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1.
Article in Chinese | MEDLINE | ID: mdl-37667162

ABSTRACT

Snake bites kill and maim many people every year. Head and face venomous snake bite is rare, easy to misdiagnose and miss diagnosis, and the fatality rate is high. In this paper, 1 case of head and face venomous snake bite poisoning was reported and 10 similar cases were reviewed. The clinical characteristics of head and face venomous snake bite poisoning were summarized to provide guidance for clinical diagnosis and treatment. Head and face venomous snake bites may lead to airway injury, edema, and airway obstruction is the main cause of early death. Timely intubation or tracheotomy to maintain oxygen supply and early use of antivenin can improve prognosis.


Subject(s)
Snake Bites , Humans
2.
Ann Oncol ; 34(5): 486-495, 2023 05.
Article in English | MEDLINE | ID: mdl-36849097

ABSTRACT

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.


Subject(s)
Cell-Free Nucleic Acids , Neoplasms , Female , Humans , DNA Methylation , Prospective Studies , Retrospective Studies , Cell-Free Nucleic Acids/genetics , Neoplasms/diagnosis , Neoplasms/genetics , Biomarkers, Tumor/genetics , Early Detection of Cancer
3.
Hum Resour Health ; 20(1): 25, 2022 03 12.
Article in English | MEDLINE | ID: mdl-35279166

ABSTRACT

BACKGROUND: In the field of tuberculosis (TB), Community Healthcare Workers (CHWs) have been engaged for advocacy, case detection, and patient support in a wide range of settings. Estimates predict large-scale shortfalls of healthcare workers in low- and middle-income settings by 2030 and strategies are needed to optimize the health workforce to achieve universal availability and accessibility of healthcare. In 2018, the World Health Organization (WHO) published guidelines on best practices for CHW engagement, and identified remaining knowledge gaps. Stop TB Partnership's TB REACH initiative has supported interventions using CHWs to deliver TB care in over 30 countries, and utilized the same primary indicator to measure project impact at the population-level for all TB active case finding projects, which makes the results comparable across multiple settings. This study compiled 10 years of implementation data from the initiative's grantee network to begin to address key knowledge gaps in CHW networks. METHODS: We conducted a cross-sectional study analyzing the TB REACH data repository (n = 123) and primary survey responses (n = 50) of project implementers. We designed a survey based on WHO guidelines to understand projects' practices on CHW recruitment, training, activities, supervision, compensation, and sustainability. We segmented projects by TB notification impact and fitted linear random-effect regression models to identify practices associated with higher changes in notifications. RESULTS: Most projects employed CHWs for advocacy alongside case finding and holding activities. Model characteristics associated with higher project impact included incorporating e-learning in training and having the prospect of CHWs continuing their responsibilities at the close of a project. Factors that trended towards being associated with higher impact were community-based training, differentiated contracts, and non-monetary incentives. CONCLUSION: In line with WHO guidelines, our findings emphasize that successful implementation approaches provide CHWs with comprehensive training, continuous supervision, fair compensation, and are integrated within the existing primary healthcare system. However, we encountered a great degree of heterogeneity in CHW engagement models, resulting in few practices clearly associated with higher notifications.


Subject(s)
Community Health Workers , Tuberculosis , Community Health Services , Cross-Sectional Studies , Humans , Motivation , Tuberculosis/diagnosis
4.
Zhonghua Wei Chang Wai Ke Za Zhi ; 25(1): 10-14, 2022 Jan 25.
Article in Chinese | MEDLINE | ID: mdl-35067028

ABSTRACT

In the last decade, the development of clinical practice guidelines in China has grown rapidly. However, with regards to the guidelines that have been established in the past, few were of high quality and in line with international standards. The main reason for this was that many clinical experts were not familiar with the procedures and rules of clinical guidelines before established, which lowered the quality seriously. Clinical practice guidelines are based on a clinical problem that is distilled into populations, interventions, comparison and outcome (PICO). After comprehensive systematic review, recommendations are made through evidence grading and strength of recommendation system. In addition, other issues should be noted such as pros and cons of the recommendation for specific population, preferences and values of the population, cost-effectiveness, and the health care system. A high-quality guideline requires multidimensional thinking (from clinicians, patients and policy makers), the implementation of a standard procedure (to ensure guidelines scientifically sound, honest and transparent), as well as the collaboration of multiple organizations (including experts, methodologists and policy makers).


Subject(s)
Cost-Benefit Analysis , Practice Guidelines as Topic , China , Humans
5.
Environ Microbiol ; 23(12): 7632-7642, 2021 12.
Article in English | MEDLINE | ID: mdl-34232541

ABSTRACT

Azole-resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land-use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non-wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34 /L98H most frequent (34/38).


Subject(s)
Aspergillus fumigatus , Azoles , Antifungal Agents/pharmacology , Azoles/pharmacology , Drug Resistance, Fungal/genetics , Fungal Proteins/genetics , Microbial Sensitivity Tests , Vietnam
6.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4909-4917, 2020 Oct.
Article in Chinese | MEDLINE | ID: mdl-33350264

ABSTRACT

To establish the quantitative analysis multi-components with a single-marker(QAMS) method for six components and fingerprint of standard decoction of Gastrodiae Rhizoma, verify the accuracy and feasibility of the method, and evaluate the quality of standard decoction. Based on UPLC with gastrodin as the internal standard, relative correction factors of p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C, parishin A and gastrodin were determined by investigating the column temperature, flow rate, chromatographic columns and multi-point concentration correction. The total contents in 18 batches of standard decoction of Gastrodiae Rhizoma and the similarity were determined to calculate the similarity. The results of standard curve method, external standard one-point method and quantitative analysis multi-components with a single-marker(QAMS) were compared, and the results showed that there was no significant difference among these three methods. By analyzing the results of standard decoctions from different origins, it can be seen that the quality of Gastrodia standard decoctions derived from Anhui and Yunnan was better, followed by Shaanxi and Hubei, and relatively poor in Gansu, with similarities all above 0.90 in the fingerprints. Therefore, the QAMS method that can measure the contents of gastrodin, p-hydroxybenzyl alcohol, parishin E, parishin B, parishin C and parishin A in standard decoction of Gastrodiae Rhizoma combined with fingerprint is accurate, feasible and fast, which can be used to evaluate the quality of standard decoction of Gastrodiae Rhizoma, and also provide a reference for the research on the quality standards of raw materials for Gastrodiae Rhizoma prepared slices and alike.


Subject(s)
Drugs, Chinese Herbal , Gastrodia , China , Chromatography, High Pressure Liquid , Reference Standards , Rhizome
7.
J Fungi (Basel) ; 6(4)2020 Nov 18.
Article in English | MEDLINE | ID: mdl-33217930

ABSTRACT

The burden of aspergillosis, especially Chronic Pulmonary Aspergillosis, is increasingly recognized, and the increasing presence of azole-resistant environmental Aspergillus fumigatus has been highlighted as a health risk. However, a sizable minority of aspergillosis is caused by Aspergillus flavus, which is assumed to be sensitive to azoles but is infrequently included in surveillance. We conducted environmental sampling at 150 locations in a rural province of southern Vietnam. A. flavus isolates were identified morphologically, their identity was confirmed by sequencing of the beta-tubulin gene, and then they were tested for susceptibility to azoles and amphotericin B according to EUCAST methodologies. We found that over 85% of A. flavus isolates were resistant to at least one azole, and half of them were resistant to itraconazole. This unexpectedly high prevalence of resistance demands further investigation to determine whether it is linked to agricultural azole use, as has been described for A. fumigatus. Clinical correlation is required, so that guidelines can be adjusted to take this information into account.

8.
Biomed Res Int ; 2020: 9627605, 2020.
Article in English | MEDLINE | ID: mdl-32908929

ABSTRACT

Young adults are susceptible to overweight and obesity and their adverse outcomes. However, limited studies have been conducted to understand this health problem in Vietnamese youths. This study was conducted to examine the rate of overweight and obesity, as well as the relationship between this condition on body perception, physical activity, and respiratory function among young adults in Hanoi, Vietnam. We performed a cross-sectional survey with 367 students aged 18-25 years at the Hanoi University of Pharmacy from June 2017 to June 2018. The result showed that the rate of overweight and obesity in our sample was 16.6%. There were 55.7% of overweight/obese students having the misperception of their body image. Results of multivariate regression analysis showed that overweight/obesity increased nearly three times (OR = 2.8, 95% CI: 1.5-5.0) the ability to be active. Overweight/obese students with physical activity had a better respiratory function. To conclude, this study underlined the associations between overweight and obesity with physical activity, body image, and respiratory function in our young sample. Further longitudinal studies should be warranted to examine their causal relationships.


Subject(s)
Body Image , Exercise , Obesity/epidemiology , Overweight/epidemiology , Adolescent , Adult , Body Mass Index , Cross-Sectional Studies , Female , Humans , Male , Obesity/physiopathology , Obesity/psychology , Overweight/physiopathology , Overweight/psychology , Prevalence , Respiratory Function Tests , Students , Urban Population , Vietnam/epidemiology , Young Adult
9.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(Z1): 21-26, 2020 Jul 10.
Article in Chinese | MEDLINE | ID: mdl-32594721

ABSTRACT

Colorectal surgery is a major therapeutic approach for various colorectal diseases. Surgery and perioperative management, such as fasting, mechanical bowel preparation, and antibiotics use, have an impact on the composition and function of gut microbiome. Abnormal microbiome reconstruction may lead to multiple complications, including infection, gastrointestinal dysfunction, anastomotic leak and disease recurrence. The aim of this review is to elucidate the roles and mechanisms of perioperative interventions of colorectal surgery on gut microbiome, which may provide a novel insight into the microbe-based therapies in the perioperative period of colorectal surgery.


Subject(s)
Colonic Diseases/surgery , Digestive System Surgical Procedures/adverse effects , Gastrointestinal Microbiome/physiology , Perioperative Care/adverse effects , Rectal Diseases/surgery , Anastomotic Leak , Colonic Diseases/microbiology , Colonic Diseases/physiopathology , Digestive System Surgical Procedures/methods , Humans , Perioperative Care/methods , Rectal Diseases/microbiology , Rectal Diseases/physiopathology
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(2): 162-166, 2020 Feb 10.
Article in Chinese | MEDLINE | ID: mdl-32164123

ABSTRACT

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Non-neonatal tetanus remains a serious public health problem, although neonatal tetanus has been eliminated in China since 2012. Non-neonatal tetanus is a potential fatal disease. In the absence of medical intervention, the mortality rate of severe cases is almost 100%. Even with vigorous treatment, the mortality rate is still 30%-50% globally. These specifications aim to regulate non-neonatal tetanus diagnosis and treatment in China, in order to improve medical quality and safety. These specifications introduce the etiology, epidemiology, pathogenesis, clinical manifestations and laboratory tests, diagnosis, differential diagnosis, grading and treatment of non-neonatal tetanus.


Subject(s)
Tetanus/diagnosis , Tetanus/therapy , China/epidemiology , Humans , Public Health , Tetanus/epidemiology
11.
Colorectal Dis ; 22(5): 537-543, 2020 05.
Article in English | MEDLINE | ID: mdl-31868954

ABSTRACT

AIM: Assessment of lymph node (LN) involvement is of crucial importance in the estimation of prognosis and choice of therapeutic options for patients with colon cancer. The relationship between the radiological size of LNs and prognosis in node-negative colon cancer remains uncertain. This study aims to investigate the prognostic impact of radiologically enlarged LNs on the survival of patients with node-negative colon cancer. METHOD: This retrospective study recruited 395 patients with Stages I and II colon cancer diagnosed between January 2012 and March 2016. Preoperative computed tomography was reviewed for the maximum short-axis diameter of regional LNs, the optimal cutoff value of which was set to 8 mm. The prognostic relevance was analysed in Kaplan-Meier and multivariable Cox proportional hazard regressions. RESULTS: Patients with tumour in the left colon, TNM Stage II and 12 or more retrieved LNs tended to have radiologically enlarged LNs. Our results suggest that 3-year recurrence-free survival (RFS) and overall survival (OS) were significantly worse in patients with enlarged LNs than those without (RFS 82.8% vs 92.4%, P = 0.026; OS 87.1% vs 95.2%, P = 0.017), which was also confirmed in multivariable analysis [RFS hazard ratio (HR) = 2.192, P = 0.018; OS HR = 3.305, P = 0.010]. Subgroup analysis revealed that in patients with Stage II disease or at least 12 retrieved LNs, radiologically enlarged LN remained an independent predictor of poor RFS and OS. CONCLUSION: The presence of radiologically enlarged LNs in patients with node-negative colon cancer had an adverse prognosis.


Subject(s)
Colonic Neoplasms , Lymph Nodes , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/surgery , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymphatic Metastasis/diagnostic imaging , Lymphatic Metastasis/pathology , Neoplasm Staging , Prognosis , Retrospective Studies
12.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(12): 1206-1211, 2019 Dec 06.
Article in Chinese | MEDLINE | ID: mdl-31795576

ABSTRACT

Tetanus consists of neonatal tetanus and non-neonatal tetanus. Although neonatal tetanus in China has been eliminated since 2012, non-neonatal tetanus remains a serious public health problem. Non-neonatal tetanus is a potential fatal disease, and the mortality rate of severe cases is almost 100% in the absence of medical intervention. Even with vigorous treatment, the mortality rate is still 30~50% globally. In order to standardize the diagnosis and treatment of non-neonatal tetanus in China, this specification is hereby formulated. This standard includes etiology, epidemiology, pathogenesis, clinical manifestations, laboratory tests, diagnosis, differential diagnosis, classification, grading and treatment of non-neonatal tetanus.


Subject(s)
Practice Guidelines as Topic , Tetanus/diagnosis , Tetanus/therapy , China , Humans , Infant, Newborn , Public Health
13.
Basic Res Cardiol ; 114(2): 8, 2019 01 14.
Article in English | MEDLINE | ID: mdl-30643968

ABSTRACT

Mice with a global deletion of α1AMPK are characterized by endothelial dysfunction and NADPH oxidase subunit 2 (NOX-2)-mediated vascular oxidative stress. However, the underlying mechanisms are incompletely understood and may involve endothelial NOX-2 upregulation or facilitated vascular infiltration of phagocytic cells. Therefore, the current study was designed to investigate the vascular effects of chronic angiotensin II (AngII) infusion in mice with an endothelial-specific α1AMPK deletion. A mouse strain with endothelial-specific α1AMPK deletion was generated by breeding α1AMPKflox/flox mice with TekCre+ or Cadh5Cre+ mice. Chronic AngII infusion (0.5 mg/kg/day for 7day) caused mild endothelial dysfunction in wild-type mice that was significantly aggravated in endothelial α1AMPK knockout mice. Aortic NOX-2 and CD68 expression were increased, indicating that infiltrating leukocytes may significantly contribute to enhanced vascular oxidative stress. Flow cytometry revealed a higher abundance of aortic CD90.2+ T-cells, CD11b+F4/80+ macrophages and Ly6G-Ly6C+ monocytes. Vascular mRNA expression of monocyte chemoattractant protein 1, CCL5 and vascular cell adhesion molecule 1 was enhanced in AngII-infused mice lacking endothelial α1AMPK, facilitating the recruitment of inflammatory cells to the vessel wall. In addition, AngII-induced upregulation of cytoprotective heme oxygenase 1 (HO-1) was blunted in mice with endothelial α1AMPK deletion, compatible with an impaired antioxidant defense in these animals. In summary, endothelial expressed α1AMPK limits the recruitment of inflammatory cells to the vessel wall and maintains HO-1 mediated antioxidant defense. Both mechanisms reduce vascular oxidative damage and preserve endothelial function during chronic AngII treatment.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Endothelium, Vascular/metabolism , Angiotensin II/toxicity , Animals , Antioxidants/metabolism , Endothelium, Vascular/drug effects , Heme Oxygenase-1/metabolism , Inflammation/metabolism , Male , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxidative Stress/drug effects , Oxidative Stress/physiology
14.
AIDS Behav ; 22(2): 629-636, 2018 02.
Article in English | MEDLINE | ID: mdl-28181013

ABSTRACT

HIV testing during pregnancy facilitates timely antiretroviral treatment for HIV-positive women. This study identifies reasons for late HIV testing among pregnant women delivering at a hospital in Ho Chi Minh City. We conducted a case-control study in which 160 cases were women who were tested for HIV late (i.e., at labor and delivery) and 160 controls were women who were tested during antenatal care (ANC). In multivariable logistic regression analysis, six variables were associated with late HIV testing: age less than 30 years, nine or fewer years of education, working as a homemaker or worker/farmer, living 20 km or more from the hospital, having received ANC at a private clinic/hospital only, and not believing that HIV testing is important during pregnancy. We recommend that national programs should provide additional effort for HIV testing during pregnancy to young women, less educated women, homemakers, and those receiving ANC at private clinics and hospitals.


Subject(s)
AIDS Serodiagnosis/methods , Anti-Retroviral Agents/administration & dosage , Delayed Diagnosis , HIV Infections/diagnosis , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/prevention & control , Adult , Age Factors , Case-Control Studies , Female , HIV , HIV Infections/epidemiology , Health Knowledge, Attitudes, Practice , Health Services Accessibility , Hospitals , Humans , Pregnancy , Prenatal Care , Socioeconomic Factors , Time Factors , Vietnam/epidemiology , Young Adult
15.
Pharmacology ; 101(1-2): 54-63, 2018.
Article in English | MEDLINE | ID: mdl-28988245

ABSTRACT

BACKGROUND/AIMS: 2-aminoethyl nitrate (CLC-1011) is a member of the class of organic nitrates that cause vasodilation by the generation of nitric oxide (•NO). These drugs are mainly used for the treatment of angina pectoris and ischemic heart disease. The aim of this study was to characterize the vasodilatory potency of this organic nitrate alone and in combination with clinically established cardiovascular drugs. METHODS: Vasodilation by CLC-1011 was tested by isometric tension studies, either alone or combined with cilostazol, valsartan, and metoprolol. Induction of oxidative stress in isolated heart mitochondria was measured by enhanced chemiluminescence. Bioactivation of CLC-1011 in aortic tissue was measured by electron paramagnetic resonance spectroscopy using an iron-based spin trap for •NO. RESULTS: We observed potent vasodilation by CLC-1011 and additive effects for all three drug combinations. In contrast to nitroglycerin (GTN), CLC-1011 did not stimulate mitochondrial oxidative stress. CLC-1011 was bioactivated to •NO in aortic tissue. CONCLUSION: In summary, the experiments described in this report demonstrate that CLC-1011 does not induce oxidative stress, is a more potent vasodilator than isosorbide-5-mononitrate and dinitrate ISDN, and displays synergistic vasodilation with other cardiovascular drugs. CLC-1011 fixed dose combinations could be used in the management of cardiovascular diseases.


Subject(s)
Aorta/drug effects , Metoprolol/pharmacology , Mitochondria, Heart/drug effects , Nitrates/pharmacology , Tetrazoles/pharmacology , Valsartan/pharmacology , Vasodilator Agents/pharmacology , Animals , Aorta/physiology , Cilostazol , Drug Combinations , Drug Synergism , Male , Mitochondria, Heart/metabolism , Oxidative Stress/drug effects , Rats, Wistar
16.
Zhonghua Zhong Liu Za Zhi ; 39(7): 485-489, 2017 Jul 23.
Article in Chinese | MEDLINE | ID: mdl-28728292

ABSTRACT

Objective: To investigate the clinical significance of detection of circulating tumor cells (CTCs) in peripheral blood from patients with osteosarcoma (OS) using the iFISH (immunofluorescence and fluorescence in situ hybridization) method. Methods: The live cells recovery rate of immune-magnetic beads was evaluated by live-cell fluorescent tracer technology. The expression of CD45 and CK18 on the cell surface of HOS and HepG2 cells was measured by flow cytometry. And the chromosome aneuploidy was detected by centromeric FISH probe CEP8. Subsequently, 23 OS patients were enrolled and divided into two groups, relapse or metastasis group and primary group. And the prognostic significance of CTCs numbers was analyzed. Results: The live cells recovery rate of immune-magnetic beads was higher than 90%. The flow cytometry results showed that HOS cells were double negative for the surface biomarkers of CD45 and CK18. In addition, the FISH-CEP8 signal abnormality rate were 96.5% in HOS cells. Thus, CTC was identified using the criteria as follows: the cells with CEP8-positive signal >2 accounted for more than 96.5% of the total cells, of which the cells with >3 positive signal were more than 65.0%. Among the enrolled patients, 19 patients had detectable CTCs in the peripheral blood. The CTCs numbers in the relapse or metastasis group and primary group were 2.846±1.281 and 1.400±1.506, respectively. The results showed that the CTCs in patients with recurrence or metastasis were significantly higher than those in primary patients (P=0.021). Conclusions: To our knowledge, this is the first evidence of existence of CTCs in OS patients. The CTCs numbers were positively associated with disease progression and poor prognosis. These results may provide a potential prognostic tool for monitoring metastasis and recurrence in OS patients. Trial registration: Chinese Clinical Trial Registry, ChiCTR-OOC-15005925.


Subject(s)
Bone Neoplasms/blood , In Situ Hybridization, Fluorescence/methods , Neoplastic Cells, Circulating/pathology , Osteosarcoma/blood , Aneuploidy , Biomarkers, Tumor/analysis , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Cell Count , Fluorescent Antibody Technique , Humans , Leukocyte Common Antigens/analysis , Neoplasm Recurrence, Local , Osteosarcoma/chemistry , Osteosarcoma/genetics , Osteosarcoma/secondary , Prognosis
17.
Eur J Clin Microbiol Infect Dis ; 36(11): 2073-2083, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28600626

ABSTRACT

The aim of this study was to explore the gut microbiota profiles of colorectal cancer (CRC) patients and to examine the relationship between gut microbiota and other key molecular factors involved in CRC tumorigenesis. In this study, a 16S rDNA sequencing platform was used to identify possible differences in the microbiota signature between CRC and adjacent normal mucosal tissue. Differences in the microbiota composition in different anatomical colorectal tumor sites and their potential association with KRAS mutation were also explored. In this study, the number of Firmicutes and Actinobacteria decreased, while the number of Fusobacteria increased in the gut of CRC patients. In addition, at the genus level, Fusobacterium was identified as the key contributor to CRC tumorigenesis. In addition, a different distribution of gut microbiota in ascending and descending colon cancer samples was observed. Lipopolysaccharide biosynthesis-associated microbial genes were enriched in tumor tissues. Our study suggests that specific mucosa-associated microbiota signature and function are significantly changed in the gut of CRC patients, which may provide insight into the progression of CRC. These findings could also be of value in the creation of new prevention and treatment strategies for this type of cancer.


Subject(s)
Bacteria/classification , Bacteria/genetics , Colorectal Neoplasms/microbiology , Gastrointestinal Microbiome/genetics , Intestinal Mucosa/microbiology , Bacterial Load , Base Sequence , Colon/microbiology , Colorectal Neoplasms/pathology , Female , Genome, Bacterial/genetics , Humans , Male , Middle Aged , Proto-Oncogene Proteins p21(ras)/genetics , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA
18.
Eur Heart J ; 38(37): 2838-2849, 2017 10 01.
Article in English | MEDLINE | ID: mdl-28329261

ABSTRACT

Aims: Epidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon. Methods and results: We developed a novel animal model to study the vascular consequences of aircraft noise exposure. Peak sound levels of 85 and mean sound level of 72 dBA applied by loudspeakers for 4 days caused an increase in systolic blood pressure, plasma noradrenaline and angiotensin II levels and induced endothelial dysfunction. Noise increased eNOS expression but reduced vascular NO levels because of eNOS uncoupling. Noise increased circulating levels of nitrotyrosine, interleukine-6 and vascular expression of the NADPH oxidase subunit Nox2, nitrotyrosine-positive proteins and of endothelin-1. FACS analysis demonstrated an increase in infiltrated natural killer-cells and neutrophils into the vasculature. Equal mean sound pressure levels of white noise for 4 days did not induce these changes. Comparative Illumina sequencing of transcriptomes of aortic tissues from aircraft noise-treated animals displayed significant changes of genes in part responsible for the regulation of vascular function, vascular remodelling, and cell death. Conclusion: We established a novel and unique aircraft noise stress model with increased blood pressure and vascular dysfunction associated with oxidative stress. This animal model enables future studies of molecular mechanisms, mitigation strategies, and pharmacological interventions to protect from noise-induced vascular damage.


Subject(s)
Aircraft , Noise, Transportation/adverse effects , Oxidative Stress/physiology , Animals , Aorta/physiology , Blood Pressure/physiology , Disease Models, Animal , Endothelium, Vascular/physiology , Hormones/metabolism , Mice, Inbred C57BL , Myocardium/metabolism , NADPH Oxidases/metabolism , Nitric Oxide Synthase Type III/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Vasculitis/physiopathology , Vasoconstriction/physiology , Vasodilation/physiology
19.
Oxid Med Cell Longev ; 2017: 4353462, 2017.
Article in English | MEDLINE | ID: mdl-28337251

ABSTRACT

Objective. Oxidative stress and endothelial dysfunction contribute to pulmonary arterial hypertension (PAH). The role of the nitrovasodilator pentaerythritol tetranitrate (PETN) on endothelial function and oxidative stress in PAH has not yet been defined. Methods and Results. PAH was induced by monocrotaline (MCT, i.v.) in Wistar rats. Low (30 mg/kg; MCT30), middle (40 mg/kg; MCT40), or high (60 mg/kg; MCT60) dose of MCT for 14, 28, and 42 d was used. MCT induced endothelial dysfunction, pulmonary vascular wall thickening, and fibrosis, as well as protein tyrosine nitration. Pulmonary arterial pressure and heart/body and lung/body weight ratio were increased in MCT40 rats (28 d) and reduced by oral PETN (10 mg/kg, 24 d) therapy. Oxidative stress in the vascular wall, in the heart, and in whole blood as well as vascular endothelin-1 signaling was increased in MCT40-treated rats and normalized by PETN therapy, likely by upregulation of heme oxygenase-1 (HO-1). PETN therapy improved endothelium-dependent relaxation in pulmonary arteries and inhibited endothelin-1-induced oxidative burst in whole blood and the expression of adhesion molecule (ICAM-1) in endothelial cells. Conclusion. MCT-induced PAH impairs endothelial function (aorta and pulmonary arteries) and increases oxidative stress whereas PETN markedly attenuates these adverse effects. Thus, PETN therapy improves pulmonary hypertension beyond its known cardiac preload reducing ability.


Subject(s)
Endothelin-1/metabolism , Oxidative Stress/drug effects , Pentaerythritol Tetranitrate/pharmacology , Vasodilator Agents/pharmacology , Acetylcholine/metabolism , Animals , Blood Pressure/drug effects , Body Weight/drug effects , Cell Line , Echocardiography , Endothelin-1/genetics , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Heart/diagnostic imaging , Heme Oxygenase-1/genetics , Heme Oxygenase-1/metabolism , Humans , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/drug therapy , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Male , Monocrotaline/toxicity , Pentaerythritol Tetranitrate/therapeutic use , Rats , Rats, Wistar , Signal Transduction/drug effects , Up-Regulation/drug effects
20.
Am J Transplant ; 16(9): 2563-73, 2016 09.
Article in English | MEDLINE | ID: mdl-27575724

ABSTRACT

Macrophages exhibit diverse phenotypes and functions; they are also a major cell type infiltrating chronically rejected allografts. The exact phenotypes and roles of macrophages in chronic graft loss remain poorly defined. In the present study, we used a mouse heart transplant model to examine macrophages in chronic allograft rejection. We found that treatment of C57BL/6 mice with CTLA4 immunoglobulin fusion protein (CTLA4-Ig) prevented acute rejection of a Balb/c heart allograft but allowed chronic rejection to develop over time, characterized by prominent neointima formation in the graft. There was extensive macrophage infiltration in the chronically rejected allografts, and the graft-infiltrating macrophages expressed markers associated with M2 cells but not M1 cells. In an in vitro system in which macrophages were polarized into either M1 or M2 cells, we screened phenotypic differences between M1 and M2 cells and identified purinergic receptor P2X7 (P2x7r), an adenosine triphosphate (ATP)-gated ion channel protein that was preferentially expressed by M2 cells. We further showed that blocking the P2x7r using oxidized ATP (oATP) inhibited M2 induction in a dose-dependent fashion in vitro. Moreover, treatment of C57BL/6 recipients with the P2x7r antagonist oATP, in addition to CTLA4-Ig treatment, inhibited graft-infiltrating M2 cells, prevented transplant vasculopathy, and induced long-term heart allografts survival. These findings highlight the importance of the P2x7r-M2 axis in chronic rejection and establish P2x7r as a potential therapeutic target in suppression of chronic rejection.


Subject(s)
Graft Rejection/drug therapy , Graft Survival/drug effects , Heart Transplantation/adverse effects , Macrophages/immunology , Purinergic P2X Receptor Antagonists/pharmacology , Receptors, Purinergic P2X7/chemistry , Animals , CD8-Positive T-Lymphocytes/immunology , Graft Rejection/etiology , Graft Rejection/pathology , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Postoperative Complications
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