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1.
Res Vet Sci ; 130: 68-72, 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32146377

RESUMO

Modified-live virus (MLV) vaccines derived from highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) were wildly used in China, which resulted in the emergence of MLV-like strains in pigs. Previous studies demonstrated that secondary bacterial infection could enhance HP-PRRSV infection-mediated inflammatory responses, but it is unknown whether early bacterial infection could enhance the HP-PRRSV MLV-like infection-mediated pathological reaction. In this paper, to gain the evidence for infection of pigs with MLV-like strains in China, we firstly analyzed the genetic characterization of the HP-PRRSV MLV-like isolate (TJxq1701) and further evaluated whether the early Streptococcus suis infection synergizes HP-PRRSV MLV-like infection-mediated pathological reaction. Our results showed that the whole genome of TJxq1701 shared the highest homology with JXA1-P80 and a total of 16 amino acids residues unique to JXA1-P80 in ORF1a, ORF1b, GP2, GP3, GP4, and GP5 were found in the corresponding locations. The results of infection experiments in pigs revealed that TJxq1701 caused transitional fever, moderate respiratory clinical sign and microscopic lung lesions in piglets, but early infection with low virulence Streptococcus suis serotype 2 (SS2) exhibited seriously clinical signs, including high fever, anorexia, and respiratory distress, leading to 60% mortality within four weeks in comparison with alone infected group. Taken together, our findings reveal that early bacterial infection could enhance the HP-PRRSV MLV-like infection-mediated pathological reaction, which provide an important clue for understanding that streptococcus infection increases the pathogenicity of MLV-like virus and a new thought for prevention and control of PRRSV.

2.
J Cancer Res Clin Oncol ; 146(4): 809-820, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146564

RESUMO

PURPOSE: MicroRNAs (miRNAs) participate in a variety of biological processes, including tumorigenesis, progression, invasion, and drug resistance to multiple cancers. Phosphatase and tensin homolog (PTEN) is a cancer suppressor gene that has been certified to be regulated by miRNAs in various tumors, including colorectal cancer (CRC). In this review, we screened articles focusing on low PTEN expression in CRC, observed the expression of related miRNAs, analyzed their correlation and relationship with clinicopathological features, and discussed the possibility of these miRNAs as prognostic molecules. METHODS: We conducted a systematic search for articles published in the Web of Science, PubMed and EBSCO databases between January 1, 2002, and July 18, 2019. We identified these studies by using combinations of the following index entries and key words: 'colorectal tumor OR colorectal neoplasm OR colorectal carcinoma OR colorectal cancer OR CRC', 'protein tyrosine phosphatase OR PTEN', and 'microRNA OR MiRNA OR miRNA OR MicroRNA'. Moreover, we evaluated the underlying association between alterations in PTEN and CRC prognosis. RESULTS: PTEN expression was obviously lower in CRC tissues than in normal mucosa. However, PTEN expression did not differ significantly between adenoma and normal tissues. PTEN tends to be negatively associated with tumor size and metastasis. MiR-21, miR-200a, miR-543, miR-32, miR-92a, miR-26a, miR-106a and miR-181a were correlated with the downregulation of PTEN. MiR-26a, miR-106a and miR-181a were obviously higher in CRC tissues than in normal tissues, while PTEN was downregulated in CRC tissues. Additionally, miRNAs were mainly positively correlated with distant metastasis, followed by TNM stage. The relationship between miRNAs and tumor differentiation is controversial. However, there were no significant differences between miRNAs and either sex or age. CONCLUSIONS: The loss of PTEN may be a diagnostic factor for CRC patients. The above-mentioned miRNAs may function as oncogenes in CRC and represent potential targets for CRC therapy. However, further prospective clinical studies are necessary.

4.
Nucl Med Commun ; 41(3): 219-227, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31895760

RESUMO

BACKGROUND: To compare the accuracy of various equations for estimating glomerular filtration rate. METHODS: Chronic kidney disease was classified by Tc-DTPA scintigraphy (reference glomerular filtration rate), estimating glomerular filtration rate was estimated using various formulas. The similarity to reference glomerular filtration rate decide the accuracy of estimating glomerular filtration rate. RESULTS: Overall, the Fengscr-cys equation had significantly higher accuracy and correct proportion in chronic kidney disease stage classification than other equations. The subgroup analysis showed that Fengscr-cys equation was slightly more precise than other equations both in the male and female patients. Moreover, in patients older than 60 years or whose reference glomerular filtration rate was above 60 ml/min, Fengscr-cys equation also showed better accuracy. CONCLUSION: Our data suggest that estimating glomerular filtration rate equations evaluated by serum cystatin C were better than serum creatinine-based equations, estimating glomerular filtration rate equations evaluated by both serum creatinine and cystatin C were better than those evaluated by serum creatinine or cystatin C alone. Among all enrolled equations, Fengscr-cys equation might be the best one to evaluate glomerular filtration rate in general Chinese paticipants.

5.
Inflammation ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897917

RESUMO

There are very few reports on the protective effect of artesunate (ARS) in ulcerative colitis (UC). This study focused on the efficacy of ARS on intestinal barrier, inflammatory response, and potential mechanism in dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. The results suggested that ARS treatment markedly alleviated DSS-induced clinical symptoms by relieving body weight loss, the disease activity index (DAI) score, and preventing colonic shortening. HE staining and scanning electron microscope analysis revealed that ARS treatment significantly protected the integrity of intestinal barrier through alleviating DSS-induced erosion of surface epithelial cells, reduction of goblet cells, and destruction of the crypt accompanied with inflammatory cells infiltration. Immunofluorescence histochemical staining and western blot assay confirmed that ARS notably inhibited the loss of Muc2 and claudin-1 in mucosal layer with a relative higher level of Bcl-2/Bax ratio and, moreover, inhibited cleaved-caspase-3 expression in colon tissue. In addition, this study reconfirmed the anti-inflammatory function of ARS evidenced by remarkably suppressing the phosphorylation of nuclear factor-κBα (IκBα) and NF-κB p65 and the expression of IL-1ß, IL-6, and TNF-α while enhancing IL-10 expression. Taken together, these data highlight that ARS has the protective effect on UC through maintaining the expression of intestinal mucosal barrier-related proteins, suppressing the apoptosis and inflammatory response. This study may facilitate to understand the action mechanism of ARS against UC.

6.
J Cell Mol Med ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31990147

RESUMO

The purpose of the present study was to evaluate the anti-cancer property of Lobetyolin on colorectal cancer and explore its potential mechanism. Lobetyolin was incubated with HCT-116 cells in the absence or presence of ASCT2 inhibitor Benser or p53 inhibitor Pifithrin-α. The levels of glutamine, glutamic acid, α-ketoglutarate, ATP and GSH were determined to measure the glutamine metabolism. Annexin V-FITC/PI staining and TUNEL assay were applied to estimate the apoptotic condition. The levels of ASCT2 were examined by RT-qPCR, Western blot and immunofluorescence staining. The expressions of cleaved-caspase-3, caspase-3, cleaved-caspase-7, caspase-7, cleaved-PARP, PARP, p53, p21, bax and survivin were detected using Western blot analysis. As a result, the treatment with Lobetyolin effectively induced apoptosis and glutamine metabolism in HCT-116 cells through ASCT2 signalling. The inhibition of ASCT2 reduced the glutamine-related biomarkers and augmented the apoptotic process. We further found that the effect of Lobetyolin on HCT-116 was related to the expressions of p21 and bax, and transportation of p53 to nucleus. The inhibition of p53 by Pifithrin-α promoted the inhibitory effect of Lobetyolin on ASCT2-mediated apoptosis. Lobetyolin also exerted anti-cancer property in nude mice. In conclusion, the present work suggested that Lobetyolin could induce the apoptosis via the inhibition of ASCT2-mediated glutamine metabolism, which was possibly governed by p53.

7.
J Pharm Biomed Anal ; 179: 112984, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31759764

RESUMO

Xiao-Ai-Jie-Du decoction (XAJDD), a traditional Chinese medicine formula, has long been used for the treatment of hepatocarcinoma, gastric cancer and colorectal cancer. It is composed of six herbal medicines, including Scutellariae Barbatae Herba, Pseudostellariae Radix, Ophiopogonis Radix, Cremastrae Pseudobulbus, Curcumae Rhizoma and Akebiae Fructus. Despite the in-depth study on its pharmacological effects on cancer prevention and treatment, the comprehensive analysis of the chemical components and the absorbed bioactive constituents are not well studied. Thus, an ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was established to detect and identify the chemical constituents in XAJDD. The absorbed components and metabolites after oral administration of XAJDD in rats were also studied. In total, 102 components were identified or tentatively characterized in XAJDD, including 30 flavonoids, 19 triterpenoids, 12 organic acids, 9 steroidal saponins, 9 cyclic peptides, 7 phenanthrenes, 5 amino acids, 3 alkaloids and 8 other compounds. After analysing the metabolites in rat plasma and urine after oral administration of XAJDD, a total of 70 compounds were identified, including 15 primary components and 55 metabolites, and metabolic pathways, including hydrogenation, hydroxylation, methylation, sulfonation, and glucuronidation were evaluated. Among these, methylation and glucuronidation were the main metabolic pathways. In conclusion, the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the chemical constituents of XAJDD in vitro and characterizing the primary components and their metabolites in vivo; moreover, the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of XAJDD.

8.
Sci Total Environ ; 704: 135245, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31818549

RESUMO

Droughts have destructive impacts on agricultural production; thus, drought projections are vital for the development of future drought mitigation strategies. This work aimed to project a standardized precipitation and evapotranspiration index (SPEI) at 3-, 6- and 12-month timescales for the period 2011-2100 under two representative concentration pathway (RCP) scenarios - RCP 4.5 and RCP 8.5 in mainland China and to assess the changes in various drought indices over a baseline period of 1961-2000. The spatiotemporal variations in drought characteristics (e.g., the drought occurrence time, duration, severity, peak, and frequency and the percentage of stations suffering from drought (PSSD) were estimated by the projected SPEI for the periods 2011-2040, 2041-2070 and 2071-2100. The results showed that mainland China would experience more frequent and severe droughts in the future than in the baseline period, as denoted by SPEI and the generated drought variables. In particular, drier areas of northwestern China were likely to suffer from worse drought conditions than those in other areas, with PSSD values of 60% and 81% by 2100 under the RCP4.5 and RCP 8.5 scenarios, respectively. Although the annual precipitation was projected to increase in most regions, drought conditions would still worsen because of increased the minimum and maximum air temperatures. However, the GCMs contributed more uncertainties to the projection of the SPEI than the stations or the RCPs, because the GCMs made a larger contribution to the variance (>40%). The SPEI performed better than the other indices that only accounted for the influence of a single variable. The relationship between crop yields and the three drought indices varied by month, crop (maize and cotton), and timescale (3- and 6-month). The drought projections from our study can provide invaluable information for stakeholders in developing regionally specific drought adaptation strategies in the face of climate change.


Assuntos
Mudança Climática , Secas , Modelos Teóricos , Chuva , Agricultura , China , Ecossistema , Monitoramento Ambiental/métodos
9.
IEEE Trans Med Imaging ; 39(2): 413-424, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31283476

RESUMO

Glaucoma is one of the leading causes of irreversible vision loss. Many approaches have recently been proposed for automatic glaucoma detection based on fundus images. However, none of the existing approaches can efficiently remove high redundancy in fundus images for glaucoma detection, which may reduce the reliability and accuracy of glaucoma detection. To avoid this disadvantage, this paper proposes an attention-based convolutional neural network (CNN) for glaucoma detection, called AG-CNN. Specifically, we first establish a large-scale attention-based glaucoma (LAG) database, which includes 11 760 fundus images labeled as either positive glaucoma (4878) or negative glaucoma (6882). Among the 11 760 fundus images, the attention maps of 5824 images are further obtained from ophthalmologists through a simulated eye-tracking experiment. Then, a new structure of AG-CNN is designed, including an attention prediction subnet, a pathological area localization subnet, and a glaucoma classification subnet. The attention maps are predicted in the attention prediction subnet to highlight the salient regions for glaucoma detection, under a weakly supervised training manner. In contrast to other attention-based CNN methods, the features are also visualized as the localized pathological area, which are further added in our AG-CNN structure to enhance the glaucoma detection performance. Finally, the experiment results from testing over our LAG database and another public glaucoma database show that the proposed AG-CNN approach significantly advances the state-of-the-art in glaucoma detection.

10.
Ying Yong Sheng Tai Xue Bao ; 30(11): 3753-3761, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31833688

RESUMO

The long duration of rainy weather in the Jianghan Plain leads to low light stress to wheat during the growing season. We examined the effects of shading at booting stage (S1) and anthesis (S2) on grain yield and physiological traits of two main wheat cultivars in Jianghan Plain, Zhengmai 9023 (ZM 9023) and Yangmai 23 (YM 23). 6-BA was sprayed before shading treatment (S1+6-BA, S2+6-BA) to explore the mitigation effect of low light stress by 6-BA. The results showed that 45% shading of full solar radiation at booting and anthesis stages significantly reduced grain yield, with greater effect at anthesis than that at the booting stage. Dry matter accumulation of grain during 14-21 days after anthesis was significantly decreased by shading. Shading at both growth stages reduced dry matter accumulation at maturity and changed the proportion of dry matter redistribution in vegetative organs. Consequently, grain yield was more dependent on the storage of photosynthetic assimilates of vegetative organs before anthesis, which resulted in a decline of grain yield in shading treatment. The grain yield of spraying 6-BA before anthesis was significantly greater than that of shading treatment, suggesting exogenous application of 6-BA could delay the senescence of flag leaf, grain filling rate and grain weight to mitigate the negative effect of shading. In addition, spraying 6-BA increased dry matter accumulation in the shading treatment at anthesis, and the translocation of post-anthesis assimilates. Grain weight of S2+6-BA was higher than that with S2, which ultimately increased grain yield as compared to the shading treatment. In conclusion, the negative impact of shading on wheat grain yield at anthesis was greater than that at booting stage. The application of exogenous 6-BA before shading at anthesis could mitigate yield loss of the shading treatment.


Assuntos
Oryza , Triticum , Grão Comestível , Fotossíntese , Folhas de Planta
11.
Ann Clin Transl Neurol ; 6(12): 2377-2383, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31838784

RESUMO

OBJECTIVE: Mutations in optineurin (OPTN) have been identified in familial and sporadic amyotrophic lateral sclerosis (ALS). We screened a cohort of Chinese patients for mutations in optineurin. We also performed an extensive literatures review of all mutations in optineurin identified previously to detect genotype-phenotype associations. METHODS: All 16 exons of the OPTN gene in a cohort of 15 familial ALS indexes and 275 sporadic ALS patients of Chinese origin were sequenced by targeted next generation sequencing. RESULTS: Two known heterozygous missense mutations in the OPTN, c.1481T> G (p.L494W), and c.1546G> C (p.E516Q), as well as one novel heterozygous missense mutation c.1690G> C (p.D564H) were each detected in one sporadic ALS patient. The patient carrying the p.E516Q mutation developed clinical features of ALS-frontotemporal dementia (FTD) and the patient carrying the p.D564H mutation showed a phenotype of ALS. They both had an aggressive course, with a survival of 18 and 14 months respectively. Literature review showed that the clinical phenotypes in OPTN mutated ALS were not homogeneous, although some individuals showed a relatively slow progression and a long duration, some mutations carriers developed an aggressive progression and a short survival. INTERPRETATION: OPTN mutations contribute to ALS in Chinese population and account for 0.8% of sporadic ALS patients and 1.5% of familial ALS in the pooled Chinese ALS cohorts. Mutations in optineurin can cause aggressive ALS+/-FTD.

12.
Prep Biochem Biotechnol ; : 1-8, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31846385

RESUMO

In order to obtain a better fermentation parameter for the production of recombinant Ganoderma lucidum immunomodulatory protein (rFIP-glu), an engineered Pichia pastoris GS115 was investigated on the fermentation time, temperature, methanol concentration and initial pH of media, while immunomodulatory activities of the rFIP-glu was confirmed. L9(33) orthogonal experiment were firstly employed to optimize various fermentation parameters in the shake-flask level. The optimized fermentation parameters were subsequently verified in a 5 L fermenter. Biological activities including cell viability and tumor necrosis factor-alpha (TNF-α) mRNA of the rFIP-glu were evaluated on murine macrophage RAW264.7 cells. The results showed that the yield of rFIP-glu was up to 368.71 µg/ml in the shake-flask, and 613.47 µg/ml in the 5 L fermenter, when the Pichia pastoris was incubated in basic media with the methanol concentration 1.0% and initial pH 6.5, and with constant shaking at 280 rpm for 4 days at 26 °C. In vitro assays of biological activity indicated that rFIP-glu had significant toxicity against RAW264.7 cells, and possessed the ability to induce TNF-α mRNA expression in macrophage RAW264.7 cells. In conclusion, engineered P. pastoris showed a good fermentation property under the optimum fermentation parameters. It could be a candidate industrial strain for further study.

13.
Chin J Integr Med ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848890

RESUMO

OBJECTIVE: To analyze the overall survival (OS) of elderly acute myeloid leukemia (AML) patients treated with oral arsenic-containing Qinghuang Powder (, QHP) or low-intensity chemotherapy (LIC). METHODS: Forty-two elderly AML patients treated with intravenous or subcutaneous LIC (1 month for each course, at least 3 courses) or oral QHP (3 months for each course, at least 2 courses) were retrospectively analyzed from January 2015 to December 2017. The main endpoints of analysis were OS and 1-, 2-, 3-year OS rates of patients, respectively. And the adverse reactions induding bone marrow suppression, digestive tract discomfort and myocardia injury were observed. RESULTS: Out of 42 elderly AML patients, 22 received LIC treatment and 20 received QHP treatment, according to patients' preference. There was no significant difference on OS between LIC and QHP patients (13.0 months vs. 13.5 months, >0.05). There was no significant difference on OS rates between LIC and QHP groups at 1 year (59.1% vs. 70.0%), 2 years (13.6% vs. 15%), and 3 years (4.6% vs. 5.0%, all >0.05). Furthermore, there was no significant difference of OS on prognosis stratification of performance status > 2 (12 months vs. 12 months), age> 75 year-old (12.0 months vs. 12.5 months), hematopoietic stem cell transplant comorbidity index >2 (12 months vs. 13 months), poor cytogenetics (12 months vs. 8 months), and diagnosis of secondary AML (10 months vs. 14 months) between LIC and QHP patients (>0.05). CONCLUSION: QHP may be an alternative treatment for elderly AML patients refusing LIC therapy.

14.
Oncol Lett ; 18(5): 5077-5084, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612018

RESUMO

At least one mutation is present in 70-80% of patients with myelodysplastic syndrome (MDS). Genetic alterations and other molecular biological markers have been included in the diagnostic and treatment guidelines for MDS. The aim of the present study was to analyze the association between genetic alterations and clinicopathological features among 47 Chinese patients with a novel diagnosis of MDS using a next-generation sequencing approach. The results indicated that from the 47 patients, 66.0% had genetic alterations. Furthermore, seven genes, U2 small nuclear RNA auxiliary factor 1 (23.4%), splicing factor 3b subunit (12.8%), ASXL transcriptional regulator 1 (10.6%), tet methylcytosine dioxygenase 2 (8.5%), BCL6 corepressor (8.5%), TP53 (8.5%) and DNA methyltransferase 3α (6.4%), indicated a higher prevalence of alterations in >5% of patients. Among the 16 (51.6%) patients with ≥2 mutations, 12 (75%) had mutations in different genetic functional groups. Variant allele frequencies in signaling pathways were generally low, suggesting that mutations in the corresponding genes were acquired relatively late during the evolution of the leukemic clones. The mutation prevalence rates of Janus kinase 2 and SH2B adaptor protein 3 were significantly higher in the MDS unclassified group and in the very high-risk groups with a karyotype as a prognostic indicator, respectively (both P<0.05). The mutation prevalence rates of SET binding protein 1 and enhancer of zeste 2 polycomb repressive complex 2 subunit were significantly higher in the high-risk group (both P<0.05). In summary, 66.0% of the 47 patients with a novel MDS diagnosis had a genetic mutation as detected by 127-target gene next-generation sequencing. The results for the genetic alterations in the present study will supplement the database of patients with MDS in China.

16.
Sci Rep ; 9(1): 14644, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601887

RESUMO

Shandong Province is an area of China with a high incidence of haemorrhagic fever with renal syndrome (HFRS); however, the general epidemic trend of HFRS in Shandong remains unclear. Therefore, we established a mathematical model to predict the incidence trend of HFRS and used Joinpoint regression analysis, a generalised additive model (GAM), and other methods to evaluate the data. Incidence data from the first half of 2018 were included in a range predicted by a modified sum autoregressive integrated moving average-support vector machine (ARIMA-SVM) combination model. The highest incidence of HFRS occurred in October and November, and the annual mortality rate decreased by 7.3% (p < 0.05) from 2004 to 2017. In cold months, the incidence of HFRS increased by 4%, -1%, and 0.8% for every unit increase in temperature, relative humidity, and rainfall, respectively; in warm months, this incidence changed by 2%, -3%, and 0% respectively. Overall, HFRS incidence and mortality in Shandong showed a downward trend over the past 10 years. In both cold and warm months, the effects of temperature, relative humidity, and rainfall on HFRS incidence varied. A modified ARIMA-SVM combination model could effectively predict the occurrence of HFRS.

17.
Appl Microbiol Biotechnol ; 103(23-24): 9239-9250, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31659419

RESUMO

Ganoderma have been regarded as a traditional source of natural bioactive compounds for centuries and have recently been exploited for potential components in the cosmetics industry. Besides Ganoderma polysaccharides and triterpenes, multiple proteins have been found in Ganoderma. With the in-depth study of these proteins, various pharmacological functions of Ganoderma have become important in the discovery and development of new products. In the review, we summarized and discussed the kinds and characteristics of Ganoderma proteins, especially on fungal immunomodulatory proteins (FIPs) which can be potentially developed into cosmeceuticals or nutricosmetics and are a suitable target for production using established biotechnological methods. Furthermore, we discuss their pharmacological activities of the proteins with a focus on their pharmacological functions related to cosmetics, such as antioxidant activity, inhibition of melanin, antibacterial activity, and regulation of inflammatory mediators. Numerous other questions also are addressed before the proteins can be widely accepted and used as cosmetic additives.

18.
Rev. esp. enferm. dig ; 111(10): 738-743, oct. 2019. tab, graf
Artigo em Inglês | IBECS-Express | ID: ibc-ET1-4900

RESUMO

Background: proton pump inhibitors (PPI) have been widely used in the clinic but inappropriate prescribing has also increased dramatically. Objective: to describe the prescribing patterns and assess the appropriateness of the prescribed PPI use in 45 hospitals in China. Materials and methods: PPI prescriptions for non-hospitalized patients were collected from hospitals in Beijing, Chengdu, Guangzhou and Hangzhou of China over a 40-day period in 2016. These data were analyzed using the prescription number, proportion and economic indicators (defined daily dose system [DDD], defined daily cost [DDC] and drug utilization index [DUI]). The evaluation criteria of PPI use was based on Martindale: The Complete Drug Reference, New Materia Medica and drug instructions. Results: in total, 357,687 prescriptions using oral PPI and 38,216 prescriptions using injectable PPI were assessed. The average age of PPI users was 53 years. The most commonly used oral PPI was rabeprazole, while the most common injectable PPI was pantoprazole. The DDD of oral rabeprazole and DDC of injectable rabeprazole were the highest. Meanwhile, only the DUI values of oral rabeprazole, lansoprazole and ilaprazole were less than 1.0. The clinical diagnosis of some users included well identified risky comorbidities such as kidney disease (2.9%). Furthermore, between 32.6% and 56.8% of the PPI prescriptions were used for inappropriate indications. Conclusion: this survey demonstrated that PPI use was accompanied by unapproved indications and excessive dosages. Comprehensive measures are urgently needed to improve PPI use and reduce unnecessary drug costs


No disponible

19.
Oncol Lett ; 18(4): 3823-3829, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31516594

RESUMO

Valosin-containing protein (VCP) promotes the development of metastasis in osteosarcoma (OS) via the PI3K/Akt signaling pathway. However, inhibition of the PI3K/Akt pathway does not completely reverse VCP-mediated invasion and migration of OS, suggesting that VCP-mediated OS invasion and migration involves additional mechanisms. In the present study, a positive correlation between the expression of VCP and cell autophagy was observed among OS tissues. Inhibiting VCP may decrease the survival of malignant cells; however, an autophagy stimulator may compensate for VCP inhibition and promote malignant cell survival. Altering the level of autophagy did not affect cell invasiveness or migration. ERK, NF-κß and beclin-1 protein expression levels were markedly decreased following VCP inhibition. These findings indicated that VCP may induce autophagy and enhance anoikis resistance without affecting cell invasiveness or migration. Via anoikis resistance, VCP may promote metastasis in OS. Therefore, targeting of the ERK/NF-κß/beclin-1 signaling pathway may be an effective therapeutic strategy for the management of OS.

20.
JAMA Ophthalmol ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513266

RESUMO

Importance: A deep learning system (DLS) that could automatically detect glaucomatous optic neuropathy (GON) with high sensitivity and specificity could expedite screening for GON. Objective: To establish a DLS for detection of GON using retinal fundus images and glaucoma diagnosis with convoluted neural networks (GD-CNN) that has the ability to be generalized across populations. Design, Setting, and Participants: In this cross-sectional study, a DLS for the classification of GON was developed for automated classification of GON using retinal fundus images obtained from the Chinese Glaucoma Study Alliance, the Handan Eye Study, and online databases. The researchers selected 241 032 images were selected as the training dataset. The images were entered into the databases on June 9, 2009, obtained on July 11, 2018, and analyses were performed on December 15, 2018. The generalization of the DLS was tested in several validation datasets, which allowed assessment of the DLS in a clinical setting without exclusions, testing against variable image quality based on fundus photographs obtained from websites, evaluation in a population-based study that reflects a natural distribution of patients with glaucoma within the cohort and an additive dataset that has a diverse ethnic distribution. An online learning system was established to transfer the trained and validated DLS to generalize the results with fundus images from new sources. To better understand the DLS decision-making process, a prediction visualization test was performed that identified regions of the fundus images utilized by the DLS for diagnosis. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristics curve (AUC), sensitivity and specificity for DLS with reference to professional graders. Results: From a total of 274 413 fundus images initially obtained from CGSA, 269 601 images passed initial image quality review and were graded for GON. A total of 241 032 images (definite GON 29 865 [12.4%], probable GON 11 046 [4.6%], unlikely GON 200 121 [83%]) from 68 013 patients were selected using random sampling to train the GD-CNN model. Validation and evaluation of the GD-CNN model was assessed using the remaining 28 569 images from CGSA. The AUC of the GD-CNN model in primary local validation datasets was 0.996 (95% CI, 0.995-0.998), with sensitivity of 96.2% and specificity of 97.7%. The most common reason for both false-negative and false-positive grading by GD-CNN (51 of 119 [46.3%] and 191 of 588 [32.3%]) and manual grading (50 of 113 [44.2%] and 183 of 538 [34.0%]) was pathologic or high myopia. Conclusions and Relevance: Application of GD-CNN to fundus images from different settings and varying image quality demonstrated a high sensitivity, specificity, and generalizability for detecting GON. These findings suggest that automated DLS could enhance current screening programs in a cost-effective and time-efficient manner.

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