To test the hypothesis that patients with concomitant lobar and deep intracerebral hemorrhages/microbleeds (mixed ICH) have predominantly hypertensive small vessel disease (HTN-SVD) rather than ...cerebral amyloid angiopathy (CAA), using in vivo amyloid imaging.
Eighty Asian patients with primary ICH without dementia were included in this cross-sectional study. All patients underwent brain MRI and
C-Pittsburgh compound B (PiB)-PET imaging. The mean cortical standardized uptake value ratio (SUVR) was calculated using cerebellum as reference. Forty-six patients (57.5%) had mixed ICH. Their demographic and clinical profile as well as amyloid deposition patterns were compared to those of 13 patients with CAA-ICH and 21 patients with strictly deep microbleeds and ICH (HTN-ICH).
Patients with mixed ICH were younger (62.8 ± 11.7 vs 73.3 ± 11.9 years in CAA,
= 0.006) and showed a higher rate of hypertension than patients with CAA-ICH (
< 0.001). Patients with mixed ICH had lower PiB SUVR than patients with CAA (1.06 1.01-1.13 vs 1.43 1.06-1.58,
= 0.003). In a multivariable logistic regression model, mixed ICH was associated with hypertension (odds ratio 8.9, 95% confidence interval 1.4-58.4,
= 0.02) and lower PiB SUVR (odds ratio 0.03, 95% confidence interval 0.001-0.87,
= 0.04) compared to CAA after adjustment for age. Compared to HTN-ICH, mixed ICH showed a similar mean age (62.8 ± 11.7 vs 60.1 ± 14.5 years in HTN-ICH) and risk factor profile (all
> 0.1). Furthermore, PiB SUVR did not differ between mixed ICH (values presented above) and HTN-ICH (1.10 1.00-1.16,
= 0.45).
Patients with mixed ICH have much lower amyloid load than patients with CAA-ICH, while being similar to HTN-ICH. Overall, mixed ICH is probably caused by HTN-SVD, an important finding with clinical relevance.
In this letter, we report the oxygen accumulation effect and its influence on resistive switching for gadolinium-doped silicon dioxide (Gd:SiO 2 ) resistance random access memory (RRAM). We find that ...oxygen absorbance by indium-tin-oxide electrode affects the conduction current mechanism, and remarkably modifies the device performance of RRAM devices. By current fitting, Schottky emission can be observed in both low and high resistance states, from which conduction model is proposed to clarify the oxygen accumulation phenomenon. Reliability tests, including endurance and high temperature retention are further carried out, evaluating the significance of oxygen accumulation effect in redox reaction for RRAM devices.
Liver fibrosis is a reversible process of extracellular matrix deposition or scar formation after liver injury. Intestinal damage and bacterial dysbiosis are important concomitant intestinal changes ...in liver fibrosis and may in turn accelerate the progression of liver fibrosis through the gut–liver axis. RhoA, an important factor in the regulation of the cytoskeleton, plays an important role in intestinal damage. We investigated the effects of ursolic acid (UA), a traditional Chinese medicine with anti-fibrotic effects, on intestinal damage and bacterial disorder through the RhoA pathway. UA treatment reduced intestinal damage by inhibiting the inflammatory factor TNF-α and increasing the expression of tight junction proteins and antibacterial peptides to protect the intestinal barrier. Moreover, the corrective effect of UA on bacterial dysbiosis was also confirmed by sequencing of the 16S rRNA gene. Potential beneficial bacteria, such as the phylum Firmicutes and the genera
Lactobacillus
and
Bifidobacterium
, were increased in the UA group compared to the CCl
4
group. In liver fibrosis mice with RhoA inhibition
via
injection of adeno-associated virus, the liver fibrosis, intestinal damage, and flora disturbances were improved. Moreover, UA inhibited the expression of RhoA pathway components. In conclusion, UA improves intestinal damage and bacterial dysbiosis partly
via
the RhoA pathway. This may be a potential mechanism by which UA exerts its anti-fibrotic effects and provides effective theoretical support for the future use of UA in clinical practice.
Male gender is a risk factor for mortality in patients with papillary thyroid carcinoma (PTC). This study investigated the impact of androgen receptor (
) gene expression on the clinical features and ...progression of PTC. The levels of
mRNA and protein in frozen, formalin-fixed, paraffin-embedded tissue samples from PTC and adjacent normal thyroid tissue were assessed by quantitative real-time polymerase chain reaction and immunohistochemical staining, respectively, and the relationships between
expression and clinical features were analyzed. The thyroid cancer cell lines, BCPAP and TPC-1, were used to evaluate the effects of
on the regulation of cell migration, and key epithelial-mesenchymal transition (EMT) markers.
mRNA expression was significantly higher in normal thyroid tissue from men than women. The sex difference in
mRNA expression diminished during PTC tumorigenesis, as
mRNA expression levels were lower in PTC than normal thyroid tissues from both men and women.
mRNA expression was significantly decreased in PTC patients with higher risk and in those with extrathyroidal extension. Overexpression of
in BCPAP cells decreased cell migration and repressed the EMT process by down-regulating mRNA expression of
,
,
,
, and
and up-regulating
gene expression. These results suggest that suppression of the androgen-
axis may lead to aggressive tumor behavior in patients with PTC.
Aims
A dramatic increase in pulmonary capillary wedge pressure (PCWP) during exercise is observed in patients with heart failure with preserved ejection fraction (HFpEF). This study was designed to ...determine whether iloprost inhalation could improve exercise haemodynamics and cardiac reserve in patients with HFpEF.
Methods
Thirty‐four HFpEF patients were enrolled in this double‐blind, randomized, placebo‐controlled, parallel‐group trial. Patients received both cardiac catheterization and underwent expired gas analysis at rest, during exercise, and before and 10 minutes after treatment with either inhaled iloprost or placebo. The primary endpoint was decrease in exercise PCWP.
Results
At baseline, enrolled patients showed an increase in PCWP during exercise (from 16 range, 14–23 mmHg to 27 21–36 mmHg; P < .0001). After iloprost inhalation, exercise PCWP was significantly reduced compared to placebo (adjusted mean: 20 16–29 mmHg vs 23 17–32 mmHg; P = .002). There was no difference for cardiac output reserve with exercise in the 2 groups (0.2 −1.3–1.2 L/min vs –0.7 −1.9–0.1 L/min; P = .099). Iloprost improved the pulmonary artery pressure flow relationships in HFpEF with exercise compared to placebo.
Conclusion
Iloprost inhalation improved haemodynamic deficits during exercise in patients with HFpEF. Prospective trials testing long‐term iloprost therapy in this population are warranted.
Radiofrequency ablation (RFA) is a minimally invasive management strategy that has been widely applied for benign and recurrent malignant thyroid lesions as an alternative to surgery in Taiwan. ...Members of academic societies for specialists in interventional radiology, endocrinology, and endocrine surgery collaborated to develop the first consensus regarding thyroid RFA in Taiwan. The modified Delphi method was used to reach a consensus. Based on a comprehensive review of recent and valuable literature and expert opinions, the recommendations included indications, pre-procedural evaluations, procedural techniques, post-procedural monitoring, efficacy, and safety, providing a comprehensive review of the application of RFA. The consensus effectively consolidates advice regarding thyroid RFA in clinical practice for local experts.
To investigate maximum tolerated dose (MTD) of axitinib, a selective vascular endothelial growth factor receptor 1-3 inhibitor, in combination with radiotherapy (RT) for advanced hepatocellular ...carcinoma (HCC).
This phase I study followed the rule of traditional 3 + 3 design. Major eligibility included: (1) patients with advanced HCC unsuitable for surgery, radiofrequency ablation or transarterial chemoembolization, or who failed after prior local-regional treatment; (2) failure on sorafenib or no grant for sorafenib from health insurance system. Eligible patients with advanced HCC received axitinib for total 8 weeks during and after RT. Three cohorts with axitinib dose escalation were planned: 1 mg twice daily (level I), 2 mg twice daily (level II) and 3 mg twice daily (level III). The prescribed doses of RT ranged from 37.5 to 67.5 Gy in 15 fractions to liver tumor(s) and were determined based on an upper limit of mean liver dose of 18 Gy (intended isotoxic RT for normal liver). The primary endpoint was MTD of axitinib in combination with RT. The secondary endpoints included overall response rate (ORR), RT in-field response rate, acute and late toxicities, overall survival (OS) and progression free survival (PFS).
Total nine eligible patients received axitinib dose levels of 1 mg twice daily (n = 3), 2 mg twice daily (n = 3) and 3 mg twice daily (n = 3). Dose-limiting toxicity (DLT) did not occur in the 3 cohorts; the MTD was defined as 3 mg twice daily in this study. ORR was 66.7%, including 3 complete responses and 3 partial responses, at 3 months after treatment initiation. With a median follow-up of 16.6 months, median OS was not reached, 1-year OS was 66.7%, and median PFS was 7.4 months.
Axitinib in combination with RT for advanced HCC was well tolerated with an axitinib MTD of 3 mg twice daily in this study. The outcome analysis should be interpreted with caution due to the small total cohort. Trial registration ClinicalTrials.gov (Identifier: NCT02814461), Registered June 27, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02814461.
Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to ...discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.
Introduction
Viral infection is an exogeneous factor for primary Sjogren’s syndrome (pSS). This study investigated the association between human papillomavirus (HPV) infections and pSS through a ...nationwide population based cohort study.
Methods
Patients with HPV infections between January, 1999 and December, 2013 were included. The incidence of new-onset pSS in patients with HPV infections and non-HPV controls were derived. The multiple Cox regression model derived the risk of pSS in patients with HPV infections. Subgroup analysis and sensitivity analysis were performed to validate the association.
Results
During a follow-up period of 12 years, the adjusted hazard ratio (aHR) of pSS in patients with HPV infections was significantly higher than that in non-HPV controls (aHR=1.64, 95% CI=1.47-1.83, P<0.001). The risk of pSS increased with age and the risk increased by 2.64-fold (95% CI= 2.37-2.93) for those older than 45 years. The significant association between HPV infections and the risk of pSS persisted in the sensitivity analysis restricted in HPV infections that lasted over 12 months (aHR=1.63, 95%CI=1.45-1.83, P<0.0001). Subgroup analyses revealed that both male (aHR=1.83, 95%CI=1.47-2.28, P<0.0001) and female (aHR=1.58, 95%CI=1.40-1.79, P<0.0001) patients with HPV infections and HPV-infected patients aged between 16 and 45 years (aHR=1.60, 95%CI=1.34-1.91, P<0.0001) and over 45 years (aHR=1.67, 95%CI=1.46-1.91, P<0.0001) were associated with a significantly greater risk of pSS.
Conclusion
Patients with HPV infections presented with a significantly higher risk of pSS, regardless of age and sex.
In this study, the hopping conduction distance and bipolar switching properties of the Gd:SiOx thin film by (radio frequency, rf) rf sputtering technology for applications in RRAM devices were ...calculated and investigated. To discuss and verify the electrical switching mechanism in various different constant compliance currents, the typical current versus applied voltage (
) characteristics of gadolinium oxide RRAM devices was transferred and fitted. Finally, the transmission electrons' switching behavior between the TiN bottom electrode and Pt top electrode in the initial metallic filament forming process of the gadolinium oxide thin film RRAM devices for low resistance state (LRS)/high resistance state (HRS) was described and explained in a simulated physical diagram model.
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