OBJECTIVETo investigate the effects of angiotensin converting enzyme inhibitor (ACEI) captopril on Calpain-mediated cardiomyocytes apoptosis and cardiac function in diabetic rats.

METHODSThirty adult male SD rats were randomly divided into 3 groups (n = 10), normal control group (NC group), diabetes mellitus group (DM group)and captopril treated group (Cap group). Streptozocin (STZ) were used to make the model of diabetes mellitus, captopril was administrated by gavage at the dose of 50 mg/kg every day, while in NC group and DM group the same volume of normal saline was administrated. Twelve weeks later, left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVDEP), maximal rise rate of left ventricular pressure (+ dp/dtmax) and maximal fall rate of left ventricular pressure (- dp/dtmax) were detected; Western blot was used to detect the expression of Calpain-1 Calpain-2, Bcl-2, Bax and total Caspase3 protein; apoptosis index (AI) were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL).

RESULTSCompared with NC group, LVDEP was significantly higher; LVSP, + dp/dtmax and - dp/dtmax were significantly decreased (P < 0.05); Bcl-2 protein expression was decreased; the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were increased; the value of AI was significantly increased. Compared with DM group, LVDEP was significantly lower; LVSP, + dp/dtmax and - dp/dtmax were significantly increased (P < 0.05); Bcl-2 protein expression was increased, the expression of Calpain-1, Calpain-2, Bax and total Caspase3 protein were decreased; the value of AI was significantly decreased (P < 0.05).

CONCLUSIONCaptopril can protect diabetic myocardial structure through inhibiting activation of Calpain-1 and Calpain-2, up-regulating the expression of Bcl-2, down-regulating the expression of Bax to inhibit Caspase3 dependent apoptosis, thereby improving the ventricular function and myocardial structure.

Angiotensin-Converting Enzyme Inhibitors ; pharmacology ; Animals ; Apoptosis ; drug effects ; Calpain ; metabolism ; Cardiomyopathies ; pathology ; Caspase 3 ; metabolism ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; physiopathology ; Male ; Myocytes, Cardiac ; cytology ; drug effects ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; metabolism

Chromogranin A (CGA) is a soluble protein existed in most secreted cells and neurons. It was recently found that the bovine CGA N terminal region has vasoinhibitory, antibacterial and antifungal activities. Since the need for effective antifungal agents increases in parallel with the expanding number of immunocompromised patients at risk for fungal infections, it becomes imperative to find antifungal compounds with low toxicity toward mammalian cells. To study the antifungal activity of CGA N terminal region, the DNA fragment encoding for the N terminal 1-76 amino acid sequence (CGA1-76) of human CGA was amplified by PCR technique. After DNA sequence analysis, the amplified DNA fragment was cloned into the Bacillus subtilis inducible and expression vector pSBPTQ constructed in this study and the resultant plasmid pSVTQ was then transformed into triple-protease deficient Bacillus subtilis strain DB403 competent cells. The transformants was screened on LB plates containing 10 microg/mL kanamycin. The positive transformant DB403 (pSVTQ) was grown on kanmycin containing 2 x MSR medium and sucrose was added to 2% final concentration for induction after 2h cultivation. The culture supernatant was used to run SDS-PAGE. The result of SDS-PAGE showed that the CGA1-76 was expressed by sucrose induction and the expressed product secreted into the medium with a yield of 5 mg/L. The expressed product reacts specifically with mouse anti CGA47-68 monoclonal antibody. The antifungal activity of the expressed product was examined by adding the culture supernatant to the fungal spore or Candida albican suspensions at appropriate proportion and found that the recombinant human CGA1-76 produced in Bacillus subtilis inhibits the growth of Fusarium sp. Alternaria sp. and Candida albican at the concerntration of 4 micromol/L. These results demonstrate that human CGA1-76 has expressed in Bacillus subtilis and the expressed product is immunogenic and has the antifungal activity.
Amino Acid Sequence ; Animals ; Antifungal Agents ; pharmacology ; Bacillus subtilis ; genetics ; metabolism ; Base Sequence ; Chromogranin A ; biosynthesis ; genetics ; pharmacology ; Cloning, Molecular ; DNA ; genetics ; Humans ; Mice ; Molecular Sequence Data ; Recombinant Proteins ; biosynthesis ; genetics ; pharmacology

OBJECTIVEThe aim of this retrospective investigation was to explore the influence of femoral osteoporosis on short-term curative effects of cementless hip arthroplasty and to evaluate the femoral metaphyseal bone mineral density (BMD) for femoral osteoporosis in order to guide prosthesis choice and rehabilitation.

METHODSWe performed 127 total arthroplasty operations between June 1999 to February 2003 and investigated 49 cementless hip replacements with the Metalcancellous cementless Lubeck II system being used in all hips. There were twenty men and twenty-nine women whose mean age at the time of the operation was 60 years (range, 52~81 years). The patients were divided into osteoporosis or normal groups according to the femoral metaphyseal BMD measured preoperatively. The average duration of follow-up was 30 months (range, 8~52 months). We evaluated all of the patients from a clinical standpoint with use of a standard-terminology questionnaire with respect to the short-term curative effects and patients' satisfaction. Hip pain status and functional ability were important indicators of treatment efficacy.

RESULTSHarris hip score and patients' satisfaction in femoral osteoporosis patients who underwent noncemented hip arthroplasty were lower (P=0.004, P=0.03) while the incidence of thigh pain was higher (P=0.03) than the patients with non-osteoporosis.

CONCLUSIONThe higher incidence of pain, as well as the decrease in function experienced by the patients in osteoporosis group, supports the case that cementless arthroplasty is not a better choice for those patients and that we had better select prosthesis based on the femoral metaphyseal BMD.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement, Hip ; adverse effects ; methods ; Bone Cements ; Bone Density ; Female ; Femur ; metabolism ; surgery ; Femur Head Necrosis ; metabolism ; surgery ; Hip Fractures ; metabolism ; surgery ; Hip Prosthesis ; adverse effects ; Humans ; Male ; Middle Aged ; Osteoarthritis ; metabolism ; surgery ; Osteoporosis ; metabolism ; surgery ; Pain ; etiology ; physiopathology ; Retrospective Studies

OBJECTIVETo investigate the fibrogenetic effects induced by rush-mat dust in rats.

METHODSSD rats were treated with 50 mg of rush-mat dust per rat by intra-tracheal instillation, sacrificed 3, 6, and 12 months respectively after exposure. The lung tissue and lung lymph-node were taken out for pathological and electron microscopic examination. The content of collagen and ceruloplasmin (CP) in lung tissues were also determined.

RESULTSAfter treatment for 12 months, fresh wet lung weight in rush-mat dust group [(2.69 +/- 0.22) g] was higher than those in saline group [(1.87 +/- 0.25) g], TiO(2) group [(2.25 +/- 0.26) g], but lower than that in SiO(2) group [(11.41 +/- 1.63) g]; dry lung weight in rush-mat dust group [(0.47 +/- 0.03) g] was higher than those in saline group [(0.32 +/- 0.03) g], TiO(2) group [(0.41 +/- 0.08) g], but lower than that in SiO(2) group [(2.06 +/- 0.28) g]; lung collagen content in rush-mat dust group [(103.08 +/- 14.79) mg] was higher than those in saline group [(75.96 +/- 13.91) mg, TiO(2) group [(85.84 +/- 17.62) mg], but lower than that in SiO(2) group [(497.50 +/- 100.80) mg]; CP content in rush-mat dust group [(18.03 +/- 1.87) U/L] was higher than those in saline group [(15.05 +/- 2.24) U/L], TiO(2) group [(16.92 +/- 1.67) U/L], but lower than that in SiO(2) group [(25.37 +/- 3.58) U/L], P < 0.05 or P < 0.01. Pathological examination showed lung macrophage alveolitis, broadening of alveolar interval, one to two grade of silicotic nodes and increased amount of type II epithelial cell in alveolar as well as slight collagenous fibrosis in lung tissue of rush-mat dust group. Under electron microscope, primary and secondary lysosome and medullary sheath-like phagocytic residual body were found in lung tissue of rush-mat dust group, meanwhile the amount of type II alveolar epithelial cell and collagen fiber were slightly increased but these changes were less than those of quartz group.

CONCLUSIONThe rush-mat dusts have slight pulmonary fibrogenetic effect on rat.

Animals ; Ceruloplasmin ; analysis ; Dust ; Environmental Pollutants ; toxicity ; Fibrillar Collagens ; analysis ; Lung ; chemistry ; pathology ; ultrastructure ; Male ; Microscopy, Electron ; Pulmonary Fibrosis ; etiology ; pathology ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; toxicity ; Titanium ; toxicity

OBJECTIVETo research many clinical data of nonunion cases and discover the reasons for low capacity of bone growth.

METHODSFrom October 1999 to April 2009,the source material of 280 nonunion cases were conducted and followed up. The data of the study included 230 males and 50 females,with an average age of 39.4 years old ranging from 19 to 62 years. The fracture position was femur in 129 cases,tibia in 83 cases,humerus in 47 cases, feet radius bone in 21 cases, the ratio was 46:29.6:16.8:7.5. The survey included primary injury process,damage degree and the effect of first treatment,hospital level of first treatment,timing of surgery for the first time, the early callus growth conditions and whether there were obvious technical errors.

RESULTSThere were 129 femoral nonunion cases with complete data,121 cases derived from closed fractures, 8 cases from open fractures; 111 cases was aseptic nonunion. 90% of femoral aseptic nonunion had no obvious callus growth, 80% of first treatment performed intraday surgical internal fixation, 10% were undergone operation within three days and 90% was early surgery totally.

CONCLUSIONLow quality of bone callus growth is the main reason for current nonunion and the early surgical fixation has much to do with low quality of bone callus growth.

Adult ; Female ; Femoral Fractures ; etiology ; surgery ; Fracture Fixation ; Fractures, Ununited ; etiology ; surgery ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tibial Fractures ; etiology ; surgery

Objective To investigate the effects of asbestos exposure on plasma miRNA expression.Methods Plasma samples were collected from control group and asbestos -exposed group (time of exposure >10 years)and three samples from each group were selected to detect differentially expressed miRNA using LC Sciences miRNA Microarray -Single.The target genes of differential miRNA were predicted by three kinds of online software,Target Scan,miRanda and PicTar.GO term enrichment and KEGG pathways were analyzed.Results The results of microarray indicated that there were 40 differential miRNA expression between exposed and control groups(P <0.05),and the signal value of 9 differential miRNA exceeded 500.After analyzing signal pathways of target genes of 5 miRNA,of which the signal values were over 500,these target genes were found mainly involved in pathways associated with cancer and metabolism,including potential function targets of FAS,TP53 and FGFR3.Conclusion Asbestos exposure can result in differentially expressed miRNA in the plasma from workers occupationally exposed to asbestos and the target genes of these miRNA may play important roles in the pathways of cancer.However,the mechanism of these miRNA in asbestos -related diseases needs to be further studied in the future.

Objective To study the bioequivalence and safety of two olmesartan medoxomil and hydrochlorothiazide tablets in Chinese healthy subjects.Methods A total of 24 healthy subjects underwent fasting and postprandial tests in a single-center,randomized,open-label,single-dose,two-formulation,two-sequence,two-period,self-cross-over controlled design.The subjects were administered a single oral dose of the test formulation and reference formulation(each containingolmesartan medoxomil 20 mg and hydrochlorothiazide 12.5 mg)in a random cross-over fashion.The plasma concentrations of olmesartan and hydrochlorothiazide were determined by LC-MS/MS.The non-compartmental model analysis of olmesartan and hydrochlorothiazide was conducted using WinNonlin 7.0 software to calculate pharmacokinetic parameters and assess bioequivalence.Results In the fasting test,the pharmacokinetic parameters of olmesartan of test and reference were as follows:Cmax were(798.35±206.78)and(664.52±168.25)ng·mL-1,AUC0-t were(4 430.71±1 294.87)and(3 976.67±1 083.54)h·ng·mL-1,AUC0-∞ were(4 551.67±1 303.06)and(4 090.37±1 103.97)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(92.39±35.96)and(96.15±38.76)ng·mL-1,AUC0_t were(548.69±217.11)and(564.41±208.68)h·ng·mL-1,AUC0-∞ were(603.04±228.59)and(619.26±223.27)h·ng·mL-1.In the fed test,the pharmacokinetic parameters of olmesartan of T and R were as follows:Cmax were(583.15±149.48)and(550.57±104.76)ng·mL-1,AUC0-t were(3 585.18±952.72)and(3 292.19±904.58)h·ng·mL-1,AUC0-∞ were(3 696.05±996.55)and(3 396.30±923.41)h·ng·mL-1.The pharmacokinetic parameters of hydrochlorothiazide of test and reference were as follows:Cmax were(70.30±17.88)and(74.70±21.65)ng·mL-1,AUC0-t were(476.60±119.39)and(492.91±144.81)h·ng·mL-1,AUC0-∞ were(523.37±132.67)and(535.81±151.92)h·ng·mL-1.In fasting and fed condition,the 90％confidence interval(90％CI)of Cmax,AUC0-t and AUC0-∞ of olmesartan and hydrochlorothiazide were in 80.00％-125.00％.Conclusion The two olmesartan medoxomil and hydrochlorothiazide tablets were bioequivalent under fasting and fed conditions,and good security.

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends. Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY= 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China. Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27％ was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ, 39,302 CNY for stage Ⅱ, 40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02％ of the overall expenditure. Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Background:The increasing prevalence of colorectal cancer (CRC) in China and the paucity of information about relevant expenditure highlight the necessity of better understanding the financial burden and effect of CRC diagnosis and treatment.We performed a survey to quantify the direct medical and non-medical expenditure as well as the resulting financial burden of CRC patients in China.Methods:We conducted a multicenter,cross-sectional survey in 37 tertiary hospitals in 13 provinces across China between 2012 and 2014.Each enrolled patient was interviewed using a structured questionnaire.All expenditure data were inflated to the 2014 Chinese Yuan (CNY;1 CNY =0.163 USD).We quantified the overall expenditure and financial burden and by subgroup (hospital type,age at diagnosis,sex,education,occupation,insurance type,household income,clinical stage,pathologic type,and therapeutic regimen).We then performed generalized linear modeling to determine the factors associated with overall expenditure.Results:A total of 2356 patients with a mean age of 57.4 years were included,57.1％ of whom were men;13.9％ of patients had stage Ⅰ cancer;and the average previous-year household income was 54,525 CNY.The overall average direct expenditure per patient was estimated to be 67,408 CNY,and the expenditures for stage Ⅰ,Ⅱ,Ⅲll,and Ⅳ disease were 56,099 CNY,59,952 CNY,67,292 CNY,and 82,729 CNY,respectively.Non-medical expenditure accounted for 8.3％ of the overall expenditure.The 1-year out-of-pocket expenditure of a newly diagnosed patient was 32,649 CNY,which accounted for 59.9％ of their previous-year household income and caused 75.0％ of families to suffer an unmanageable financial burden.Univariate analysis showed that financial burden and overall expenditure differed in almost all subgroups (P ＜ 0.05),except for sex.Multivariate analysis showed that patients who were treated in specialized hospitals and those who were diagnosed with adenocarcinoma or diagnosed at a later stage were likely to spend more,whereas those with a lower household income and those who underwent surgery spent less (all P ＜ 0.05).Conclusions:For patients in China,direct expenditure for the diagnosis and treatment of CRC seemed catastrophic,and non-medical expenditure was non-ignorable.The financial burden varied among subgroups,especially among patients with different clinical stages of disease,which suggests that,in China,CRC screening might be cost-effective.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies