Calomel is a common traditional Chinese medicine (TCM) containing mercury in clinical external application. Although the toxicity of calomel has attracted concern, there is no unified standard yet in clinical external application. Risk assessment is used for evaluating the potential health effects of hazardous substances. The purpose of this article was to evaluate the health risk of calomel in clinical external application on the basis of toxicity data, to ensure safe and rational application of TCM containing calomel. The toxicity data of transdermal administration of calomel or mercurous chloride were collected by searching the literature. The daily maximum exposure dosage of calomel in clinical external application was estimated by following the four procedures of risk assessment, and Margin of Safety (MOS) as an evaluation indicator was then calculated to evaluate the safety of calomel on clinical application. It has been reported that the adult in single transdermal administration of calomel at 1. 5 g was lethal. Based on the LOAEL of calomel for long-term transdermal exposure (1 month) in rats was 0.096 g · kg(-1) · d(-1), the NOAEL of calomel for patients (about 60 kg) by external application within 2 weeks was estimated to be 1.46 mg · kg(-1) · d(-1). When MOS value equals to 1, the daily maximum exposure of calomel in clinical external application within 2 weeks was calculated to be 1.1 g. The results suggest that daily single dose of calomel in clinical external application should be lower than 1.5 g for adults, and more attention should be paid to changes in hepatic and renal function of patients when repeated dose more than 1.1 g within 2 weeks. The approach of risk assessment could be helpful in rational application of TCM containing mercury.
Animals ; Humans ; Medicine, Chinese Traditional ; Mercury Compounds ; toxicity ; No-Observed-Adverse-Effect Level ; Rats ; Risk Assessment

Objective:To observe and identify the inhibitory effect of oncostatin M (OSM) combined with dacarbazine (DTIC) on mouse melanoma cells B16 in vitro and in vivo. Methods:The inhibitory effect of OSM combined with DTIC on the proliferation and apoptosis of B16 melanoma cell line B16 were determined through MTT assay and flow cytometry, respectively. The change in nu-cleus morphology of B16 cells was observed under a fluorescence microscope by Hoechst staining method. The effects of single agents OSM and DTIC, as well as OSM-DTIC joint treatments, on tumor in mice in vivo were observed by inoculating B16 cells into C57 BL of six mice. Results:The OSM, DTIC, and combined OSM-DTIC treatments inhibited the proliferation of B16 cells by (11.2±2.3)%, (25.3±4.6)%, and (32.5±3.8)%, respectively (P<0.05). Apoptosis of B16 occurred at (1.32±0.42)%, (10.64±2.13)%, and (15.86±2.76)%, respectively (P<0.05). Cell morphology showed a significant increase in nuclear fragmentation, as proven by OSM-DTIC combined treatment. In the in vivo experiment, DTIC caused an apparent inhibition on the growth of mouse melanoma compared with the control group, and the joint treatment showed that the addition of OSM enhanced the tumor suppression effect of DTIC. Conclusion: OSM combined with DTIC has a synergistic effect that inhibits proliferation and apoptosis of B16 in vitro. This approach suggests a new po-tential treatment for melanoma.

Objective To analyze the predictive value of N-terminal B-type natriuretic peptide precursor(NT-proBNP) on auricular thrombosis in patients of coronary heart disease (CHD) combined with atrial fibrillation (AF).Methods The clinical data of 124 patients of CHD combined with AF were analyzed retrospectively.All patients were divided into research group (60 cases,compliance with auricular thrombosis) and control group (64 cases,non-compliance with auricular thrombosis),according to the occurrence of auricular thrombosis.The values of NT-proBNP,fasting plasma glucose (FPG),postprandial plasma glucose(2 h PG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),oxidized low density lipoprotein (ox-LDL),high sensitivity C reactive protein (hs-CRP) and left ventricular ejection fraction (LVEF),left ventricular end diastolic diameter (LVEDd) and left atrial diameter (LAD) were detected and compared between two groups.The relative factors to the occurrence of auricular thrombosis were confirmed by multivariate Logistic analysis.The best cutoff point of NT-proBNP was confirmed by the areas under the receiver operating characteristic curve (ROC).Results The values of NT-proBNP,ox-LDL,hs-CRP,LVEDd and LAD in research group were higher than those in control group [(4 312.6 ± 209.1) pmol/L vs.(3 421.6 ± 156.8) pmol/L,(4.0 ± 0.9) mmol/L vs.(3.4 ± 0.8) mmol/L,(7.4 ± 1.3)mg/L vs.(5.8 ± 1.0) mg/L,(74.3 ± 6.8) mm vs.(58.1 ± 5.5) mm,(39.6 ± 4.3) mm vs.(32.5 ± 3.8) mm],LVEF and HDL-C were lower than those in control group [(48.2 ± 3.1)％ vs.(57.3 ± 3.8)％,(0.72 ± 0.16)mmol/L vs.(1.08 ±0.27) mmol/L],and there were significant differences (P ＜0.05).There were no significant differences in the values of FPG,2 h PG and TC between two groups (P ＞ 0.05).Multivariate Logistic analysis showed that NT-proBNP and LAD were independent factors to the occurrence of auricular thrombosis (P =0.009,0.028).There was significant difference in the occurrence of auricular thrombosis between patients with NT-proBNP ＞ 4 250 pmol/L and patients with NT-proBNP≤4 250 pmol/L (P =0.028).Conclusion NT-proBNP is an independent predictor for the occurrence of auricular thrombosis to patients of CHD combined with AF.

Objective To assess the effect of video-assisted thoracoscopic thymectomy in treatment of myasthenia gravis (MG) and the factors associated with clinical efficacy. Methods 183 patients with MG who underwent video-assisted thoracoscopic thymectomy from January 2011 to May 2016 were enrolled, and the clinical data were retrospectively analyzed. Therapeutic efficacy was evaluated based on the MGFA. Furthermore, the potential factors associated with the clinical efficacy were analyzed using univariate analysis and Cox's proportional hazards regression model. Results 173 in 183 patients completed the whole follow-up. Among whom, 115 patients achieved complete stable remission (66.5%), 13 patients achieved pharmacologic remission (7.5%), 2 patients achieved minimal manifestations (1.2%), 20 patients had no changes (11.6%), 8 patients showed recurrent MG (4.6%), and 3 patients died (1.7%). Further analysis shown age (RR = 1.53, P = 0.031), pathological type of thymus (RR = 5.84, P = 0.022) and MGFA classification (RR = 3.72, P = 0.028) were main factors associated with the therapeutic efficacy. Conclusions Thoracoscopic expand resection is effective in the treatment of MG patients with satisfactory therapeutic efficacy, and age, pathological type and MGFA type were the main factors associated with the therapeutic efficacy.

Objective To evaluate ischemia preconditioning (IP) and intermittent ischemia (II) in ameliorating the incidence of paraplegia. MethodCross clamping of the infrarenal aorta in New-Zealand rabbit was used to establish a spinal cord ischemia model. 25 rabbits were randomly divided into 3 groups. The continuous ischemia(CS) group (n=10) with the aorta clamped for 40 minutes. While in the IP group (n=6) the aorta was clamped for 3 sessions each lasting for 5 min, with 5 min interval between the sessions before 40 minutes clamping, in the Ⅱ group (n=9) the 40 min clamping was interposed by a 15 min interval. The muscle force of the lower extremity, the excitatory amino acid (EAA) in CSF, the malondiadehyde (MDA)in spinal cord and the pathology were compared between the groups.Result The muscle force of the lower extremity was better in Ⅱ and IP group than that in CS group (3.4?1.0) in Ⅱ, (3.5?0.8) in IP vs (1.3?1.4) in CS, all P

Adult ; Aged ; Cantharidin ; therapeutic use ; Carcinoma, Hepatocellular ; therapy ; Embolization, Therapeutic ; Female ; Humans ; Liver Neoplasms ; therapy ; Male ; Middle Aged ; Portal Vein ; Treatment Outcome

Objective To study the characteristics of pharmacokinetics and pharmacodynamics of insulin dry powder inhalation and its relative bioavailability as compared with subcutaneous injection of regular insulin. Methods In this open,single-center,randomized,two-period,cross-over,euglycemic glucose clamp study,18 healthy volunteers(14 men and 4 women),aged(24.9?1.7)years,with body mass index(20.6?1.2)kg/m~2, received the insulin dry powder inhalatin(80 U)or regular insulin(15 U)subcutaneous administration.The blood samples of this study at 0,20,30,40,50,60,70,80,90,100,110,120,135,150,165,180,195, 210,225,240,270,300,330,360,390,420,450 and 480 rain were taken for serum insulin measurement, meanwhile,glucose infusion rates(GIR)were determined per 5 minutes over a period of 8 hours.Results The C_(max)were(57.9?17.8 vs 114.5?29.7)mU/L(tested vs reference preparation),T_(max)were(46.7?45.6 vs 107.8?33.7)min,GIR_(max)were(3.35?0.98 vs 5.17?1.75)mg?kg~(-1)?min~(-1)and T_(GIRmax)were(88.3?17.0 vs 151.9?34.6)min.The relative bioavailability was(10.26?2.25)%,and the relative bioefficacy was(14.33?7.26)%.Conclusion The study shows that insulin dry powder inhalation is absorbed via lungs and its action sets in earlier than that of the regular insulin injected subcutaneously.These pharmacokinetie and pharmacodynamic data may provide a reliabe guide for further clinical trial.

Objective To investigate the relation between retinol binding protein-4(RBP4) levels and metabolic parameters and to explore the correlation between RBP4-G 803 A SNP and metabolic syndrome.Methods One hundred and sixteen metabolic syndrome(MS) patients with type 2 diabetes mellitus and 93 healthy controls were included.Serum RBP4 level was measured by RIA.RBP4-G 803 A different genotypes were examined by PCR and sequence analysis.Results RBP4 levels showed significant positive correlations with BMI,waist circumference,FINS,HOMA-IR,and TG in all the participants,with TG,TC,and LDL-C in control,with DBP in males,and with age,FINS,HOMA-IR,TG and SBP in females.In multiple stepwise regression analysis,RBP4 was independently associated with BMI,waist circumference,TG and age.Serum RBP4 concentrations were significantly higher in MS group than in control.RBP4 levels were higher in males as compared to females.In control,RBP4 level was lower in subjects with regular exercise.There was no significant difference in the frequency of RBP4-G 803 A genotypes and alleles in MS group and neither difference in metabolic parameters between the carriers of GG+GA and AA.Conclusion In Chinese Han population,serum RBP4 concentrations are correlated with various metabolic parameters and there is no relation between RBP4-G 803 A SNP and metabolic syndrome.

Objective To characterize the association of adiponectin,leptin and free fatty acids(FFA)with adiposity,insulin resistance,lipid profiles and inflammatory markers in type 2 diabetes.Methods We measured fasting serum adiponectin,leptin,FFA,high-sensitive C reactive protein(hs-CRP) levels and metabolic parameters in 77 cases of type 2 diabetic patients with or without obesity and 26 healthy subjects.Results Following parameters were significantly higher in type 2 diabetic patients than in healthy subjects: fasting serum leptin(?g/L)(4.5?3.9 vs 4.1?2.1),hsCRP(mg/L)(0.69?1.07 vs 0.33?0.47),FFA(?mol/L)(566?227 vs 391?129) and triglyceride(mmol/L)(1.61?1.02 vs 1.01?0.40);however,following parameters were significantly lower in type 2 diabetic patients than in healthy subjects: serum adiponectin(mg/L)(5.5?3.4 vs 9.1?4.1),highdensity lipoprotein cholesterol(HDL-C)(mmol/L)(1.22?0.27 vs 1.48?0.26), apolipoprotein AI(mmol/L)(1.35?0.19 vs 1.49?0.18) and apolipoprotein AII(mmol/L)(0.29?0.07 vs 0.34?0.06) concentrations(P

Objective To detect the expression of FoxO1 and FoxO3a in liver and muscle tissue from KKAy diabetic mice.Methods Study group consists of 7 KKAy diabetic mice until 12 weeks,thereafter fed high fat diet for 4 weeks.It was diagnosed as diabetes when blood glucose was more than(16.7 mmol/L) in two consequent weeks.Control group consists of 7 C57BL mice 16 week old.Dispatched the mice and took quadriceps of femoris muscle and liver tissue to detect the FoxO1 and FoxO3a protein expression by Western blot with antibody.Results Liver and muscle FoxO1 expression was higher in KKAy diabetic mice than that in C57BL mice.FoxO3a expression was much higher in liver than in muscle in both groups.Muscle FoxO3a expression was higher in KKAy diabetic mice than that in control mice.Conclusion FoxO1 and FoxO3a in liver and muscle expressed differently in diabetic mice and control mice.They may play a role in mechanisms of insulin resistance and type 2 diabetes mellitus.