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BackgroundBRII-196 and BRII-198 are two anti-SARS-CoV-2 monoclonal neutralizing antibodies with modified Fc region that extends half-life and are being developed as cocktail therapy for the treatment of COVID-19. Safety, tolerability, pharmacokinetics, and immunogenicity of BRII-196 and BRII-198 were investigated in healthy adults. MethodsSingle ascending doses of BRII-196 and BRII-198 were evaluated in parallel in the first-in-human, placebo-controlled phase 1 studies. A total of 32 healthy adults were randomized and received a single intravenous infusion of 750, 1500, and 3000 mg of BRII-196 (n=12), BRII-198 (n=12), or placebo (n=8) and were followed for 180 days. ResultsAll infusions were well tolerated at infusion rates between 0.5 mL/min to 4 mL/min with no dose-limiting adverse events, deaths, serious adverse events, or any systemic or local infusion reactions. Most treatment-emergent adverse events were isolated asymptomatic laboratory abnormalities of Grade 1-2 in severity. Each mAb displayed pharmacokinetics expected of Fc-engineered human IgG1 with mean terminal half-lives of approximately 46 days and 76 days, respectively, with no evidence of significant anti-drug antibody development. ConclusionsBRII-196 and BRII-198 were well-tolerated. Clinical results support further development as therapeutic or prophylactic options for SARS-CoV-2 infection.
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Objective:To investigate and evaluate if pulse oxygen saturation/fraction of inhaled oxygen (SpO 2/FiO 2) can be used, as replacement of arterial partial pressure of oxygen/fraction of inhaled oxygen (PaO 2/FiO 2), to assess oxygenation in acute respiratory distress syndrome (ARDS) patients at different high altitudes in Yunnan Province, and to find a rapid and non-invasive method for the diagnosis of ARDS at different altitudes. Methods:Patients with ARDS at different high altitudes in Yunnan Province from January 2019 to December 2020 were enrolled. The patients were divided into three groups according to different altitudes, and received different oxygen therapies according to their respective medical conditions. Group 1 consisted of patients with moderate to severe ARDS from the department of critical care medicine of the First Affiliated Hospital of Kunming Medical University (average altitude approximately 1 800 m), and received mechanical ventilation to maintain SpO 2 of 0.90-0.96 with a low FiO 2 for more than 30 minutes, and SpO 2, FiO 2, PaO 2 were recorded. Group 2 consisted of patients with moderate to severe ARDS at the department of critical care medicine of People's Hospital of Diqing Tibetan Autonomous Prefecture (mean altitude about 3 200 m), and received oxygen with an attached reservoir mask to maintain SpO 2 of 0.90-0.96 for 10 minutes, and then SpO 2, FiO 2, and PaO 2 were recorded. Group 3 consisted of patients with mild to moderate-severe ARDS who admitted to the emergency department of the People's Hospital of Lijiang (average altitude approximately 2 200 m); when SpO 2 < 0.90, patients received oxygen with the oxygen storage mask, and the FiO 2 required to maintain SpO 2 ≥ 0.90 was recorded, and SpO 2, FiO 2, PaO 2 were recorded after oxygen inhalation for 10 minutes. Spearman coefficient was used to analyze the correlation between SpO 2/FiO 2 and PaO 2/FiO 2 in each group. Linear analysis was used to derive the linear equation between SpO 2/FiO 2 and PaO 2/FiO 2, and to evaluate arterial pH, arterial partial pressure of carbon dioxide (PaCO 2), FiO 2, tidal volume (VT), positive end-expiratory pressure (PEEP) and other related factors which would change the correlation between SpO 2/FiO 2 and PaO 2/FiO 2. The receiver operator characteristic curve (ROC curve) was plotted to calculate the sensitivity and specificity of using SpO 2/FiO 2 instead of PaO 2/FiO 2 to assess oxygenation of ARDS patients. Results:Group 1 consisted of 24 ARDS patients from whom 271 blood gas analysis results were collected; group 2 consisted of 14 ARDS patients from whom a total of 47 blood gas analysis results were collected; group 3 consisted of 76 ARDS patients, and a total of 76 blood gas analysis results were collected. The PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa) in groups 1, 2 and 3 were 103 (79, 130), 168 (98, 195) and 232 (146, 271) respectively, while SpO 2/FiO 2 were 157 (128, 190), 419 (190, 445) and 319 (228, 446) respectively. Among the three groups, patients in group 1 had the lowest PaO 2/FiO 2 and SpO 2/FiO 2, while patients in group 3 had the highest. Spearman correlation analysis showed that PaO 2/FiO 2 was highly correlated with SpO 2/FiO 2 in groups 1, 2 and 3 ( r values were 0.830, 0.951, 0.828, all P < 0.05). Regression equation was fitted according to linear analysis: in group 1 SpO 2/FiO 2 = 58+0.97×PaO 2/FiO 2 ( R2 = 0.548, P < 0.001) ; in group 2 SpO 2/FiO 2 = 6+2.13×PaO 2/FiO 2 ( R2 = 0.938, P < 0.001); in group 3 SpO 2/FiO 2 = 53+1.33×PaO 2/FiO 2 ( R2 = 0.828, P < 0.001). Further analysis revealed that PEEP, FiO 2, and arterial blood pH could affect the correlation between SpO 2/FiO 2 and PaO 2/FiO 2. ROC curve analysis showed that the area under ROC curve (AUC) was 0.848 and 0.916 in group 1 with moderate to severe ARDS; based on the regression equation, the corresponding SpO 2/FiO 2 cut-off values at a PaO 2/FiO 2 of 100 mmHg and 200 mmHg were 155, 252 with a sensitivity of 84.9% and 100%, specificity of 87.2% and 70.6%, respectively. Patients with moderate to severe ARDS in group 2 (AUC was 0.945 and 0.977), the corresponding SpO 2/FiO 2 cut-off values at PaO 2/FiO 2 of 100 mmHg and 200 mmHg were 219 and 432 with the sensitivity of 100% and 85.2%, specificity of 82.5% and 100%, respectively. Patients with mild to moderate-severe ARDS in group 3 (AUC was 0.903 and 0.936), the corresponding SpO 2/FiO 2 cut-off values at a PaO 2/FiO 2 of 200 mmHg and 300 mmHg were 319 and 452 with the sensitivity of 100% and 100%, specificity of 80.9% and 86.2%, respectively. Conclusion:SpO 2/FiO 2 and PaO 2/FiO 2 in ARDS patients at different high altitudes in Yunnan Province have a good correlation, and non-invasive SpO 2/FiO 2 can be used to replace PaO 2/FiO 2 to assess the oxygenation in ARDS patients.
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BackgroundCorona Virus Disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China since late December 2019. Crude case fatality ratio (CFR) with dividing the number of known deaths by the number of confirmed cases does not represent the true CFR and might be off by orders of magnitude. We aim to provide a precise estimate of the CFR of COVID-19 using statistical models at the early stage of the epidemic. MethodsWe extracted data from the daily released epidemic report published by the National Health Commission P. R. China from 20 Jan 2020, to 1 March 2020. Competing risk model was used to obtain the cumulative hazards for death, cure, and cure-death hazard ratio. Then the CFR was estimated based on the slope of the last piece in joinpoint regression model, which reflected the most recent trend of the epidemic. ResultsAs of 1 March 2020, totally 80,369 cases were diagnosed as COVID-19 in China. The CFR of COVID-19 were estimated to be 70.9% (95% CI: 66.8%-75.6%) during Jan 20-Feb 2, 20.2% (18.6%-22.1%) during Feb 3-14, 6.9% (6.4%-7.4%) during Feb 15-23, 1.5% (1.4%-1.6%) during Feb 24-March 1 in Hubei province, and 20.3% (17.0%-25.3%) during Jan 20-28, 1.9% (1.8%-2.1%) during Jan 29-Feb 12, 0.9% (0.8%-1.1%) during Feb 13-18, 0.4% (0.4%-0.5%) during Feb 19-March 1 in other areas of China, respectively. ConclusionsBased on analyses of public data, we found that the CFR in Hubei was much higher than that of other regions in China, over 3 times in all estimation. The CFR would follow a downwards trend based on our estimation from recently released data. Nevertheless, at early stage of outbreak, CFR estimates should be viewed cautiously because of limited data source on true onset and recovery time.
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Objective:To establish a predictive model that can predict the effectiveness and safety of endoscopic surgery for pediatric upper urinary tract calculi, and evaluate its diagnostic efficacy through internal validation.Methods:The data was selected from the prospective database of pediatric upper tract calculi constructed by Beijing Friendship Hospital Affiliated to Capital Medical University from June 2014 to April 2019. A total of 348 children were recruited in this investigation including 250 boys and 98 girls, with a median age of 3.0 years(Interquartile Range 1.4, 7.0 years). Totally 375 endoscopic surgeries were performed, with an overall stone free rate (SFR) of 88.0% (330/375) and complication rate (CR) of 23.2% (87/375). This research used univariate and multivariate logistic regression analysis to evaluate and screen the predictors of SFR and CR. The nomogram of SFR and CR was established by using the selected predictive factors. The differentiation degree of the model was evaluated by the area under the curve (AUC), the consistency between the prediction probability and the actual risk was evaluated by the calibration curve, and the clinical benefits of the model application were assessed by the decision curve.Results:The results of multivariate analysis demonstrated that stone burden, operation duration, intraoperative perfusion, stone location and operative options were the postoperative predictors of SFR and CR for children. Besides, BMI was also a predictor of postoperative CR. The AUC of the model (model 1: SFR; model 2: CR) based on the above predictive factors was 0.81 and 0.73, respectively. The predictive probability of the calibration curve showed that the model had a good consistency with the actual value. The decision curve showed that the application of model 1 to predict SFR had significant clinical benefits when the threshold value was greater than 20%, and the application of model 2 to predict the postoperative CR had a significant clinical benefit when the threshold was greater than 10%.Conclusions:Nomogram based on stone burden, operation time, intraoperative perfusion, stone location and operative options was validated internally with preferable predictive power on the effectiveness and safety of pediatric endoscopic surgery. This model can be used to predict the clinical effects of pediatric endoscopic lithotripsy. BMI was also an important factor for the safety of pediatric endoscopic procedures.
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Objective To evaluate the surgical efficacy of tibial plateau osteotomy for treatment of old tibial plateau fracture.Methods From March 2007 to March 2018,18 old tibial plateau fractures were treated by tibial plateau osteotomy at the Department of Orthopedics,Central Hospital of Jilin City.They were 12 males and 6 females with a mean age of 41.2 years (from 19 to 60 years).The fracture healing time,healing rate and the Hospital for Special Surgery (HSS) score for knee function at the last follow-up were recorded.Results This series were followed up for an average of 24 months (from 12 to 36 months).Of them,17 obtained clinical healing,giving a healing rate of 94.4%.The healing time ranged from 4 to 16months (average,10 months).By the HSS score at the last follow-up,11 cases were rated as excellent,4 as good,2 as fair and one as poor.Conclusion Tibial plateau osteotomy is an effective treatment for old tibial plateau fractures.
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Objective@#To evaluate the effect of low-dose hormone replacement therapy(HRT)on menopausal-related symptoms in young patients with cervical squamous cell carcinoma.@*Methods@#From March 2016 to September 2018,eighty patients aged 45 years below with cervical squamous cell carcinoma of stage Ⅰ-Ⅱ and iatrogenic menopause were recruited,who were diagnosed at Zhejiang Cancer Hospital and Women's Hospital Affiliated to Medical College of Zhejiang University. Fourty of them performed low dose HRT(1 mg estradiol valerate a day or 1.25 mg tibolone a day),twenty performed standard dose HRT(1 mg estradiol valerate and 1.25 mg tibolone a day),another twenty do not perform HRT as a control group. The levels of follicle stimulating hormone(FSH),estradiol(E2),menopausal symptoms(the improved Kupperman score)and incidence of side effects were assessed before and 1,3,6 months after the intervention. @*Results@#There were significant differences in E2 levels,FSH levels and improved Kupperman scores among the low dose group,the standard dose group and the control group(all P<0.05). With the extension of intervention time,E2 levels in the low dose group and the standard dose group increased first and then decreased,FSH levels and improved Kupperman scores decreased(all P<0.05). Compared with the control group,E2 levels,FSH levels and improved Kupperman scores in the standard dose group changed more significantly(all P<0.05). E2 and FSH levels in the low dose group changed less than that in the standard dose group(all P<0.05),while improved Kupperman scores was close to that in the standard dose group. The incidence rate of side effects in the low dose group was 2.50%,which was lower than 20.00% in the standard dose group(P<0.05). @*Conclusion@#For young patients with cervical squamous cell carcinoma,using low dose HRT may less affects E2 and FSH levels than using the standard dose,but could achieve similar effects in treatment of menopausal-related symptoms.
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Objective To compare the predictive value of radiomics signature extracted from MRI plain and enhancement sequence for the disease-free survival (DFS) of rectal cancer. Methods We retrospectively analyzed fifty-one patients with rectal adenocarcinoma confirmed by biopsy from October 2010 to December 2013 in Cancer Hospital Chinese Academy of Medical Sciences.All patients underwent neoadjuvant chemotherapy(nCRT)followed total mesorectal excision(TME),and MRI scans were performed before nCRT.Follow-up time for the survival patients were more than 3 years.The image segmentation was performed on the T2WI sequence of the small FOV and the multi-phase enhancement sequence venous phase,respectively.Least absolute shrinkage and selection operator(LASSO)Cox regression was applied to extract radiomics features and the imaging signature was constructed. According to the radiomics score of each patient,the patients were divided into the high risk group with shorter DFS and the low risk group with longer DFS. A 3-year DFS was calculated for radiomics signature using the Kaplan-Meier product limit method with univariate log-rank analysis testing for differences in the training and validation cohort, respectively. And the predictive ability of the model was evaluated by concordance index (C-index). Results The training set and the validation set were 36 and 15 cases, respectively. During follow-up 32 patients experienced relapse(26 distant,3 local and 3 both),and 19 cases were censored.Twelve features were extracted in the enhanced sequence.The radiomics signatures were significant for DFS in the training set and the validation set(P=0.000 2 and 0.009 1,respectively).The C-index of the model were 0.904 and 0.700 in the training set and the validation set, respectively. The model has the better ability to predict survival.Two features were extracted in the plain sequence.The radiomic signature was significant for DFS in the training set(P=0.005 0),while the radiomics signature was not significant for DFS in the validation set (P=0.767 0). The C-index of the model were 0.711 and 0.500 in the training set and the validation set, respectively.Conclusions Radiomics signature extracted from MRI venous phase enhancement sequence superior to plain sequence for predicting the DFS of rectal cancer before nCRT.
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Objective To explore relationship between the change of serum N terminal brain natriuretic peptide (NT-proBNP) , central venous oxygen saturation (SCVO2 ) and venous-arterial partial pressure of carbon dioxide [P(v-a)CO2 ] levels and prognosis in elderly patients with septic shock .Methods 94 cases of elderly patients with septic shock ,treated from March 2015 to July 2016 in Intensive Care Unit (ICU) of our hospital ,were chosen as the observation group A ,another 80 cases of nonsevere sepsis patients were chosen as the observation group B ,and a total of 56 patients healthy volunteers with the physical examination at the same peri-od of time in our hospital as normal control group .The serum NT-proBNP level was detected by electrochemiluminescence immuno-assay ,and PvCO2 ,PaCO2 and SCVO2 levels were detected by blood gas analyzer .records of patients with central venous blood car-bon dioxide .The NT-proBNP and P (v-a) CO2 levels in the serum of the three groups were compared between the groups of pa-tients in the observation group (SCVO2 ) .Logistic regression analysis was used to analyze the prognostic factors in elderly patients with septic shock ,and the receiver operating characteristic curve (ROC) was used to analyze the predictive value of NT-proBNP ,P (v-a)SCVO2 and SCVO2 levels .Results The serum NT-proBNP level of the observation group A was higher than that in the the observation group B and the control group (P<0 .05) .The SCVO2 level of the A group was lower than that in the B group ,and the P(v-a)CO2 level of the A group was higher than that in the B group ,the difference was statistically significant (P<0 .05) .The age , NT-proBNP ,P(v-a)CO2 ,lactic acid level and APACHE II score in the death group were higher than those in the survival group , and the difference was statistically significant (P< 0 .05) .SCVO2 level in the death group was lower than that in the survival group ,and the difference was statistically significant (P<0 .05) .Logistic multivariate regression analysis showed that NT-proBNP , P(v-a)CO2 and SCVO2 levels were the risk factors for the prognosis of elderly patients with septic shock .ROC curve showed AUC and the sensitivity of P(v-a)CO2 were higher than those of NT-proBNP ,SCVO2 .Conclusion The levels of serum NT-proBNP ,SC-VO2 and P(v-a)CO2 are related to the prognosis of elderly patients with septic shock ,and P(v-a)CO2 has a high value in the prog-nosis of the patients with septic shock ,and has a good clinical value .
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Objective To analyze the clinical value of serum and cerebrospinal fluid(CSF) procalcitonin in the diagnosis of adult central nervous system(CNS) infection to provide reference for its clinical diagnosis and treatment .Methods Sixty adult patients with CNS diseases admitted to our hospital from February to December 2015 were selected as the research subjects .All patients were suspected of CNS infection at initial visiting due to suspected CNS symptoms and signs ,and the CSF pathogenic examination and separation were performed to determine the types of infected pathogenic microorganisms .Meanwhile serum and CSF procalcito-nin was detected .The detection results of CSF pathogen and procalcitonin were summarized .The detection results of CSF pathogen served as the gold standard ,serum and CSF procalcitonin> 0 .5 ng/mL as infection positive .The diagnostic test fourfold table was adopted .Then the procalcitonin detection results and CSF pathogenic microorganism detection data were inputted .The consistency of serum and CSF procalcitonin for judging CNS infection was analyzed and calculated .The sensitivity ,specificity and accuracy of serum and CSF procalcitonin detection method for detecting pathogenic microorganisms were analyzed .Results Among 60 cases ,31 cases were bacterial infection ,22 cases were viral infection and no pathogenic bacterium was detected out in 7 cases ,the positive rate was 88 .34% .In the serum procalcitonin detection :49 cases were positive and 11 cases were negative ;in CFS procalcitonin detec-tion:37 cases were positive and 23 cases were negative .The Kappa coefficients of serum procalcitonin and CFS pathogenic detection results was 0 .769 ,indicating that serum procalcitonin and CFS pathogenic detection results had higher consistency ;the Kappa coef-ficients of CSF procalcitonin and CFS pathogenic detection results was 0 .315 ,indicating that CFS procalcitonin and CFS pathogenic detection results had poor consistency .The sensitivity ,accuracy and specificity of serum procalcitonin for diagnosing CNS infection were 96 .08% ,93 .33% and 77 .78% respectively ,which of CSF procalcitonin were 73 .33% ,45 .00% and 38 .46% respectively ;se-rum procalcitonin detection had a higher clinical value in the diagnosis of adult CNS infection ,while CSF procalcitonin detection had little value .Conclusion The serum procalcitonin detection method has higher sensitivity ,accuracy and specificity for the diagnosis of adult CNS infection ,possesses a better guidance role in selecting the treatment scheme and evaluating the curative effect ,and has higher clinical value in adult patients with CNS bacterial infection .
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Objective To determine the expression of human protection of telomeres 1 (hPOT1) and its relationship with Helicobacter pylori (HP) infection in gastric carcinoma.Methods The expressions of hPOT1 protein and hPOT mRNA were detected in 53 gastric carcinoma specimens (observed group) and 20 normal gastric mucosa tissues (control group) by SP immunohistochemical method and in situ hybridization (ISH), respectively.HP infection was examined by Warthin-Starry method in observed group.Results The positive expression rate of hPOT1 protein was 84.91% (45/53) in observed group, higher than that in control group [30.00 % (6/20)] (P < 0.01).The positive expression rate of hPOT1 mRNA was 58.49 % (31/53) in observed group, higher than that in control group [10.00 % (2/20)] (P < 0.05).The positive co-expression rate of hPOT1 protein and mRNA was 56.60 % (30/53), both had positive relationship in gastric carcinoma (r =0.394, P < 0.05).The rate of HP infection in 53 cases of gastric carcinoma was 52.83 % (28/53).The positive expression rates of hPOTI protein and mRNA in observed group with HP infection were significantly higher than those in observed group without HP infection[protein: 96.43 % (27/28) vs 72.00 % (18/25), P <0.05;mRNA: 85.75 % (24/28) vs 28.00 % (7/25), P < 0.01].Conclusions hPOT1 may be associated with occurrence of gastric carcinoma.Combined detection of hPOT1 protein and mRNA can be used for the diagnosis of gastric carcinoma.HP infection may be associated with abnormal expression of hPOT1 in occurrence of gastric carcinoma.
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Objective To investigate the effect of calcitriol pulse therapy on maintenance hemodialysis patients'microinflammation and oxidative stress.Methods The clinical data of 106 patients with maintenance hemo-dialysis were retrospectively analyzed.106 patients were randomly divided into two groups,each group had 53 cases. The observation group was treated with high dose pulse oral calcitriol therapy(2.0μg,twice a week),while the control group received conventional calcitriol therapy (0 .5 μg ,qd ).Both two groups were treated for 12 weeks.Then,the levels of iPTH,serum calcium and phosphorus,microinflammation and oxidative stress before and after treatment were compared.Results There was no difference between the two groups in iPTH indicators(t =0.354,P >0.05).After treatment,the levels of iPTH,hs -CRP,IL -6,TGF -β1,MDA,MPO in both two groups all decreased(t =7.678, 7.417,13.663,25.709,16.114,9.940,all P 0.05;t =0.777,1.310, 1.210,1.957,all P >0.05 ),which of the observation group were significantly higher than the control group in 12 weeks(t =2.805,P =0.006;t =3.070,P =0.002).Conclusion For treatment of patients with maintenance hemodialysis,calcitriol pulse therapy can reduce systemic microinflammatory response and enhance antioxidant capacity.
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The cultivation of general practitioner is a key to improve China's community-based medical and health care system.Zunyi Medical University,in the process of cultivating tuition-free students with the mode of serving and staying in the countryside after their graduation,always upholds the principles of being oriented by post competence,being led by medical humanities,optimizing featured courses about general practitioner,carrying out students-centered teaching methodology,focusing on training students' autonomous learning ability,and fully building the practical teaching system,so as to strive to cultivate high-quality talents in the field of general medicine to make them better serve the rural community-based medical institutions.
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BACKGROUND/AIMS: To develop a clinical score for the prediction of nonalcoholic steatohepatitis (NASH) using routine parameters in patients with nonalcoholic fatty liver disease who had abnormal liver function tests and/or fatty liver detected by ultrasonography. MATERIALS AND METHODS: To identify parameters associated with the presence of NASH by evaluating anthropometric characteristics and routine biomarkers of 82 patients with histologically proven NAFLD and to develop a clinical score for predicting NASH according to the area under the curve of receiver operating characteristics (AUC) of parameters. RESULTS: Four parameters [alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), C-reactive protein (CRP), and apolipoprotein B (ApoB)/apolipoprotein A1 (ApoA1) ratio] were significantly linked to NASH. The AUROCs of ALT, GGT, CRP, and ApoB/ApoA1 ratio for the prediction of NASH were 0.829, 0.892, 0.708, and 0.712, respectively. The AUROC of the combined clinical score for the prediction of NASH was 0.904 (95% CI, 0.885-1.002) at a cut-off of 3.8 points with a sensitivity of 90.2%, specificity of 87.0%, positive predictive value of 88.3%, and negative predictive value of 91.5%. CONCLUSION: In the present study, a clinical score was developed for the noninvasive prediction of NASH; the score was based on a combination of routine biochemical parameters and was useful in distinguishing NASH from NAFLD.
Subject(s)
Alanine Transaminase/blood , Apolipoproteins B/blood , C-Reactive Protein/metabolism , Diagnostic Tests, Routine/methods , Non-alcoholic Fatty Liver Disease/diagnosis , gamma-Glutamyltransferase/blood , Biomarkers/blood , Female , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Function Tests , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Predictive Value of Tests , ROC Curve , Retrospective Studies , Severity of Illness Index , UltrasonographySubject(s)
Cerebral Infarction/chemically induced , Forehead , Glucocorticoids/adverse effects , Retinal Artery Occlusion/chemically induced , Triamcinolone Acetonide/adverse effects , Vitiligo/drug therapy , Adolescent , Glucocorticoids/administration & dosage , Humans , Male , Triamcinolone Acetonide/administration & dosageABSTRACT
Objective This study is to investigate the inhibitory effect of Arsenic Trioxide ( As2O3 ) on salivary adenoid cystic carcinoma -2(ACC-2)cell xenografts and angiogenesis in nude mice .Methods The nude mice with ACC-2 cell xenografts were randomly distributed into four groups ,control normal saline ( NS) ,5-Fu group[5-Fu10 mg/(kg· d)],low-dose group[As2O32.5 mg/(kg· d)],and high-dose group[As2O3 5.0 mg/(kg· d)].0.2 mL NS or drugs were given by intraperitoneal injection for 10 days.Tumor volume and weight were measured ,the microstructure was observed by HE staining ,the expression of VEGF and MVD were detected by immunohistochemistry .Results The average tumor volume was significantly smaller and the average tumor weight was significantly lighter in As 2 O3 groups than in control groups ,especially in the high-dose group, the inhibitory rate were 52.17%and 56.04%(P<0.01).Compared with the control group,the MVD of treat-ment group was markedly decreased ,the pipe diameters were smaller in treatment group .The expression levels of VEGF and MVD were significantly lower in As 2 O3 groups than in control group , especially in the high -dose group.Conclusion As2O3 has obviously inhibitory effects on growth of ACC -2 cell xenografts and angiogenesis in nude mice by suppressing the expression of VEGF and MVD .The anticancer effect of As 2 O3 is related to the As2O3 concentration .
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Objective To investigate the expression and function of thymus and activation regulated chemokine (TARC) and its special receptor CCR4 at placenta villous in the first trimester placenta villous.Methods Placenta villous was collected from healthy women undergoing artificial abortion at 6 to 8 weeks of gestation,mRNA levels of TARC,CCR4 were analyzed using semi-quantitative reverse transcription (RT)-PCR methods.Immunohistochemistry assay was used to assess the protein localization and expression of TARC,CCR4.Additionally,extravillous cytotrophoblasts were isolated and cultured.Expression of TARC and CCR4 was measured by immunofluorescence assay.Invasion of cell line HTR8/SVneo was analyzed by transwell assay at concentration of 10,25,50 and 100 ng/ml of TARC matched with RPMI 1640 fetal bovine serum free eulture medium as control group.In the mean time,blocking experiment was also added to detect TARC regulating cell invasion,which were classified into four groups:control,100 ng/ml rhTARC,20 μg/ml anti-TARC + 100 ng/ml rhTARC,100 ng/ml rhTARC + 20 μg/ml IgG.The influence of 100 ng/ml TARC on expression level of integrin-α5 and integrin-β1 were measured by using western-blot assay.Results (1)In vivo assay:expression of TARC and CCR4 mRNA were detectable in first trimester placenta villous,TARC protein was localized in cytotrophoblasts,syncytiotrophoblasts and cell column especially on the distal portion,while CCR4 protein was localized on invading interstitial cytotrophobalsts.(2)In vitro assay:①TARC,CCR4 was also expressed in primary isolated extravillous cytotrophoblasts by immunofluorescence assay; ②Matrigel invasion assay demonstrated that TARC had specific dose dependent stimulatory effects on the cells invading through the matrigel precoated filter,the number of cells migration into the lower chamber were:142 ± 31 at 10 ng/ml group,161 ±46 at 25 ng/ml group,201 ±30 at 50 ng/ml group,312 ±48 at 100 ng/ml group,117 ± 33 at control group,the significant response observed from 25 ng/ml (P < 0.05)and reached a peak effect at 100 ng/ml (P < 0.01); ③Blocking experiment demonstrated that when trophoblast invasion was monitored in response to TARC neutralizing antibody (15 μg/ml) together with rhTARC 100 ng/ml.The stimulatory activity of rhTARC was completely overcome,with the cells invasion into the lower chambers were 100 ng/ml rhTARC,20 μg/ml anti-TARC + 100 ng/ml rhTARC,100 ng/ml rhTARC +20 μg/ml IgG,control:313 ±47,113 ±41,287 ±75 and 128 ±23,respectively;④Western-blot assay demonstrated that if cells were treated with 100 ng/ml rhTARC,the expression of integrin-α5 were significantly increased(P <0.01),integrin-β1 level also increased when compared with control(P <0.05).Conclusion TARC was expressed specifically at human fetal-maternal interface.Trophoblast invasion and migration mainly was regulated by up-regulation integrin-α5 and integrin-β1,which plays an role in trophoblasts differentiation and placentation.
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ObjectiveTo explore the biological features of colorectal adenoma with chicken-skin mucosa ( CSM ) and its clinical significance.MethodsExpression of cell proliferation markers ( Ki-67 and COX-2) and apoptosis-related factors ( survivin and caspase-3) in normal colorectal mucosa,colorectal adenoma without CSM,colorectal adenoma with CSM and colorectal adenocarcinoma were detected by immunohistochemistry SP method and enzyme-linked immunosorbent assay (ELISA).ResultsImmunohistochemical results revealed a decreased trend in expressions of Ki-67 and COX-2 from colorectal adenocarcinoma through colorectal adenoma with and without CSM to normal colorectal mucosa,while the expressions of survivin and caspase-3 showed an increased trend.By ELISA,the expressions of Ki-67,COX-2,surviving and caspase-3 showed no significant difference (P > 0.05 ) between colorectal adenoma with CSM and coloreetal adenocarcima,while these variables were significantly different (P < 0.05) between coloreetal adenoma with and without CSM,so as well between normal colorectal mucosa and other 3 groups.ConclusionThe biological characteristics of colorectal adenoma with CSM are different from those without,showing an activated cell proliferation and inhibited cell apoptosis with increased carcinogenesis risk.
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Objective To evaluate the application of plasma drug monitoring in pediatric HIV/AIDS patient antiretroviral therapy adherence monitoring.Methods Totally 261 plasma samples and related information were collected from three consecutive follow-up visits of 87 HIV-infected children treated in Shangcai county CDC of Henan province from March to October 2009.The plasma concentrations of antiretroviral drugs were measured by a developed high performance liquid chromatography-mass spectrometry method.Potential adherence influencing factors, such as regimen, age, gender, parent conditions, previous ART exposure and therapy duration, were analyzed by univariate logistic regression.Results Plasma concentration of antiretroviral drugs lower than LLTR (1 000 ng/ml) was the criteria to identify missed dose.The concentrations of 28 plasma samples were lower than LLTR, which meant missing dose.There were 17 patients (19.5%) with their concentrations lower than LLTR at least once in three follow-up visits.Logistic regression analysis of adherence related factors showed that compared with the children whose parents were both alive, the children whose mother and (or) father died were more likely to miss dose.The odds ratio was 4.13(95% credibility interval:1.37-12.46, P values was 0.012).Conclusions HIV-infected children have adherence problems when receiving antiretroviral therapy.Plasma therapeutic drug monitoring can be one of the effective methods to monitor the adherence.
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Objective To study the ability of adhesion, proliferation and differentiation of human adipose mesenchymal stern cells,which were cultured in PLGA,and thus to provide a basis for their in vivo implantation.Methods PLA was mixed with PGA in a ratio of 1∶ 1,and PLGA was obtained by insert moldling with organic solvents.In vitro, human adipose mesenchymal stem cells were adhered to PLGA.The attachment and the proliferation of human adipose mesenchymal stem cells in PLGA were analysed by scanning electron microscope,and the morphological change of the cells was investigated before and after induction.Results Human adipose mesenchymal stem cells were able to attach, proliferate and secrete extracellular matrix in porous PLGA (pore size:100~400 pm) with porosity of 85 %, and to differentiate into round lipoblast-like cells under the induction of adipose medium.After 14 days, the particulate of PLGA was overlaid by extracellular matrix .Conclusion Human adipose mesenchymal stem cells have the capacity to adhere to PLGA and proliferate, indicating that PLGA can be used as a carrier for human adipose mesenchymal stem cells in adipose tissue engineering.
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Objective:To study the effect of bone marrow stroma cell( BM SC) transplantation combined with multi-pore mineralization ossein(Bio-Oss) in the plerosis of mandibular defect.Methods:A round whole-layer defect in the diameter of 1.5 cm was created on each side of mandible in 16 whit e New Zealand rabbits.The rabbits were randomly divided into two groups.In group 1 BMSCs were collected and cultured with mineralization induce medium for 2 wee ks. Then cell suspension at the density of 5?10 7 /ml and gelatum were mixed a nd dripped into Bio-Oss bones, incubated in DMEM in 50 ml/L CO 2 incuba tor at 37 ℃ for 4-6 h.The BMSC-Bio-Oss was applied to make plerosis of the m andibular defects.In group 2 the defects were repaired with the Bio-Oss ossein only.Samples were collected after 8 and 12 weeks after opreation respectively an d observed with radiology and histology.Results:12 weeks after o peration, (1)in group 1 previous defects were basically consisted of new bone tissue;(2)in group 2 the previous defects were mainly consisted of fibrous tis sue. Conculsions:BMSC-Bio-Oss transplantation may effectively repair bone defect.