Cancer patients with BMI greater than 25 were more likely to have PICC complications.

No abstract

Recently, fabrication of functional porous polymer films with patterned surface structures at the scale from nanometer to micrometer has been attracting increasing interests in material science and nanobiotechnology. In this work, we present new preparation of two series of multifunctional amphiphilic copolymers and preparation of their microporous thin films on solid substrates. First, diblock dendritic poly(l-lysine)-b-poly(l-lactide)s and triblock dendritic poly(l-lysine)-b-poly(l-lactide)-b-dendritic poly(l-lysine)s (C1-C6) were synthesized through 4-dimethylaminopyridine (DMAP)-catalyzed living ring-opening polymerization of (l-)-lactide with (l-)-lysine dendron initiators, and their structures were characterized by nuclear magnetic resonance spectrometer (NMR), gel permeation chromatography (GPC) and matrix-assisted laser desorption/ionization Fourier-transformed mass spectra (MALDI-FTMS). Employing the breath-figure (BF) fabrication strategy, thin films of the synthesized amphiphiles (C1-C6) were drop-cast, and their surface topologies were examined by scanning electron microscopy (SEM) and atomic force microscopy (AFM), and the effects of new amphiphile structure and drop-casting parameters of amphiphile concentration, humidity and temperature on self-assembly of ordered porous surface were studied. Furthermore, the influence of surface energy of drop-casting substrates was additionally investigated. With a human cervical epithelial carcinoma cell line (HeLa), cytotoxicity of the prepared honeycomb-structured films by new amphiphile C6 was evaluated by thiazoyl-blue-tetrazolium-bromide (MTT) assay, and HeLa cell growth behavior with microporous amphiphile films as the scaffolds was also examined. It was found that tunable micropore diameter sizes and well ordered surface topologies of BF films could be achieved for the new prepared amphiphiles, and utilization of the honeycomb-like microporous films as scaffolds indicated favorable enhancement in cell proliferation. Therefore, the honeycomb-structured films by these biocompatible multifunctional amphiphiles may provide new materials as 3D-scaffold materials for potential application in tissue engineering and regeneration.

Background Low doses of febuxostat or benzbromarone are widely used in Asian countries, but lacking studies to compare the efficacy and safety of the two urate-lowering drugs. Methods To compare the efficacy and safety of low-dose febuxostat with low-dose benzbromarone in patients with primary gout, a randomized controlled, open-label trial was performed among male patients with primary gout for urate-lowering therapy (ULT) in a dedicated gout clinic in China. Randomization was carried out by a third-party institution according to random number table. Patients were randomly assigned 1:1 to febuxostat group (Feb group) (20 mg daily) or benzbromarone group (Ben group) (25 mg daily) and treated for 12 weeks. General information and biochemical data were collected at baseline and at every visit monthly. Clinical characteristics before and after the ULT were analyzed in the two groups by SPSS and EmpowerStats software. Results Two hundred forty patients were enrolled and randomized in the two groups, with 214 patients completing 12 weeks’ ULT (105 in the Feb group and 109 in the Ben group). After 12 weeks, substantial percentages of patients in both Feb and Ben group achieved the target serum uric acid (sUA) (< 360 μmol/L) and serum urate levels were reduced significantly for both groups (Feb 39.5% and 156.83 μmol/L vs. Ben 35.7% and 163.99 μmol/L). Multivariate analysis suggests baseline sUA level and renal function were associated with the outcome of the rate of achieving target sUA (RAT). Sub-group analysis suggests low doses of febuxostat and benzbromarone rendered better RAT for patients with sUA < 540 μmol/L and creatinine clearance rate (Ccr) ≤ 110 mL min −1 1.73 m −2 at baseline. The drugs were well tolerated, and the incidence of gout flares in Feb group was similar with that in Ben group (22.85% vs. 33.94%). Conclusion Overall, febuxostat 20 mg daily and benzbromarone 25 mg daily reduced sUA, and gout patients with sUA level < 540 μmol/L or Ccr ≤ 110 mL min −1 1.73 m −2 at baseline had better chance to achieve target uric acid levels. The current study suggests sUA level and renal function are key factors to consider when recommending low doses of febuxostat and benzbromarone to gout patients. Trial registration Registered with ChiCTR, No. ChiCTR1800019352 (retrospectively registered).

To investigate the role of centromere protein U (CENPU) in human bladder cancer (BCa), CENPU gene expression was evaluated in human BCa tissues. We used real-time quantitative PCR (qPCR) and found that CENPU gene expression in human BCa tissues was higher compared to that observed in cancer-adjacent normal tissues. High CENPU expression was found to be strongly correlated with tumor size and TNM stage. Kaplan-Meier survival analysis indicated that high CENPU levels were associated with reduced survival. We used a lentivirus to silence endogenous CENPU gene expression in the BCa T24 cell line. CENPU knockdown was confirmed by qPCR. Cellomic imaging and BrdU assays showed that cell proliferation was significantly reduced in the CENPU-silenced cells compared to that noted in the control cells. Flow cytometry revealed that in the CENPU-silenced cells the cell cycle was arrested at the G1 phase relative to that in the control cells. In addition, apoptosis was significantly increased in the CENPU-silenced cells. Giemsa staining showed that CENPU-silenced cells, compared to control cells, displayed a significantly lower number of cell colonies. The genome-wide effect of CENPU knockdown showed that a total of 1,274 differentially expressed genes was found, including 809 downregulated genes and 465 upregulated genes. Network analysis by Ingenuity Pathway Analysis (IPA) resulted in 25 distinct signaling pathways, including the top-ranked network: ‘Cellular compromise, organismal injury and abnormalities, skeletal and muscular disorders’. In-depth IPA analysis revealed that CENPU was associated with the HMGB1 signaling pathway. qPCR and western blot analysis demonstrated that in the HMGB1 signaling pathway, CENPU knockdown downregulated expression levels of ILB, CXCL8, RAC1 and IL1A. In conclusion, our data may provide a potential pathway signature for therapeutic targets with which to treat BCa.

Metastasis and malposition were significant risk factors for PICC-related UEVT in breast cancer patients. With early diagnosis and standardized anticoagulant treatment, a better clinical outcome could be achieved. Further prospective and large sample studies are needed.

Isatin was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. This study aimed to elucidate the underlying mechanism behind isatin's ability to inhibit neuroblastoma cell metastasis. Our results demonstrated that isatin could inhibit neuroblastoma cell proliferation, invasion, and migration in a dose-dependent manner. Moreover, isatin inhibited the expression level of monoamine oxidase A as well as that of its downstream protein hypoxia-inducible factor 1α. Further study indicated that isatin inhibited reactive oxygen species production, extracellular signal-regulated kinase activation, vascular endothelial growth factor receptor-1 phosphorylation, and chemokine receptor type 4 expression. All results support the potential antimetastatic effect of isatin in neuroblatoma cells.

Clinical studies have shown a link between hyperuricemia (HU) and diabetes, while the exact effect of soluble serum urate on glucose metabolism remains elusive. This study aims to characterize the glucose metabolic phenotypes and investigate the underlying molecular mechanisms using a novel spontaneous HU mouse model in which the uricase ( Uox ) gene is absent. In an attempt to study the role of HU in glycometabolism, we implemented external stimulation on Uox knockout (KO) and wild-type (WT) males with a high-fat diet (HFD) and/or injections of multiple low-dose streptozotocin (MLD-STZ) to provoke the potential role of urate. Notably, while Uox- KO mice developed glucose intolerance in the basal condition, no mice spontaneously developed diabetes, even with aging. HFD-fed Uox- KO mice manifested similar insulin sensitivity compared with WT controls. HU augmented the existing glycometabolism abnormality induced by MLD-STZ and eventually led to diabetes, as evidenced by the increased random glucose. Reduced β-cell masses and increased terminal deoxynucleotidyl TUNEL-positive β-cells suggested that HU-mediated diabetes was cell death dependent. However, urate-lowering therapy (ULT) cannot ameliorate the diabetes incidence or reverse β-cell apoptosis with significance. ULT displayed a significant therapeutic effect of HU-crystal–associated kidney injury and tubulointerstitial damage in diabetes. Moreover, we present transcriptomic analysis of isolated islets, using Uox -KO versus WT mice and streptozotocin-induced diabetic WT (STZ-WT) versus diabetic Uox -KO (STZ-KO) mice. Shared differentially expressed genes of HU primacy revealed Stk17β is a possible target gene in HU-related β-cell death. Together, this study suggests that HU accelerates but does not cause diabetes by inhibiting islet β-cell survival.