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1.
Nutrients ; 13(3)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33803057

RESUMO

Danshensu, a traditional herb-based active component (Salvia miltiorrhiza Bunge), has garnered attention, due to its safety, nutritional value, and antioxidant effects, along with cardiovascular-protective and neuroprotective abilities; however, its effect on the retinal tissues and functional vision has not been fully studied. The objective of this study was to analyze the protective effect of danshensu on retinal tissues and functional vision in vivo in a mouse model of light-induced retinal degeneration. High energy light-evoked visual damage was confirmed by the loss in structural tissue integrity in the retina accompanied by a decline in visual acuity and visual contrast sensitivity function (VCSF), whereas the retina tissue exhibited severe Müller cell gliosis. Although danshensu treatment did not particularly reduce light-evoked damage to the photoreceptors, it significantly prevented Müller cell gliosis. Danshensu exerted protective effects against light-evoked deterioration on low spatial frequency-based VCSF as determined by the behavioral optomotor reflex method. Additionally, the protective effect of danshensu on VCSF can be reversed and blocked by the injection of a dopamine D1 receptor antagonist (SCH 23390). This study demonstrated that the major functional vision promotional effect of danshensu in vivo was through the dopamine D1 receptors enhancement pathway, rather than the structural protection of the retinas.

2.
Diagnostics (Basel) ; 11(3)2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33806580

RESUMO

(1) Background: To further validate METCAM/MUC18 as a diagnostic biomarker for prostate cancer, a modified Lateral Flow Immune Assay (LFIA) with increased sensitivity and specificity was designed by taking advantage of the extremely high affinity between biotin and streptavidin and used. (2) Methods: The combination of a commercial biotinylated rabbit antibody (EPP11278), or the home-made biotinylated chicken antibody, and the nano-gold conjugated home-made chicken antibody or a commercial rabbit antibody (EPP11278), had the higher sensitivity and specificity in this modified LFIA to establish calibration curves from the two recombinant METCAM/MUC18 proteins and were used for determining METCAM/MUC18 concentrations in serum specimens from normal individuals, benign prostatic hyperplasia (BPH) patients, prostatic intraepithelial neoplasia (PIN) patients, prostate cancer patients with various Gleason scores, and treated patients. (3) Results: Data obtained by this modified LFIA were statistically better than traditional LFIA and prostate-specific antigen (PSA) test. Interestingly, serum METCAM/MUC18 concentrations were higher in pre-malignant PIN patients than prostate cancer patients and both were higher than normal individuals, BPH patients, and treated patients. Serum METCAM/MUC18 concentrations were directly proportional to most serum PSA. (4) Conclusions: Elevated serum METCAM/MUC18 concentrations may be used for predicting the malignant potential of prostate cancer at an early premalignant (PIN) stage, which is not achievable by the current PSA test.

3.
Polymers (Basel) ; 13(6)2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801104

RESUMO

Poly-γ-glutamate/apatite (PGA-AP) nanoparticles were prepared by chemical coprecipitation method in the presence of various concentrations of poly-γ-glutamate (γ-PGA). Powder X-ray diffraction pattern and energy-dispersive spectroscopy revealed that the main crystal phase of PGA-AP was hydroxyapatite. The immobilization of γ-PGA on PGA-AP was confirmed by Fourier transform infrared spectroscopy and the relative amount of γ-PGA incorporation into PGA-AP was determined by thermal gravimetric analysis. Dynamic light scattering measurements indicated that the particle size of PGA-AP nanoparticles increased remarkably with the decrease of γ-PGA content. The adsorption of aqueous Cu(II) onto the PGA-AP nanoparticles was investigated in batch experiments with varying contact time, solution pH and temperature. Results illustrated that the adsorption of Cu(II) was very rapid during the initial adsorption period. The adsorption capacity of PGA-AP nanoparticles for Cu(II) was increased with the increase in the γ-PGA content, solution pH and temperature. At a pH of 6 and 60 °C, a higher equilibrium adsorption capacity of about 74.80 mg/g was obtained. The kinetic studies indicated that Cu(II) adsorption onto PGA-AP nanoparticles obeyed well the pseudo-second order model. The Langmuir isotherm model was fitted well to the adsorption equilibrium data. The results indicated that the adsorption behavior of PGA-AP nanoparticles for Cu(II) was mainly a monolayer chemical adsorption process. The maximum adsorption capacity of PGA-AP nanoparticles was estimated to be 78.99 mg/g.

5.
Br J Pharmacol ; 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33788266

RESUMO

BACKGROUND AND PURPOSE: Increasing evidence suggests systemic inflammation-caused skeletal muscle atrophy as a major clinical feature of cachexia. Triptolide obtained from Tripterygium wilfordii Hook F possesses potent anti-inflammatory and immunosuppressive effects. The present study aims to evaluate the protective effects and molecular mechanisms of triptolide on inflammation-induced skeletal muscle atrophy. EXPERIMENTAL APPROACH: The effects of triptolide on skeletal muscle atrophy were investigated in lipopolysaccharide (LPS)-treated C2C12 myotubes and C57BL/6 mice. Protein expressions and mRNA levels were analyzed by western blot and qPCR respectively. Skeletal muscle mass, volume and strength were measured by histological analysis, micro-CT and grip strength respectively. Locomotor activity was measured by the open field testing. KEY RESULTS: Triptolide (10-100 fM) upregulated protein synthesis signals (IGF-1/p-IGF-1R/IRS-1/p-Akt/p-mTOR) and downregulated protein degradation signal atrogin-1 in C2C12 myotubes. In LPS (100 ng·ml-1 )-treated C2C12 myotubes, triptolide upregulated MyHC, IGF-1, p-IGF-1R, IRS-1 and p-Akt. Triptolide also down-regulated ubiquitin-proteasome molecules (n-FoxO3a/atrogin-1/MuRF1), proteasome activity, autophagy-lysosomal molecules (LC3-II/LC3-I and Bnip3), and inflammatory mediators (NF-κB, Cox-2, NLRP3, IL-1ß, and TNF-α). However, AG1024, an IGF-1R inhibitor, suppressed triptolide-mediated effects on MyHC, myotube diameter, MuRF1 and p62 in LPS-treated C2C12 myotubes. In LPS (1 mg·kg-1 , i.p.)-challenged mice, triptolide (5 and 20 µg·kg-1 ·day-1 , i.p.) decreased plasma TNF-α levels, and it increased skeletal muscle volume, cross-sectional area of myofibers, weights of the gastrocnemius and tibialis anterior muscles, forelimb grip strength and locomotion. CONCLUSIONS AND IMPLICATIONS: These findings reveal that triptolide prevented LPS-induced inflammation and skeletal muscle atrophy and have implications for the discovery of novel agents for preventing muscle wasting.

6.
Int J Clin Pract ; : e14169, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33788372

RESUMO

OBJECTIVES: To provide epidemiologic evidence of whether gout increases the risk of new-onset glaucoma. METHODS: We conducted a 13-year nationwide, population-based, retrospective cohort study to examine the association between the history of gout and risk of glaucoma by using the Longitudinal Health Insurance Database (LHID) of Taiwan. The gout cohort included 52,943 patients with newly diagnosed gout who were recruited between 2000 and 2012. Each patient was propensity score matching with 1:1 person without gout from the LHID. To determine glaucoma occurrence, the study population was followed up until the end of 2013. Cumulative incidence, hazard ratios (HRs), and 95% confidence intervals (CIs) were calculated after adjusting for age, sex, comorbidities, and ever ophthalmic visit. A Cox proportional hazard model was used to analyze the association between gout and incidence of glaucoma among patients with different potential risks. RESULTS: The adjusted HR for newly diagnosed glaucoma in the gout cohort was 1.00 (95% CI = 0.93-1.07, p=0.931), compared with the non-gout cohort. Stratified subgroup analysis revealed that the HRs of glaucoma were 1.36 (95% CI = 1.09-1.70, p=0.007), 0.99 (95% CI = 0.87-1.12, p=0.871), and 0.95 (95% CI = 0.87-1.03, p=0.235) in patients with gout aged 20-39, 40-54, and ≥55 years, respectively (p for interaction = 0.011). CONCLUSION: This nationwide population-based cohort study revealed that gout patients in the age group 20-39 years had a higher risk of glaucoma than non-gout controls.

7.
PLoS Comput Biol ; 17(3): e1008821, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33739970

RESUMO

Adenosine receptors (ARs) have been demonstrated to be potential therapeutic targets against Parkinson's disease (PD). In the present study, we describe a multistage virtual screening approach that identifies dual adenosine A1 and A2A receptor antagonists using deep learning, pharmacophore models, and molecular docking methods. Nineteen hits from the ChemDiv library containing 1,178,506 compounds were selected and further tested by in vitro assays (cAMP functional assay and radioligand binding assay); of these hits, two compounds (C8 and C9) with 1,2,4-triazole scaffolds possessing the most potent binding affinity and antagonistic activity for A1/A2A ARs at the nanomolar level (pKi of 7.16-7.49 and pIC50 of 6.31-6.78) were identified. Further molecular dynamics (MD) simulations suggested similarly strong binding interactions of the complexes between the A1/A2A ARs and two compounds (C8 and C9). Notably, the 1,2,4-triazole derivatives (compounds C8 and C9) were identified as the most potent dual A1/A2A AR antagonists in our study and could serve as a basis for further development. The effective multistage screening approach developed in this study can be utilized to identify potent ligands for other drug targets.

8.
Huan Jing Ke Xue ; 42(2): 513-522, 2021 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742845

RESUMO

To evaluate the health benefits brought about by air environmental treatment and determine the main drivers of health risk, we calculated the health and economic benefits attributed to PM2.5 control in Eastern and Central China from 2013 to 2017 by combining PM2.5 concentrations with a human activity enhanced exposure-response model. The relative contributions of changes in four factors related to the PM2.5 health burden were also quantified, namely total population, population aging, baseline mortality rates, and ambient exposure. The results show that the population weighted PM2.5 concentration decreased by 28.73% and the proportion of the population exposed to annual PM2.5 concentrations lower than or equal to 35 µg·m-3 increased from 11.23% to 27.91% across the study area during this period. Avoided deaths were decreased to 14.43%, which equates to avoided economic losses of approximately 559 billion RMB. If PM2.5 concentration meets the Chinese Ambient Air Quality Standard Grade Ⅱ (35 µg·m-3) or Grade Ⅰ (15 µg·m-3), or the World Health Organization Air Quality Guidelines (AQG) standards (10 µg·m-3), a 8.22%, 55.05%, and 79.36% reduction in the total deaths could be achieved in the base year (2017) with equivalent total economic benefits of approximately 319, 2137, and 3081 billion RMB, respectively. Total population, population aging, baseline mortality rates, and PM2.5 concentrations contributed -2.69%, -12.38%, 1.66%, and 14.57% to PM2.5-related deaths. Overall, during the study period, the reduction in PM2.5 concentrations has been the main factor contributing to the reduction in the public health burden. China has implemented significant air pollution control measures; however, the health burden associated with high PM2.5 concentrations in densely populated areas is still extremely high, requiring an aggressive air pollution control strategy.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , China , Exposição Ambiental , Humanos , Material Particulado/análise , Saúde Pública
9.
Artigo em Inglês | MEDLINE | ID: mdl-33651428

RESUMO

BACKGROUND AND AIM: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Both HBV and HCV infections lead to risks of end-stage liver diseases and extrahepatic manifestations. This study aimed to investigate hepatic and extrahepatic comorbidities in hemodialysis patients with HBV or HCV infections compared with those without viral hepatitis. METHODS: A total of 1910 hemodialysis patients, including 159 HCV viremic patients (HCV group), 217 seropositive for HBV surface antigen (HBsAg, HBV group) and 1534 seronegative for both anti-HCV and HBsAg (non-B and non-C [NBNC] group), from 23 hemodialysis centers were enrolled. Comorbidities were classified into 10 categories by the International Classification of Diseases-10th Revision. RESULTS: Among the 1910 patients, the mean age was 64.6 years, and 52.7% were male patients. A total of 1834 (96%) patients had at least one comorbidity, and the mean number of comorbidities was 2.9 ± 1.5 per person. The three most common comorbidities were hypertension, diabetes, and ischemic heart diseases. The mean number of comorbidities per person was significantly higher in the HCV group (3.3 ± 1.7) than in the HBV (2.7 ± 1.5, P < 0.001) and NBNC groups (2.9 ± 1.5, P = 0.004), mainly due to the higher prevalence of ischemic heart disease, respiratory disorders, and mental/behavioral disorders. The HBV and NBNC groups exhibited comparable burdens of comorbidities. CONCLUSIONS: Hemodialysis patients had a high prevalence of multiple comorbidities. Hemodialysis patients with HCV exhibited a higher burden of comorbidities, especially ischemic heart diseases, respiratory disorders, and mental/behavioral disorders, than HBV and NBNC patients did.

10.
Org Lett ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739843

RESUMO

A novel dehydrogenative coupling reaction of N-fluorocarboxamides with polyfluoroarenes forming C(sp2)-C(sp3) bonds enabled by copper catalysis has been accomplished. N-Fluorocarboxamides are postulated to undergo copper-mediated dehydrogenative cross-coupling reaction with electron-deficient polyfluoroarenes via a radical pathway. Benzylic C-H bonds and aliphatic C-H bonds in N-fluorocarboxamides could proceed smoothly and demonstrated excellent regioselectivity. The detailed mechanism presented is supported by control experiments and density functional theory calculations.

11.
Redox Biol ; 41: 101926, 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33752108

RESUMO

Chemosensitivity to cisplatin derivatives varies among individual patients with intractable malignancies including ovarian cancer, while how to unlock the resistance remain unknown. Ovarian cancer tissues were collected the debulking surgery in discovery- (n = 135) and validation- (n = 47) cohorts, to be analyzed with high-throughput automated immunohistochemistry which identified cystathionine γ-lyase (CSE) as an independent marker distinguishing non-responders from responders to post-operative platinum-based chemotherapy. We aimed to identify CSE-derived metabolites responsible for chemoresistant mechanisms: gold-nanoparticle (AuN)-based surface-enhanced Raman spectroscopy (SERS) was used to enhance electromagnetic fields which enabled to visualize multiple sulfur-containing metabolites through detecting scattering light from Au-S vibration two-dimensionally. Clear cell carcinoma (CCC) who turned out less sensitive to cisplatin than serous adenocarcinoma was classified into two groups by the intensities of SERS intensities at 480 cm-1; patients with greater intensities displayed the shorter overall survival after the debulking surgery. The SERS signals were eliminated by topically applied monobromobimane that breaks sulfane-sulfur bonds of polysulfides to result in formation of sulfodibimane which was detected at 580 cm-1, manifesting the presence of polysulfides in cancer tissues. CCC-derived cancer cell lines in culture were resistant against cisplatin, but treatment with ambroxol, an expectorant degrading polysulfides, renders the cells CDDP-susceptible. Co-administration of ambroxol with cisplatin significantly suppressed growth of cancer xenografts in nude mice. Furthermore, polysulfides, but neither glutathione nor hypotaurine, attenuated cisplatin-induced disturbance of DNA supercoiling. Polysulfide detection by on-tissue SERS thus enables to predict prognosis of cisplatin-based chemotherapy. The current findings suggest polysulfide degradation as a stratagem unlocking cisplatin chemoresistance.

12.
Environ Toxicol ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33713530

RESUMO

Secondary metabolites in marine organisms exhibit various pharmacological activities against diseases, such as cancer. In this study, the anti-proliferative effect of JBIR-100, a macrolide isolated from Streptomyces sp., was investigated in breast cancer cells. Cell growth was inhibited in response to JBIR-100 treatment concentration- and time-dependently in both MCF-7 and MDA-MB-231 breast cancer cells. JBIR-100 caused apoptosis, as verified by caspase activation and the cleavage of PARP. Western blotting revealed that JBIR-100 modulated the expression of Akt/NF-κB signaling components and Bcl-2 family members. Overexpression of Mcl-1 partially rescued MCF-7 cells from JBIR-100-induced cytotoxicity. In addition, transmission electron microscopy analyses, confocal analysis, and western blot assay indicated that JBIR-100 inhibited autophagy in MCF-7 cells. Exposure to the autophagy inhibitor did not synergize JBIR-100-induced apoptosis. In summary, our results suggested that JBIR-100 may be potentially used for breast cancer therapy.

13.
Zhongguo Gu Shang ; 34(3): 228-34, 2021 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-33787166

RESUMO

OBJECTIVE: To investigate the clinical efficacy and superiority of direct lateral interbody fusion combined with posterior percutaneous screw fixation in the treatment of lumbar tuberculosis. METHODS: From June 2013 to August 2016, the clinical data of 83 patients with lumbar tuberculosis were retrospectively analyzed, including 55 males and 28 females, aged from 27 to 72 (49.5±13.5) years. These 83 patients were divided into two groups according to different operation methods, 35 cases in group A were treated with direct lateral interbody fusion combined with posterior percutaneous screw fixation;48 cases in group B were treated with anterior traditional extraperitoneal debridement combined with posterior internal fixation. After operation, regular quadruple antituberculosis drugs were continued for 18 months. The operation time, intraoperative blood loss, hospital stay, bone graft fusion time and complications were compared between the two groups. Visual analogue score (VAS) of lumbar pain, Oswestry Disability Index (ODI), sagittal Cobb angle, erythrocyte sedimentation rate (ESR) and C-reactive protein(CRP) values before and after operation were analyzed. RESULTS: The operation was successfully completed in both groups, and the operation mode was not changed during operation. The operation time, intraoperative blood loss and hospital stay were (149.4±13.3) min, (354.3±69.0) ml, (9.4±1.6) d in group A and(116.8±10.0) min, (721.9±172.3) ml, (11.8±1.7) d in group B, respectively, with significant difference between the two groups (P<0.05). The follow up time was (24.2±5.1) months in group A and (24.0±5.0) months in group B, there was no significant difference between two groups (P>0.05). At the follow-up of 4 months after operation, one patient in group A was found to have enlarged psoas major abscess on the contralateral side, and was cured after secondary operation. No sinus formation, cerebrospinal fluid leakage, internal fixation loosening, fracture or distal junction kyphosis were found during follow-up. The fusion time was (5.1±1.6) months in group A and (5.1± 1.7) months in group B, there was no significant difference between two groups (P>0.05). The VAS, ODI score, sagittal Cobb angle, ESR and CRP value of the lesion segment at the last follow-up of the two groups were significantly improved (P<0.05), but there was no significant difference between two groups (P>0.05). CONCLUSION: The two kinds of operation can obtain satisfactory clinical effect. Direct lateral interbody fusion combined with posterior percutaneous screw fixation can reduce intraoperative blood loss and hospital stay, which is conducive to early rehabilitation of patients.


Assuntos
Parafusos Pediculares , Fusão Vertebral , Tuberculose da Coluna Vertebral , Idoso , Transplante Ósseo , Desbridamento , Feminino , Humanos , Vértebras Lombares/cirurgia , Masculino , Estudos Retrospectivos , Vértebras Torácicas , Resultado do Tratamento , Tuberculose da Coluna Vertebral/cirurgia
14.
Biochem Biophys Res Commun ; 551: 155-160, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33740622

RESUMO

OBJECTIVES: Clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by low-grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (RP-ILD) and skin ulcers with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is thought to function as an inhibitor of tumours and inflammation. Here, we aimed to investigate the roles of BATF2 in Th cell differentiation of CADM with an anti-MDA5 autoantibody (anti-MDA5+ CADM). METHODS: Naive CD4+ T cells from human peripheral blood mononuclear cells (PBMCs) of healthy controls (HCs) were isolated and then cultured with IL-12, TGF-ß or TGF-ß plus IL-6 following anti-CD3 and anti-CD28 stimulations. The expression of BATF2 was measured by real-time PCR. The percentages of Th1, Th17 and Treg CD4+ T cells were detected by flow cytometry. BATF2 knockdown of CD4+ T cells was performed using small interfering RNAs (siRNAs). RESULTS: The expression of BATF2 in PBMCs was higher in anti-MDA5+ CADM patients than in healthy controls. The BATF2 mRNA expression was increased under Th1 and Treg polarization but decreased under Th17 polarization. Th17 cell activation-associated genes were possibly increased while Th1 and Treg cell differentiation-associated genes were inhibited by posttranscriptional gene silencing of BATF2 in CD4+ T cells. CONCLUSIONS: BATF2 promoted Th1 and Treg cell differentiation but suppressed Th17 cell activation in anti-MDA5+ CADM.

15.
Genome ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661713

RESUMO

Subgenome asymmetry (SA) has routinely been attributed to different responses between the subgenomes of a polyploid to various stimuli during evolution. Here, we compared subgenome differences in gene ratio and relative diversity between artificial and natural genotypes of several allopolyploid species. Surprisingly, consistent differences were detected between these two types of polyploid genotypes although they differ in times exposed to evolutionary selection. The estimated ratio of shared genes between a subgenome and its diploid donor was invariably higher for the artificial allopolyploid genotypes than those for the natural genotypes, which is expected as it is now well-known that many genes in a species are not shared among all individuals. As the exact diploid parent for a given subgenome is unknown, the estimated ratios of shared genes for the natural genotypes would also include difference among individual genotypes of the diploid donor species. Further, we detected the presence of SA in genotypes before the completion of the polyploidization events as well as in those which were not formed via polyploidization. These results indicate that SA may, to a large degree, reflect differences between its diploid donors or that changes occurred during polyploid evolution are defined by their donor genomes.

16.
Sci Rep ; 11(1): 5022, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658578

RESUMO

We hypothesized that epigenetics is a link between smoking/allergen exposures and the development of Asthma and chronic obstructive pulmonary disease (ACO). A total of 75 of 228 COPD patients were identified as ACO, which was independently associated with increased exacerbations. Microarray analysis identified 404 differentially methylated loci (DML) in ACO patients, and 6575 DML in those with rapid lung function decline in a discovery cohort. In the validation cohort, ACO patients had hypermethylated PDE9A (+ 30,088)/ZNF323 (- 296), and hypomethylated SEPT8 (- 47) genes as compared with either pure COPD patients or healthy non-smokers. Hypermethylated TIGIT (- 173) gene and hypomethylated CYSLTR1 (+ 348)/CCDC88C (+ 125,722)/ADORA2B (+ 1339) were associated with severe airflow limitation, while hypomethylated IFRD1 (- 515) gene with frequent exacerbation in all the COPD patients. Hypermethylated ZNF323 (- 296) / MPV17L (+ 194) and hypomethylated PTPRN2 (+ 10,000) genes were associated with rapid lung function decline. In vitro cigarette smoke extract and ovalbumin concurrent exposure resulted in specific DNA methylation changes of the MPV17L / ZNF323 genes, while 5-aza-2'-deoxycytidine treatment reversed promoter hypermethylation-mediated MPV17L under-expression accompanied with reduced apoptosis and decreased generation of reactive oxygen species. Aberrant DNA methylations may constitute a determinant for ACO, and provide a biomarker of airflow limitation, exacerbation, and lung function decline.

17.
Hepatol Int ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33677787

RESUMO

BACKGROUND: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan. METHODS: Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR12) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported. RESULTS: The SVR12 rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6-96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8-99.6%), respectively. Among 82 patients who failed to achieve SVR12, 13 (15.9%) were attributed to virologic failures. The SVR12 rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations. CONCLUSIONS: SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan.

18.
J Formos Med Assoc ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33674232

RESUMO

BACKGROUND: Major trauma has been one of the leading causes of morbidity, mortality, and functional disability, resulting in substantial societal burden. The aim of this study was to estimate the trends in burden of adult major trauma in Taiwan during 2003-2015. METHODS: Adult patients with initial encounter of major trauma (injury severity score ≥ 16) were abstracted from the claim data of National Health Insurance (NHI) in Taiwan from January 2003 to December 2015. We explored the trends of incidence and mortality rates over time stratified by age and sex, as well as life expectancy (LE), loss-of-LE, lifetime healthcare expenditure and total loss-of-LE compared with age, sex and calendar-year matched referents simulated from the vital statistics of Taiwan. RESULTS: A total of 71,731 cases of adult major trauma, and an estimated loss of 979,676 life-years were found with an increasing trend in cumulative incidence rate (CIR18-84) during 2003-2015. The incidence rates were significantly higher in men than women. For both sexes, the incidence rates for those aged 65 and above were about 2-3 times higher than those of all other age groups. The one-year case fatality rates among the elderly were about 31-61%, higher than all other ages. The lifetime healthcare expenditures per person were 47,616 USD in men and 43,416 USD in women. CONCLUSION: There is a consistently increasing trend in incidence and mortality of major trauma in Taiwan, especially among elderly people. For Taiwan, an aged society beginning since 2018, the challenge should be tackled more effectively in the coming decades.

19.
Pain Med ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33690860

RESUMO

OBJECTIVE: To examine the prevalence and duration of skeletal muscle relaxant (SMR) treatment among commercially insured adults. METHODS: We used the MarketScan Research Database to identify a cohort of adults 18 to 64 years who had ≥ two-year continuous enrollment between 2005 and 2018. We estimated the prevalence of SMR treatment using a repeated cross-sectional design and derived treatment duration using the Kaplan-Meier method. Analyses were stratified by age group, sex, geographic region, individual SMR agent, and musculoskeletal disorder. RESULTS: 48.7 million individuals were included. Treatment prevalence ranged from 61.5 to 68.3 per 1000. About one-third of users did not have a preceding musculoskeletal disorder diagnosis. Cyclobenzaprine was the dominant agent accounting for >50% of prescriptions. The considerable growth in the use of baclofen, tizanidine, and methocarbamol paralleled with a decline in carisoprodol and metaxalone use. The prevalence was highest in the South while lowest in the Northeast. The median treatment duration was 14 days with 4.0%, 1.9%, and 1.0% of individuals using SMRs for more than 90, 180, and 365 days. Compared with cyclobenzaprine, patients initiating baclofen, tizanidine, and carisoprodol had longer treatment duration. CONCLUSIONS: SMRs are widely used in the United States. Their use slightly increased in recent years but trends varied among individual agents, patient groups, and geographic regions. Despite limited evidence to support efficacy, a sizable number of U.S. adults used SMRs for long-term and off-label conditions. Further study is needed to understand determinants of treatment as well as outcomes associated with such use.

20.
Nat Rev Urol ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692499

RESUMO

Prostate cancer is a global health problem, but incidence varies considerably across different continents. Asia is traditionally considered a low-incidence area, but the incidence and mortality of prostate cancer have rapidly increased across the continent. Substantial differences in epidemiological features have been observed among different Asian regions, and incidence, as well as mortality-to-incidence ratio, is associated with the human development index. Prostate cancer mortality decreased in Japan and Israel from 2007 to 2016, but mortality has increased in Thailand, Kyrgyzstan and Uzbekistan over the same period. Genomic analyses have shown a low prevalence of ERG oncoprotein in the East Asian population, alongside a low rate of PTEN loss, high CHD1 enrichments and high FOXA1 alterations. Contributions from single-nucleotide polymorphisms to prostate cancer risk vary with ethnicity, but germline mutation rates of DNA damage repair genes in metastatic prostate cancer are comparable in Chinese and white patients from the USA and UK. Pharmacogenomic features of testosterone metabolism might contribute to disparities seen in the response to androgen deprivation between East Asian men and white American and European men. Overall, considerable diversity in epidemiology and genomics of prostate cancer across Asia defines disease characteristics in these populations, but studies in this area are under-represented in the literature. Taking into account this intracontinental and intercontinental heterogeneity, translational studies are required in order to develop ethnicity-specific treatment strategies.

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