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@#Abstract: Objective To explore the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and insulin resistance (IR) in male patients with type 2 diabetes mellitus (T2DM) combined with metabolic-related fatty liver disease (MAFLD). Methods A total of 454 male patients with T2DM combined with MAFLD in National Metabolic Management Center (MMC) of the Affiliated Hospital of Jiangsu University from May 2018 to July 2020 were enrolled. The general clinical data of subjects were collected, blood routine and biochemical indexes were tested, homeostasis model insulin resistance index (HOMA-IR) was calculated, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured. Accordingtothe MHR quartile, patients were divided into group Q1 (MHR≤0.38), group Q2 (0.38<MHR≤0.48), group Q3 (0.48<MHR≤0.64) and group Q4 (MHR>0.64) to compare the differences in measured indicators above. In addition, patients were divided into two groups according to HOMA-IR, HOMA-IR<2.5 and HOMA-IR≥2.5, and the differences in MHR were compared. Results The patients were divided into four groups according to MHR:group Q1 (n=115), group Q2 (n=110), group Q3 (n=120) and group Q4 (n=109). Fasting insulin (FINS) were respectively 6.17(4.20,9.76), 7.73(4.94,10.66), 8.92(5.32,11.33) and 9.13(5.25,12.27) mU/L, 2-hour postprandial insulin were 22.75(12.87,39.59), 27.55(16.44,39.77), 30.98(17.46,43.11) and 31.28(18.54,45.92) U/L. HOMA-IR were 3.12(1.63,4.25), 3.72(2.26,4.66), 3.87(2.48,5.44) and 3.95(2.42,5.31). Neutrophil (Neu) were 3.10(2.60,3.70), 3.20(2.50,3.93), 3.60(2.80,4.28), 4.20(3.30,5.00)×109/L. Subcutaneous fat area (SFA) were (181.27±53.60), (192.64±62.41), (199.53±61.40) and (203.69±71.51) cm2. They all increased gradually. However, the levels of high-density lipoprotein cholesterol (HDL-c) [1.18(1.06,1.35), 1.02(0.86,1.17), 0.96(0.80,1.03) and 0.80(0.69,0.92) mmol/L] and low-density lipoprotein cholesterol (LDL-c) [(3.00±0.79), (2.76±0.83), (2.67±0.85) and (2.59±0.92) mmol/L] decreased gradually. Pearson's or Spearman's correlation analysis showed that MHR was positively correlated with FINS, 2-hour postprandial insulin (2hINS), HOMA-IR, VFA and SFA (r=0.190, 0.153, 0.184, 0.114, 0.127, P<0.05). The coronary heart disease history, systolic blood pressure,diastolic blood pressure,fasting plasmaglucose (FPG), FINS, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood uric acid (Ur), body mass index (BMI), VFA, SFA and MHR of patients in group HOMA-IR≥2.5 were higher than group HOMA-IR<2.5 (P<0.05). Conclusion MHR is positively correlated with IR in male patients with T2DM combined with MAFLD, and as MHR increases, the degree of IR is higher.
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OBJECTIVE@#To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).@*METHODS@#The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed.@*RESULTS@#The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections.@*CONCLUSION@#Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Subject(s)
Humans , Middle Aged , Aged , Aged, 80 and over , Multiple Myeloma/drug therapy , Retrospective Studies , Dexamethasone/therapeutic use , Antibodies, Monoclonal/therapeutic use , Bortezomib/therapeutic use , Renal Insufficiency/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
BACKGROUND@#Existing evidence suggests that fruit consumption is a significant influencing factor for chronic obstructive pulmonary disease (COPD), but this is unclear in the Chinese population. We examined the association of fresh fruit consumption with the risk of COPD-related hospitalization and death in a nationwide, population-based prospective cohort from China.@*METHODS@#Between 2004 and 2008, the China Kadoorie Biobank recruited >0.5 million adults aged 30 to 79 years from ten diverse regions across China. After excluding individuals diagnosed with major chronic diseases and prevalent COPD, the prospective analysis included 421,428 participants. Cox regression was used to calculate the hazard ratios (HRs) for the association between fresh fruit consumption and risk of COPD-related hospitalization and death, with adjustment for established and potential confounders.@*RESULTS@#During a mean follow-up of 10.9 years, 11,292 COPD hospitalization events and deaths were documented, with an overall incidence rate of 2.47/1000 person-years. Participants who consumed fresh fruit daily had a 22% lower risk of COPD-related hospitalization and death compared with non-consumers (HR = 0.78, 95% confidence interval [CI]: 0.71-0.87). The inverse association between fresh fruit consumption and COPD-related hospitalization and death was stronger among non-current smokers and participants with normal body mass index (BMI) (18.5 kg/m 2 ≤ BMI < 24.0 kg/m 2 ); the corresponding HRs for daily fresh fruit consumption were 0.78 (95% CI: 0.68-0.89) and 0.69 (95% CI: 0.59-0.79) compared with their counterparts, respectively.@*CONCLUSIONS@#High-frequency fruit consumption was associated with a lower risk of COPD in Chinese adults. Increasing fruit consumption, together with cigarette cessation and weight control, should be considered in the prevention and management of COPD.
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@#BACKGROUND: Cardiac arrest (CA) is a critical condition that is a concern to healthcare workers. Comparative studies on extracorporeal cardiopulmonary resuscitation (ECPR) and conventional cardiopulmonary resuscitation (CCPR) technologies have shown that ECPR is superior to CCPR. However, there is a lack of studies that compare the protective effects of these two resuscitative methods on organs. Therefore, we aim to perform experiments in swine models of ventricular fibrillation-induced CA to study whether the early application of ECPR has advantages over CCPR in the lung injury and to explore the protective mechanism of ECPR on the post-resuscitation pulmonary injury. METHODS: Sixteen male swine were randomized to CCPR (CCPR; n=8; CCPR alone) and ECPR (ECPR; n=8; extracorporeal membrane oxygenation with CCPR) groups, with the restoration of spontaneous circulation at 6 hours as an endpoint. RESULTS: For the two groups, the survival rates between the two groups were not statistically significant (P>0.05), the blood and lung biomarkers were statistically significant (P<0.05), and the extravascular lung water and pulmonary vascular permeability index were statistically significant (P<0.01). Compared with the ECPR group, electron microscopy revealed mostly vacuolated intracellular alveolar type II lamellar bodies and a fuzzy lamellar structure with widening and blurring of the blood-gas barrier in the CCPR group. CONCLUSIONS: ECPR may have pulmonary protective effects, possibly related to the regulation of alveolar surface-active proteins and mitigated oxidative stress response post-resuscitation.
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OBJECTIVE@#To compare the clinical efficacy of cupping treatment combined with antibiotics and antibiotics alone for bacterial pneumonia in children.@*METHODS@#A total of 72 children with bacterial pneumonia were randomly divided into an observation group (36 cases, 1 case dropped off) and a control group (36 cases). The children in the control group were treated with intravenous drip of cefodizine sodium [80 mg/(kg•d)] for 7 days. Based on the treatment of the control group, the children in the observation group were treated with cupping treatment on the bladder meridian of the back on the first day and the fourth day of antibiotic treatment; each cupping treatment was given for 5-10 min; the treatment of observation group was given for 7 days. The days for complete fever reduction, TCM syndrome scores and Canadian acute respiratory illness flu scale (CARIFS) scores before and after treatment were observed, and the clinical efficacy was evaluated.@*RESULTS@#The days for complete fever reduction in the observation group were shorter than that in the control group (@*CONCLUSION@#Cupping treatment combined with antibiotics has similar efficacy with antibiotics alone for bacterial pneumonia in children, but shows better effect in shortening the duration of fever and improving pulmonary symptoms.
Subject(s)
Child , Humans , Anti-Bacterial Agents , Canada , Cough , Cupping Therapy , Pneumonia, Bacterial , Treatment OutcomeABSTRACT
Background@#Acute kidney injury (AKI) frequently occurs in cardiopulmonary resuscitation patients. Studies comparing the effects of extracorporeal membrane oxygenation (ECMO) with conventional cardiopulmonary resuscitation (CCPR) on AKI were rare. This study aimed to compare the effects of ECMO with those of CCPR on survival rate and AKI and explore the underlying mechanisms in a swine model of cardiac arrest (CA).@*Methods@#Sixteen male pigs were treated with ventricular fibrillation to establish CA model and then underwent CCPR (CCPR group, n = 8) or ECMO during cardiopulmonary resuscitation (ECPR group, n = 8). The study endpoints were 6 h after return of spontaneous circulation (ROSC) or death. Serum and urine samples were collected at baseline and during the 6 h after ROSC. The biomarkers of AKI were detected by enzyme-linked immunosorbent assay. The apoptosis of renal tubular epithelial cells was discovered by transmission electron microscope (TEM) and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Apoptosis-related genes were detected by immune-staining and Western blotting. Data were compared by Student's t-test.@*Results@#All pigs in ECPR group were successfully resuscitated with a higher 6-h survival rate (8/8) compared to CCPR group (6/8). The expressions of AKI biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase2 (TIMP2), insulin-like growth factor-binding protein 7 (IGFBP7), liver fatty acid-binding protein (LFABP), and kidney injury molecule1 (Kim-1) were all increased along with the time after ROSC in both groups and lower in ECPR group compared with CCPR group. Especially, products of urinary TIMP and IGFBP levels (TIMP*IGFBP) were significantly lower at ROSC4 (0.58 ± 0.10 ng/ml vs. 1.18 ± 0.38 ng/ml, t = 4.33, P = 0.003) and ROSC6 (1.79 ± 0.45 ng/ml vs. 3.00 ± 0.44 ng/ml, t = 5.49, P < 0.001); urinary LFABP was significantly lower at ROSC6 (0.74 ± 0.06 pg/ml vs. 0.85 ± 0.11 pg/ml, t = 2.41, P = 0.033); and urinary Kim-1 was significantly lower at ROSC4 (0.66 ± 0.09 pg/ml vs. 0.83 ± 0.06 pg/ml, t = 3.99, P = 0.002) and ROSC6 (0.73 ± 0.12 pg/ml vs. 0.89 ± 0.08 pg/ml, t = 2.82, P = 0.016). Under light microscope and TEM, the morphological injures in renal tissues were found to be improved in ECPR group. Moreover, apoptosis was also alleviated in ECPR group.@*Conclusions@#Compared with CCPR, ECMO improves survival rate and alleviates AKI in a swine model of CA. The mechanism of which might be via downregulating AKI biomarkers and apoptosis in kidney.
Subject(s)
Animals , Humans , Male , Cardiopulmonary Resuscitation , China , Disease Models, Animal , Extracorporeal Membrane Oxygenation , Heart Arrest , Therapeutics , Swine , Ventricular FibrillationABSTRACT
For over last couple of decades, there has been a robust activity aimed towards the discovery of novel anti-cancer therapeutics. An approach to identify starting points for new drug candidates is high throughput screening of compound library collection. In this work, we describe the application of a Tetrazolium-based, 96-well small scale screening assay to screen a mini library of 19 compounds bearing Oxazolo[5,4-d]pyrimidine structures against human umbilical vein endothelial cells. Primary actives identified against HUVEC were retested and the IC50 value compounds were estimated for HUVEC. The screening program (Primary screening) identified 4 compounds with inhibition rate percentage ≥ 70% each. Retest screening of these compounds, taking into account criteria required for high cytotoxic compounds, afforded a panel of 1 compound for further biological analysis. This compound had IC50 value of 12.19µM, 12.16µM, 10.24µM, 20.43µM for HUVECs, SGC7901, MCF7, and HeLa respectively. Furthermore, a clonogenic assay was performed in order to confirm the cytotoxic activity of the selected compound on the survival and proliferation of MCF7. This compound was found to significantly effect the survival and proliferation of MCF7. Taken together, the selected compound, namely SCYJ32, was found to be highly cytotoxic against the numerous cell lines. Further studies are ongoing in order to unravel various mechanisms of action of this novel small compound.
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This study was amid to construct the pharmacophore model of L-type calcium channel antagonist in the application of screening Drugbank and TCMD. This paper repositions the approved drugs resulting from virtual screening and discusses the relocation-based drug discovery methods, screening antihypertensive drugs with L-type calcium channel function from TCMD. Qualitative hypotheses wre generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle. Datebase searching method was used to evaluate the generated hypotheses. The optimum hypothesis was used to search Drugbank and TCMD. This paper repositions the approved drugs and evaluates the antihypertensive effect of the chemical constituent of traditional Chinese medicine resulting from virtual screening by the matching score and literature. The results showed that optimum qualitative hypothesis is with six features, which were two hydrogen-bond acceptors, four hydrophobic groups, and the CAI value of 2.78. Screening Drugbank achieves 93 approved drugs. Screening TCMD achieves 285 chemical constituents of traditional Chinese medicine. It was concluded that the hypothesis is reliable and can be used to screen datebase. The approved drugs resulting from virtual screening, such as pravastatin, are potentially L-type calcium channels inhibitors. The chemical constituents of traditional Chinese medicine, such as Arctigenin III and Arctigenin are potentially antihypertensive drugs. It indicates that Drug Repositioning based on hypothesis is possible.
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Animals , Rabbits , Antihypertensive Agents , Chemistry , Pharmacology , Calcium Channel Blockers , Chemistry , Pharmacology , Calcium Channels, L-Type , Genetics , Metabolism , Drug Repositioning , Methods , Molecular Structure , Myocardium , MetabolismABSTRACT
To establish an HPLC-MS/MS method for the analysis of quercetin, kaempferid and isorhamnetin in rats plasma and study its pharmamacokinetics after an intragastrical administration of Hippophae rhamnoides extracts. Five healthy male Sprague-Dawley (SD) rats were given single doses of H. rhamnoides extracts (quercetin 26.35 mg x kg(-1), kaempferid 4.040 mg x kg(-1), isorhamnetin 31.37 mg x kg(-1)), and then their orbital sinus blood samples were collected at different time points. The drug plasma concentration of the three flavonoids was determined by HPLC-MS/MS method. After that, the main pharmacokinetics parameters were calculated by using Kinetica 5. 0. 11 software. The methodological test showed that the linear concentration ranges of quercetin, kaempferid and isorhamnetin were 7.500-600.0 μg x L(-1) (R2 = 0.998 5), 1.000-80.00 μg x L(-1) (R2 = 0.998 5 ) and 10.00-800.0 μg x L(-1) (R2 = 0.998 0), respectively. The inner and inter-days precisions were both less than 14.0%. The plasma samples showed a good stability and consistency with the requirement of biological sample analysis after the samples were frozen once and placed at - 20 degrees C for 15 d and room temperature for 6 h and the treated analytes were placed at -20 degrees C for 24 h. For quercetin, the pharmacokinetic parameter t(½β), AUC(0-∞), MRT(0.∞), C.(max) and T(max) were (113.3 ± 19.37) min, (12 542.14 ± 3 504.05) μg x h x L(-1), (119.6 ± 13.29) h, (164.6 ± 27.33) μg x L(-1) and (5.199 ± 0.840 3) h, respectively. For kaempferid, the pharmacokinetic parameters t(½β), AUC(0-t), MRT(0-∞), C(max) and T(max) were (79.85 ± 17.15) min, (934.51 ± 94.59) μg x h x L(-1), (81.50 ± 13.75) h, (80.15 ± 14.24) μg x L(-1) and (3.827 ± 0.902 7) h, respectively. For isorhamnetin, the pharmacokinetic parameters t1,2,, AUC(0-t), MRT(0-∞), C(max) and T(max) were (118.3 ± 20.73) min, (26 067.77 ± 4 124.60) μg x h x L(-1), (129.0 ± 16.30) h, (269.6 ± 29.32) μg x L(-1) and (6.513 ± 1.450) h, respectively. The HPLC-MS/MS analysis method established in this study was proved to be sensitive and accurate and could be applied in the pharmacokinetic study of quercetin, kaempferid and isorhamnetin in rat plasma.
Subject(s)
Animals , Male , Rats , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Pharmacokinetics , Hippophae , Chemistry , Kaempferols , Blood , Pharmacokinetics , Quercetin , Blood , Pharmacokinetics , Rats, Sprague-Dawley , Tandem Mass Spectrometry , MethodsABSTRACT
Objective: To explore the relationship between gender-specific of obesity indices and the 10-year risk for cardiovascular disease (CVD) among elderly population in southern Taiwan. Methods: Data were collected from Pingtung County in southern Taiwan through a health screening program, carried out from March 2007 to May 2008.The following obesity indices were included: (1) body mass index (BMI); (2) waist circumference (WC); (3) waist-to-hip ratio (WHR); (4) waist-height ratio (WHtR). The present study used the risk assessment tool of the Framingham Heart Study and adopted ≦10% as low risk, 11~20% as moderate risk, and >20% as high risk for CVD. Multiple logistic regression was used to predict the risk indices of obesity causing 10-year risk for CVD. Results: A total of 831 participants were recruited in the screen program. The prevalence of the obesity indices was as follow: BMI 21.3%; WC 14.6%; WHR 47.1%; and WHtR 65.2%. A total of 118participants were found to have 10-year CVD risk groupings>20%, a prevalence rate of 14.2%. The 10-year risk for CVD is higher in men; subjects≧65 years old in both genders have a higher prevalence of moderate and high risk for CVD. After using multiple logistic regression, the results showed that men who are abnormal in WHR, WHtR, have higher moderate and high 10-year risk for CVD; In this study, men didn't find this risk in BMI and WC. Women on all four obesity indices are not the predictive factors of 10-year risk for CVD. Conclusion: The predictive factors of 10-year risk for CVD were found in WHR and WHtR of men.
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Objective To investigate the predictive value of class Ⅲ β-tubulin protein expression in tumor tissue for the efficacy of taxol combined chemotherapy in stage Ⅲ s/Ⅳ gastric carcinoma patients.Methods Tumor biopsy samples were obtained and class Ⅲ β-tubulin protein expression were examined by immunohistochemical staining before chemotherapy.According to different expression of class Ⅲ β-tubulin,the patients were divided into two groups,group A(low expression of class Ⅲ β-tubulin),group B(high expression of class Ⅲ β-tubulin).The patients were assigned to be received 4 to 6 cycles of Taxol and S-1 chemotherapy regimens and followed up until death or lost.Response rate(RR),overall survival(OS)and time to tumor progression(TTP)were assessed.Results There was no significant difference in clinical characteristics among patients with different expression rate.The RR was higher and TIP was longer in group A than in group B(53.3 % vs 36.7 %,198 days vs 146 days,P < 0.05 respectively),and no significant differences of OS in two groups(P > 0.05).Conclusion The expression level of class Ⅲ β-tubulin in tumor tissue is probably a predictor for the efficacy of taxol in gastric cancer patients,taxol combined chemotherapy is more suitable for patients with lower expression of class Ⅲ β-tubulin.
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To investigate the radiosensitizing effects of dihydroartemisinin [DHA] and its underlying mechanisms in cervical cancer cells. This experimental study was conducted between May 2009 and August 2012 in the School of Radiation Medicine and Protection, Soochow University, Suzhou, China. HeLa and Siha cells were assigned as the control group and DHA as treated group. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-2H-tetrazolium bromide [MTT] assay, clonogenic assay, cell cycle analysis, and apoptosis analysis were carried out in 2 cell lines of both groups. The inhibitory effect of DHA on the HeLa and Siha cell lines was dependent on both concentration and time. Dihydroartemisinin increased the radiosensitivity of HeLa cells, but not of Siha cells. Apoptosis and the gap2/mitosis [G2/M] phase transition induced by x-irradiation was enhanced by DHA treatment in HeLa cells. Irradiation, combined with DHA, decreased Wee1 expression while increasing Cyclin B1 expression in HeLa cells. Dihydroartemisinin potently abrogates G2 checkpoint control in HeLa cells. It can relieve the G2/M arrest induced by irradiation; thus, it can be used as an effective radiosensitizer, which will probably promote the entry of more irradiation-damaged cells into mitosis
Subject(s)
Uterine Cervical Neoplasms , Cell Cycle , HeLa Cells , Radiation-Sensitizing AgentsABSTRACT
Purpose: To develop Taqman fluorescence quantitative polymerase chain reaction (PCR) method for investigating the characteristics of the distributions of Ureaplasma urealyticum (UU) biovars and to explore the relationship between UU biovars and antimicrobial resistance. Materials and Methods: By the method of culture, Ureaplasma species were detected. Taqman fluorescence quantitative PCR for detecting UU biovars were developed and UU clinical isolates were detected to distinguish biovars. The broth micro-dilution susceptibility testing methods were used to determine UU susceptibility. Results: By Taqman PCR method, UU biovars was successfully detected. Of 126 samples, biovar 1 was found in 73 (57.94%). There was a statistical difference between genital-urinary tract infection group and asymptomatic group (P<0.05). In the region, UU biovar 1 to 9 kinds of agents kept higher susceptibility rates, but biovar 2 maintained higher susceptibility rates only to tetracyclines. Compared with biovar 1, UU biovar 2 resistance rates to 7 kinds of agents were higher (P<0.05). Conclusions: (1) Our new established Taqman PCR method is a useful tool for screening UU biovars. (2) UU biovar 1 predominated in asymptomatic population; whereas in genital-urinary tract infection population UU biovar 2 had a higher proportion. (3) The characteristics of drug resistance were different between UU biovars. Overall, both two biovars remained higher susceptibility rates to tetracyclines. A majority of biovor 1 strains were sensitive to macrolides and quinolones; while only a small number of biovar 2 strains kept sensitive to roxithromycin and quinolones, a large proportion of biovar 2 strains were found in intermediate ranges.
Subject(s)
Bacterial Typing Techniques , Drug Resistance, Bacterial , Female , Humans , Male , Microbial Sensitivity Tests , Polymerase Chain Reaction/methods , Ureaplasma urealyticum/classification , Ureaplasma urealyticum/drug effects , Ureaplasma urealyticum/geneticsABSTRACT
Objective To evaluate the value of serum tumor markers in diagnosis of over 80 years old patients with colorectal cancer.Methods Serum CA199,CA242 and CEA of 68 cases senile patients with colorectal cancer and 35 cases senile patients with benign large intestinal diseases were detected by ELISA.Results Serum levels of CA199,CA242 and CEA in patients with colorectal cancer were (37.95 ± 15.95 ) U/ml,( 50.08 ± 24.20 ) U/ml,( 22.34 ± 17.35 ) μg/L respectively and were significantly higher than that in patients with benign large intestinal diseases CA199 ( 10.73 ± 6.27 ) U/ml,CA242 ( 8.00 ± 3.52 ) U/ml,CEA(2.32 ± 1.01 )μg/L.In addition,the level of these three markers was increased with the progress of colorectal cancer and the sensitivity of diagnosis was related with the stages of colorectal cancer.Parallel combined testing methods increased the diagnostic sensitivity to 83.6%,and serial combined testing increased the diagnostic specificity to 88.7 %.Conclusions Serum tumor markers showed certain values in the diagnosis of the senile patients with colorectal carcinoma.Furthermore,the combined determination of tumor markers is helpful for early diagnosis of colorectal cancer and increases the sensitivity and specificity in diagnosing of colorectal carcinoma.
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Objective To detect epidermal growth factor receptor (EGFR) 19, 21 exon gene mutation and gene copy number in lung adenocarcinoma tissue, and to analyze the relationship of EGFR 19, 21 mutation with copies number. MethodsEGFR mutations and gene copy number in the tissue samples embedded by paraffin and fixed by for marlin from 58 cases of lung adenocarcinoma were detected by RT-PCR and FISH. The statistical data were analyzed by chi-square test.ResultsOf 58 cases, the overall single mutation rate of EGFR exon 19, 21 was 43.1% (25/58), and 2 cases contained both types of the mutation.The overall FISH positive rate of EGFR was 51.7 % (30/58), including 8 positive amplification and 22 highly ploidy amplification. The testing results showed that there had no statistically differences in FISH positive rates of EGFR mutation among different differentiation lung adenocarcinoma tissues(P >0.05), and the FISH positive rates of EGFR mutation in poorly differentiated cancer were lower than those in moderatedly differentiated and well-differentiated cancer (P <0.05). EGFR mutation was closely related to EGFR gene copies (P <0.01). ConclusionThere are high EGFR mutation frequencies and FISH positive rates in lung adenocarcinoma tissue; Combined detection of EGFR mutation and gene copy number may provide a better approach in selecting patients who may benefit from anti-EGFR target therapy.
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<p><b>OBJECTIVE</b>To study the pulmonary toxicity to rats induced by different sized SiOz particles.</p><p><b>METHODS</b>One hundred and five male SD rats were divided into seven groups randomly according to their weight. Experimental rats were exposed to 20, 50, 80, 140, 280 and 800 nm SiO2 particles at the dose of 400 mg/m3 by inhalation for 2 hours respectively. The control group was exposed without SiO2 particles. At the 24th, 48th, 72th hour after exposure, five rats were sacrificed at each time point and the total cellular scores, total protein, lactate dehydrogenase (LDH) in BALF and the histopathological changes in lungs were observed.</p><p><b>RESULTS</b>The total cellular score, total protein and lactate dehydrogenase in bronchoalveolar lavage fluid (BALF) of all experimental groups were higher than the control group. Between 800 nm group and the control group, there were no significant changes in total cellular sare, total protein and LDH in BALF (P > 0.05). At 48 h, the total cellular score of 280 nm group had no significantly change compared with the control group, but the total protein and LDH in BALF of 280 nm group were significantly higher than the control group (P < 0.05). The total cellular score at 24 h and the total protein at 24, 48 h had no significantly changes compared with the control group, but other indexes of 140 nm group were significantly higher than the control group. All the indexes of the 20, 50, 80 nm group were significantly higher than the control group (P < 0.05), and higher than 800 nm group mostly time. The TCS, total protein and LDH in BALF increased firstly and then reduced. The experimental group visible part pulmonary alveolus gap varying degree proliferation accumulation, its periphery has massive phlogocyte accumulation,such as granular cells and macrophage.</p><p><b>CONCLUSION</b>Under this condition ,the SiO2 particles can cause lung damage more serious with the smaller diameter SiO2 particles. As time going on, the damage caused by SiO2 particles is not so serious as before.</p>
Subject(s)
Animals , Male , Rats , Bronchoalveolar Lavage Fluid , Cell Biology , Cell Count , Inhalation Exposure , Lung , Metabolism , Pathology , Nanoparticles , Toxicity , Particle Size , Rats, Sprague-Dawley , Silicon Dioxide , ToxicityABSTRACT
To investigate the effects of β-elemene on the ANG β -AT1 receptor pathway in rats with liver fibrosis,a model of hepatic fibrosis was induced by hypodermical injection of carbon tetrachloride (CCl4) into Wistar male rats.β-elemene was intraperitonealy administered into the rats for 8 weeks (0.1 mL/100 g body weight per day).Masson staining was used to observe the liver fibrosis of rats and liver functions were measured by enzymatic kinetic analysis.The content of hydroxyproline in liver tissues was detected by specimen alkaline hydrolysis.The level of plasma ANG Ⅱ in bloodplasma was detected by radioimmunoassay.The expression of AT1R in rat liver were measured using reverse transcriptional-polymerase chain reaction and immunohistochemistry respectively.The results showed that β-elemene could reduce the collagen disposition in liver and inhibit the progression of liver fibrosis.In addition,the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis were also suppressed by β-elemene.It is concluded that the ANG Ⅱ -AT1 receptor pathway plays an important role in the development of hepatic fibrosis and β-elemene could down-regulate the levels of plasma ANG Ⅱ and the expression of hepatic AT1R in rats with liver fibrosis.
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<p><b>OBJECTIVE</b>To test the infeciton efficiency of recombinant adenoviral vector carrying HBsAg-HSP70 chimeric gene and to abserve its biological characteristics.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMC) were separated from healthy blood donor and they were infected by Ad-HSP70-HBsAg on the first day of isolation. DCs were induced in medium with cytokines IL-4, GM-CSF and TNF-alpha in vitro. The biological characteristics of DC induced were analyzed by inverted fluorecent microscope, RT-PCR, flow cytometer (FACS), and mixed lymphocyte reaction (MLR).</p><p><b>RESULTS</b>The traced gene-GFP were abserved in DCs by inverted fluorecent microscope and HSP70-HBsAg gene mRNA expression was detected by RT-PCR after the Ad-HSP70-HBsAg infection. FACS analysis shown that the expression of CD1a, CD80, CD86 and HLA-DR on surfece of two groups of DCs were similar. MLR showed that there are not a statitic difference of stimulated index (SI) between two groups.</p><p><b>CONCLUSION</b>Results indicated that Ad-HSP70-HBsAg can effectively infected DCs without affecting its biological characteristics.</p>
Subject(s)
Humans , Adenoviridae , Genetics , Physiology , Cells, Cultured , Cytokines , Genetics , Allergy and Immunology , Dendritic Cells , Allergy and Immunology , Virology , Genetic Vectors , Genetics , HSP70 Heat-Shock Proteins , Genetics , Allergy and Immunology , Hepatitis B Surface Antigens , Genetics , Allergy and Immunology , Lymphocyte Culture Test, Mixed , Recombinant Fusion Proteins , Genetics , Allergy and ImmunologyABSTRACT
Objective To investigate the effects ofamiodarone (AMD) on simvastatin (SV) in human liver microsomes and the possible underlying mechanisms. Methods Time-, NADPH- and concentration-dependent inhibitions were tested in HLM. The logarithm of relative inhibition values was plotted versus preincubation time (0, 5, 10, 15, 20min) for a series concentration of AMD used (0, 2, 5,25, 50 μ mol/L), and the slopes determined by linear regression. These slope values represente the observed inactivation rate constants (kobs). A double-reciprocal plot was then constructed using the reciprocal of the ko~ (y-axis) and the reciprocal of the associated inhibitor concentration (x-axis) to estimate the values ofkinact and K, which were two principal kinetic constants that were specific for mechanism-based inhibition (MBI).drug-drug interactions (DDI) potential was predicted based on in vitro data and by using the in vitro-in vivo extrapolation. Results The time-, concentration- and NADPH-dependent charactga'istics confirmed that when SV was the substrate of CYP3A4, the inhibition of AMD to CYP3A4 is MBI. Kj and kinact value were calculated to be 5.1 μ mol/L and 0.018min-1 The Clint of SV was reduced 2.96-5.63 fold when it was administrated with AMD. Conclusion Based on the results, AMD would inhibit SV metabolism via the mechanism-based manner, which would lead to DDI when they are taken together. Careful clinical observation is recommended when AMD and SV have to be simultaneously prescribed.
ABSTRACT
<p><b>OBJECTIVE</b>To detect the PAX3/PAX7-FKHR fusion transcripts to identify genetic alteration in embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) tissues.</p><p><b>METHODS</b>One-step reverse transcription- polymerase chain reaction (RT-PCR) were used to detect the expression of the PAX3/PAX7-FKHR fusion transcrips in 16 cases of rhabdomyosarcoma (7 cases of ARMS, 9 cases of ERMS) and 16 specimens were compared to the surrounding normal tissue. Comparative genomic hybridization (CGH) was employed to detect the genomic imbalance (DNA loss or amplification) in 16 RMS cases.</p><p><b>RESULTS</b>PAX3-FKHR fusion transcripts were positive in 3/7 and PAX 7-FKHR fusion transcripts were positive in 2/7 of ARMS patients, respectively, and were all negative in ERMS and Control tumors. There were different chromosome variations for each RMS, chromosome amplification was frequently seen in 1p36 (69%), 5q32 (56%), 8q21 (63%), 13q14 (69%), 19q (63%), 20q (56%). Chromosome loss was frequently seen in 3p21-pter (56%), 9p23-pter (50%), 10q (69%), 16/16q24 (56%).</p><p><b>CONCLUSION</b>One-step RT-PCR assay for detection specific fusion gene provides a useful tool for confirmation of the diagnosis of RMS in diagnostically difficult cases and in retrospective studies. Chimeric gene transcript resulting from specific chromosomal translocations is a reliable index for the molecular diagnosis of RMS.</p>