作者机构：
[Li, Shang-Ze; Huang, Xi-Cheng; Zhang, Xiao-Dong; Li, Chao; Du, Run-Lei; Chen, Jie] Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Hubei, Peoples R China.;[Li, Shang-Ze; Song, Xue-Min] Wuhan Univ, Res Ctr Anesthesiol & Crit Care Med, Zhongnan Hosp, Wuhan 430071, Hubei, Peoples R China.;[Liu, Wenbin] Wuhan Polytech Univ, Coll Hlth Sci & Nursing, Wuhan 430023, Hubei, Peoples R China.
通讯机构：
[Xue-Min Song] R;[Run-Lei Du] H;Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, Hubei Province, 430072, PR China<&wdkj&>Research Centre of Anesthesiology and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, 430071, PR China
摘要：
PURPOSE: To explore the relationship between Mycoplasma hyorhinis infection and tyrosine kinase inhibitor (TKI) resistance in lung adenocarcinoma patients. METHODS: Mycoplasma hyorhinis infection can be verified with the monoclonal antibody PD4, which specifically recognizes a distinct protein of M. hyorhinis. Immunohistochemistry (IHC), using PD4 to detect M. hyorhinis, was performed on paraffin-embedded lung adenocarcinoma tissues of patients who had epidermal growth factor (EGFR) mutations and had received oral TKI. The number of patients enrolled in our study was 101. Assessments following TKI treatment were performed until objective disease progression or stable disease at the cutoff date was reached. In all of the patients, the primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: Immunohistochemistry revealed that 61 of 101 cases (60.4%) of lung adenocarcinoma were positive for M. hyorhinis, which comprised of 31 low-positive cases and 30 high-positive cases; the remaining 40 cases (39.6%) were negative. The median PFS was significantly longer in the negative group [18months (95% CI 14.15-21.85)] than in the low-positive group [10months (95% CI 7.70-12.30); hazard ratio (HR) 4.095, 95% CI 2.254-7.438; p < 0.001] and in the high-positive group [4months (95% CI 2.85-5.15); HR 31.703, 95% CI 14.425-69.678; p < 0.001]. The results of the subgroup analysis were satisfactory. The PFS benefit with negative M. hyorhinis infection was consistent across subgroups. CONCLUSIONS: In this retrospective, exploratory analysis, M. hyorhinis infection significantly reduced PFS. With increased levels of M. hyorhinis infection, the progression of the disease was more advanced, likely due to the hydrolysis of TKI by M. hyorhinis. A strong correlation was found between M. hyorhinis infection and TKI resistance in lung adenocarcinoma. This study provides potent evidence that M. hyorhinis hydrolyses TKI and will assist in the research of related mechanisms in the future. IMPLICATIONS FOR CANCER SURVIVORS: It provides an option to improve the efficacy of TKI, including strategies to decrease M. hyorhinis infection, thereby reducing long-term distress in TKI resistance patients with EGFR mutations.
摘要：
Wilms tumor (WT) is the most common malignant renal tumor in children. The aim of this study was to identify potential susceptibility gene of WT for better prognosis. Weighted gene coexpression network analysis is used for the detection of clinically important biomarkers associated with WT. In the study, 59 tissue samples from National Cancer Institute were pretreated for constructing gene co-expression network, while 224 samples also downloaded from National Cancer Institute were used for hub gene validation and module preservation analysis. Three modules were found to be highly correlated with WT, and 44 top hub genes were identified in these key modules eventually. In addition, both the module preservation analysis and gene validation showed ideal results based on other dataset with 224 samples. Meanwhile, Functional enrichment analysis showed that genes in module were enriched to sister chromatid cohesion, cell cycle, oocyte meiosis. In summary, we established a gene co-expression network to identify 44 hub genes are closely to recurrence and staging of WT, and 6 of these hub genes was closely related to the poor prognosis of patients. Our findings revealed that those hub genes may be used as potential susceptibility gene for clinical diagnosis and prognosis of this tumor.
关键词：
Blood glucose;Gestational diabetes mellitus;Trace elements
摘要：
Purpose: We investigated the impacts of plasma levels of magnesium (Mg), zinc (Zn), calcium (Ca), iron (Fe), copper (Cu), selenium (Se), and chromium (Cr) on GDM risk and the potential mediation effect of blood glucose levels on the relationship between trace elements and GDM risk. Methods: This nested case-control study was based on data from a birth cohort study conducted in Wuhan, China in 2013-2016. A total of 305 GDM cases and 305 individually-matched controls were included in the study. Conditional logistic regression models were used to estimate the associations between plasma trace element concentrations and GDM risk. A mediation analysis was conducted to explore whether blood glucose levels act as a mediator between trace element levels and GDM risk. Results: An IQR increment in plasma levels of Fe and Cu was associated with a significant increase in GDM risk [OR = 2.04 (95 % CI 1.62, 2.57) and OR = 1.52 (95 % CI 1.25, 1.82)], respectively. On the other hand, an IQR increment in plasma levels of Zn and Ca was associated with a significant decrease in GDM risk [OR = 0.55 (95 % CI 0.43, 0.71) and OR = 0.72 (95 % CI 0.56, 0.92)], respectively. The mediation analysis showed significant mediation of the association between Cu and GDM risk via the FBG (%mediated: 19.27 %), 1 h-PBG (12.64 %), 2h-PBG (28.44 %) pathways. Conclusions: Plasma levels of Zn and Ca were negatively associated with GDM risk, while Fe and Cu were positively associated. Blood glucose levels act as a mediator between plasma trace element exposures and GDM risk.
期刊：
Disaster Medicine and Public Health Preparedness,2021年16(6):2458-2463 ISSN：1935-7893
通讯作者：
Wang, ZM
作者机构：
[Gao, Xudong] Wuhan Polytechn Univ, Coll Med & Hlth Sci, Wuhan, Peoples R China.;[Wang, Zhimin; Wang, ZM; Tan, Lingling] Univ South China, Dept Nursing, Affiliated Hosp 2, Hengyang, Peoples R China.;[Kong, Chan] Huazhong Univ Sci & Technol, Tongji Hosp, Gen Med Dept, Tongji Med Coll, Wuhan, Peoples R China.;[Fan, Hongru] Huazhong Univ Sci & Technol, Hosp Wuhan 1, Dept Cardiovasc Dis, Wuhan, Peoples R China.;[Zhang, Juan] Huazhong Univ Sci & Technol, Hosp Wuhan 2, Dept Nursing, Wuhan, Peoples R China.
通讯机构：
[Wang, ZM ] U;Univ South China, Dept Nursing, Affiliated Hosp 2, Hengyang, Peoples R China.
关键词：
bereavement;grief counseling;COVID-19;health care workers
摘要：
Objectives: This research aimed to examine health care workers' grief counseling for bereaved families of Coronavirus disease 2019 (COVID-19) victims in China. Our research may provide a new opportunity to stimulate development of grief counseling in China.Methods: A cross-sectional survey was conducted with 724 health care workers selected by convenience sampling from seven hospitals in Wuhan. Data collection tools included a sociodemographic questionnaire, the skills of grief counseling scale (SGCS), and the attitudes of grief counseling scale (AGCS).Results: The average SGCS score was 18.96±4.66, whose influencing factors consisted of sense of responsibility, frequency of contact with bereaved families, and relevant training (P<0.05). The average AGCS score was 33.36±8.70, whose influencing factors consisted of other grief counseling skills, communication skills, education background, and relevant training (P<0.05).Conclusions: The skills and attitudes toward grief counseling among health care workers combating COVID-19 were at a lower level in Wuhan, China, indicating the need to build a comprehensive grief counseling system, establish a standardized training course, and strengthen the popularization of grief counseling services to the public.
摘要：
Aim To identify the intention of Chinese pregnant women to undertake physical activity (PA) using the theory of planned behaviour. Design A cross-sectional survey. Methods From April - October 2017, a cross-sectional questionnaire was completed by 746 pregnant women from the Health Birth Cohort in Wuhan, China. The theory of planned behaviour variables as well as sociodemographic characteristics was recorded, and the Pregnancy PA Questionnaire was together used to assess their PA during pregnancy. Results Only 11.3% of the women met the international guideline. The intention to undertake PA was found it to be positive in 63.9% of pregnant women. Structural equation modelling analysis revealed that behavioural attitudes, subjective norms, and perceived behavioural control (PBC) influenced PA by directly influencing the behaviour intention. Both behavioural attitude and subjective norms influenced PA by indirectly affecting the behaviour. Overall, the model described 60% variance of the behavioural intention to undertake PA during pregnancy. Conclusion PBC was confirmed to be a prominent factor in determining behavioural intention to undertake PA during pregnancy. Pregnant women should be helped and appropriately guided by health providers to overcome barriers to PA. Effect This study investigates the effect of perceived behavioural control (PBC) on the intention to undertake physical activity (PA). The findings suggest that nurses' and midwives' attention should be focused on how to promote the improvement of perceived behavioural control ability of pregnant women to improve pregnant women's PA intention. The attitude of pregnant women on taking up PA and their ability to control behaviours can be improved with support from family or healthcare providers.
通讯机构：
[Wang, Si-Hua] H;Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Thorac Surg, 1277 Jiefang Rd, Wuhan 430022, Peoples R China.
摘要：
Background. Obliterative bronchiolitis (OB) remains the major complication limiting long-term survival of patients after lung transplantation. We aimed to explore the effects of the selective NACHT, LRR, and PYD domains-containing protein 3 (Nlrp3) inflammasome inhibitor MCC950 on the pathogenesis of OB. Methods. Mouse orthotopic tracheal transplants were performed to mimic OB. MCC950 (50 mg/kg) or saline was intraperitoneally injected daily. The luminal occlusion rate and collagen deposition were evaluated by hematoxylin and eosin and Masson’s trichrome staining, respectively. Infiltration of CD4+, CD8+ T cells, and neutrophils was detected with immunohistochemical staining. The frequencies of T helper 1 cell (Th1), T helper 17 cell (Th17), and regulatory T cells (Treg) were measured by flow cytometry. Cytokine levels were measured by ELISA kits. Results. MCC950 treatment significantly inhibited Nlrp3 inflammasome activation after allogeneic tracheal transplant and markedly decreased the luminal occlusion rate and collagen deposition in the allograft. The numbers of infiltrating CD4+, CD8+ T cells, and neutrophils in the allograft were also significantly reduced by MCC950 treatment. MCC950 dramatically decreased the frequencies of Th1/Th17 cells and the levels of interferon gamma/interleukin (IL)-17A and increased the Treg cell frequencies and IL-10 level; however, these effects were abolished by the addition of IL-1β and IL-18 both in vitro and in vivo. OB was also rescued by the addition of IL-1β and/or IL-18. Conclusions. Blocking Nlrp3 inflammasome activation with MCC950 ameliorates OB lesions. The mechanistic analysis showed that MCC950 regulated the balance of Th1/Th17 and Treg cells and that this process is partially mediated by inhibition of IL-1β and IL-18. Therefore, targeting the Nlrp3 inflammasome is a promising strategy for controlling OB after lung transplantation.
期刊：
LETTERS IN DRUG DESIGN & DISCOVERY,2020年17(7):884-890 ISSN：1570-1808
通讯作者：
Liu, Wenbin;Du, Runlei;Cao, Rihui
作者机构：
[Jia, Yifan] Wuhan Univ, Dept Pain Management, Renmin Hosp, Wuhan 430060, Peoples R China.;[Liu, Wenbin] Wuhan Polytech Univ, Coll Hlth Sci & Nursing, Wuhan 430023, Peoples R China.;[Zhang, Xiaodong; Yu, Difei; Du, Runlei] Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China.;[Huang, Qiuhua; Cao, Rihui; Qiu, Liqin] Sun Yat Sen Univ, Sch Chem, Guangzhou 510275, Peoples R China.
通讯机构：
[Liu, Wenbin; Du, Runlei] W;[Cao, Rihui] S;Wuhan Polytech Univ, Coll Hlth Sci & Nursing, Wuhan 430023, Peoples R China.;Wuhan Univ, Coll Life Sci, Hubei Key Lab Cell Homeostasis, Wuhan 430072, Peoples R China.;Sun Yat Sen Univ, Sch Chem, Guangzhou 510275, Peoples R China.
关键词：
Synthesis;quinolone;antiproliferative;autophagy;mechanism of action;ATG5 protein.
摘要：
Background: Quinolines have been characterized as a class of potential antitumor agents, and a large number of natural and synthetic quinolines acting as antitumor agents were reported. Methods: A series of 7-chloro-4(1H)-quinolone derivatives were synthesized. The antiproliferative effect of these compounds was evaluated by MTT assay against five human tumor cell lines. The mechanism of action of the selected compound 7h was also investigated. Results and Discussion: Most of the compounds had more potent antiproliferative activities than the lead compound 7-chloro-4(1H)-quinolone 6b. Compound 7h was found to be the most potent antiproliferative agent against human tumor cell lines. Further investigation demonstrated that compound 7h triggered ATG5-dependent autophagy of colorectal cancer cells by promoting the functions of LC3 proteins. Conclusion: These results were useful for designing and discovering more potent novel antitumor agents endowed with better pharmacological profiles.
摘要：
Cadmium (Cd) is a well-recognized, hazardous toxic heavy metal, and the adverse effects of high-level Cd exposure on human health have been well documented. However, little is known about the health effects of low-level environmental Cd exposure on pregnant women. The objective of this study was to assess urinary metabolic alterations in pregnant women exposed to environmental Cd, and to identify informative biomarkers. Urine samples from 246 pregnant women in the first trimester of pregnancy were collected, and urinary Cd concentrations were quantified using inductively coupled plasma mass spectrometry (ICP-MS). Urinary metabolomics was analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Cd-related metabolic biomarkers were examined by comparing the samples of the first and third tertiles of Cd exposure classifications, using a partial least-squares discriminant (PLS-DA) model. Five putative biomarkers were identified, including L-cystine, L-tyrosine, dityrosine, histamine, and uric acid, all of which were related to oxidative stress and nephrotoxic effects induced by Cd exposure. The results show that low-level environmental Cd exposure could induce metabolite profile alterations in pregnant women, which might be associated with adverse health effects. Our findings provide new insights into the early molecular events following Cd exposure, and may be valuable for the health risk assessment of Cd exposure during pregnancy.
通讯机构：
[Zhong, Jixin] C;[Zhao, Shi] O;Case Western Reserve Univ, Cardiovasc Res Inst, Cleveland, OH 44106 USA.;Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA.
摘要：
OBJECTIVE: Myeloid-related protein-14 (MRP14) and its binding partner MRP8 play an essential role in innate immune function and have been implicated in a variety of inflammatory diseases. However, the role of MRP14 in obesity-induced inflammation and insulin resistance is not well defined. This study investigated the role of MRP14 in macrophage-mediated adipose tissue inflammation and obesity-induced insulin resistance. SUBJECTS AND RESULTS: Wild-type (WT) and Mrp14(-/-) mice were fed with a high-fat diet or normal chow for 12 weeks. Tissue-resident macrophages in both adipose tissue and liver from obese WT mice expressed higher levels of MRP14 in the visceral adipose fat and liver compared with the lean mice. Mrp14(-/-) mice demonstrated a significantly improved postprandial insulin sensitivity, as measured by intraperitoneal glucose tolerance test and insulin tolerance testing. Macrophages secreted MRP14 in response to inflammatory stimuli, such as LPS. Extracellular MRP8/14 induced the production of CCL5 and CXCL9. Deficiency of MRP14 did not affect macrophage proliferation, mitochondrial respiration, and glycolytic function, but Mrp14(-/-) macrophages showed a reduced ability to attract T cells. Depletion of the extracellular MRP14 reduced the T cell attracting ability of WT macrophages to a level similar to Mrp14(-/-) macrophages. CONCLUSION: Our data indicate that MRP14 deficiency decreases obesity-induced insulin resistance and MRP8/14 regulates T-cell recruitment through the induction of T-cell chemoattractant production from macrophages.
摘要：
Introduction: Reduced bone mass will increase bone fragility and risk of fractures. Thus, it is better to note its determinants as early as possible. Objective: This study aimed to find and determine the determinants for low bone mineral density (BMD) in preschool children. Methods: Between November 2014 and April 2015, a matched case-control study was performed to detect information on growth and development condition and consumption frequency of products of cases with low BMD and controls with normal BMD. Anthropometric data measurement and blood tests were conducted. Besides, the questionnaires concerning the mentioned information were completed to get relevant determinants. A paired t-test, the McNemar test and univariate and multiple conditional logistic regression models were used to explore the association between these factors and low BMD. Results: In total, 88 (28 boys, 60 girls) incident cases (4.15 +/- 0.78 years) of low BMD and 88 sex- and age-matched (+/- 2 months) controls (4.16 +/- 0.80 years) of normal BMD were enrolled. The results of multiple conditional logistic regression analysis indicated that if children had larger chest circumference (odds ratio [OR] = 0.763), longer duration of breastfeeding (OR = 0.899) and lower frequency of eating snacks (OR= 0.439), the risk of low BMD would decrease. Conclusions: Our findings suggest that pre-school children with an association of larger chest circumference, longer duration of breastfeeding and lower frequency of eating snacks could have lower risk for low BMD. Intended measures to strengthen those protective factors could be effective in reducing the cases of low BMD.
摘要：
The S100 proteins, a family of calcium-binding cytosolic proteins, have a broad range of intracellular and extracellular functions through regulating calcium balance, cell apoptosis, migration, proliferation, differentiation, energy metabolism, and inflammation. The intracellular functions of S100 proteins involve interaction with intracellular receptors, membrane protein recruitment/transportation, transcriptional regulation and integrating with enzymes or nucleic acids, and DNA repair. The S100 proteins could also be released from the cytoplasm, induced by tissue/cell damage and cellular stress. The extracellular S100 proteins, serving as a danger signal, are crucial in regulating immune homeostasis, post-traumatic injury, and inflammation. Extracellular S100 proteins are also considered biomarkers for some specific diseases. In this review, we will discuss the multi-functional roles of S100 proteins, especially their potential roles associated with cell migration, differentiation, tissue repair, and inflammation.
关键词：
High performance liquid chromatography;Oral administration;Pharmacokinetics;Acetonitrile;Herbicides;Pesticides;Quality control;Liver
摘要：
2,4-Dichlorophenoxyacetic acid (2,4-D) is a chlorophenoxy herbicide used worldwide. We describe a high-performance liquid chromatography (HPLC) method with UV detection for the determination of 2,4-D in female and male rat serum. This allows to observe the change of serum 2,4-D concentration in rats with time and its pharmacokinetics characteristics with a simple, rapid, optimized and validated method. The serum samples are pretreated and introduced into the HPLC system. The analytes are separated in a XDB-C18 column with a mobile phase of acetonitrile (solvent A) and 0.02 M ammonium acetate (containing 0.1% formic acid) (solvent B) using a gradient elution at a flow rate of 1.0 mL/min. The wavelength for UV detection was set at 230 nm. Calibration curve for 2,4-D was constructed over a range of 0.1-400 mg/L. The method was successfully applied to study the pharmacokinetics of 2,4-D in rats in this study. After oral administration of 300 mg/kg and 60 mg/kg 2,4-D, the mean Cmax values were 601.9 and 218.4 mg/L, the AUC0-->infinity values were 23,722 and 4,127 mgxh/L and the clearance (Cl) were 1.10 and 0.02 L/(hxkg), respectively. The developed method was found to be specific, precise, reproducible and rapid.
