric acid as well as renal MDA, IL-6, TNF-α, IL-1ß, NF-kB and caspase-3 levels. Furthermore, SRPF augmented the activities of renal SOD, CAT, GSH and GPx. SRPF also improved renal histopathological damages caused by CTX administration. In conclusion, these results suggested that SRPF showed substantial protective effects against CTX-mediated renal toxicity via its antioxidant and anti-inflammatory effects.

Knockdown of Long Non-coding RNA LINC00473 Protects CHON-001 Cells against Interleukin-1ß-Induced Cell Injury.

Osteoarthritis (OA) is a chronic joint disease with high prevalence. However, effective treatment options for OA are still lacking. It was previously reported that LINC00473 was upregulated in patients with OA and upregulated LINC00473 might be associated with the progression of OA; however, the role of LINC00473 in OA remains to be investigated. CHON-001 human chondrocyte cells stimulated with 10 ng/mL interleukin (IL)-1ß were utilized to mimic OA in vitro. Protein expression, cell apoptosis and cell proliferation of CHON-001 cells were investigated by Western blot, Annexin V and propidium iodide (PI) double staining, cell counting-8 kit assay and immunofluorescence staining respectively. The result indicated IL-1ß triggered viability decrease and apoptosis in CHON-001 cells, which was alleviated by LINC00473 knockdown. Meanwhile, IL-1ß-induced upregulation of cleaved caspase 3 and Bax were ameliorated by LINC00473 knockdown. Likewise, IL-1ß-induced downregulation of X-linked inhibitor of apoptosis protein was alleviated by LINC00473 knockdown. In addition, LINC00473 knockdown protected CHON-001 cells against IL-1ß by inhibiting the methylation of LIM mineralization protein (LMP)-1 gene. Moreover, c-Jun N-terminal kinase (JNK)/nuclear factor-kappaB (NF-κB) signaling pathway was proved to be involved in the cell protective effect of LINC00473 knockdown in IL-1ß treated CHON-001 cells. Taken together, LINC00473 knockdown defended CHON-001 cells from IL-1ß induced cell injury via inhibition of the methylation of LMP-1. Thus, LINC00473 might possibly act as a novel therapeutic target for OA.

LIM mineralization protein-1 inhibits IL-1ß-induced human chondrocytes injury by altering the NF-κB and MAPK/JNK pathways.

Osteoarthritis (OA) is a common degenerative disease that is associated with the degradation of articular cartilage. Accumulating evidence has confirmed that LIM mineralization protein-1 (LMP-1) is an important agent of bone formation and has been shown to be osteoinductive in various types of disease. However, the underlying mechanisms of LMP-1 in the pathogenesis of OA remain unknown. The present study aimed to evaluate the role and potential mechanism of LMP-1 in IL-1ß-stimulated OA chondrocytes. CHON-001 cells were transfected with pcDNA3.1-LMP-1, pcDNA3.1, negative control-small interfering (si)RNA or LMP-1 siRNA for 24 h and then induced by IL-1ß for 12 h to establish an OA model in vitro. Cell viability, apoptosis and inflammatory cytokine (IL-6, IL-8 and TNF-α) release were assessed using MTT assay, flow cytometry and ELISA, respectively. The expression levels of LMP-1, cleaved-caspase 3, phosphorylated (p)-p65, p65, p-JNK and JNK were analyzed using reverse transcription-quantitative PCR and western blotting. Overexpression of LMP-1 notably alleviated the IL-1ß-induced inflammatory response in CHON-001 cells, as shown by increased cell viability, decreased apoptosis, suppressed expression of cleaved-caspase 3 and a decreased cleaved-caspase 3/caspase 3 ratio. Moreover, IL-1ß-induced secretion of IL-6, IL-8 and TNF-α in CHON-001 cells; this was reversed by pcDNA3.1-LMP-1. However, knocking down LMP-1 expression exert opposite effects on the IL-1ß-induced inflammatory response in CHON-001 cells, as evidenced by the decreased cell viability, increased apoptosis, enhanced expression of cleaved-caspase 3 and cleaved-caspase 3/caspase 3 ratio and enhanced secretion of IL-6, IL-8 and TNF-α observed. The present data demonstrated that LMP-1 siRNA notably inhibited LMP-1 expression, suppressed cell viability, promoted apoptosis and enhanced cleaved-caspase 3 expression and cleaved-caspase 3/caspase 3 ratio. In addition, LMP-1 siRNA promoted the release of inflammatory factors in CHON-001 cells. It was also found that pcDNA3.1-LMP-1 inhibited p-p65 and p-JNK expression, as well as decreasing the p-p65/p65 and p-JNK/JNK ratio. Nevertheless, there was no significant difference in the mRNA expression levels of p65 and JNK between the groups. Taken together, these findings indicated that overexpression of LMP-1 alleviated IL-1ß-induced chondrocytes injury by regulating the NF-κB and MAPK/JNK pathways, suggesting that LMP-1 may be a valuable therapeutic agent for OA treatment.

HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2.

Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.

LncRNA RUSC1-AS1 promotes osteosarcoma progression through regulating the miR-340-5p and PI3K/AKT pathway.

Dysregulation of long noncoding RNA (lncRNA) is frequently involved in the progression and development of osteosarcoma. LncRNA RUSC1-AS1 is reported to be upregulated and acts as an oncogene in hepatocellular carcinoma, cervical cancer and breast cancer. However, its role in osteosarcoma has not been studied yet. In the present study, we investigated the role of RUSC1-AS1 in osteosarcoma both in vitro and in vivo. The results showed that the expression of RUSC1-AS1 was significantly upregulated in osteosarcoma cell line U2OS and HOS compared to that in human osteoblast cell line hFOB1.19. Similar results were found in human samples. Silencing RUSC1-AS1 by siRNA significantly inhibited U2OS and HOS cell proliferation and invasion, measured by CCK-8 and transwell assay. Besides, knockdown of RUSC1-AS1 increased cell apoptosis in osteosarcoma cell lines. In addition, RUSC1-AS1 promoted the epithelial-mesenchymal transition (EMT) process of osteosarcoma cells. In vivo experiments confirmed that RUSC1-AS1 knockdown had an inhibitory effect on osteosarcoma tumor growth. Mechanically, we showed that RUSC1-AS1 directly binds to and inhibits miR-340-5p and activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrated that RUSC1-AS1 promoted osteosarcoma development both in vitro and in vivo through sponging to miR-340-5p and activating the PI3K/AKT signaling pathway. Therefore, RUSC1-AS1 becomes a potential therapeutic target for osteosarcoma.

Integrative Expression and Prognosis Analysis of DHX37 in Human Cancers by Data Mining.

DHEA-Box Helicase 37 (DHX37) is a putative RNA helicase. It is involved in various RNA secondary structure alteration processes, including translation, nuclear splicing, and ribosome assembly. It is reported to be associated with the neurodevelopmental disorder with brain anomalies, and a recent study suggests that DHX37 is a functional regulator of CD8 T cells. Dysregulation of the CD8 T cell function is closely related to defective antitumor immune responses. In the present study, we investigated the expression, mutation, and prognostic role of DHX37 in human cancers, mainly by mining publicly available datasets. Our results suggested that DHX37 was significantly upregulated in 17 kinds of tumors. Mutations including deletions, insertions, and substitutions of DHX37 were widely detected. Besides, the expression of DHX37 was negatively correlated with immune-related genes PD-L1, RGS16, and TOX, and it was positively associated with TIM3, LAG3, and NCOR2. Through biofunctional analysis, we observed that DHX37 was significantly enriched in cancer-related pathways such as cell cycle, DNA replication, mismatch repair, RNA degradation, and RNA polymerase. In conclusion, the study explored the significance of DHX37 in human cancers. DHX37 may serve as a potential target for cancer immunotherapy.

Effectiveness of montelukast for uremic pruritus in hemodialysis patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Uremic pruritus (UP) is a common and tormenting symptom in end-stage renal disease patients undergoing maintenance hemodialysis. An increasing number of studies have been published in recent years to support the effectiveness of montelukast for UP. We will conduct a comprehensive systematic review and meta-analysis to evaluate effectiveness of montelukast for UP in hemodialysis patients. METHODS: The following electronic databases were searched: Pubmed, Embase, Web of Science, Cochrane Library, the China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and China Science and Technology Journal Database. The range of publication time was from the inception of the database to December 2020. Two reviewers will independently conduct article selection, data collection, and assessment of risk of bias. Any disagreement will be resolved by discussion with the third reviewer. Meta-analysis will be performed by Review Manager 5.3. The Cochrane Collaboration tool will be used to assess the risk of bias. RESULTS: This study will provide a systematic synthesis of current published data to explore the effectiveness of montelukast for UP in hemodialysis patients. CONCLUSIONS: This systematic review and meta-analysis will provide clinical evidence for the effectiveness of montelukast for UP in hemodialysis patients and inform our understanding of the value of montelukast in improving pruritus symptoms. This study will help clinicians, patients, and policy makers to make better decisions regarding the appropriate role of montelukast as a part of patient management routines. STUDY REGISTRATION NUMBER: INPLASY2020100043.

The protective role of omentin-1 in IL-1ß-induced chondrocyte senescence.

Osteoarthritis is a common type of degenerative joint disease. Inflammation-related chondrocyte senescence plays a major role in the pathogenesis of osteoarthritis. Omentin-1 is a newly identified anti-inflammatory adipokine involved in lipid metabolism. In this study, we examined the biological function of omentin-1 in cultured chondrocytes. The presence of omentin-1 potently suppresses IL-1ß-induced cellular senescence as revealed by staining with senescence-associated beta-galactosidase (SA-ß-Gal). At the cellular level, omentin-1 attenuates IL-1ß-induced G1 phase cell-cycle arrest. Mechanistically, we demonstrate that omentin-1 reduced IL-1ß-induced expression of senescent factors including caveolin-1, p21, and PAI-1 as well as p53 acetylation through ameliorating SIRT1 reduction. Notably, silencing of SIRT1 abolishes IL-1ß-induced senescence along with the induction of p21 and PAI-1, suggesting that the action of omentin-1 in chondrocytes is dependent on SIRT1. Collectively, our results revealed the molecular mechanism through which the adipokine omentin-1 exerts a beneficial effect, thereby protecting chondrocytes from senescence. Thus, omentin-1 could have clinical implication in the treatment of osteoarthritis.