A Retrospective Study of Preferable Alternative Route to Right Internal Jugular Vein for Placing Tunneled Dialysis Catheters: Right External Jugular Vein versus Left Internal Jugular Vein

Background

Right internal jugular vein (IJV) is a preferred access route for tunneled (cuffed) dialysis catheters (TDCs), and both right external jugular vein (EJV) and left IJV are alternative routes for patients in case the right IJV isn’t available for TDC placement. This retrospective study aimed to determine if a disparity exists between the two alternative routes in hemodialysis patients in terms of outcomes of TDCs.

Methods

49 hemodialysis patients who required TDCs through right EJV (n = 21) or left IJV (n = 28) as long-term vascular access were included in this study. The primary end point was cumulative catheter patency. Secondary end points include primary catheter patency, proportion of patients that never required urokinase and incidence of catheter-related bloodstream infections (CRBSI).

Results

A total of 20,870 catheter-days were evaluated and the median was 384 (interquartile range, 262–605) catheter-days. Fewer catheters were removed in the right EJV group than in the left IJV group (P = 0.007). Mean cumulative catheter patency was higher in the right EJV group compared with the left IJV group (P = 0.031). There was no significant difference between the two groups in the incidence of CRBSI, primary catheter patency or proportion of patients that never required urokinase use. Total indwell time of antecedent catheters was identified as an independent risk factor for cumulative catheter patency by Cox regression hazards test with an HR of 2.212 (95% CI, 1.363–3.588; p = 0.001).

Conclusions

Right EJV might be superior to left IJV as an alternative insertion route for TDC placement in hemodialysis patients whose right IJVs are unavailable.     

Integrated Intercalation‐Based and Interfacial Sodium Storage in Graphene‐Wrapped Porous Li4Ti5O12 Nanofibers Composite Aerogel

Sodium storage in both solid–liquid and solid–solid interfaces is expected to extend the horizon of sodium‐ion batteries, leading to a new strategy for developing high‐performance energy‐storage materials. Here, a novel composite aerogel with porous Li₄Ti₅O₁₂ (PLTO) nanofibers confined in a highly conductive 3D‐interconnected graphene framework (G‐PLTO) is designed and fabricated for Na storage. A high capacity of 195 mA h g^?1 at 0.2 C and super‐long cycle life up to 12 000 cycles are attained. Electrochemical analysis shows that the intercalation‐based and interfacial Na storage behaviors take effect simultaneously in the G‐PLTO composite aerogel. An integrated Na storage mechanism is proposed. This study ascribes the excellent performance to the unique structure, which not only offers short pathways for Na⁺ diffusion and conductive networks for electron transport, but also guarantees plenty of PLTO–electrolyte and PLTO–graphene interfacial sites for Na⁺ adsorption.     

Skin aging caused by intrinsic or extrinsic processes characterized with functional proteomics

The skin provides protection against environmental stress. However, intrinsic and extrinsic aging causes significant alteration to skin structure and components, which subsequently impairs molecular characteristics and biochemical processes. Here, we have conducted an immunohistological investigation and established the proteome profiles on nude mice skin to verify the specific responses during aging caused by different factors. Our results showed that UVB‐elicited aging results in upregulation of proliferating cell nuclear antigen and strong oxidative damage in DNA, whereas chronological aging abolished epidermal cell growth and increased the expression of caspase‐14, as well as protein carbonylation. Network analysis indicated that the programmed skin aging activated the ubiquitin system and triggered obvious downregulation of 14‐3‐3 sigma, which might accelerate the loss of cell growth capacity. On the other hand, UVB stimulation enhanced inflammation and the risk of skin carcinogenesis. Collectively, functional proteomics could provide large‐scale investigation of the potent proteins and molecules that play important roles in skin subjected to both intrinsic and extrinsic aging.     

dBRWD3 Regulates Tissue Overgrowth and Ectopic Gene Expression Caused by Polycomb Group Mutations

To maintain a particular cell fate, a unique set of genes should be expressed while another set is repressed. One way to repress gene expression is through Polycomb group (PcG) proteins that compact chromatin into a silent configuration. In addition to cell fate maintenance, PcG proteins also maintain normal cell physiology, for example cell cycle. In the absence of PcG, ectopic activation of the PcG-repressed genes leads to developmental defects and malignant tumors. Little is known about the molecular nature of ectopic gene expression; especially what differentiates expression of a given gene in the orthotopic tissue (orthotopic expression) and the ectopic expression of the same gene due to PcG mutations. Here we present that ectopic gene expression in PcG mutant cells specifically requires dBRWD3, a negative regulator of HIRA/Yemanuclein (YEM)-mediated histone variant H3.3 deposition. dBRWD3 mutations suppress both the ectopic gene expression and aberrant tissue overgrowth in PcG mutants through a YEM-dependent mechanism. Our findings identified dBRWD3 as a critical regulator that is uniquely required for ectopic gene expression and aberrant tissue overgrowth caused by PcG mutations.     

Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4^−/− mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.Cerebral aneurysm rupture causes subarachnoid hemorrhage (SAH), which is associated with a high mortality due to its secondary complications, including hemorrhage, hydrocephalus and delayed cerebral ischemia (DCI).^{1, 2, 3} Therapeutic interventions against the secondary complications, especially DCI, are yet limited, as the pathological mechanism underlying that is not fully understood.^{2, 3, 4, 5, 6, 7} Current hypotheses of the development of the secondary complications mainly include cerebral vasospasm (CVS) and the microcirculation disturbance, as well as parenchymal arterial lesions, microthrombosis and neuroinflammation.^{1, 2, 4, 7, 8, 9}Previous studies have shown that the blockade of cerebral lymphatic drainage deteriorated the secondary cerebral ischemia after SAH, suggesting that the cerebral lymphatic drainage pathway could be involved in the pathological mechanism of SAH.^{10, 11} However, the central nervous system (CNS) was considered lack of a conventional lymphatic drainage system in the past. Recently, several studies have shown that the brain has in fact the proper lymphatic system, including sinus-associated lymphatic vessels and the glymphatic system (GS).^{12, 13, 14, 15} Sinus-associated lymphatic vessels express all of the molecular hallmarks of lymphatic endothelial cells, contain cerebrospinal fluid (CSF) and immune cells, and drain into the deep cervical lymph nodes.^{12, 13}There is a histologically defined space in the brain, the Virchow–Robin space, where the subarachnoid space meets the paravascular space (or perivascular space in somewhere, PVS).¹⁶ The GS is a specialized brain-wide anatomic structure locating at the PVS surrounding the brain vasculature, which is ensheathed with the astroglial endfeet and astroglial water channel aquaporin-4 (AQP4).^{14, 15} The GS facilitates the efficient lymphatic clearance of extracellular solutes and fluid in the brain through astroglial-mediated interstitial fluid bulk flow.¹⁴Impairment of GS involves neurological conditions including traumatic brain injuries,¹⁷ ischemic stroke¹⁸ and aged brain.¹⁹ Interestingly, brain imaging study with magnetic resonance imaging reported weakened GS perfusion following acute stroke or SAH.^{18, 20} However, little is known about whether the GS is involved in the secondary complications of SAH. Here, we examined the potential involvement of GS in SAH-associated pathology progression with in vivo two-photon microscopy and CLARITY technique.^{21, 22} Our data showed that subarachnoid blood flowed into the brain parenchyma rapidly through the PVS, causing CVS, vasculitis, widespread microinfraction and neuroinflammation in the animal model of SAH and SAH patients. Prevention of CVS with Fasudil²³ did not improve the neurological impairment nor alleviated the pathology, while the PVS clearance with tissue-type plasminogen activator (tPA) infusion improved the behavioral recovery and reduced neuroinflammation in the brain. Interestingly, AQP4^−/− mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. Our study therefore suggested that the paravacular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.     

Epidemiological Study of RRT-Treated ESRD in Nanjing - A Ten-Year Experience in Nearly Three Million Insurance Covered Population

Background

The growing burden of end-stage renal disease (ESRD) has been a great challenge to the health care system of China. However, the exact epidemiological data for ESRD in China remain unclear. We aimed to investigate the epidemiology of ESRD treated by renal replacement therapy (RRT) in Nanjing based on analysing ten-year data of Nanjing three million insurance covered population.

Methods

Using the electronic registry system of Urban Employee Basic Medical Insurance (UEBMI), we included all subjects insured by UEBMI in Nanjing from 2005 to 2014 and identified subjects who developed ESRD and started RRT in this cohort.

Results

The UEBMI population in Nanjing increased from 1,301,882 in 2005 to 2,921,065 in 2014, among which a total of 5,840 subjects developed ESRD and received RRT. Over the 10-year period, the adjusted incidence rates of RRT in the UEBMI cohort gradually decreased from 289.3pmp in 2005 to 218.8pmp in 2014. However, the adjusted prevalence rate increased steadily from 891.7pmp in 2005 to 1,228.6pmp in 2014. The adjusted annual mortality rate decreased from 138.4 per 1000 patient-years in 2005 to 97.8 per 1000 patient-years in 2014. The long-term survival rate fluctuated over the past decade, with the 1-year survival rate ranging from 85.1% to 91.7%, the 3-year survival rate from 69.9% to 78.3% and the 5-year survival rate from 58% to 65.4%.

Conclusion

Nanjing is facing an increasing burden of ESRD with its improvement of medical reform. The ten-year complete registry data on RRT in urban employees in Nanjing provided a unique opportunity to understand the real threat of ESRD confronting China during its process of health care transition.     

A Meta-Analysis of the Association between ESR1 Genetic Variants and the Risk of Breast Cancer

BackgroundSingle nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results.MethodsWe pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified.ResultsThree SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555–0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730–0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037–2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations.ConclusionRs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk.