bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular disease is a risk factor for osteoporosis: a case-control study in Chinese women
Authors: Chai Hao , Ge Jirong , Li Li , Li Jianyang , Ye Yunjin
Published: December 2020

Background: Osteoporosis and cardiovascular disease (CVD) are age-related diseases. According to some studies, patients with CVD have a higher risk of bone loss. This retrospective study intended to reveal the correlation between osteoporosis and CVD in Chinese women. Although epidemiological evidence has provided evidence of the relationship between the two, it lacks clinical data in southeast China.Methods: The 2873 participants completed the baseline survey from January 2007 to October 2019, and 2496 were included in this retrospective study. We divided all subjects into the osteoporosis group and the non-osteoporosis group based on their bone mineral density. Dual-energy x-ray absorptiometry (DXA) was used to examine bone mineral density. The general information came from the questionnaire survey and medical records. Results: According to the criterion, the osteoporosis group had 799 subjects, with a mean age of 64.19 years. The non-osteoporosis group had 1697 subjects, with a mean age of 61.03 years. Subjects in the osteoporosis group had a significantly higher prevalence of hypertension and coronary heart disease. Besides, there was a higher probability of drinking tea and drinking milk in the osteoporosis group. In correlation analysis, the occurrence of osteoporosis correlated positively with hypertension and coronary heart disease. Logistic regression analysis showed that the odds of osteoporosis was high if participants had hypertension, coronary heart disease, or drank tea and drank milk. Conclusions: This study indicated that patients with osteoporosis had a higher prevalence of CVD in Chinese women, and CVD is one of the hazard factors for osteoporosis.
Bone Involvement in Antiretroviral-Therapy–Naïve HIV-Infected Young Men
Authors: Atencio Patricia , Cabello Alfonso , Conesa-Buendia Francisco , Perez-Tanoira Ramon , Prieto-Perez Laura , Carrillo Irene , Alvarez Beatriz , Arboiro-Pinel Rosa , Diaz-Curiel Manuel , Herrero-Beaumont Gabriel , Mediero Aranzazu , Gorgolas Miguel
Published: December 2020

Background: Low bone mineral density has been described as a non–AIDS (Acquired Immune Deficiency Syndrome)-related event in HIV (human immunodeficiency virus)-patients but it is poorly studied in young HIV-infected men who have received no previous antiretroviral therapy.Methods: A cross-sectional study of 245 naïve-HIV-infected men over 21 and under 50 years old was carried out between January 2014 and September 2017. Results: The mean age was 36.4 years, been 68% Caucasian and 29.3% Latin American. At the time of diagnosis, 91% of patients had stage-A (median CD4+ T-cell 481cells/μL, IQR, 320–659). 10% had a count below 200 CD4 cells/μL, and 40% had a CD4/CD8 cell-count-ratio below 0.4. Regarding lifestyle and risk factors, 14.1% presented underweight, 36.1% engaged in no regular exercise, 51.9% had previous exposure to tobacco and 35.3% reported drug use. Low levels of vitamin D were seen in 87.6% of the men studied. Low BMD (Z-score<2.0) was found in 22,8% of the patients. Conclusions: We find prevalence of bone involvement among naïve HIV-infected men under 50 years old. Further studies are necessary to evaluate if BMD assessment should be recommended in young HIV-infected patients.
Identifying the genetic basis and molecular mechanisms underlying phenotypic correlation between complex human traits using a gene-based approach
Authors: Zheng Jiashun , Gu Jialiang , Fuller Chris , Li Hao
Published: December 2020

Phenotypic correlations between complex human traits have long been observed based on epidemiological studies. However, the genetic basis and underlying mechanisms are largely unknown. The recent accumulation of GWAS data has made it possible to analyze the genetic similarity between human traits through comparative analysis. Here we developed a gene-based approach to measure genetic similarity between a pair of traits and to delineate the shared genes/pathways, through three steps: 1) translating SNP-phenotype association profile to gene-phenotype association profile by integrating GWAS with eQTL data; 2) measuring the similarity between a pair of traits by a normalized distance between the two gene-phenotype association profiles; 3) delineating genes/pathways supporting the similarity. Application of this approach to a set of GWAS data covering 59 human traits detected significant similarity between many known and unexpected pairs of traits; a significant fraction of them are not detectable by SNP based similarity measures. Examples include Height and Schizophrenia, Cancer and Alzheimer’s Disease, and Rheumatoid Arthritis and Crohn’s disease. Functional analysis revealed specific genes/pathways shared by these pairs. For example, Height and Schizophrenia are co-associated with genes involved in neural development, skeletal muscle regeneration, protein synthesis, magnesium homeostasis, and immune response, suggesting growth and development as a common theme underlying both traits. Our approach can detect yet unknown relationships between complex traits and generate mechanistic hypotheses, and has the potential to improve diagnosis and treatment by transferring knowledge from one disease to another.
Determinants of Growth Monitoring and Promotion Service Utilization Among Children 0-23 Months of Age in Northern Ethiopia: Unmatched Case Control Study
Authors: Aliyu Jemal , Menber Yonatan , Wassihun Yosef , Fentahun Netsanet , Dagne Samuel
Published: December 2020

Background: One of the strategies to promote child health and reduce child mortality is growth monitoring and promotion services. But, there is limited information on determinants of Growth Monitoring and Promotion service utilization. Objective: To identify determinants of growth monitoring and promotion (GMP) service utilization among children 0-23 months of age in Legambo district, South Wollo zone, Northern Ethiopia, 2020.Methods: Community based un-matched case control study was conducted on 363 (91 cases and 272 controls) study participants from March 15 to April 15, 2020. Multi-stage sampling technique was employed to select the study participants. Bivariable and multivariable logistic regressions were performed and adjusted odds ratio with 95% confidence intervals was estimated to identify determinants of GMP service utilization.Results: Good maternal knowledge (AOR) = 2.42; 95% CI: 1.23, 4.75), favorable attitude (AOR = 2.45; 95% CI; 1.20, 4.98), counseling on GMP (AOR = 2.34; 95% CI; 1.19, 4.56), Attending ante natal care services (AOR = 2.46; 95% CI: 1.18, 5.16), index child age 12-17 months(AOR = 3.45; 95% CI: 1.26, 9.41) and 18-23 months (AOR = 4.38; 95% CI: 1.53, 12.49), and short distance to health facilities (AOR = 4.53; 95% CI; 1.99, 10.28) were determinants of GMP service utilization.Conclusion: Index child age, good knowledge, favorable attitude, attending ante natal care services, receiving nutritional counseling and short distance to health facility were determinants of GMP service utilization. Nutritional interventions should emphasis nutritional counseling and accessibility of growth monitoring and promotion services.
Activation of protein kinase A signaling and inhibitions of glycine/glutathione biosynthesis involves in the transition from prediabetes to diabetes based on metabolomics data analysis
Authors: Zhao Ning , Gu Zhan , Li Li , Jiang Miao , Chen Weini , Liu Biao , Zhu Junxuan , Guo Yuming , He Xiaojuan , Zhang Chi , Niu Xuyan , Zhan Junping , Cheng Shiping , Kong Hongwei , Lu Cheng , Lu Aiping
Published: December 2020

Metabolomics is expected to identify potential metabolites and related pathways, and further reveal the underlying mechanisms of the transition from prediabetes to diabetes. In this study, a metabolomics-based gas chromatography-mass spectrometry (GC-MS) technique was used for demonstrating the serum metabolic profiles among healthy, prediabetes, and diabetes at fasting state and 2h oral glucose tolerance test (2h OGTT) state. With Ingenuity Pathway Analysis (IPA) tool, the comparative analysis showed no significant differences in the pathway analysis (P > 0.05) between prediabetes and diabetes at either fasting state or 2h OGTT state. The self-comparative analysis demonstrated the glycine/glutathione biosynthesis in diabetes were more inhibited than that in prediabetes or healthy control at 2h OGTT state compared with fasting state (P<0.05). In addition, the protein kinase A signaling pathway in prediabetes or diabetes was significantly inhibited more than that in healthy control (P<0.05). Therefore, the glycine/glutathione biosynthesis and protein kinase A signaling could differentiate the diabetic subjects from the prediabetic and healthy control subjects, and may involve in prediabetes transition to diabetes. This study provided more metabolomics information for the transition from prediabetes to diabetes.
Influence of Food Taboos and Beliefs on Anaemia among Pregnant Women In Isiolo County, Kenya
Authors: Agustino Sora , Kimiywe Judith , Ogutu James
Published: December 2020

Background: Food taboos have a long history that could be used to explain the presence of certain dietary tradition in every culture. Pregnancy imposes the need for considerable extra calorie and nutrient requirements. A balanced and adequate diet is therefore of utmost importance during pregnancy and lactation to meet the increased needs of the mother and to prevent nutritional stress. Isiolo County is inhabited by communities that still practice all aspect of their culture, religion and beliefs. Some of the beliefs that surround the diet of pregnant women, can harm the pregnant woman and the child. This study sought to assess the common food taboos and beliefs during pregnancy and their influence on anaemia among pregnant women in Isiolo County. Methods: The study utilized a descriptive cross-sectional research design. The study population was divided into 3 clusters based on the sub-counties in County. Both qualitative and quantitative data were obtained by trained research assistants from a sample size of 374 distributed proportionately among the three sub-counties and analyzed using SPSS version 23. Correlation coefficients were used to establish relationships between variables of the study and logistic regression was used to identify the association of explanatory variables with the outcome variable. A p-value of <0.05 was used to determine significant results. Content analysis was used to present qualitative data gathered from focus group discussion. Results: The study found a high prevalence (68.02%) of anaemia during pregnancy in Isiolo County. Cultural beliefs and food taboos had negative effect on the prevalence of anaemia among pregnant mothers χ2 (3, N=369) = 8.201, p<0.001. Conclusion: There is a high prevalence of anemia in pregnancy associated with cultural beliefs. We recommend partnerships between National Ministry of health and County government department of health to promote campaigns aimed at eliminating negative cultural beliefs.
Assessing Multiple Sclerosis‑Related Quality of Life among Iranian Patients Using the MSQOL-54 Tool: A cross-sectional study
Authors: Namazi Niloofar , Ziaei Shadi , Afzal Golnaz , Barati Saghar , Mohebbi Rezvaneh , Mir Mahshad , Esmaily Hadi , Mehralian Gholamhossein
Published: December 2020

BackgroundThe main objectives of this study were to assess quality of life (QoL), consumption patterns of dietary supplements, as well as physical/mental health status in patients with multiple sclerosis (MS). The present study also aimed to determine the association between demographic characteristics and physical as well as mental health composite (PHC and MHC) scores using the Multiple Sclerosis Quality of Life-54 (MSQoL-54) questionnaire.MethodsThis cross-sectional study was conducted on a group of patients with MS (n=382) referring to Shahid Kazemi Pharmacy, based in the city of Tehran, Iran, as a national pharmacy providing specialized pharmaceutical care to these individuals from February 2019 to March 2020 via the implementation of the MSQoL-54 questionnaire. ResultsA total number of 382 patients with MS participated in this study, including 89 (23.3%) men and 293 (76.7%) women, aged 40±10.9 years old (range: 18-84 years old). The overall score of the MSQoL-54 questionnaire was also by 41.58, and that was 69.60 and 62.99 from 100 for PHC and MHC, respectively. Conclusions The study results demonstrated that advanced age, longer disease duration, and lower levels of education were significantly associated with lower QoL. Trial registration IR.SBMU.PHARMACY.REC.1398.240.
Can Non-Invasive Assessment of Liver Fibrosis Be Used As A Predictor of Prognosis for HCC Patients with HBV-Related Cirrhosis?
Authors: Mu Siyu , Xu Lin
Published: December 2020

Backgroud: Most liver cancer patients have backgroud of HBV-related liver cirrhosis. We are still not sure whether non-invasive assessments of liver fibrosis can be used as predictors of prognosis. In this study, we investigate the relationship between aspartate aminoytransferase (AST)-to-platelet(PLT) ratio index (APRI) and the prognosis of hepatocellular carcinoma (HCC) patients with liver cirrhosis.Methods: The clinical data of HCC patients with cirrhosis who received hapatectomy in our hospital were analyzed retrospectively. Receiver Operating Characteristic (ROC) curve was used to determine APRI cut-off value to predict the prognosis. Kaplan-Meier survival (Log-rank test) and Cox regression analyses were used for univariate and multivariate analysis of the prognosis in all patients, and the differences were compared between the APRI high-value and low-value groups. Independent sample t test was used to compare the differences of clinical data between the APRI high-value and low-value groups.Results: The cut-off value was determined as 0.61 according to the ROC curve, and the high-value group was defined as APRI ≥ 0.61, while the low-value group was defined as APRI<0.61. By the end of follow-up data, the proportion of patients died from liver failure in high-value group was higher than that in low-value group (χ2 =5.232, P=0.022). The results of survival analysis showed that the maximum of tumor diameter >0.5cm, multiple tumors, invasion of liver capsule, vascular tumor thrombus, AFP>20ng/ml and APRI ≥ 0.61were independent risk factors influencing the disease free survival (DFS) time after resection for HCC patients with cirrhosis (P<0.05). The 1-year, 2-year, and 5-year disease free survival rates of APRI low-value and high-value groups were 79.4%, 61.4%, 43.7% and 71.4%, 51.6%, 27.0%. The recurrence rate of APRI low-value and high-value groups were 20.5%, 38.1%, 54.1% and 28.0%, 47.1%, 69.8%, respectively (P=0.000). APRI value of patients with portal hypertension (PH) and Child-pugh B class were higher than those without PH and Child-pugh A class (P<0.05).Conclusion: HCC patients with liver cirrhosis whose APRI ≥ 0.61 had worse prognosis after resection.
Gastric Electrical Stimulation Increases The Proliferation of Interstitial Cells of Cajal and Alters Enteric Nervous System in Diabetic Rats
Authors: Wang Cai , Zhang Hui , Zhao Le , Gao Tao , Liu Xia , Chen Yan
Published: December 2020

Background: Lack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. The aims of the present study were to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved.Methods: Sixty rats were randomized into the normal rats, diabetic rats (DM), diabetic rats with sham GES (DM+SGES), and three diabetic rats with GES (DM+GES1, DM+GES2 and DM+GES3). The proliferation of ICC and expressions of 5-HT2B, nNOS, CHAT, PGP9.5 and GDNF were evaluated by immunofluorescence staining or Western blot. The expressions of 5-HT in blood and tissue were determined by ELISA.Results: (1) The proliferation of ICC was hardly observed in the DM group together with the DM+SGES group but increased in the three DM+GES groups. (2) The expression of 5-HT2B was decreased in the DM group and enhanced in the DM+GES groups. Similarly, the expressions of 5-HT in the blood and distal stomach tissue were increased in the DM+GES groups. (3) Both nNOS labeled neurons and CHAT positive neurons were reduced in myenteric plexus of the DM group, while plenty of these neurons were observed the DM+GES groups. (4) The expression of GDNF protein in the diabetic rats was down-regulated, while GES increased the expression of GDNF.Conclusion: GES improves the proliferation of ICC possibly related with 5-HT/5-HT2B signal pathway, and alters enteric nervous system 52 partly though the GDNF expression.
Effects of Sub-Atmospheric Pressure and Dissolved Oxygen Concentration on Lesions Generated in Ex Vivo Tissues by High Intensity Focused Ultrasound
Authors: He Min , Zhong Zhiqiang , Zeng Deping , Gong Xiaobo , Wang Zhibiao , Li Faqi
Published: December 2020

BackgroundAcoustic cavitation plays an important role in the medical treatment using high intensity focused ultrasound (HIFU), but unnecessarily strong cavitation also could deform the morphology and enlarge the size of lesions. It is known that the increase of ambient hydrostatic pressure (Pstat) can control the acoustic cavitation but the question how decrease of Pstat and dissolved oxygen concentration (DOC) influences the strength of cavitation has not been thoroughly answered.MethodsEx vivo bovine liver tissues were immersed in degassed water with different DOC of 1.0 mg/L, 1.5 mg/L and 2.0 mg/L. Ultrasound (US) of 1 MHz and the spatial and temporal average intensity (Isata) of 6500 W/cm2 was used to expose two groups of in vitro bovine livers for two seconds; one group was under atmospheric pressure (Pstat = 1 bar) and the other was under sub-atmospheric pressure (Pstat = 0.1 bar). Acoustic cavitation was detected by a passive cavitation detector (PCD) during the exposure process. Echo signals at the focal zone of HIFU were monitored by B-mode ultrasound imaging before and after exposure.ResultsThe results demonstrated a significant difference of broadband acoustic emissions from the cavitation bubbles, echo signals on B mode image, morphology of lesions under various condition of ambient pressure and DOC. The lesion volume in tissue was increased with the increase of ambient pressure and DOC.ConclusionCavitation could be suppressed through sub-atmospheric pressure and low DOC level in liver tissue, which could provide a method of controlling cavitation in HIFU treatment to avoid unpredictable lesions.
Awareness of Colorectal Cancer and Associated Factors Among Adult Patients in Jimma, South-West Ethiopia.
Authors: Hamza Abdulmenan , Argaw Zeleke , Gela Debela
Published: December 2020

Background: Colorectal cancer (CRC) is the first commonest diagnosed cancer in men and the fourth commonest in women in Ethiopia. The most significant factors that may increase the risk of having CRC were modifiable. However, little is known about the awareness of CRC and associated factors among adult patients in study area. Therefore, the study aimed to assess the awareness of CRC and associated factors among adult patients in Jimma, South-West Ethiopia, 2020. Methods: The institution-based quantitative cross-sectional study design was conducted among 422 patients from March 8 to April 30, 2020. The study participants were recruited by a systematic random sampling method and data was collected semi-structured interviewer-administered questionnaires. Descriptive, bivariate, and multivariate logistic regression was implemented. The statistical level of significance was stated at p-value < 0.05. Result: A 100% response rate in this study was recorded. More than half (57.6%) of the study participants had low awareness of colorectal cancer. Smoking (78.2%) and bloody stool (49.3%) were the most known risk factors and symptoms. There is a significant association between awareness of colorectal cancer with gender, residency, monthly income, level of education, information sources, and heard about CRC. Conclusion: Overall awareness of patients towards CRC was inadequate. Participants with high levels of education and females had better awareness, however; the overall awareness of them was insufficient. Therefore, there is a need for awareness campaigns and health education for promoting colorectal cancer awareness.
Human Breast Milk Assessed by the Deuterium Dose Mother Technique with Less Than 30 g Deuterium Using the Agilent 4500S for Fourier Transform Infrared Spectroscopy: A Pilot Study in the Democratic Republic of Congo
Authors: Murhima’Alika Christine Chimanuka , Balemba Ghislain Maheshe , Mapendo Daniella Bugugu , Kapapa Aminata , Munthali Grace , Owino Victor , Wilmet Michèle Dramaix , Donnen Philippe , Balaluka Ghislain Bisimwa
Published: December 2020

Background: Good breastfeeding practice is essential in preventing malnutrition in children. The deuterium method is the best technique for assessing human breast milk output. We investigated whether deuterium doses < 30 g can be used to assess human breast milk using saliva and the new Agilent 4500S for Fourier transform infrared spectroscopy (FTIR). Methods: In a cross-sectional study, the breastmilk output of lactating mothers was evaluated using four different doses of deuterium in the Miti-Murhesa Health Zone (Democratic Republic of Congo). Lactating mothers of infants aged 3-23 months were recruited and assigned to a dosage group. Weight, height, and mid-upper arm circumference were measured and the body mass index calculated as weight/height2. Body composition (fat mass, free fat mass, total body water, and breastmilk output) was assessed using standard deuterium dilution methods. One-way ANOVA was used to compare the means in different groups and the chi² test to compare proportions. Results: Seventy-five lactating mothers were included in the study: 19 received 6 g, 20 received 10 g, 18 received 15 g, and 18 received 20 g deuterium. The mean ± standard deviation infant age was 10.6 ± 5.2, 11.1 ± 4.4, 10.9 ± 4.4, and 11.0 ± 3.9 months, respectively (p=0.076). We found no difference in the age and anthropometric parameters of the lactating mothers in the different groups. The mean ± standard deviation breast milk output rate was 796.6 ± 292.4, 260.8± 23.2, 749.8 ± 244.2, and 733.6 ± 207.1 g/d in the 6 g, 10 g, 15 g, and 20 g groups, respectively (p=0.883). Conclusions: The different doses of deuterium administered to lactating mothers resulted in similar breast milk output values. Thus, it is possible to evaluate human breast milk with deuterium doses <30 g when using the Agilent 4500S.
Leveraging Phone Based Mobile Technology to Improve Data Quality at Health Facilities in Rural Malawi: A Best Practice Project
Authors: Tizifa Tinashe Alinafe , Nkhono William , Mtengula Spencer , Vugt Michele van , Munn Zachary , Kabaghe Alinune Nathanael
Published: December 2020

Background: To further reduce malaria burden, identification of areas with highest burden for targeted interventions needs to occur. Routine health information has the potential to indicate where and when clinical malaria occurs the most. Developing countries mostly use paper-based data systems however they are error-prone as they require manual aggregation, tallying and transferring of data. We piloted the use of electronic data capture (EDC) using a cheap and user friendly software in rural Malawian primary healthcare setting to improve the quality of health records. Methodology: We used audit and feedback tools from Joanna Briggs Institute’s (Practical Application of Clinical Evidence System and Getting Research into Practice) in four primary healthcare facilities. Using this approach, we identified the best available evidence for a malaria information system (MIS). Baseline audit of the existing MIS was conducted in the facilities based on available best practice for MIS; this included ensuring data consistency and completeness in MIS by sampling 25 random records of malaria positive cases. Implementation of an adapted evidence-based EDC system using tablets on an OpenDataKit platform was done. We then conducted an end line audit following implementation. Users had interviews on experiences and challenges concerning EDC at the beginning and end of the survey.Results: The existing MIS was paper-based, occupied huge storage space, had some data losses due to torn out papers and were illegible in some facilities. The existing MIS did not have documentation of necessary parameters such as malaria deaths and treatment within 14 days. Training manuals and modules were absent. One health center solely had data completeness and consistency at 100% of the malaria-positive sampled records. Data completeness and consistency rose to 100% with readily available records containing information on recent malaria treatment. Interview findings at the end of the survey showed that EDC was acceptable among users and they agreed that the tablets and the OpenDataKit were easy to use, improved productivity and quality of care. Conclusions: Improvement of data quality and use in the Malawian rural facilities was achieved through the introduction of EDC using OpenDataKit. Health workers in the facilities showed satisfaction with the use of EDC. (Word limit: 350 words, current: 349)
Delayed Exercise Therapy after acute Ankle Sprain Increases Functional Ankle Instability – The Later, the Worse: A Retrospective Analysis.
Authors: Raeder Christian , Tennler Janina , Praetorius Arthur , Ohmann Tobias , Schoepp Christian
Published: December 2020

Background:The lateral ankle sprain (LAS) is one of the most common injuries in everyday life and sports. Approximately 20-40% of patients with a LAS develop a chronic ankle instability (CAI). The underlying mechanisms for CAI have not yet been clearly clarified. An inadequate rehabilitation after LAS can be speculated, since the LAS is often handled as a minor injury demanding less treatment Therefore, the aim of this retrospective study was to first determine the CAI rate depending on age and sex and second, to identify possible risk factors for developing CAI. Methods:Between 2015 and 2018 we applied the diagnostic code “sprain of ankle” (ICD S93.4) to identify relevant cases from the database of the BG Klinikum Duisburg, Germany. Patients received a questionnaire containing the Tegner-Score as well as the patient-related outcome measures including the Cumberland Ankle Instability Tool (CAIT) and the Foot and Ankle Disability Index. Additionally, there were questions about the cause of accident, time points of therapy onset, as well as the number of recurrent sprains. There was a total of 647 completed datasets which were separated into a CAI and a COPER group according to a CAIT cut-off score of <24.Results:The overall CAI rate was 17.3%. We identified a higher risk for CAI in females and within the age segment of 41 to 55 years. A later therapy onset (>4 weeks) after acute LAS significantly worsens ankle function in CAIT (p<.05). There was a significantly higher CAIT score in patients having no recurrent sprain compared to patients having 1-3 recurrent sprains (p<.001) or 3-5 recurrent sprains (p<.001).Conclusion:Females and older age groups have a higher risk for developing CAI which implies to perform specific prevention programs improving ankle function following LAS. A delayed onset of exercise therapy seems to be an important risk factor for the development of CAI. A further risk factor, suggested by literature, is the number of recurrent sprains that could be also confirmed by our data. Therefore, we recommend an early onset of functional exercise therapy after acute LAS in the future to minimize the development of CAI.
Development of in Vitro Resistance to Daptomycin in Enterococcus Faecium and Estimation of Its Fitness Cost
Authors: Zeng Weiliang , Chen Tao , Wu Qing , Xu Ye , Yu Kaihang , Zhang Ying , Liu Shixing , Cao Jianming , Zhou Tieli
Published: December 2020

BackgroundDaptomycin has broad-spectrum antibacterial activity against Gram-positive pathogens, but recent studies have revealed cases where daptomycin has failed to treat multidrug-resistant bacteria, such as vancomycin-resistant Enterococcus faecium. However, the resistance evolution of E. faecium to daptomycin in vitro and fitness cost remain unclear. In this study, we sought to analyze the resistance development and mechanism of E. faecium to datomycin, and futher to investigate the relationship between daptomycin resistance and fitness cost.MethodsTo investigate the development of daptomycin resistance in E. faecium, 6 daptomycin-susceptible (DAP-S) clinical isolates, including 3 vancomycin-resistant E. faecium (VRE) and 3 vancomycin-susceptible E. faecium (VSE), were exposured to daptomycin in vitro by serial passage experiment. Then the different resistance mechanisms of daptomycin-resistant (DAP-R) mutants were analyzed by polymerase chain reaction (PCR), cytochrome C binding assay and transmission electron microscopy. Furthermore, we also estimated the changes of fitness cost among each highly DAP-R mutants by bacterial growth curve measurement, in vitro competition experiments, infection model of Galleria mellonella larvae and biofilm formation assays.ResultsIn vitro, a total of 21 DAP-R mutants with minimal inhibitory concentration (MIC) of 4 to 512 μg/mL were obtained, and these mutants carried more than one mutation of LiaFSR and YycFG system encoding genes. More positive charges were detected among highly DAP-R mutants than parent isolates, and the cell walls of SC1174-D and SC1762-D mutants were remarkly thicker than those of the parent isolates. In comparison with parent isolates, besides, the growth, competition ability and virulence were significantly reduced, while the biofilm formation capacity was markedly elevated among each highly DAP-R mutants.ConclusionsOur findings suggest that E. faecium isolates are able to rapidly acquire DAP resistance in vitro through different dynamic resistance mechanisms, which often accompany by significant fitness cost. Intriguingly, DAP and glycopeptide antibiotics may present collateral-sensitivity during E. faecium acquired DAP resistance in vitro.
Practical Experience of Humanistic Care Among Medical Staff in Stroke Wards: A Qualitative Research Study Conducted in China
Authors: Li Min , Zhu Wenjing , Yang Ziqing , Luo Qing , Chen Huang , Duan Yan , Chen Ken , Xie Hongzhen
Published: December 2020

BackgroundAs a special patient group, stroke patients have a significant attachment to humanistic care. There are, however, still many problems in clinical practice. Medical staff in stroke wards are the main providers of humanistic care. Finding out the opinions of staff that provide the medical service is vitally important for stroke patients that need access to curative and humanistic care.ObjectiveThe aim of the study was to explore the psychological experiences of doctors, nurses and physiotherapists during the implementation of humanistic care in a stroke ward.MethodMedical staff including doctors, nurses and physiotherapists were selected from stroke wards in general hospitals (minimum level two) from 13 cities within six provinces in China. A purposive sampling method was used until no new data were generated (n=18). Semi-structured interviews were conducted by using a phenomenological research method. The Colaizzi seven-step method was used for analysis.ResultThe end user’s experience incorporated four themes: (1) Gradually improving the perception of humanistic caring in a stroke ward. (2) Required improvement of consciousness and ability of humanistic care implementors in a stroke ward. (3) Main problems and contradictions associated with implementing humanistic care in stroke wards. (4) Critical needs of staff in a stroke ward.ConclusionSteady advances have been made in the prevention and treatment of stroke in China. Care behaviour of staff in stroke wards has gradually improved. Nevertheless, while implementing humanistic care in stroke wards, the consciousness and ability of medical staff needs to be improved, in addition to the practical problems and contradictions affecting the development of humanistic care. In order to improve the level of humanistic care in stroke wards, attention should be paid to the overall improvement of the personal qualities of medical staff in stroke wards and the integration of a humanistic management mode.
Pre-treatment Controlling Nutritional Status (CONUT) Score and Carcinoembryonic Antigen Level Provide Tumour Progression and Prognostic Information in Gastric Cancer ： A Retrospective Study
Authors: chen xiuqing , wu peiwen , shen ximei , yang liyong
Published: December 2020

BackgroundThis study explores the role of combining the controlling nutritional status (CONUT) score and the carcinoembryonic antigen (CEA) level on predicting tumour stage and prognosis in gastric cancer (GC) patients.MethodsA total of 682 GC patients were included in this retrospective study. CONUT scores and CEA levels were combined to establish a new scoring system: CONUT-CEA score. Cut-off values for distinguishing patients between stage IV and non-stage IV were established by receiver operating characteristic curves. Cut-off values for predicting prognosis were determined by maximum x2 method.ResultsThe CONUT and CEA cut-off values for discriminating stage IV patients from non-stage IV patients were 2.0 and 5.58 ng/ml, respectively. Logistic regression model demonstrated that high CONUT-CEA score was related to advanced tumour stage. Among non-stage IV patients, CONUT and CEA cut-off values of 2.0 and 9.50 ng/ml predicted overall survival (OS), respectively. The Cox proportional risk model revealed that high CONUT-CEA score was notable related to decreased OS (2 vs 0: hazard ratios (HR) =2.358, 95% confidence intervals (CI)=1.412–3.940, P=0.001) and decreased disease-free survival (2 vs 0: HR=1.980, 95% CI=1.072–3.656, P=0.003). ConclusionsThe CONUT-CEA score may be a good biomarker for predicting tumour stage and prognosis in GC patients.
Circulating Metabolomic Profiling Detects Novel Markers of Myocardial Infarction among Cardiac-chest Pain Cases
Authors: Aa Nan , Lu Ying , Yu Mengjie , Tang Heng , Lu Zhenyao , Sun Runbin , Wang Liansheng , Li Chunjian , Yang Zhijian , Aa Jiye , Kong Xiangqing , Wang Guangji
Published: December 2020

Background: A unique human plasma metabolic pattern of myocardial infarction (MI) has been recognized for over a decade. The discriminant metabolites are potential diagnosis and warning markers, and have connections with traditional cardiovascular risk factors and circulating transcriptomics. Methods: A total of 146 chest pain (85 MIs and 61 non-MI chest pain cases) and 84 control individuals were recruited. GC/MS and LC/MS were applied to identify and quantify the plasma metabolites. The metabolites were analyzed by multivariate statistical analysis to describe different patterns of CADs with chest pain. Receiver operating characteristic （ROC） and odds ratio (OR) were calculated to identify potential markers of MI cases, and the markers were further evaluated based on human circulating transcriptomics from the GEO database. The correlation of metabolites to clinical indices was assessed. Results: MI can be clearly distinguished from non-MI chest pain cases by the metabolites we identified, better than by medical history combined with routine biochemical parameters. Pathway analysis highlighted an upregulated methionine metabolism and downregulated arginine biosynthesis that were deeply involved in MI cases. Among all the metabolites, deoxyuridine (dU) and methionine scored highly in ROC (>0.91) and are related to LDH and AST (p<0.05). OR values (logOR>2) suggested, with or without adjusting by lipid levels, age, smoking, diabetes and hypertension, that dU and methionine are risk factors for alerting about MI occurrence. Transcriptomics data showed elevations of plasma CDA and UPP1, and a decrease of cardiac MARS, which are consistent with the increased levels of plasma dU and methionine, respectively. Conclusions: For the first time, dU and methionine were suggested as markers for MI diagnosis and as high-risk markers to alert about an onset of MI. Plasma metabolite changes are not only directly related to cardiac damage but also could be related to circulating cells.
Based on the Effect of Huazhengsanji Prescription and Cisplatin on Hypoxia-Induced HepG2 Hepatoma Cells HIF-1α and VEGF
Authors: Wang Shanshan , Yangyang Liu , Xiaohao Xu , Tiejun Liu , Zunhua Shu , Xiong Zhuang
Published: December 2020

BackgroundHepatoma is one of the most common malignant tumors in my country, and its occurrence and development play an important role in the molecular mechanism of hypoxia microenvironment and angiogenesis. Huazhengsanji prescription(HZSJ) is an empirical prescription for the treatment of liver cancer, but its specific anti-tumor molecular mechanism is still unclear, and whether it has a synergistic effect with cisplatin(DDP), a chemotherapy drug for liver cancer, has not been reported yet. This article discusses the inhibition of the proliferation and migration of HepG2 hepatocarcinoma cells and the difference in the expression of HIF-1α and VEGF when the HZSJ, DDP and the two are used in combination, and compares and analyzes the mechanism of the HZSJ in enhancing the anticancer sensitivity of chemotherapeutics.MethodsHepG2 Hepatoma cells were divided into blank control group, hypoxia model group, DDP group, HZSJ group, HZSJ+DDP group, and the hypoxia environment was induced by the CoCl2 method. MTT method detects cell proliferation ability, scratch test detects cell migration ability, immunofluorescence method and western blot detect HIF-1α and VEGF protein expression.ResultsHZSJ has the effect of inhibiting the proliferation and migration of HepG2 cells, and has obvious concentration-dependent; The combined application of HZSJ and DDP has significantly stronger inhibitory effect on cell proliferation than the HZSJ group (P<0.01) and the DDP group (P<0.01, P<0.001). High-dose HZSJ can inhibit the migration ability of HepG2 cells (P<0.01); the combination of HZSJ and DDP can significantly reduce the migration rate of HepG2 cells after induction (P<0.01, P<0.01, P <0.01). The results of immunofluorescence and western blot showed that: compared with the blank control group, the expression levels of HIF-1α and VEGF protein in the model group were significantly increased (P<0.05, P<0.01, P<0.001); compared with the model group and DDP The expression of HIF-1α protein in the high-dose HZSJ group (200μg/mL) and the combination group decreased (P<0.05, P<0.01, P<0.001), but there was no difference between the groups. Compared with the model group, the high-dose HZSJ group (200μg/mL) can reduce the expression of VEGF (P<0.05); compared with the model group and the DDP group, the combination group can reduce the expression of VEGF (P< 0.01, P<0.001), and has obvious concentration dependence.ConclusionsHZSJ can inhibit the proliferation and migration of HepG2 hepatoma cells under hypoxia, which may be related to the reduction of HIF-1α and VEGF expression, and its increase in the anticancer sensitivity of the chemotherapy drug DDP may be related to both The synergistic inhibition of VEGF expression is related.
Tumorigenicity of Ascites-Derived Tumor Cells: Insights Into the Molecular Mechanisms of Ovarian Cancer Progression and Therapy Resistance
Authors: Ding Yi , Labitzky Vera , Legler Karen , Qi Minyue , Schumacher Udo , Schmalfeldt Barbara , Stürken Christine , Oliveira-Ferrer Leticia
Published: December 2020

Background: Ovarian cancer (OvCa) cells disseminate primarily intraperitoneally. Here, detached tumor cell aggregates (spheroids) from the primary tumor are generally regarded as “metastatic units”, which exhibit a survival benefit, probably due to the protective microenvironment and their unique molecular characteristics. Hence, current therapeutic concepts such as classical chemotherapy are not sufficient preventing growth and spread of OvCa spheroids. Methods: In the current study we analyzed the cellular composition of ascites from ovarian cancer patients using flow cytometry and the tumorigenic potential of the different subpopulations in an intraperitoneal mouse model. Comparative transcriptome analyses (RNAseq) from ascites-derived tumor cells spheroids (n=10) vs. tumor samples from different metastatic sites (n=30) were further performed in order to identify key molecular players responsible for the special cellular characteristics of OvCa spheroids. Results: In vitro culture of ascites-derived cells gave rise to two different subpopulations: an adherent cell population (ADs) including mainly CD90+ cells with highly proliferative rates in vitro but no tumorigenic potential in vivo, and a non-adherent cell population (NADs) containing principally EpCAM+/CD24+ cells with low proliferative potential in vitro. NADs included cell aggregates and single cells, the first showing a high content (> 80%) of tumor cells (EpCAM+/CD24+). Enriched tumor cell spheroids from the ascites using cell strainers showed higher tumorigenic potential in vivo in comparison to the original ascites-derived cell population. Interestingly, the different metastatic spread patterns observed in the mice resembled the tumor dissemination pattern found in the corresponding patients. RNAseq analyses from tumor-spheroids revealed up-regulation of genes involved in chemoresistance (TGM1, HSPAs, MT1s), cell-adhesion and cell barrier (PKP3, CLDNs, PPL) and the oxidative phosphorylation (OXPHOS) process compared to the solid tumor tissue samples. Additionally, down-regulation of extracellular matrix components and angiogenesis-related genes could be observed. Targeting OXPHOS by metformin treatment led to reduced viability of ascites-derived spheroids from OvCa patients, showing to some extent a synergistic effect with cisplatin treatment. Conclusions: the actual study contributes to a better understanding of the biology of ovarian cancer spheroids and to the identification of new treatment opportunities in advanced ovarian cancer.
Identification of a Metabolism-Related Risk Signature to Predict the Outcome and Immune Infiltration of Esophageal Squamous Cell Carcinoma
Authors: Liu Yu , Wang Liyu , Liu Hengchang , Tian He , Fan Tao , Xue Liyan , Zheng Bo , Tan Fengwei , Xue Qi , Gao Shugeng , li chunxiang , He Jie
Published: December 2020

Background: Metabolic reprogramming is associated with tumor heterogeneity and progression. Understanding the characteristics of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) might help us to uncover new biomarkers for patient outcomes and targets for therapies.Methods: In this study, metabolism-related genes were screened from mRNA microarray data (GSE53624, GSE53622). Consensus clustering analysis was used to divide tumors into subgroups. Survival analysis and univariate Cox analysis were performed to select prognostic genes. A metabolism-related gene signature was established with multivariate Cox proportional hazards regression (PHR) analysis in the training group (GSE53624). Gene set enrichment analysis (GSEA) and CIBERSORT were used to analyze functional enrichment and immune cell infiltration.The gene signature and immune infiltration were verified in two public databases (GSE53622, TCGA-ESCC) and in two independent cohorts, 95 and 119 ESCC patients, by immunohistochemistry (IHC) analysis. Results: Based on prognosis-related metabolic gene expression, three cluster subgroups (k = 3) were identified with significantly different immune cell infiltration patterns, clinical features and overall survival (OS) times. Then, we developed a multigene (INPP5E, CD38 and POLR3G) prognostic signature that showed better predictive ability and was found to be an independent prognostic risk factor in ESCC database and two public database analyses. This result could also be verified by multicenter IHC experiment and indicated the clinical application potential. In addition, GSEA showed that several tumor-related pathways were associated with the prognostic signature. Furthermore, the immune cell infiltration of regulatory T cells (Tregs) and plasma cells displayed an obvious correlation with prognostic signature and IHC experiment in 119 cohort also support this result.Conclusions: Our study indicated that the metabolism-related prognostic gene could stratify patients into subgroups and was associated with immune infiltration, clinical features and outcomes. The three-gene prognostic signature from metabolic-related gene displays a good ability to predict OS and the infiltration of immunosuppressive Tregs and plasma cells.
WBP2 Negatively Regulates Hippo Pathway By Competitively Binding To WWC3 With LATS1 To Promote The Malignant Phenotype Of Non-Small Cell Lung Cancer
Authors: Han Qiang , Rong Xuezhu , Lin Xu-Yong , Zhang Xiupeng , Fan Chuifeng , Zhao Huanyu , Wang Enhua
Published: December 2020

Background: WW domain binding protein-2 (WBP2) can function as a YAP/TAZ co-activator and play a vital role in promoting breast cancer progression. However, the expression and potential molecular mechanism of WBP2 in the context of lung cancer are not fully understood. Methods: Expression and subcellular localization of WBP2 in clinical samples and in lung cancer cell lines were analyzed with respect to various clinical pathological parameters using Chi-square tests. We used a series of cell function experiments and tumor formation experiments in nude mice to verify the effect of WBP2 on tumor cell proliferation and invasion. Dual-directional regulation of WBP2 expression, immunoprecipitation, luciferase reporter assays, and quantitative PCR analyses were used to explore the regulatory mechanisms and identify associated molecular markers.Results: We determined that WBP2 was highly expressed in lung cancer specimens and cell lines and that this expression was closely related to the pTNM stage, lymph node metastasis, and poor prognosis of patients. Additionally, gain and loss of function experiments revealed that WBP2 could significantly promote the proliferation and invasion of lung cancer cells both in vivo and in vitro. To elucidate the underlying molecular mechanism, we determined that wild-type WBP2 could competitively bind to the WW domain of WWC3 with LATS1 through its PPxY motifs to inhibit the formation of the WWC3-LATS1 complex, reduce the phosphorylation level of LATS1, and ultimately promote YAP nuclear translocation to suppress the activity of the Hippo pathway. Conclusions: From the aspect of upstream molecules of Hippo signaling, WBP2 promotes the malignant phenotype of lung cancer cells in a unique manner that is not directly dependent upon YAP, thus providing a corresponding experimental basis for the development of targeted therapeutic drugs for lung cancer.