Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 535
Filtrar
1.
J Clin Microbiol ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32051260

RESUMO

A rapid and accurate method to identify the species and antibiotic resistance of Candida in blood is vital to increase the survival rates of patients with bloodstream infections. However, the extremely low levels of Candida in blood make rapid diagnosis by standard blood culture difficult. In this study, we constructed a direct blood culturing method (i.e., the M1 method) by a rapid enrichment method with magnetic beads coated with a recombined human mannan-binding lectin (rhMBL, i.e., M1 protein), which demonstrated much higher Candida-binding capacity than that of full-length MBL expressed in vitro (i.e., M2). With the M1 method, individual colonies were obtained before the standard blood culture method for each species of Candida spp. tested at < 1 CFU/ml (an average of 29 h earlier). Additionally, the clinical sensitivity of the M1 method was 90.5% compared with that of the standard blood culture method when detecting frozen plasma from patients. More significantly, the turnaround time of the M1 method for blood culture could be reduced by approximately 37-43 h compared with that of the standard blood culture method in clinical sample identification.

2.
Mol Cell Biochem ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32056105

RESUMO

This study evaluated the cardioprotective effects of a miR-1275 mimic in a rat model of myocardial ischemia-reperfusion (I/R)-induced myocardial injury (MI). Three groups of rats were established: a sham-operated group, a MI group and a MI+miR-1275 group pretreated for 1 week i.p. with a miR-1275 mimic at a concentration of 30 pmol/mL. MI was induced by I/R. The levels of myocardial enzymes in serum were estimated in all rats, together with haemodynamic functions. The effects of the miR-1275 mimic were determined based on the serum concentrations of inflammatory mediators in the treated vs. sham and MI rats. In addition, western blot assay and immunohistochemical analyses were performed to examine the effect of the miR-1275 mimic on the Wnt/NF-kB signalling pathway in MI rats. Treatment with the miR-1275 mimic attenuated the altered levels of myocardial enzymes and haemodynamic functions seen in MI rats. The myocardial infarct was smaller in rats treated with the miR-1275 mimic than in MI rats. The miR-1275 mimic also reduced myocardiocyte apoptosis and ameliorated the altered Wnt/KF-kB pathway. These results demonstrate the efficacy of the miR-1275 mimic in preventing myocardial I/R-induced MI in rats, by regulating the Wnt/NF-κB pathway.

3.
Hum Pathol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31926212

RESUMO

Immunotherapies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) axis have been emerging as a promising therapeutic strategy to treat lung cancer. PD-1 is preferentially expressed by activated T lymphocytes; but whether/how its expression by tumor-associated macrophages (TAMs) in lung adenocarcinoma remains elusive. Herein, we investigate the frequency of PD-1 expression on TAMs in mouse allografts by flow cytometry analysis and evaluate the spatial distribution and clinicopathological significance of PD-1+ TAMs in 213 cases of human lung adenocarcinoma specimens by immunohistochemical staining. We find the expression of PD-1 by both mouse and human TAMs. Mouse PD-1+ TAMs possess unique transcriptional profile as compared to PD-1- TAMs. Furthermore, PD-1 is preferentially expressed by CD163+ TAMs in the tumor stroma than those in the tumor islets of lung adenocarcinoma. Stromal PD-1+ TAM infiltration is an independent predictor of reduced survival as determined by univariate (p < 0.001) and multivariate (p = 0.023) analysis. Moreover, patients with high stromal PD-1+ TAMs but low tumor cell PD-L1 expression have the shortest survival (p = 0.0001). Our study demonstrates that PD-1+ TAMs have unique gene expression characteristics and PD-1+ TAMs in the tumor stroma is a potential prognostic factor in lung adenocarcinoma, suggesting that a better understanding of PD-1+ TAMs will be beneficial for immunotherapy of lung adenocarcinoma patients.

4.
Biomed Pharmacother ; 124: 109852, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31972357

RESUMO

BACKGROUND: Breast cancer is the most common malignant tumor in women. Due to limited treatment outcome and high rate of metastasis, the prognosis is especially poor for triple-negative breast cancer. It is urgent to discover and develop novel agents for treatment of breast cancer. Herein, we investigated the potential mechanisms of Oleandrin's (a cardiac glycoside) cytotoxic activity against breast cancer cells. METHODS: Cell proliferation was assessed by xCELLigence Real-Time Cell Analyzer (RTCA)-MP system. Apoptotic cells were detected by using Annexin V/PI staining and nuclear fragments observation. The effect of oleandrin on ATP1B3 expression and markers of ER stress were determined by western blot. A primary cell sensitivity assay was performed via a collagen gel droplet-embedded culture drug sensitivity method (CD-DST). RESULTS: Oleandrin suppressed cell proliferation and colony formation in the three breast cancer cell lines but did not affect normal mammary epithelial cells. Additionally, the expression of ATP1B3 was higher in the three breast cancer cell lines compared to MCF10A cells. Treatment with oleandrin increased the number of apoptotic cells and led to nuclear pyknosis, fragmentation, and apoptotic body formation in breast cancer cells. Furthermore, oleandrin treatment increased expression of Bax and Bim but decreased that of Bcl-2. Treatment with oleandrin also upregulated the expression of endoplasmic reticulum stress associated proteins, including eIF2α, ATF4, and CHOP, but not PERK. oleandrin treatment also induced the phosphorylation of PERK and eIF2α. Of note, oleandrin exhibited antitumor effects on patient-derived breast cancer cells under three-dimensional culture conditions. CONCLUSIONS: Taken together, our results suggest that oleandrin induces mitochondrial-mediated apoptosis by activating endoplasmic reticulum stress in breast cancer. Moreover, oleandrin may be an effective strategy for the treatment of breast cancer.

5.
Lab Invest ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949244

RESUMO

Glioblastoma multiforme (GBM) is characterized by highly invasive growth, which leads to extensive infiltration and makes complete tumor excision difficult. Since cytoskeleton proteins are related to leading processes and cell motility, and through analysis of public GBM databases, we determined that an actin-interacting protein, zyxin (ZYX), may involved in GBM invasion. Our own glioma cohort as well as the cancer genome atlas (TCGA), Rembrandt, and Gravendeel databases consistently showed that increased ZYX expression was related to tumor progression and poor prognosis of glioma patients. In vitro and in vivo experiments further confirmed the oncogenic roles of ZYX and demonstrated the role of ZYX in GBM invasive growth. Moreover, RNA-seq and mass-spectrum data from GBM cells with or without ZYX revealed that stathmin 1 (STMN1) was a potential target of ZYX. Subsequently, we found that both mRNA and protein levels of STMN1 were positively regulated by ZYX. Functionally, STMN1 not only promoted invasion of GBM cells but also rescued the invasion repression caused by ZYX loss. Taken together, our results indicate that high ZYX expression was associated with worse prognosis and highlighted that the ZYX-STMN1 axis might be a potential therapeutic target for GBM.

6.
Hepatol Int ; 14(1): 105-114, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31898210

RESUMO

BACKGROUND: Controversy exists on whether tenofovir disoproxil fumarate (TDF) is superior to entecavir (ETV) in lowering the risk of hepatocellular carcinoma (HCC) development. This meta-analysis was performed to clarify this issue with critical clinical and methodological considerations. METHODS: PubMed, EMBASE, and Cochrane Library were searched from inception to Oct 28, 2019. Randomized control trials and observational studies reporting the impact of TDF and ETV on the risk of HCC in patients with chronic hepatitis B (CHB) were eligible. Risk ratios (RRs) calculated with cumulative incidence rate and/or annual incidence rate, or hazard ratio (HR) were pooled using random-effect models. Subgroup analyses were performed to assess the potential impact of between-study level and within-study level factors. RESULTS: A total of 32 studies with 78,136 CHB patients were included. Overall cumulative incidence rate of HCC was lower in TDF group than ETV group (3.07% vs. 5.25%; RR 0.55; 95% CI 0.42-0.72). However, this difference was not statistically significant in pooled results of hazard ratio (HR 0.87; 95% CI 0.73-1.04) and RR calculated with annual incidence rate (RR 0.88; 95% CI 0.67-1.16). Potential confounding factors at between-study level included prior nucleos(t)ide usage, disease stage at baseline and region of study. More importantly, at within-study level, disparity in follow-up duration between TDF and ETV groups may impact the result, usually favoring a treatment with shorter follow-up duration. CONCLUSIONS: Compared with ETV, TDF treatment tended to have a lower overall cumulative incidence rate of HCC. However, disparity in follow-up duration may be a key factor to influence the result.

7.
Med Sci Monit ; 26: e919565, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904008

RESUMO

BACKGROUND Controversies exist in imaging modalities for predicting adenoma consistency. In this study, we proposed a method of predicting consistency by magnetic resonance T2-sequence imaging based on adenoma to cerebellar peduncle signal (TCTI) ratio. MATERIAL AND METHODS Between January 2013 and May 2017, 191 consecutive patients with pituitary adenoma diagnosed at our institution were retrospectively studied. The consistency grade for each lesion was assigned. And the TCTI ratio based on preoperative and postoperative T2-weighted imaging was calculated. RESULTS The median TCTI ratio was 1.55, 1.28, and 1.25 for soft, fibrous, and hard adenomas, respectively. The differences were significant for all groups (p<0.001). A cutoff value of 1.38 for soft adenomas was found to be 80.2% sensitive and 88.7% specific. The median ratio of the outermost layer of residual tumor was 1.25 (SD±0.408, 95% CI 1.27-1.42). It was less than that ratio of the upper, lower quarter, and middle region of adenoma, respectively, and the inter-group differences were all statistically significant with p≤0.001. The extent of resection for the soft group was significantly greater than that of the hard group (85.3% vs. 70.6%, p=0.011). Analysis of Variance (ANOVA) revealed that the consistency grade was the influencing factor of degree of resection. p=0.003. CONCLUSIONS The TCTI ratio showed a good correlation with pituitary adenoma consistency. We also determined the optimal ratio of the residual adenoma.

8.
Head Neck ; 42(2): 289-301, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31710172

RESUMO

BACKGROUND: Proton radiotherapy (PRT) may be a less toxic alternative to photon radiotherapy (XRT) for patients with head and neck squamous cell carcinoma (HNSCC). However, the molecular responses of HNSCC cells to PRT vs XRT are unclear. METHODS: Proteomics analyses of protein expression profiles by reverse-phase protein arrays were done for two human papillomavirus [HPV]-negative and two HPV+ cell lines. Expression patterns of 175 proteins involved in several signaling pathways were tested. RESULTS: Compared with PRT, XRT tended to induce lower expression of DNA damage repair-and cell cycle arrest-related proteins and higher expression of cell survival- and proliferation-related proteins. CONCLUSIONS: Under these experimental conditions, PRT and XRT induced different protein expression and activation profiles. Further preclinical verification is needed, as are studies of tumor pathway mutations as biomarkers for choice of treatment or as radiosensitization targets to improve the response of HNSCC to PRT or XRT.

9.
Epigenomics ; 12(1): 53-67, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31833387

RESUMO

Aim: To explore the role of miRNA-150-5p (miR-150-5p) in liver fibrosis. Materials & methods: miRNA expression profiles, CCl4-induced liver fibrosis progression and regression rodent models, quantitative real-time PCR, miR-150-5p mimics and inhibitors, cell proliferation and apoptosis detection, RNA sequencing and bioinformatics analysis were employed. Results: Liver tissue miR-150-5p expression was positively associated with liver fibrosis progression and regression; however, miR-150-5p exhibited a cell-specific expression pattern, namely, it was enhanced in hepatocytes but reduced in hepatic stellate cells (HSCs) during liver fibrosis; miR-150-5p overexpression promoted HSC apoptosis and sensitized hepatocyte apoptosis; miR-150-5p mimic had a larger influence on the transcriptomic stability of HSCs than that of hepatocytes; miR-150-5p mediated activation of interferon signaling pathways might be responsible for HSC apoptosis. Conclusion: miR-150-5p exhibited an opposite regulation and function pattern between HSCs and hepatocytes during liver fibrosis.

10.
Bioresour Technol ; 295: 122284, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669869

RESUMO

The application of MBR in high saline wastewater treatment is mainly constrained by poor nitrogen removal and severe membrane fouling caused by high salinity stress. A novel carriers-enhanced MBR system was successfully developed for treating saline mariculture wastewater, which showed efficient TN removal (93.2%) and fouling control. High-throughput sequencing revealed the enhancement mechanism of bio-carriers under high saline condition. Bio-carriers substantially improved the community structure, representatively, nitrifiers abundance (Nitrosomonas, Nitrospira) increased from 2.18% to 9.57%, abundance of denitrifiers (Sulfurimonas, Thermogutta, etc.) also rose from 3.81% to 14.82%. Thereby, the nitrogen removal process was enhanced. Noteworthy, ammonia oxidizer (Nitrosomonas, 8.26%) was the absolute dominant nitrifiers compared with nitrite oxidizer (Nitrospira, 1.13%). This supported the finding of shortcut nitrification-denitrification process in hybrid system. Moreover, a series of biomacromolecule degraders (Lutibacterium, Cycloclasticus, etc.) were detected in bio-carriers, which could account for the mitigation of membrane fouling as result of EPS and SMP degradation.


Assuntos
Microbiota , Águas Residuárias , Reatores Biológicos , Desnitrificação , Membranas Artificiais , Nitrificação , Nitrogênio , Eliminação de Resíduos Líquidos
11.
J Hepatol ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31813573

RESUMO

BACKGROUND & AIMS: C-C motif chemokine receptor 2 (CCR2) has been recognized as a promising target for the treatment of liver fibrosis. PC3-secreted microprotein (PSMP)/microseminoprotein (MSMP) is a novel chemotactic cytokine and its receptor is CCR2. In the present study we investigated the expression and role of PSMP in liver fibrosis/cirrhosis. METHODS: PSMP expression was studied in patients with fibrosis/cirrhosis and in 3 murine models of liver fibrosis, including mice treated with carbon tetrachloride (CCl4), bile-duct ligation, or a 5-diethoxycarbonyl-1,4-dihydrocollidine diet. The role of PSMP was evaluated in Psmp-/- mice and after treatment with a PSMP antibody in wild-type mice. The direct effects of PSMP on macrophages and hepatic stellate cells were studied in vitro. RESULTS: In this study, we found that PSMP was highly expressed in fibrotic/cirrhotic tissues from patients with different etiologies of liver disease and in the 3 experimental mouse models of fibrosis. Damage-associated molecular pattern molecules HMGB-1 and IL-33 induced hepatocytes to produce PSMP. PSMP deficiency resulted in a marked amelioration of hepatic injury and fibrosis. In CCl4-induced hepatic injury, the infiltration of macrophages and CCR2+ monocytes into the liver was significantly decreased in Psmp-/- mice. Consistent with the decreased levels of intrahepatic macrophages, proinflammatory cytokines were significantly reduced. Moreover, adeno-associated virus-8 vectors successfully overexpressing human PSMP in Psmp-/- mouse livers could reverse the attenuation of liver injury and fibrosis induced by CCl4 in a CCR2-dependent manner. Treatment with a specific PSMP-neutralizing antibody, 3D5, prevented liver injury and fibrosis induced by CCl4 in mice. At the cellular level, PSMP directly promoted M1 polarization of macrophages and activation of LX-2 cells. CONCLUSION: PSMP enhances liver fibrosis through its receptor, CCR2. PSMP is a potentially attractive therapeutic target for the treatment of patients with liver fibrosis. LAY SUMMARY: Our present study identifies the essential role of the protein PSMP for the development and progression of liver fibrosis in humans and mice. PSMP promotes liver fibrosis through inflammatory macrophage infiltration, polarization and production of proinflammatory cytokines, as well as direct activation of hepatic stellate cells via its receptor CCR2. A PSMP antibody can significantly reduce liver fibrosis development in vivo. These findings indicate that PSMP is a potential therapeutic target and its antibody is a potential therapeutic agent for the treatment of liver fibrosis.

12.
Support Care Cancer ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31768732

RESUMO

PURPOSE: To evaluate the impact of disclosure/nondisclosure of cancer diagnosis on patients' posttraumatic stress symptoms (PTSS), posttraumatic growth (PTG), and quality of life (QOL). METHODS: Patients with primary hepatocellular carcinoma (HCC) who were admitted for potentially curative treatments in a teaching hospital were recruited. Patients were interviewed at admission regarding their QOL and their attitude towards disclosure of diagnosis. They were interviewed again for QOL, PTSS, and PTG at discharge and at 1 month after discharge. RESULTS: There were 300 patients recruited, 88.3% of whom preferred disclosure of cancer diagnosis. In fact, 162 patients (54.0%) received disclosure of their cancer diagnosis before discharge (disclosed group). However, for the 138 patients whose diagnoses were concealed by their families (uninformed group), 116 patients (84.1%) had learned of their diagnosis of HCC independently within 1 month after discharge. Comparing the scores at 1 month after discharge with scores at discharge showed that the PTSS score significantly declined for patients in the disclosed group and the PTG score significantly decreased for the uninformed patients at 1 month after discharge (p < 0.001 for both comparisons). Additionally, compared with the uninformed group, patients in the disclosed group had lower scores for PTSS (p < 0.001), higher scores for PTG (p < 0.001), better emotional functioning (p < 0.001), and better global QOL (p = 0.006) at 1 month after discharge. CONCLUSIONS: Our findings indicate that concealing the diagnosis of cancer from patients is unlikely to succeed. Additionally, disclosure of diagnosis is beneficial for HCC patients in reducing PTSS and improving PTG and QOL.

13.
Bioengineering (Basel) ; 6(4)2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31757031

RESUMO

Chlorantraniliprole (CAP) is a widely used insecticide in many areas due to its excellent insecticidal ability and mammalian safety, however, the removal of CAP has not been extensively studied. In this study, a bacterial strain GW13, which is capable of co-metabolizing CAP, was isolated from a vegetable field soil. The strain was identified as Pseudomonas sp. based on its physico-biochemical characteristics and 16S rRNA gene analysis. The bacterial strain GW13 could degrade CAP through co-metabolism, and glucose was the best additional carbon resource. In the presence of 1.0 g/L glucose, GW13 could co-metabolize over 80% of 200 mg/L CAP in 24 h. The degradation rate increased after 6 h and slowed again after 10 h. The GW13 genome analysis revealed many genes associated with metabolism, showing the degradation mechanism of GW13 from the genomic perspective. The EAWAG-BBD (Swiss Federal Institute of Aquatic Science and Technology Biocatalysis/Biodegradation Database) prediction results showed that the main pathway for CAP degradation is amide hydrolysis, which is consistent with many genes associated with amidase in the GW13 genome. This study may facilitate research on CAP biodegradation mechanisms in the environment.

14.
Lab Invest ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748682

RESUMO

Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.

15.
Clin Proteomics ; 16: 38, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31719821

RESUMO

Background: Neuroticism is a core personality trait and a major risk factor for several mental and physical diseases, particularly in females, who score higher on neuroticism than men, on average. However, a better understanding of the expression profiles of proteins in the circulating blood of different neurotic female populations may help elucidate the intrinsic mechanism of neurotic personality and aid prevention strategies on mental and physical diseases associated with neuroticism. Methods: In our study, female subjects were screened for inclusion by the Eysenck Personality Questionnaire (EPQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI) scales and routine physical examination. Subjects who passed the examination and volunteered to participate were grouped by neuroticism using EPQ scores (0 and 1 = low neuroticism group; > 5 = high neuroticism group). Proteins in serum samples of the two neuroticism groups were identified using isobaric tags for relative and absolute quantification (iTRAQ) technology. Results: A total of 410 proteins exhibited significant differences between high and low neuroticism, 236 proteins were significantly upregulated and 174 proteins were significantly downregulated. Combine the results of GO and KEGG enrichment analysis of differences proteins between high and low neuroticism with the PPI network, it could be observed that the Alpha-synuclein (SNCA), ATP7A protein (ATP7A), Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (GNG2), cyclin-dependent kinase 6 (CDK6), myeloperoxidase (MPO), azurocidin (AZU1), Histone H2B type 1-H (HIST1H2BH), Integrin alpha-M (ITGAM) and Matrix metalloproteinase-9 (MMP9) might participate in the intrinsic mechanism of neuroticism by regulating response to catecholamine stimulus, catecholamine metabolic process, limbic system development and transcriptional misregulation in cancer pathway. Conclusions: Our study revealed the characteristics of the neurotic personality proteome, which might be intrinsic mechanism of the neurotic population.

16.
J Clin Gastroenterol ; 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31651571

RESUMO

BACKGROUND AND AIM: The prevalence of lean/nonobese nonalcoholic fatty liver disease (NAFLD) ranges widely in studies. Thus, here, we aimed to perform a meta-analysis on NAFLD prevalence in the lean or nonobese population to give clarity. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched to identify studies reporting NAFLD prevalence in the lean/nonobese population. Lean or nonobese was defined by body mass index cutoffs reported by authors in original studies. NAFLD prevalence based on community, population, or health checkups was combined with random-effect model after logit transformation. Subgroup analysis and meta-regression were further performed to investigate the heterogenicity. RESULTS: A total of 45 studies were enrolled in the final analysis, with 55,936 lean/nonobese subjects included, among whom 7351 NAFLD patients were diagnosed. Overall, the pooled NAFLD prevalence of the lean or nonobese population was 10.2% (95% confidence interval: 7.6%-13.6%) and 15.7% (95% confidence interval: 12.5%-19.6%), respectively. Compared with western studies, the NAFLD prevalence in the lean or nonobese population was lower in eastern studies. In addition, the NAFLD prevalence in both the lean and nonobese population showed a general upward trend during recent years. The prevalence was similar in community-based and health checkup-based studies. Lean/nonobese NAFLD patients had significantly lower rates of hypertension, lower uric acid and fasting plasma glucose, and a higher level of high-density lipoprotein than nonlean/obese patients. CONCLUSIONS: The prevalence of NAFLD in the lean/nonobese population is not rare in either the western or eastern regions of the world. This meta-analysis of prevalence assessment and clinical characteristics should enable higher confidence in more specific interventions and health care standards for these patients.

17.
Med Educ Online ; 24(1): 1679944, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31630670

RESUMO

Background: There is a strong need to include training of research methods in training programs for physicians. International clinical research training programs (CRTP) that comprehensively introduce the methodology of clinical research and combined with practice should be a priority. However, few studies have reported a multimodal international CRTP that provides clinicians with an introduction to the quantitative and methodological principles of clinical research. Objective: This manuscript is intended to comprehensively describe the development process and the structure of this multimodal training program. Methods: The CRTP was comprised of three distinct, sequential learning components: part 1 - a six-week online eLearning self-study; part 2 - a series of three weekly interactive synchronous webinars conducted between Durham, North Carolina, USA and Beijing, China; and part 3 - a five-day in-person workshop held at Beijing Friendship Hospital, Capital Medical University (BFH-CMU). Self-assessment quiz scores and participation rates were used to evaluate effectiveness of the training program. Participants' demographic characteristics, research experience, satisfaction and feedback on the program were collected using questionnaires. Results: A total of 50 participants joined the CRTP. Forty-four participants (88%) completed the program satisfaction questionnaires. The average quiz score of the six eLearning units varied from 31% to 73%. Among the three components of the program, the online eLearning self-study was felt to be the most challenging. Thirty-nine (89%) of the surveyed respondents were satisfied with all components of the training program. Among the respondents, 43 (98%) felt the training was helpful in preparing them for future clinical research projects and expressed willingness to recommend the program to other colleagues. Conclusions: We established a multimodal international collaborative training program. The program demonstrated acceptable participation rates and high satisfaction among Chinese clinicians. It provides a model that may be used by others developing similar international clinical research training programs for physicians.

18.
Cancer Med ; 8(17): 7207-7218, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31605439

RESUMO

AIMS: The aim of this study was to investigate the tumor microenvironment immune types (TMIT) based on tumor cell programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) distribution and whether distinct TMIT subtypes (TMIT I, PD-L1high /TILhigh ; TMIT II, PD-L1low /TILlow ; TMIT III, PD-L1high /TILlow ; and TMIT IV, PD-L1low /TILhigh ) differentially affect clinical outcomes of patients with lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC). METHODS AND RESULTS: Immunohistochemistry (IHC) was applied to evaluate the expression of PD-L1 and the spatial distribution of programmed cell death 1 (PD-1) and CD8 TILs on the surgically resected specimens from 205 cases of LAC and 149 cases of SCC. PD-1 and CD8 TILs were more frequently distributed in SCC than those in LAC, regardless of their infiltrating in the tumor islets or stroma. The density of TILs was a poor prognostic factor in LAC but a favorable one in SCC. PD-L1 levels and its clinical prognostic significance differed in LAC vs SCC. LAC patients with TMIT III and SCC patients with TMIT I had the longest survival, respectively (P = .0197 and .0049). Moreover, TMIT stratification based on tumor cell PD-L1 expression and stromal CD8+ TILs could be considered as an independent prognostic factor of SCC patients' survival as determined by both univariate and multivariate analysis. CONCLUSION: Our study indicates that different type of TMIT provides its specific microenvironment with diverse impact on survival of LAC and SCC patients and highlights the importance of the integrative assessment of PD-L1 status and TILs' spatial distribution to predict patients' prognosis.

19.
J AOAC Int ; 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31540587

RESUMO

A consensus industrial reference was necessary to be established for meeting the U.S. Food and Drug Administration's current Good Manufacturing Practice Compliance for the manufacture and quality control of dietary ingredients and supplements that contain ginger rhizome, dry extract, and/or purified nonvolatile ginger constituents. An analytical method has been developed, validated, and previously published for identifying and quantifying 6-,8- and 10-gingerols, 6-, 8- and 10-shogaols, 6-paradol, and zingerone. HPLC with UV-Vis detector was used for the determination of nonvolatile ginger constituents by following AOAC Guidelines for Single-Laboratory Validation. Sample was accurately weighed and diluted with acidified water and methanol mixture. The sample solution was then sonicated and filtered through a PTFE filter and analyzed under a linear gradient scheme instrument condition. A reverse-phase superficially porous particle C18 column and an absorption wavelength of 230 nm were used for analyte separation and determination. The method was demonstrated to be selective, linear (R² > 0.999), specific, accurate (91.1-103.2% spike recovery rate), and precise (RSDr < 5%, RSDR < 8%) and therefore met all AOAC Standard Method Performance Requirements (2017.012) criteria. With a relatively short run time (12 min) and optimized extraction solvent system, the method has been validated to simultaneously determine nonvolatile ginger constituents in a variety of dietary ingredients and dietary supplements matrices including dry extract, powder, tablet, capsule, liquid capsule, softgel capsule, and oleoresin.

20.
Hepatol Int ; 13(6): 766-776, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31559605

RESUMO

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) commonly affects subjects with obesity, yet non-obese NAFLD is increasingly being recognized. We aimed to investigate the clinicopathological and genetic characteristics of non-obese NAFLD patients. METHODS: The clinical, histological and genetic data of 84 NAFLD patients with biopsy for abnormal liver function test were reviewed. Both NAS-CRN and SAF scoring systems were applied for histopathological evaluation. PNPLA3 and TMS6F2 genotyping were also performed. RESULTS: All of the 84 patients were histologically diagnosed with non-alcoholic steatohepatitis (NASH), with 36 of them (42.9%) being non-obese (BMI < 25 kg/m2). Compared with the obese group, non-obese group were predominantly females (88.9% vs 52.1%, p < 0.001), tended to have higher prevalence of diabetes (p = 0.068). More importantly non-obese patients had a significant higher prevalence of advanced fibrosis (F ≥ 3) (58.3% vs 29.2%, p = 0.013), and a trend of higher degree of ballooning (p = 0.061). In addition, values of liver stiffness measurement were also significantly higher in non-obese group (12.1 kPa vs 8.1 kPa, p = 0.032). There was also a trend of higher prevalence of TM6SF2 T allele in non-obese group (p = 0.085), while the prevalence of PNPLA3 risk allele did not differ between two groups. Multivariate analysis showed that higher fasting glucose (p = 0.038) and lower serum platelets (p = 0.040) were two independent predictors for advanced fibrosis in non-obese patients. CONCLUSIONS: Non-obese NASH patients have a female predominance and more advanced fibrosis. Liver biopsy is crucial to evaluate the severity of disease in non-obese patients especially those with abnormal liver biochemistry. CLINICAL TRIAL NUMBER: NCT03386890.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA