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1.
Ecotoxicol Environ Saf ; 207: 111284, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32942100

RESUMO

Questions remain about the effects of rare earth elements (REEs) on reproductive health, and no study has explored in utero exposure to REEs and risk of orofacial clefts (OFCs). We recruited subjects from a case-control study conducted in Shanxi Province, China. Concentrations of fifteen REEs were quantified in umbilical cord samples by means of Inductively Coupled Plasma Mass Spectrometry measurements. We employed logistic regression and weighted quantile sum (WQS) regression models to estimate the association between REEs exposures and OFCs. Of 226 subjects included in our study, 34 were cleft lip only, 44 were cleft lip with cleft palate and 6 were cleft palate only. In the logistic regression model, concentrations above the median of all subjects were associated with an increased OFCs risk of 2.35-fold (95% CI: 1.22, 4.53) for Lanthanum and 2.12-fold for Neodymium (95% CI: 1.10, 4.10) adjusting for maternal age, BMI, gestational weeks, sex of infants and passive smoking. In WQS model, a quartile increase in the index resulting in an increase of 3.10 (95% CI: 1.38, 6.96) in the odds of OFC. Lanthanum and Neodymium were suggested to be important factors. The results were largely consistent for OFC subtypes. In conclusion, in utero exposure to mixtures of REEs increased the risk of OFCs. Lanthanum and Neodymium were likely to be important factors in the development of OFCs.

2.
J Nanosci Nanotechnol ; 21(1): 181-194, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33213622

RESUMO

With continuous improvements in nanotechnology, the development of micro/nanoscale pores and fractures in reservoirs can be more clearly identified, and great progress has been made in tight sandstone and shale. Bedrock has an ultralow porosity and is a reservoir with low permeability. To study the characteristics of micro/nanoscale pore development and reveal their petroleum significance in the eastern segment of the Altun Piedmont, research has been conducted with the use of cathodoluminescence, field emission scanning electron microscopy and energy spectrum analysis, formation microresistivity image logging, high-pressure mercury injection and nuclear magnetic logging. The results have shown that the porosity of the bedrock reservoir in the eastern segment of the Altun Piedmont, as measured by helium injection and nuclear magnetic logging, is between 0.004% and 9.76%, the average porosity is between 1.663% and 3.844%, and the permeability is between the maximum of 0.002 mD and 33.239 mD. The average permeability is between 0.02 mD and approximately 3.836 mD. Micro/nanopores are generally developed, with the majority being intragranular micro/nanopores, intercrystalline micro/nanopores and microcracks, as summarized by the field emission scanning electron microscopy and energy dispersive spectroscopy analysis. Four differently sized pores develop: micropores account for approximately 20%, transition pores account for approximately 30%, and mesopores and macropores account for approximately 25% each. The pore throat development below 100 nm is greater than 50% according to the collation of experimental data from high-pressure mercury intrusion; therefore, micro/nanopores are the main storage space in the study area, and the gas logging shows good results. Micro/nanopores are also one of the main reservoir spaces of bedrock reservoirs in conjunction with the conventional reservoir space, and thus, micro/nanopores have important petroleum significance.

3.
Br J Pharmacol ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33140855

RESUMO

BACKGROUND AND PURPOSE: Psoriasis is a chronic immune-mediated inflammatory skin disease that easily recurs and is difficult to cure. DGT is a novel synthesized heterocyclic diterpenoid, whose structure has not been previously reported. Hence, we investigated the potent therapeutic activity of DGT against psoriasis, specifically the hyperproliferation of epidermal keratinocytes, angiogenesis and pathogenic inflammatory responses. EXPERIMENTAL DESIGN: We identified its pharmacokinetics in skin after topical administration. We characterized its therapeutic properties in vitro and in vivo using cell proliferation assay, cell apoptosis assay, diethylstilbestrol-induced mouse vaginal epithelial cell mitosis model, tube formation assay, cell migration assay, chick embryonic chorioallantoic membrane (CAM) assay, histological, flow cytometric analysis, imiquimod (IMQ)- induced psoriasis-like model. KEY RESULTS: DGT was mainly distributed in the epidermis and dermis, which indicated that DGT was suitable as a topical treatment. DGT inhibited cell proliferation and induced apoptotic cell death of keratinocytes in vitro and in vivo. Moreover, DGT inhibited endothelial cell proliferation, tube formation and migration of in vitro angiogenesis, as well as in vivo CAM angiogenesis. In an IMQ-induced psoriasis-like skin inflammation murine model, topical administration of DGT ameliorated keratinocyte proliferation and inflammatory response, especially IL-17-related psoriasiform dermatitis. Furthermore, our results identified that DGT prevented these pathological processes of psoriasis through suppression of STAT3 phosphorylation. CONCLUSION AND IMPLICATION: DGT shows great potential as a novel therapeutic agent for the treatment of psoriatic skin disease.

4.
J Asian Nat Prod Res ; : 1-8, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225746

RESUMO

Two new compounds named epipaxilline (1) and penerpene J (2) were isolated from the marine-derived fungus Penicillium sp. KFD28. Their structures including absolute configurations were determined on the basis of spectroscopic methods and ECD analysis. Compounds 1 and 2 showed inhibitory activities against PTP1B with IC50 values of 31.5 and 9.5 µM, respectively, and compound 2 also showed inhibitory activities against TCPTP with IC50 value of 14.7 µM.

5.
J Diabetes Complications ; : 107766, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33168395

RESUMO

INTRODUCTION: The epithelial tight junctions of intestine were impaired in murine model of type 2 diabetes mellitus (T2DM). The aim of this work was to investigate the alteration of intestinal barrier in T2DM patients. METHODS: 90 patients with T2DM and 28 healthy controls were recruited. Serum lipopolysaccharide (LPS), Zonulin, and intestinal fatty acid binding protein (IFABP) were measured by ELISA, based on which a derived permeability risk score (PRS) was calculated. Subgroup analyses were conducted based on the glycemic control (HbA1c < 7%, or HbA1c ≥ 7%), the amount of chronic diabetic complications, and the use of aspirin at the time. RESULTS: Serum LPS, Zonulin, and IFABP, and PRS of T2DM group were significantly higher than those of the control group (p < 0.05 for all). Serum LPS and PRS was higher in T2DM patients with poor glycemic control (both p < 0.05). Patients with more chronic complications of diabetes had higher serum LPS and IFABP, and PRS (all p < 0.05). No differences were found in these serum markers between T2DM patients being treated with aspirin or not. CONCLUSIONS: Intestinal barrier function was impaired in T2DM patients. Poor glycemic control and more chronic complications of diabetes were associated with worse intestinal barrier function. Treatment with aspirin did not aggravate the impairment of intestinal barrier in T2DM patients.

6.
Brief Bioinform ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201180

RESUMO

The prevalence of dropout events is a serious problem for single-cell Hi-C (scHiC) data due to insufficient sequencing depth and data coverage, which brings difficulties in downstream studies such as clustering and structural analysis. Complicating things further is the fact that dropouts are confounded with structural zeros due to underlying properties, leading to observed zeros being a mixture of both types of events. Although a great deal of progress has been made in imputing dropout events for single cell RNA-sequencing (RNA-seq) data, little has been done in identifying structural zeros and imputing dropouts for scHiC data. In this paper, we adapted several methods from the single-cell RNA-seq literature for inference on observed zeros in scHiC data and evaluated their effectiveness. Through an extensive simulation study and real data analysis, we have shown that a couple of the adapted single-cell RNA-seq algorithms can be powerful for correctly identifying structural zeros and accurately imputing dropout values. Downstream analysis using the imputed values showed considerable improvement for clustering cells of the same types together over clustering results before imputation.

7.
BMC Bioinformatics ; 21(Suppl 5): 405, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106157

RESUMO

BACKGROUND: In recent years, Traditional Chinese Medicine (TCM) and alternative medicine have been widely used along with western drugs as a complementary form of treatment. In this study, we first use the scientific literature to identify western drugs with obvious side effects. Then, we find TCM alternatives for these western drugs to ameliorate their side effects. RESULTS: We used depression as a case study. To evaluate our method, we showed the relation between herb-ingredients-target-disease for representative alternative herbs of western drugs. Further, a protein-protein interaction network of western drugs and alternative herbs was produced, and we performed enrichment analysis of the targets of the active ingredients of the herbs and examined the enrichment of Gene Ontology terms for Biological Process, Cellular Component, and Molecular Function and KEGG Pathway levels, to show how these targets affect different levels of gene expression. CONCLUSION: Our proposed method is able to select herbs that are highly relevant to the target indication (depression) and are able to treat the side effects caused by the target drug. The compounds from our selected alternative herbal medicines can therefore be complementary to the western drugs and ameliorate their side effects, which may help in the development of new drugs.


Assuntos
Antidepressivos/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Descoberta do Conhecimento , Medicina Tradicional Chinesa/estatística & dados numéricos , Plantas Medicinais/química , Humanos
8.
Antiviral Res ; 184: 104953, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065138

RESUMO

BACKGROUND & AIMS: Normal/mildly elevated ALT (<2 × ULN) CHB patients are potentially at risk of progression to cirrhosis and/or hepatocellular carcinoma (HCC). We aimed to assess the outcomes of anti-viral therapy for normal/mild elevation of ALT CHB patients. METHODS: CHB patients (n = 432) who have had liver biopsied were determined. It was determined that the outcomes of anti-viral therapy in CHB patients with normal/mild elevation of ALT, in response to nucleoside/nucleotide analogues (NAs) (n = 190) and pegylated interferon (PEG-IFN) (n = 30) treatment for up to 72 weeks. Non-anti-viral treated patients were used as control (n = 40). RESULTS: There was about 50% of the CHB patients showed hepatic inflammatory necrosis ≥ G2 and/or fibrosis ≥ S2 among >30-years-old. The rate of undetectable HBV DNA in NAs and PEG-IFN groups was ~50%, ~80% or ~90% at week 24, 48 or 72, respectively. HBeAg clearance rate was lower in NAs treated than that in PEG-IFN group at week 48 (6% vs 20%, P < 0.05). ALT normalization rate was increased by 1.18-fold at week 72. HBsAg decline in HBeAg+ patients treated with NAs or PEG-IFN was 0.418 or 1.217 log IU/mL (P < 0.0001) at week 48; whereas HBsAg decline was 0.176 or 0.816 log IU/mL (P < 0.001) in HBeAg- patients. HBsAg at baseline and week 24 were strong predictors of "low HBsAg at week 48". CONCLUSION: Long term anti-viral therapy inhibits HBV replication effectively in ALT<2 × ULN CHB patients. PEG-IFN therapy is recommended for HBeAg+ patients with baseline HBsAg<4.37 log IU/ml and HBeAg- patients with baseline HBsAg<2.66 log IU/ml to achieve "low HBsAg at week 48".

9.
J Int Med Res ; 48(10): 300060520957500, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33050766

RESUMO

OBJECTIVES: This study presented the feasibility of oxycodone as the sole opioid for general anaesthesia in minor/moderate surgery. METHODS: In this prospective, observational, descriptive study, 62 patients were enrolled and received intravenous oxycodone as the sole opioid for the induction and maintenance of general anaesthesia. We observed all of these patients to determine whether oxycodone alone could provide sufficient intraoperative and postoperative analgesia, as well as to record the extubation times and adverse events. RESULTS: A total oxycodone dose of 0.316 ± 0.05 mg/kg was used for induction and maintenance of general anaesthesia. The dose could maintain haemodynamic stability during surgery and good postoperative analgesia. Oxycodone caused deep sedation (nine patients had Ramsey sedation scores ≥4), leading to respiratory depression and long stays in the post-anaesthesia care unit (PACU). The extubation time (16.9 ± 6.4 minutes) increased with increasing oxycodone doses. CONCLUSION: Oxycodone can be used as the sole opioid for general anaesthesia in minor/moderate surgery. However, care should be taken because of its deep sedation effect.Trial registration: This study is registered at the Chinese Clinical Trial Registry (www.chictr.org.cn): ChiCTR-opc-16009175.

10.
J Clin Transl Hepatol ; 8(3): 255-261, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083247

RESUMO

Background and Aims: Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. Methods: We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Results: Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. Conclusions: The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.

11.
J Clin Transl Hepatol ; 8(3): 277-284, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33083250

RESUMO

Background and Aims: To evaluate the efficacy of Fuzheng Huayu (FZHY), a Chinese herbal formula, plus entecavir (ETV) in regression of liver fibrosis in chronic hepatitis B (CHB) patients with significant fibrosis/cirrhosis. Methods: The current study was a two-center, randomized, double-blind and placebo-controlled pilot study. Fifty-two currently untreated chronic hepatitis B patients with Ishak fibrosis score ≥3 points were identified and 1:1 randomized into FZHY plus ETV combination and placebo plus ETV groups. The second liver biopsy was performed after 48-week treatment. Necroinflammatory improvement and regression of fibrosis were assessed. Fine changes in different collagen features in paired liver biopsies were evaluated by dual-photon microscopy for both groups. Results: Forty-nine patients completed the full course of treatment; forty-six of them underwent second liver biopsy (for which twenty-two were in the combination group and twenty-four were in the control group). Compared to those in the control group, patients in the combination group had significantly higher rate of fibrosis regression (82% vs. 54%) (p<0.05). Furthermore, the necroinflammatory improvement was greater in the combination group than in the control group (59% vs. 25%, p<0.05). Among the more than 80 collagen parameters in the dual-photon analysis, 5 decreased significantly in the combination group compared to the control group (p<0.05). However, no significant improvement was detected in either biochemical, virologic or serologic responses between these two groups at week 48. Conclusions: The combination therapy of FZHY plus ETV for 48 weeks resulted in a higher rate of necroinflammatory improvement and fibrosis regression than ETV alone in chronic hepatitis B patients with significant fibrosis/cirrhosis. The clinical trial number is ChiCTR-TRC-11001377.

12.
Environ Health Perspect ; 128(10): 107010, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33124919

RESUMO

BACKGROUND: Groundwater is a main drinking-water source for Chinese rural residents. The overall pollution status of organic micropollutants (OMPs) and metals in the groundwater and corresponding health risks are unknown. OBJECTIVES: Our objective was to comprehensively screen for and assess the health risks of OMPs and metals in groundwater of rural areas in China where groundwater is used for drinking so as to provide a benchmark for monitoring and improving groundwater quality in future developments. METHODS: One hundred sixty-six groundwater samples were collected in the rural areas of China, and 1,300 OMPs and 25 metals were screened by GC-MS, LC-QTOF/MS, and ICP-MS analysis. To assess the noncarcinogenic and carcinogenic risks of the detected pollutants, missing toxicity threshold values were extrapolated from existing databases or predicted by quantitative structure-activity relationship (QSAR) models. Monte Carlo simulation was performed to account for uncertainties in the exposure parameters and toxicity thresholds. RESULTS: Two hundred thirty-three OMPs and 25 metals were detected from the 166 samples. The concentration summation for the detected OMPs ranged from 2.9 to 1.7×105ng/L among the different sampling sites. Cumulative noncarcinogenic risks for the OMPs were estimated to be negligible. However, high metal risks were calculated in 23% of the sites. Forty-two carcinogens (including 38 OMPs) were identified and the cumulative carcinogenic risks in 34% of the sites were calculated to be >10-4 (i.e., one excess cancer case in a population of 10 thousand people). The carcinogenic risks were estimated to be mainly associated with exposures to the metals, which were calculated to contribute 79% (0-100%) of the cumulative carcinogenic risks. DISCUSSION: The overall status of OMPs and metals pollution in the groundwater and the corresponding health risks were determined preliminarily, which may provide a benchmark for future efforts in China to ensure the safety of drinking water for the local residents in rural areas. The joint application of QSARs and Monte Carlo simulation provided a feasible way to comprehensively assess the health risks of the large and ever-increasing number of pollutants detected in the aquatic environment. https://doi.org/10.1289/EHP6483.

13.
Viruses ; 12(10)2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33092282

RESUMO

Adeno-associated virus is the leading viral vector for gene therapy. AAV-DJ is a recombinant variant developed for tropism to the liver. The AAV-DJ structure has been determined to 1.56 Å resolution through cryo-electron microscopy (cryo-EM). Only apoferritin is reported in preprints at 1.6 Å or higher resolution, and AAV-DJ nearly matches the highest resolutions ever attained through X-ray diffraction of virus crystals. However, cryo-EM has the advantage that most of the hydrogens are clear, improving the accuracy of atomic refinement, and removing ambiguity in hydrogen bond identification. Outside of secondary structures where hydrogen bonding was predictable a priori, the networks of hydrogen bonds coming from direct observation of hydrogens and acceptor atoms are quite different from those inferred even at 2.8 Å resolution. The implications for understanding viral assembly mean that cryo-EM will likely become the favored approach for high resolution structural virology.

14.
Poult Sci ; 99(9): 4334-4342, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32867977

RESUMO

The H9N2 avian influenza virus has been widely spread in poultry around the world. It is proved to the world that the avian influenza virus can directly infect human beings without any intermediate host adaptation in "1997 Hong Kong avian influenza case," which shows that the avian influenza virus not only causes significant losses to the poultry industry but also affects human health. In this study, we aimed to address the problem of low protection of avian H9N2 subtype influenza virus vaccine against H9N2 wild-type virus. We have rescued the H9.4.2.5 branched avian influenza virus isolated in South China by reverse genetics technology. We have recombined these virus (rHA/NA-GD37 and rHA/NA-GD38) which contain hemagglutinin and neuraminidase genes from the H9N2 avian influenza virus (MN064850 or MN064851) and 6 internal genes from the avian influenza virus (KY785906). We compared the biological properties of the virus for example virus proliferation, virus elution, thermostability, and pH stability. Then, we evaluated the immune effects between rHA/NA-GD37 and GD37, which show that the recombinant avian influenza virus-inactivated vaccine can stimulate chickens to produce higher antibody titers and produce little inflammatory response after the challenge. It is noticeable that the recombinant virus-inactivated vaccine had better immune impact than the wild-type inactivated vaccine. Generally speaking, this study provides a new virus strain for the development of a H9N2 vaccine.

15.
Aliment Pharmacol Ther ; 52(8): 1399-1406, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32886813

RESUMO

BACKGROUND: Guidelines recommend liver biopsy to rule out significant inflammatory activity in chronic hepatitis B (CHB) patients with elevated hepatitis B virus (HBV) DNA but without other indications for treatment. AIM: To study rates and determinants of clinically significant liver inflammation. METHODS: We selected patients with HBV DNA > 2000 IU/mL from the SONIC-B database. The presence of significant inflammation (METAVIR ≥ A2 or HAI ≥ 9) was assessed by liver biopsy and correlated with alanine aminotransferase (ALT) levels (according to AASLD upper limits of normal [ULN]) and stratified by the presence of significant liver fibrosis (Ishak ≥ 3 or METAVIR ≥ F2). RESULTS: The cohort included 2991 patients; 1672 were HBeAg-positive. ALT was < ULN in 270 (9%), 1-2 times ULN in 852 (29%) and > 2 times ULN in 1869 (63%). Significant fibrosis was found in 1419 (47%) and significant inflammatory activity in 630 (21%). Significant inflammatory activity was found in 34% of patients with liver fibrosis, compared to 9.5% of those without (P < 0.001). Among patients without fibrosis, significant inflammatory activity was detected in 3.6% of those with normal ALT, 5.0% of those with ALT 1-2 times ULN and in 13% of those with ALT > 2 times ULN (P < 0.001). ALT < 2 times ULN had a negative predictive value of 95% for ruling out significant inflammatory activity among patients without liver fibrosis. CONCLUSIONS: Among patients without significant fibrosis, an ALT level < 2 times ULN is associated with < 5% probability of significant inflammatory activity. If fibrosis can be ruled out using non-invasive methods, liver biopsy solely to assess inflammatory activity should be discouraged.

16.
Med Eng Phys ; 84: 174-183, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32977916

RESUMO

BACKGROUND: This paper describes the design and test of an automated functional electrical stimulation (FES) system for poststroke rehabilitation training. The aim of automated FES is to synchronize electrically induced movements to assist residual movements of patients. METHODS: In the design of the FES system, an accelerometry module detected movement initiation and movement performed by post-stroke patients. The desired movement was displayed in visual game module. Synergy-based FES patterns were formulated using a normal pattern of muscle synergies from a healthy subject. Experiment 1 evaluated how different levels of trigger threshold or timing affected the variability of compound movements for forward reaching (FR) and lateral reaching (LR). Experiment 2 explored the effect of FES duration on compound movements. RESULTS: Synchronizing FES-assisted movements with residual voluntary movements produced more consistent compound movements. Matching the duration of synergy-based FES to that of patients could assist slower movements of patients with reduced RMS errors. CONCLUSIONS: Evidence indicated that synchronization and matching duration with residual voluntary movements of patients could improve the consistency of FES assisted movements. Automated FES training can reduce the burden of therapists to monitor the training process, which may encourage patients to complete the training.

17.
Int J Infect Dis ; 100: 379-381, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32979589

RESUMO

Pulmonary actinomycosis (PA) is an uncommon pulmonary infectious disease that often is misdiagnosed. Metagenomic next-generation sequencing (mNGS) is a highly sensitive and culture-independent new molecular technology for precise infectious disease diagnosis. Here we report a PA case diagnosed by the combination of a radial endobronchial-ultrasonography guide sheath (R-EBUS-GS) and mNGS, along with a brief review of the literature.

18.
Clin Cancer Res ; 26(22): 5914-5925, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933996

RESUMO

PURPOSE: Pancreatic cancer is among the most aggressive malignancies and is rarely discovered early. However, pancreatic "incidentalomas," particularly cysts, are frequently identified in asymptomatic patients through anatomic imaging for unrelated causes. Accurate determination of the malignant potential of cystic lesions could lead to life-saving surgery or spare patients with indolent disease undue risk. Current risk assessment of pancreatic cysts requires invasive sampling, with attendant morbidity and sampling errors. Here, we sought to identify imaging biomarkers of high-risk pancreatic cancer precursor lesions. EXPERIMENTAL DESIGN: Translocator protein (TSPO) expression, which is associated with cholesterol metabolism, was evaluated in premalignant and pancreatic cancer lesions from human and genetically engineered mouse (GEM) tissues. In vivo imaging was performed with [18F]V-1008, a TSPO-targeted PET agent, in two GEM models. For image-guided surgery (IGS), V-1520, a TSPO ligand for near-IR optical imaging based upon the V-1008 pharmacophore, was developed and evaluated. RESULTS: TSPO was highly expressed in human and murine pancreatic cancer. Notably, TSPO expression was associated with high-grade, premalignant intraductal papillary mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasia (PanIN) lesions. In GEM models, [18F]V-1008 exhibited robust uptake in early pancreatic cancer, detectable by PET. Furthermore, V-1520 localized to premalignant pancreatic lesions and advanced tumors enabling real-time IGS. CONCLUSIONS: We anticipate that combined TSPO PET/IGS represents a translational approach for precision pancreatic cancer care through discrimination of high-risk indeterminate lesions and actionable surgery.

19.
Reprod Toxicol ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32971236

RESUMO

Deficient or excessive quantities of essential trace elements (ETEs)1 in the fetal environment can compromise developmental processes. We investigated whether concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in umbilical cord tissue are associated with risk for neural tube defects (NTDs). Umbilical cord tissues from 166 cases of NTD cases and 166 matched controls were collected and element concentrations were measured using inductively coupled plasma-mass spectrometry. Associations between ETE concentrations and the risk for NTDs were estimated using multivariate logistic regression while adjusting for potential confounders. Bayesian kernel machine regression (BKMR) was used to examine the joint effects of these ETEs. We found that median concentrations of Ni were higher but those of Mo and Co were lower in the NTD group than in the control group. Co was the only element that was associated with NTD risk after adjusting for confounders (OR 0.31, 95 % CI 0.12-0.79 for the second and OR 0.37, 95 % CI 0.15-0.91 for the top tertile relative to the lowest tertile). The association between Co and NTD risk was confirmed with the BKMR model. In addition, a joint effect of the six ETE mixture on NTD risk was observed: the risk decreased with the levels of the mixture from 25th percentile through 75th percentile. In conclusion, higher levels of Co were associated with lower risk for NTDs, and NTD risk decreased with the levels of the six ETEs as a co-exposure mixture, suggesting a protective effect.

20.
Asian J Surg ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-32988708

RESUMO

Long-term overall survival (OS) after liver resection for non-cirrhotic hepatocellular carcinoma (NCHCC) has been reported recently. The aim of this study was to review outcomes systematically and analyze risk factors for survival after surgical resection for HCC without cirrhosis. A literature search was performed of the PubMed and Embase databases for papers published between January 1995 and October 2012, which focused on hepatic resection for HCC without underlying cirrhosis. Cochrane systematic review methodology was used for this review. Outcomes were OS, operative mortality and disease-free survival (DFS). Pooled hazard ratios (HR) were calculated using the random effects model for parameters considered as potential prognostic factors. Totally, 26 retrospective case series were eligible for inclusion. The 1-, 3- and 5-year OS rate after surgical resection of NCHCC ranged from 62% to 100%, 46.3%-78.0%, and 30%-64%, respectively. The corresponding DFS rates ranged from 48.7% to 84%, 31.0%-66.0%, and 24.0%-58.0%, respectively. Five variables were related to poor survival: multiple tumors (HR 1.68, 95%CI 1.25-2.11); larger tumor size (HR 2.66, 95%CI 1.69-3.63); non-clear resection margin (R0 resection) (HR 3.52, 95%CI 1.63-5.42); poor tumor stage (HR 2.61, 95%CI 1.64-3.58); and invasion of the lymphatic vessels (HR 4.85, 95%CI 2.67-7.02). In sum, hepatic resection provides excellent OS rates for patients with NCHCC, and results have tended to improve recently. Risk factors for poor prognosis comprise multiple tumors, lager tumor size, non-R0 resection and invasion of the lymphatic vessels.

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