Summary
Background
Renal dysfunction remains an issue in tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients.
Aim
To evaluate renal safety of TDF according to the Kidney ...Disease: Improving Global Outcomes (KDIGO) guidelines.
Methods
We retrospectively recruited CHB patients who received either TDF or entecavir (ETV) monotherapy from January 2008 to August 2015. After excluding confounding conditions, 253 patients who received TDF were randomly matched 1:2 with 506 patients who received ETV through the propensity scores, which consisted of age, gender, cirrhosis, chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR). Renal function deterioration was defined as a drop in GFR category accompanied with a ≥25% eGFR decline. Cumulative incidences of and hazard ratios (HRs) for renal dysfunction were analysed.
Results
The mean eGFR decline was significantly greater in the TDF group over 48 months (TDF vs ETV: 15.73 mL/min/1.73 m2, 95% confidence interval CI: 13.76‐17.70 vs 5.96 mL/min/1.73 m2, 95% CI: 4.72‐7.19; P < 0.001). The cumulative incidence of renal function deterioration was significantly higher in the TDF group (TDF vs ETV: 11.1%, 95% CI: 7.4‐14.8 vs 1.7%, 95% CI: 1.0‐2.4; P < 0.001). After adjusting for age, pre‐existing CKD and diabetes, TDF was independently associated with an increased risk of renal function deterioration (HR 5.36, 95% CI: 2.16‐13.35; P < 0.001). Pre‐existing CKD (HR 6.71, 95% CI: 2.25‐17.65), proteinuria (HR 3.39, 95% CI: 1.23‐9.39), and haematuria (HR 4.25, 95% CI: 1.32‐13.68) were also independent factors of renal dysfunction.
Conclusion
By following the KDIGO guidelines, we confirmed that TDF was associated with a higher risk of renal dysfunction as compared to ETV.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Most oral squamous cell carcinoma (OSCC) tumors arise from oral premalignant lesions. Oral submucous fibrosis (OSF), usually occurring in male chewers of betel quid, is a premalignant stromal disease ...characterized by a high malignant transformation rate and high prevalence. Although a relationship between the inhabited microbiome and carcinogenesis has been proposed, no detailed information regarding the oral microbiome of patients with OSF exists; the changes of the salivary microbiome during cancer formation remain unclear. This study compared the salivary microbiomes of male patients with OSCC and a predisposing OSF background (OSCC-OSF group) and those with OSF only (OSF group). The results of high-throughput sequencing of the bacterial 16S rRNA gene indicated that OSF-related carcinogenesis and smoking status significantly contributed to phylogenetic composition variations in the salivary microbiome, leading to considerable reductions in species richness and phylogenetic diversity. The microbiome profile of OSF-related malignancy was associated with increased microbial stochastic fluctuation, which dominated the salivary microbiome assembly and caused species co-occurrence network collapse. Artificial intelligence selection algorithms consistently identified 5 key species in the OSCC-OSF group: Porphyromonas catoniae, Prevotella multisaccharivorax, Prevotella sp. HMT-300, Mitsuokella sp. HMT-131, and Treponema sp. HMT-927. Robust accuracy in predicting oral carcinogenesis was obtained with our exploratory and validation data sets. In functional analysis, the microbiome of the OSCC-OSF group had greater potential for S-adenosyl-l-methionine and norspermidine synthesis but lower potential for l-ornithine and pyrimidine deoxyribonucleotide synthesis and formaldehyde metabolism. These findings indicated that the salivary microbiome plays important roles in modulating microbial metabolites during oral carcinogenesis. In conclusion, our results provided new insights into salivary microbiome alterations during the malignant transformation of OSF.
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CMK, NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear. Here, we found that ...PDIA4 expression was upregulated in a variety of tumor cell lines and human lung adenocarcinoma tissues. Knockdown and overexpression of PDIA4 in tumor cells showed that PDIA4 facilitated cell growth via the reduction of caspases 3 and 7 activity. Consistently, Lewis lung carcinoma cells overexpressing PDIA4 grew faster than did parental cells in tumor-bearing mice, as shown by a reduced survival rate, increased tumor size and metastasis, and decreased cell death and caspases 3 and 7 activity. PDIA4 knockdown resulted in opposite outcomes. Moreover, results obtained in mice with spontaneous hepatoma indicated that PDIA4 deficiency significantly reduced hepatic tumorigenesis and cyst formation and increased mouse survival, tumor death, and caspases 3 and 7 activity. Mechanistic studies illustrated that PDIA4 negatively regulated tumor cell death by inhibiting degradation and activation of procaspases 3 and 7 via their mutual interaction in a CGHC-dependent manner. Finally, we found that 1,2-dihydroxytrideca-5,7,9,11-tetrayne, a PDIA4 inhibitor, reduced tumor development via enhancement of caspase-mediated cell death in TSA tumor-bearing mice. These findings characterize PDIA4 as a negative regulator of cancer cell apoptosis and suggest that PDIA4 is a potential therapeutic target for cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Optimal myocardial protection for donated hearts is crucial to improve outcomes of heart transplantation and reduce morbidity and mortality. This study aimed to compare the ...efficacy of myocardial protection using single dose of Bretschneider's histidine–tryptophan–ketoglutarate (HTK) solution and repeated doses of cold blood cardioplegia (CBC) in donor heart preservation. Methods Sixty-seven patients undergoing heart transplantation in Tri-Service General Hospital, Taipei, Taiwan between 2002 and 2012 were enrolled in this study. Patients were divided into an HTK group and a CBC group based on the preservation solution used to protect the donated hearts. The perioperative variables and postoperative outcomes were retrospectively reviewed. Results There were no statistic differences about demographic data in donors and recipients between the 2 groups. There were no significant differences in postoperative cardiac enzymes, hemodynamic data, length of stay in intensive care, or 30-day mortality between the groups. The HTK group showed a trend of shorter pumping time ( P = .091). Multivariate analyses reveal that the HTK group had higher postoperative inotropic score ( P < .001) and shorter pumping time ( P = .02). Conclusions Single dose of Bretschneider's HTK solution could effectively reduce pumping time and afford similar myocardial protection compared with repeated doses of CBC in the preservation of donated hearts.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The multi-sensor fusion scheme has become more and more popular these days with its great potential to estimate reliable navigation information for the modern development in automated driving system ...(ADS) and mobile mapping systems (MMS). Since these systems are combined with numerous navigation sensors, thus their geometric relationship should be precisely known. This study focuses on practical aspects when calibrating LiDAR-IMU mounting parameters (lever-arms and bore-sight angles) in land-based MMS. This calibration model is based on expressing the mounting parameters within the direct georeferencing equation for each epoch time and conditioning a set of INS/GNSS and LiDAR navigation solutions to lie on it. There is no need for a required information about the planar features in the calibration field as part of the unknowns. Such conditions are only benefitable in the residential area where the presence of sufficient planes in form of building is abundant. We present an approach for recovery the mounting parameters by conditioning the high-definition (HD) point cloud map-based LiDAR information and INS/GNSS navigation solutions through the least-squares solutions. The presented results and discussion mainly focus on practical examples with data from land-based MMS. Preliminary results indicate that correct calibration parameters are not only capable to improve the performance of point cloud georeferencing but also dramatically provide reliable performance evaluation of navigation estimation. Moreover, these findings show that the studied method is not only applicable in the featureless environment but also in its practicality to the self-driving applications.
Hyperperfusion syndrome is a devastating complication of carotid stent placement. The shortening of cerebral circulation time after stent placement is seen as a good indicator of the development of ...hyperperfusion syndrome. The purpose of our study was to evaluate whether patients with ipsilateral transverse sinus stenosis are prone to having shortened cerebral circulation time after stent placement, subsequently leading to the possible development of hyperperfusion syndrome.
Forty-nine patients with >70% unilateral carotid stenosis undergoing stent placement were recruited for analysis. Group A consisted of patients with a stenotic ipsilateral transverse sinus >50% greater than the diameter of the contralateral transverse sinus; the remaining patients were in group B. Quantitative DSA was used to calculate cerebral circulation time. Cerebral circulation time was defined as the time difference between the relative time to maximal intensity of ROIs in the proximal internal carotid artery and the internal jugular vein. ΔCCT was defined as cerebral circulation time before stent placement minus cerebral circulation time after stent placement. ΔCCT, white matter hyperintensity signals, and sulcal effacement in MR imaging were compared between the 2 groups.
ΔCCT was significantly shorter in group A (0.65 ± 1.3) than in group B (-0.12 ± 1.4). Three patients had white matter hyperintensity signals in group A, and 1 developed hyperperfusion syndrome. Group B showed no MR imaging signs of hyperperfusion syndrome.
Ipsilateral hypoplastic transverse sinus was associated with prolonged cerebral circulation time before stent placement and greatly shortened cerebral circulation time after stent placement. Inadequate venous drainage might play a role in impaired cerebral autoregulation and might influence the development of poststenting hyperperfusion syndrome.
Because angiotensin-converting enzyme (ACE) activity is implicated widely in biological systems, we aimed to identify its novel quantitative trait loci for the purposes of understanding ACE activity ...regulation and pharmacogenetics relating to ACE inhibitor (ACEI). We performed a two-stage genome-wide association study: (1) from 400 young-onset hypertension (YOH) subjects and (2) a confirmation study with an additional 623 YOH subjects. In the first stage, eight single nucleotide polymorphisms (SNPs) of the ACE structural gene and one SNP of ABO genes were significantly associated with ACE activity. SNP rs4343 in exon17 near the well-known insertion/deletion polymorphism had the strongest association. We confirmed in the second stage that three SNPs: rs4343 in ACE gene (P=3.0 x 10⁻²⁵), rs495828 (P=3.5 x 10⁻⁸) and rs8176746 (P=9.3 x 10⁻⁵) in ABO gene were significantly associated with ACE activity. We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees), and showed a potential differential blood pressure response to ACEI in subjects with varied numbers of ACE-activity-raising alleles. These findings may broaden our understanding of the mechanisms controlling ACE activity and advance our pharmacogenetic knowledge on ACEI.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Here we aim to develop a facile emulsion-based method to prepare tripod gold nanoparticles (AuNPs) with high suspension stability in an aqueous environment. A gyroid-structured polymer template ...formed by the hydrolysis of a degradable block copolymer, polystyrene (PS)-b-poly(l-lactide), is used for the fabrication of AuNPs. Also, a successful emulsification of dichloromethane (DCM) in the aqueous phase is developed by using thiolated polyethylene glycol (PEG-SH) as the stabilizer. Subsequently, the nanohybrids of PS/Au can be fabricated by templated electroless plating, and then selectively dissolving in the DCM dispersive phase. Most interestingly, a dedicated process for the simultaneous release of the tripod AuNPs from the dissolution of PS associated with PEG-SH at the interface of the emulsion is achieved, giving PEG-SH-functionalized tripod AuNPs dispersed in the aqueous phase, which significantly improves the suspension stabilization of tripod AuNPs. The in situ temperature-programmed electrospray-differential mobility analysis provides a quantitative, statistical analysis of mobility diameter, dynamic shape factor, polydispersity, and colloidal stability.
The memory performance of hafnium oxide (HfO x )-based resistive memory containing a thin reactive Ti buffer layer can be greatly improved. Due to the excellent ability of Ti to absorb oxygen atoms ...from the HfO x film after post-metal annealing, a large amount of oxygen vacancies are left in the HfO x layer of the TiN/Ti/HfO x /TiN stacked layer. These oxygen vacancies are crucial to make a memory device with a stable bipolar resistive switching behavior. Aside from the benefits of low operation power and large on/off ratio (>100), this memory also exhibits reliable switching endurance (>10 6 cycles), robust resistance states (200°C), high device yield (~100%), and fast switching speed (<10 ns).
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