Volume 93  ·   Issue 22  ·  2013

To explore the protective effects of beraprost plus simvastatin on monocrotaline-induced pulmonary arterial hypertension in rats.

Forty male Sprague-Dawley rats were allocated to control (C), untreated pulmonary arterial hypertension (P), beraprost (B), simvastatin (S) and combination groups (Com)(n=8 each).Normal saline was injected subcutaneously into group C and then there was no other intervention for 21 days.Group P, B, S and Com rats received subcutaneous injections of monocrotaline (MCT,60 mg/kg) and then isovolumetric normal saline, beraprost (100μg·kg^-1·d^-1), simvastatin (2 mg·kg^-1·d^-1) and beraprost (100μg·kg^-1·d^-1) plus simvastatin (2 mg·kg^-1·d^-1) by daily gastric lavage for 21 days.At Day 22, heart rate (HR), mean arterial pressure (MAP) and mean pulmonary pressure (mPAP) were detected and right heart ventricular hypertrophy index (RVHI) was calculated.The histopathology changes and tunica media thickness percentage of pulmonary arteries (WT%) were evaluated by pulmonary tissue staining.The results were analyzed statistically.

The differences of HR and MAP were not significant among 5 groups (all P>0.05).The levels of mPAP,RVHI and WT% in group B ((27.4±3.7) mm Hg,0.35±0.03,26.7%±2.4%), group S ((29.9±4.4) mm Hg, 0.36±0.03,28.2%±1.9%) and group Com ((23.1±3.9) mm Hg, 0.32±0.03, 17.4%±3.3%) were lower than those in group P ((35.4±5.7) mm Hg, 0.41±0.05, 42.8%±5.9%)(all P<0.05).

The combined use of beraprost and simvastatin may delay the increase of mPAP and remodeling of pulmonary vessels and inhibit right ventricular hypertrophy in pulmonary arterial hypertension rats.Its efficacy is superior to that of monotherapy.

To evaluate the application value of cardiopulmonary exercise testing in patients with chronic thromboembolic pulmonary hypertension (CTEPH).

A total of 116 consecutive patients admitted into the Cardiology Department of Fuwai Hospital.They were divided into 3 groups of CTEPH (n=44), CPE (without pulmonary hypertension in chronic pulmonary embolism)(n=24) and control (without pulmonary embolism or pulmonary hypertension)(n=48) respectively.Their levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured.Incremental cardiopulmonary exercise testing was performed to compare its differential results among 3 groups and evaluate the correlation between NT-proBNP and its parameters.

The body mass index (BMI) in the CTEPH group was lower than those in the CPE and control groups ((23.8±3.9) vs (26.1±3.6) and (26.7±3.2) kg/m2), both P<0.05) | the medical history in the CTEPH group was longer than those in the CPE and control groups ((58±48) vs (12±10) and (29±25) months, both P<0.05).The plasma concentrations of NT-proBNP in the CTEPH group were higher than those in the CPE and control groups ((1678±1255) vs (577±167) and (608±247) pmol/L, both P<0.05).All of them completed the test and there were no severe complications such as syncope or exacerbation of disease.Maximum oxygen consumption (VO₂max), percentage of predicted maximum oxygen consumption (VO₂%), oxygen consumption in relation to body weight (VO₂/kg), anaerobic threshold and O₂ pulse in the CTEPH group were significantly lower than those in the CPE and control groups (P<0.05).The ratios of dead space volume (VD) to tidal volume (VT) in the CTEPH and CPE groups were higher than those in the control group (P<0.05).The plasma concentrations of NT-proBNP were inversely correlated with right ventricular internal diameter (r=-0.690,P=0.000) and VO ₂/kg (r=-0.496,P=0.000).The right ventricular internal diameter (β=0.583, P=0.000) and VO₂/kg (β=0.233, P=0.032) were strong independent determinants of NT-proBNP.

As a reliable pathophysiological indictor of CTEPH, cardiopulmonary exercise testing may be used objectively and safely to evaluate the cardiopulmonary function of CTEPH patients.

To explore the exercise characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH).

From November 2010 to September 2012, 76 consecutive IPAH patients and 24 healthy controls from Fuwai Cardiovascular Hospital were enrolled to undergo cardiopulmonary exercise testing.The exercise parameters were compared.Correlations among peak oxygen consumption, anaerobic threshold, peak oxygen pulse, New York Heart Association (NYHA) class, N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walking distance (6 MWD) and cardiac index are analyzed in IPAH.

There were 21 males and 55 females in IPAH and 8 males and 16 females in controls.Their mean ages were (31.5±10.6) and (35.5±6.4) years respectively.Significant differences (P=0.000) existed between two groups in peak oxygen consumption ((12.7±3.3) vs (25.6±5.8) ml·min^-1·kg^-1), anaerobic threshold ((9.8±2.5) vs (16.7±3.9) ml·min^-1·kg^-1), peak oxygen pulse ((5.3±1.6) vs (9.9±2.5) ml/bpm) and ventilator efficiency (slope of minute ventilation in relation to CO₂ produced)((42.6±2.0) vs (25.5±3.5)).In IPAH, peak oxygen consumption was significantly correlated with NYHA class (r=-0.509, P=0.000), 6MWD (r=0.443, P=0.002) and NT-proBNP levels (r=-0.423, P=0.011).And anaerobic threshold was significantly correlated with NYHA class (r=-0.362, P=0.002), 6MWD (r=0.343, P=0.004) and NT-proBNP levels (r=-0.275, P=0.017).Peak oxygen pulse and ventilator efficiency were both correlated well with total pulmonary vascular resistance.Partial correlation analysis demonstrated that there were significant correlations among peak oxygen consumption, anaerobic threshold, NYHA class, NT-proBNP levels and 6MWD after adjusting for age, gender and weight.

Peak oxygen consumption and anaerobic threshold decrease ventilator efficiency in IPAH patients.Cardiopulmonary exercise testing is an invasive tool of assessing safely the function of IPAH patients.

To explore the blood oxygen saturation and heart rate changes of the Antarctic expeditioners.

During August 2010 to April 2011, the changes in blood oxygen saturation, heart rate and plateau reaction of 16 Antarctic expedition team in different plateau environments (Tibetan plateau versus Antarctic plateau) were monitored with the noninvasive pulse oximeter MD300-C.The extent of acute mountain sickness was determined according to the Lake Louise Consensus acute mountain reaction symptom scores and judgment method.

The changes of blood oxygen saturation, heart rate at different altitudes of 110, 3650, 4300 m (96.8%±1.2%,89.1%±1.2%,86.1%±2.0%, (75.0±5.4) times/min, (104.0±4.3) times/min, (113.0±5.2) times/min,F=214.155,240.088,both P<0.05).With rising latitude and elevation gradient in Antarctic plateau, the changes of blood oxygen saturation, heart rate at different altitudes of 2000, 2500,3000, 3500 and 4087 m (91.9%±1.3%,90.5%±1.3%,87.6%±1.4%,85.0%±1.8%, 81.5%±2.2%, (85.9±3.2) times/min, (90.6±2.8) times/min, (97.8±4.1) times/min, (102.0±3.4) times/min, (106.3±3.9) times/min, F=105.418,90.174,both P<0.05).Levels of blood oxygen saturation and heart rate were both correlated with the risk of altitude sickness (r=-0.446 and 0.565, both P<0.05).

As the increases of altitude, there are significant changes in oxygen saturation, heart rate of the Antarctic expeditioners.And with the increases of altitude, the risk of altitude sickness gradually increases.

To evaluate the safety and efficacy of preoperative computed tomography urography (CTU) three-dimensional reconstruction,intraoperative radiology and ultrasound guidance followed by percutaneous nephrolithotomy (PCNL) in the treatment of complex renal calculi.

We summarized the clinical data of 210 patients with complex renal calculi treated at our hospital from December 2008 to December 2011 in this retrospective study.In the one-stop diagnosis and treatment group (n=119),the optimal puncture approach was designed according to CTU imaging and three-dimensional reconstruction.Percutaneous track was established by ultrasound and radiology guided puncture.PCNL was performed with EMS system.The control group (n=91) underwent PCNL without radiological guidance.The success rate of puncture, mean accessing time, mean operative duration, intraoperative volume of blood loss and stone-free rate after one operative session were observed.Post-operative follow-ups were conducted until June 2012.

Compared to the control group, the one-stop diagnosis and treatment group showed a higher success rate of puncture[98.3% (117/119) vs 92.3% (84/91), P=0.037], a shorter operative duration[97.8±13.20 vs 110.0±14.73 min, P=0.043]and a higher stone-free rate after one operative session[92.4% (110/ 119) vs 83.5% (76/91), P=0.037].No significant difference was detected in the mean accessing time[15.3±3.7 vs 13.9±3.9 min,P=0.398]or intraoperative volume of blood loss[195.8±84.15 vs 263.3±82.06 ml, P=0.059].No severe complications occurred.No recurrence of calculi was noted during the follow-up period.

One-stop diagnosis and treatment plan (CTU 3-D reconstruction plus radiology, ultrasound guidance followed by PCNL) may identify the puncture path, improve the successful rate of puncture and stone-free rates and reduce the complications of PCNL.

To evaluate the independent risk factors for failure of continuous venovenous hemodialysis (CVVHD) in the treatment of acute kidney injury (AKI) following cardiac surgery.

Adult patients without any prior pre-operative history of chronic renal disease suffering AKI following cardiac surgery and undergoing CVVHD at our center from January 2005 to December 2012 were recruited and divided into either a success group or a failure group.All pre-, intra- and post-operative data were collected and retrospectively analyzed.

Ninety-three adult patients were enrolled.Among them, sixty-three patients survived with a failure rate of 32.2% and a mortality rate of 19.4%.Through univariate analysis and multivariate Logistic regression, independent risk factors for failure of CVV HD in the treatment of post-operative AKI included preoperative LVEF (OR=0.61,95% CI 0.42-0.85) and duration of oliguria until dialysis (OR=2.76, 95% CI 1.51-5.83).

Pre-operative impaired left ventricular function is an important risk factor for failure of CVVHD in the treatment of AKI after cardiac surgery.The sooner the implementation of CVVHD, the better prognosis.

To explore the effects of etiological classification and the distance between residence and hemodialysis unit on cardiovascular complications and treatments in maintenance hemodialysis (MHD) patients.

A total of 756 MHD patients were collected from 12 hemodialysis centers of Guiyang, China between January 2011 and May 2012.Their distribution characteristics and correlations were based on medical records.And statistical analyses were performed.

The ratio of males and females was 1.45∶1.And their mean age was (49.1±14.7) years old.And 496 (65.6%) cases suffered from cardiovascular complications.The analysis of multi-factor Logistic regression revealed that distance between residence and dialysis unit was an independent risk factor of cardiovascular complications.The group of the farthest distance (>30 km) had the worst influence on dialysis adequacy Kt/V score, urea clearance rate, dialysis frequency and time per week.And the levels of blood phosphorus, triglyceride and cholesterol in the fourth group had marked elevations.It had a significant positive correlation with distance (P<0.05).

The distance between residence and dialysis unit is an independent risk factor of cardiovascular complications in MHD patients.The farthest distance (>30 km) has the greatest influence on dialysis adequacy.

To assess the clinical efficacies of three types of anatomical hepatic inflow occlusion method in hepatectomy for liver neoplasms.

A non-randomized concurrent controlled trial was performed from January 2011 to October 2012,a total of 180 consecutive patients with liver neoplasms underwent hepatectomy similarly.They were divided into 3 groups according to the hepatic inflow occlusion methods during resection:HHV group (hemi-hepatic vascular inflow occlusion,n=60), MPV group (main portal vein inflow occlusion,n=60) and HPP group (hemi-portal vein preserved inflow occlusion,n=60).The primary endpoints were intraoperative blood loss and transfusion requirement while the secondary outcomes were assessed with operating duration, postoperative morbidity, hospital stay, gastrointestinal function and postoperative liver injury.

No significant differences existed among three groups in demographic and tumor characteristics and operation-related background (P>0.05).No mortality happened in 30 days postoperatively in all patients.Intraoperative volume of blood loss had no significant differences among three groups (P=0.272).Among the patients requiring transfusion, HPP group had the least transfusion requirement (HHV group: (5.00±1.51) U, MPV group: (3.50±1.41) U, HPP group: (2.50±0.93) U,P=0.004).MPV group showed a significant shorter operating duration (HHV group: (227±59) min, MPV group: (198±56) min, HPP group: (221±79) min, P=0.042).No significant differences were found among three groups in hospital stay (P=0.673) or postoperative morbidity (P=0.735),including hepatic insufficiency, infection and ascites.HHV group showed an earlier recovery of gastrointestinal function (HHV group: (60±12) h, MPV group: (69±9) h, HPP group: (64±8) h,P=0.000).MPV group had a significantly lower level of aminotransferase at Day 1 and 3 postoperation (d1 ALT: HHV group: (403±271) U/L, MPV group: (304±211) U/L, HPP group: (448±396) U/L,P=0.033; d1 AST: HHV group: (394±271) U/L, MPV group: (278±189) U/L, HPP group: (432±405) U/L,P=0.017;d3 ALT:HHV group: (309±193) U/L, MPV group: (232±161) U/L, HPP group: (325±277) U/L,P=0.048; d3 AST: HHV group: (136±105) U/L, MPV group: (91±73) U/L, HPP group: (120±87) U/L, P=0.024).But no significant differences were found among three groups regarding total bilirubin, albumin, prealbumin and prothrombin time activity (P<0.05) during any postoperative stage.

All three types of anatomical vascular occlusion method are both safe and efficacious in hepatectomy.But no single method has absolute advantage over the other two.HPP method has the best hemostatic effect, MPV offers better postoperative liver function and HHV promotes early recovery of gastrointestinal function.

To preliminarily assess the prognosis of patients with multiple organ dysfunction syndrome (MODSE) and analyze their influencing factors.

The clinical data of 365 MODSE patients admitted into Chinese PLA General Hospital during January 2009 to June 2012 were analyzed retrospectively.According to 28-day outcomes, they were divided into 2 groups (28-day survival and non-survival) while 4 groups according to age.Then these prognosis were evaluated with the current scoring systems ( (acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ and Ⅲ), sample acute physiological score (SAPS Ⅱ) and multiple organ dysfunction score (MODS) ).The predictive powers were compared by receiver operating characteristic (ROC) curve.Finally a binary Logistic regression analysis was performed to evaluate the relevant influencing prognostic factors of MODSE.

The mean age was (77.8±9.1) years, mean number of failed organs (3.6±1.2) and a 28-day mortality 45.8%.The ages of non-survival group were older than those of survival group ((78.1±9.1) vs (76.7±11.0) years).The number of organ failures ((4.3±1.1) vs (3.1±1.0)) and scores (APACHE Ⅱ: (28±7) vs (20±8), APACHE Ⅲ: (106±27) vs (75±31),SAPS Ⅱ: (64±16) vs (46±18), MODS: (9±3) vs (6±3)) of non-survivals were significantly higher than that of survivals.The area under ROC curve of these four score systems were 0.790, 0.781, 0.780 and 0.780 respectively.Compared to the above systems, SAPS Ⅱ had the best performance in sensitivity while APACHE Ⅱ was more valuable in specificity.All clinical data underwent binary Logistic regression and the results showed that plasma concentration of albumin and mean arterial pressure (MAP) offered beneficial outcomes while age and number of organ failures had unfavorable prognosis.The greater patient age, the higher their mortality.

All four scoring systems have accurate prognostic predications of MODSE patients.And the predictive power of APACHE Ⅱ is the best.Plasma concentration of albumin, MAP, age and organ failure number are independent prognostic factors in MODSE patients.

To explore the prevalence of Bordetella pertussis (B. pertussis) infection in unvaccinated or incomplete vaccinated infants with cough for a prolonged duration.

The serum samples and nasopharyngeal secretions were collected from 176 patients with cough for a prolonged duration (≥2 weeks) from 2011 to 2012 at Children′s Hospital Affiliated to Capital Institute of Pediatrics.Multiplex PCR of nasopharyngeal secretion was employed to identify B.pertussis.And enzyme-linked immunosorbent assay (ELISA) was used to detect antibody to pertussis toxin (PT-IgG).Total bacterial DNA was exacted from nasopharyngeal secretion and two-target IS481/PT of B.pertussis was detected by PCR.The sera and nasopharyngeal secretions were also collected from household contacts with cough for a prolonged duration.Their clinical characteristic and epidemiological profiles were collected and analyzed.

B.Pertussis infection was demonstrated in 51 cases (29.0%).The patients ages were from 23 days to 4 years.Among them,46 cases (90.2%) were aged under 12 months and 5 cases (9.8%) over 12 months.And 40 cases were unvaccinated (31 cases <3 months old, 4 cases 3- 12 months old, 5 cases>5 years old) and 11 cases incompletely vaccinated.There were 31 males and 20 females.More patients were found in spring and summer than those in autumn and winter.Nine infant cases had 12 household contacts.Among 12 household contacts, 3 were PCR positive and 12 PT-IgG positive.Pertussis was remarkably critical in infants.Serious complications included failure to thrive, pneumonia, respiratory failure and seizures.

B.pertussis infection is an important cause in unvaccinated or incomplete vaccinated infants with prolonged cough.Peak seasons of pertussis are spring and summer.Undiagnosed adolescents and adults with pertussis may be a significant source for transmission of B.pertussis to other susceptible children.Infants aged under 1 year are at risk for severe pertussis and life-threatening complications.As a rapid and sensitive method of detecting B.pertussis, PCR may be used in early phase.

To explore the characteristics of lung function in preterm infants with varying degrees of bronchopulmonary dysplasia (BPD).

There were 407 infants (278 males and 129 females) were recruited from Shenzhen Children′Hospital between January 2011 and October 2012.Among them 188 term infants (term group) and 113 preterm infants (non-BPD preterm group) were selected as controls.A total of 106 BPD infants from the observation group were divided into mild (n=48), moderate (n=42) and severe (n=16) sub-groups according to the definition of BPD.Infants with diseases interfering with lung function, such as congenital heart disease, congenital diaphragmatic hernia, or thoracic wall deformities, were excluded.Lung function was tested at a postmenstrual age (PMA) of 44 weeks.q test, Dunnett C test and Spearman analysis were used for statistical analysis.

The age range was 17- 116 d, test weight range 1.83- 7.00 kg and test height range 40.0- 64.0 cm.In non-BPD preterm group, the respiratory rate (RR) was higher than that in term group ((50±13) vs (44±10) times/min,P<0.01),while the tidal volume (T V), ratio of time to peak tidal expiratory time and expiratory time (Tpef/Te) and peak expiratory flow (TPEF) were all less than those in term group ((25±9) vs (29±7) ml,29%±9% vs 33%±8%, (59±23) vs (65±25) ml/s,all P<0.05).Neither functional residual capacity (FRC) nor lung clearance index (LCI) had significant statistical difference between two groups ((20±5) vs (19±5) ml/kg, 8.4±2.8 vs 8.7±3.4, all P>0.05).In moderate and severe BPD groups, RR ((57±9), (58±10) times/min) were both higher than that in non-BPD group (both P<0.05) while RR in mild group ((53±13) times/ min) had no statistical significant difference with non-BPD group (P>0.05).The values of TV and LCIin mild, moderate and severe BPD groups have no statistical significance with non-BPD group (all P>0.05).Except for mild BPD group (24%±13%, (18±5) ml/kg), Tpef/Te and FRC in both moderate and severe groups (20%±9% and 18%±5%, (15±3) and (15±4) ml/kg) were less than those in non-BPD group (all P<0.05).Only in severe BPD group ((85±11) ml/s), TPEF was higher than that in non-BPD group (P<0.05).Correlation analysis showed that, except for LCI, all of these parameters were significantly associated with the degree of BPD (all P<0.05).

For BPD and non-BPD preterm infants, there are various changes in respiratory rhythme, lung volume, ventilation inhomogeneity, ventilatory efficiency and small airway resistance.The increases of pulmonary elastic recoil and degree of major airway constriction are obvious in moderate and severe BPD infants.

To explore the correlations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients.

The core-needle biopsy specimens were collected from 563 patients undergoing 4- 8 cycles of neoadjuvant chemotherapy between January 2001 to January 2009.And immunohistochemical assays were employed to detect the levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 proliferation index simultaneously.Molecular subtypes were divided on the basis of immunohistochemical results.And the associations between molecular subtypes and responses to neoadjuvant chemotherapy were analyzed in 563 patients.

The pathological complete response (pCR) rates of patients with hormone receptor-negative/HER2- negative subtype (HR-/HER2-), HER2- positive subtype (HER2+) and hormone receptor-positive/HER2- negative subtype (HR+/HER2-) were 38.9%, 17.9% and 8.3% respectively.In univariate analysis, there were significant differences in pCR rates among the groups (P<0.001).In multivariate analysis, the patients with HER2+ subtype had a significantly higher pCR rate than those with HR+/HER2- subtype (OR=0.344, P=0.002).Whereas the patients with HER2+ subtype had a significantly lower pCR rate than those with HR-/HER2- subtype (OR=2.453, P=0.007).Among HR+/HER2- subtypes, a higher pCR rate was observed in the group of high expression level of Ki-67 proliferation index (Ki-67≥20%)(P=0.004).But no significant differences existed in pCR rates between the group of high expression level of hormone receptor and the group of non-high expression level (P=0.256).

There were correlations between molecular subtypes and responses to neoadjuvant chemotherapy in primary breast cancer patients.Patients of HER2+ and HR-/HER2- subtype are more likely to respond to neoadjuvant chemotherapy.Among HR+/HER2- subtypes, those with a high level of Ki-67 proliferation index tend to benefit from neoadjuvant chemotherapy.

To systematically assess the effects of neoadjuvant chemotherapy on the prognostic risk of invasive transitional bladder cancer.

All known randomized controlled trials (RCTs) on neoadjuvant chemotherapy in the treatment of invasive transitional bladder cancer, published from the date of database building to September 2012, were retrieved from such databanks as Pubmed, CBMdisc, Embase and Cochrane.The data on 5-year survival rate of included studies were extracted for further heterogeneity exploration, subgroup analysis and statistical pooling with the Rev Man 5.10 software.

Fourteen subjects involving 2072 cases and 2086 controls were published from 1991 to 2012.The overall odds ratio of survival suggested a 21% relative reduction in mortality risk for neoadjuvant chemotherapy compared to that on control (OR=0.79, 95% CI:0.70-0.90).In subgroup analysis according to different neoadjuvant chemotherapies, MCV (methotrexate, cisplatin and vinblastine) and MVAC (methotrexate, vinblastine, adriamycin and cisplatin) chemotherapies showed significant benefit to overall survival with 28% and 25% reduction in risk of death respectively (OR=0.72,95% CI:0.60-0.86,OR=0.75,95% CI:0.59-0.96).However, no significant difference existed in effects between C (cisplatin) chemotherapy, CM (cisplatin and methotrexate) chemotherapy and CD (cisplatin and docetaxel) chemotherapy and controls.In subgroup analysis according to local treatment of cystectomy or radiotherapy after neoadjuvant chemotherapy, the patients with cystectomy showed significant benefits in overall survival with 25% reduction in risk of death (OR=0.75,95% CI:0.65-0.87).However, the patients with radiotherapy or radiotherapy plus cystectomy showed no significant benefits in overall survival.

MCV and MVAC neoadjuvant chemotherapies improve survival among patients with bladder cancer.And neoadjuvant chemotherapy has better long-term survival after cystectomy.

Intracellular Ca²⁺ overload is a key factor in contrast-induced renal tubular toxicity. Na⁺/Ca²⁺ exchanger (NCX) system is one of main pathways of intracellular Ca²⁺ overload.We explore the effects of KB-R7943, an inhibitor of reverse mode of NCX, on contrastinduced acute kidney injury (CI-AKI).

Rats were divided into control, CI-AKI and pretreatment groups with KB-R7943 (5, 10 mg/kg).CI-AKI was induced by diatrizoate administration in rats with cholesterol-supplemented diet for 8 weeks.Renal function and hemodynamics were determined at Day 1 post-administration.Renal histopathology was observed under light microscope.Renal tubular apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Renal endothelin-1 (ET-1) was measured by radioimmunoassay.The oxidative markers of renal malondialdehyde (MDA) and catalase (CAT) were measured.The expression of NCX was evaluated by reverse transcription-polymerase chain reaction (RT-PCR).

Levels of serum creatinine (Scr,μmol/L) in CI-AKI rats ((149±35) μmol/L) were significantly higher than those of normal rats ((55±4) μmol/L, P<0.01).Renal ET-1, MDA and CAT, resistance index (RI) of renal blood vessels increased significantly in CI-AKI rats.The contrast-induced increases in Scr and RI of renal blood vessels were suppressed significantly and dose-dependently by pretreatment with KB-R7943.Histopathological and TUNEL results showed that contrast-induced severe renal tubular necrosis and apoptosis were significantly and dose-dependently attenuated by KB-R7943.KBR7943 significantly suppressed the contrast-induced increments of ET-1, MDA and CAT.No significant changes in NCX1 mRNA expression were observed following contrast administration.

Renal oxidative stress and ET-1 overproduction via the activation of reverse mode of NCX play an important role in the pathogenesis of CI-AKI.And inhibition of reverse mode of NCX expressed in renal tubular epithelial cell has protective effects on CI-AKI.

To explore the role of c-Myc in mesenchymal stromal cell-mediated drug resistance and elucidate the molecular mechanism of acute myeloid leukemia (AML) from the version of tumor microenvironment.

AML cell lines U937 and KG1a were co-cultured with mesenchymal stromal cells (MSC) from bone marrow of healthy donors between January to March 2012.The AML cell lines plated alone was cultured as controls.Apoptosis induced by mitoxantrone was measured by flow cytometry and Annexin V/PI double and 4′-6-diamidino-2-phenylindole (DAPI) staining.And c-Myc protein was detected by Western blot under both culturing conditions.After a pre-treatment of c-Myc inhibitor 10058-F4, the apoptosis of AML cell was also evaluated.

Apoptosis of AML cells (U937 and KG1a) significantly decreased during co-culturing with MSC (9.88%±1.53% vs 42.83%±2.03%,P=0.004;20.60%±2.87% vs 42.53%±5.29%,P=0.030).Drug resistance was implicated.The co-culturing of AML cells with MSC significantly induced an up-regulation of c-Myc.The inhibition of c-Myc with 10058-F4 could induce apoptosis of AML cells.After an addition of 10058-F4 into the co-culture system, the apoptotic rate of KG1a cells significantly increased from 23.87%±1.55% to 57.23%±3.88% (P=0.009).Similarly the apoptotic rates spiked from 16.07%±2.11% to 53.47%±4.08% in U937 cells (P=0.004) to overcome the stromal cell-mediated drug resistance.

The co-culturing of AML cells and MSC induces an up-regulation of c-Myc protein so as to cause the emergence of chemoresistance.Therefore targeting c-Myc protein may provide a novel therapeutic strategy of AML.