Objective To investigate the effect of all-trans retinoic acid (ATRA) on transforming growth factor β1 (TGF-β1)/Notch signaling pathway in injured podocytes induced by adriamycin (ADR) in vitro.Methods Podocytes cultured in vitro were randomly divided into normal group,model group,ATRA treatment control group,12-hour ATRA intervention group and 24-hour ATRA intervention group.Morphological changes were observed by using light microscope.The expressions of TGF-β1,podocin,Notch 1,Jagged 1 mRNA were evaluated through real-time polymerase chain reaction (RT-PCR) and the corresponding proteins were detected by using Western blot.Results (1) No obvious changes between normal group and ATRA treatment control group were revealed as the plump podocytes and distinct outline were found in light microscope,while podocytes in model group showed disordered arrangement,fuzzy boundary,atrophy,hypertrophy and increased cellular debris.Of note,the podocytes in 12-hour ATRA intervention group and 24-hour ATRA intervention group almost returned to normal.(2) In contrast with those in model group,the amounts of TGF-β1,Notchl,Jaggedl mRNA levels decreased in 12-hour ATRA intervention group (1.34 ±0.43 vs.4.16 ±0.31,1.67 ±0.2 vs.4.21 ±0.92,2.08 ±0.27 vs.5.14 ±0.63,q =23.83,11.45,19.67,all P ＜0.05) and 24-hour ATRA intervention group (1.22 ± 0.16 vs.4.16 ± 0.31,1.73 ± 0.53 vs.4.21 ± 0.92,2.08 ± 0.29 vs.5.14 ± 0.63,q =24.85,11.18,19.67,all P ＜ 0.05),and the differences were significant;similar trend was detected in the protein levels (1.04 ± 0.03 vs.4.31 ± 0.10,1.06 ± 0.04 vs.4.47 ± 0.24,1.07 ± 0.04 vs.4.20 ± 0.16,1.06 ±0.03 vs.4.31 ±0.10,1.07 ±0.03 vs.4.47 ±0.24,1.09 ±0.03 vs.4.20 ±0.16,q =163.50,69.61,90.36,162.50,69.40,89.78,all P ＜ 0.05),and the differences were significant;whereas the level of podocin mRNA (1.13 ±0.05 vs.0.40 ± 0.06,1.16 ± 0.03 vs.0.40 ± 0.06,q =36.50,38.00,all P ＜ 0.05) and protein (1.01 ± 0.01 vs.0.44 ±0.01,1.02 ±0.01 vs.0.44 ±0.01,q =180.25,183.41,all P ＜0.05) increased,and the differences were sig nificant.(3) The expressions of Notch1,Jagged1 mRNA were positively correlated with TGF-β1 mRNA (r =0.84,1.00,all P ＜ 0.05),but negatively correlated with podocin mRNA (r =-0.95,-0.94,all P ＜ 0.05) in model group.Conclusions ATRA might alleviate podocyte injury through cutting the expressions of TGF-β1,Notch1,Jagged1 and raising the expression of podocin in injured podocytes induced by ADR.

ObjectiveTo investigate the effects of ziprasidone on the behavior and the expression of pERK1/2 in posttraumatic stress disorder(PTSD) model rats.Methods 24 adult male SD rats weighing (200 ±20) g were randomly divided into four groups (n =6):control group,single prolonged stress and foot shock (SPS&S) group,ziprasidone group and ziprasidone + U0126 group.The fear response to environment,high alertness,and anxiety & depression behavior of rats were tested by the open field,elevated plus-maze,and the expression of pERK1/2 was measured by Western blot.ResultsIn open field test(OFT),the SPS&S group( (76.23 ± 54.76) cm for horizontal motion distance,(4.60 ± 1.14) for the number of entering central region) showed significant difference compared with control group ( (343.77 ± 74.22 ) cm,( 12.40 ± 3.36 ) ) or ziprasidone group ( ( 274.98± 83.56) cm,( 12.00 ± 2.92) ) (P ＜ 0.01 ),but showed no significant difference with ziprasidone + U0126 group ( ( 138.14 ± 41.98) cm,(5.00 ± 1.58) ) (P ＞ 0.05 ).The results of elevated plus maze (EPM) were in accordance with the results of OFT.The expression of pERK1/2 in SPS&S group and ziprasidone + U0126 group showed significant decrease when compared with control group or ziprasidone group (P ＜ 0.01 ).ConclusionZiprasidone can obviously improve fear response to environment,high alterness and anxiety & depression behavior of rats,and these effects of ziprasidone may be carried out by up-regulation the expression of pERK1/2.

Objective Acute kidney injury (AKI) is a common complication after cardiac surgery,especially in elderly patients,and related with poor prognosis.Although much advances in therapies of AKI have been obtained,the prognosis of patients did not improved.In the absence of proven interventions,a reasonable strategy would be to identify modifiable risk factors for AKI.The objective of the present study was to explore modifiable risk factors of acute kidney injury after cardiac surgery with cardiopulmonary bypass in elderly patients.Methods Data from 457 consecutive elderly patients (age ≥60 years old)who underwent cardiac surgery with cardiopulmonary bypass in the Guangdong General Hospital between January 2007 and December 31,2009 were analyzed in this retrospective research.The primary outcome was AKI according to the serum creatinine criteria of the RIFLE (renal Risk,Injury,Failure,Loss of renal function and End-stage renal disease) classification as an increase in serum creatinine ＞ 50％ from baseline to peak value within the first seven postoperative days.The baseline serum creatinine was defined as the latest serum creatinine before cardiac surgery.Univariate anadysis was carried out for patients'demographics data and multivariate analysis by logistic regression was used to obtain the independent risk factors for AKI.Results Among 457 elderly patients,patients mean age was (65.22 ± 4.17) years and they comprised 253 (55.4％) men and 204 (44.6％) women.AKI occurred in 313 (68.5 ％) participants.Compared with patients without postoperative AKI,the media length of intensive care unit was longer in patients with postoperative AKI,4.0 (2.0-7.5) days versus 2.0 (1.0-3.0) days,respectively.In logistic regression model,malc (odds ratio[OR] 1.894,95％ confidence interval[CI] 1.136-3.157),age above 65 years (OR 2.391,95％ CI 1.381-4.142),hypertension (OR 2.286,95％ CI 1.249-4.184),estimated glomerular filtration rate less than 60 ml/min (OR 1.933,95％ CI 1.111-3.362),preoperative uric acid ＞ 450 μ mol/L (OR 2.938,95％ CI 1.633-5.285),use of angiotensin converting enzyme inhibitors/angiotensin receptor inhibitors (ACE1/ARB) before cardiac surgery (OR 2.196,95％ CI 1.283-3.759),use of ACEL/ARB after surgery (OR 0.329,95％ CI 0.156-0.691),use of diuretics (OR 0.149,95％ CI 0.068-0.326),time of cardiopulmonary bypass above 120 min (OR 5.228,95％ CI 3.023-9.041) and prolonged mechanical ventilation (OR 2.921,95％ CI 1.527-5.586) were independent factors of AKI after cardiac surgery with cardiopulmonary bypass.Conclusion Preoperative uric acid above 450μmol/L was a modifiable risk factor of AKI after cardiac surgery with cardiopulmonary bypass in elderly patients.Therapies aimed at mitigating high preoperative uric acid may offer protection against this complication.

Objective To measure the expression of indoleamine 2, 3-dioxygenase(IDO)in condy-loma acuminatum (CA) lesions, and to evaluate its ability to locally metabolize tryptophan. Methods Immunohistochemical study was performed to observe the protein expression of IDO in skin lesions of patients with CA, and count the number of IDO-positive cells. Immunofluorescence assay was conducted to estimate the relationship between IDO-positive cells and dendritic cells. Epidermal cells and keratinocytes were isolated from warts of 30 patients with CA and prepuces of 11 healthy controls respectively, and both in vitro incubated with tryptophan solution for 4 hours. Then, high-performance liquid chromatography (HPLC)was performed to detect the level of tryptophan metabolite, kynurenine, in the culture supernatant of the above cells, which could reflect the ability of epidermal cells to metabolize tryptophan. Results Rare IDO-positive cells were found in the normal skin, but a lot of IDO-positive cells gathered in the epidermis of the wart tissues. The IDO-positive cell/total cell ratio was significantly higher in the wart tissues than in the normal skin(48.3%± 15.4%vs. 5.2%± 2.4%, P<0.05). The fluorescence signals of IDO-positive cells and CD1a-positive Langerhans cells were not overlapped with each other, suggesting that IDO-positive cells were derived from epidermal cells of the wart tissues. Compared with the keratinocytes from the healthy skin, the epidermal cells from warts had a stronger ability to metabolize tryptophan in vitro. Conclusion A large number of IDO-positive cells exist in CA warts, and may be involved in occurrence of CA.

[ ABSTRACT] AIM: To investigate the influence of advanced glycosylation end products-modified bovine serum albumin (AGE-BSA) on mammalian target of rapamycin complex 1 (mTORC1), urokinase-type plasminogen activator re-ceptor ( uPAR) , and cell mobility in the podocytes, and to further explore the probable relationship.METHODS: The conditionally immortalized mouse podocyte cell line was cultured in vitro.MTT assay and immunofluorescence were used to analyze the cell viability and cytoskeleton of the podocytes treated with the stimuli and intervention agents.The activity of mTORC1 and the expression level of uPAR in normal podocytes and podocytes treated with control BSA or AGE-BSA were detected by Western blotting.The migration ability of the podocytes was determined by would-healing assay.Rapamycin was added to inhibit the activity of mTORC1 along with the addition of AGE-BSA to observe the changes of uPAR and the motility of podocytes.RESULTS:No significant difference of the cell viability or cytoskeleton in the podocytes treated with the stimuli and intervention agents was observed.AGE-BSA up-regulated the activity of mTORC1 and the expression of uPAR, and induced the high mobility of the podocytes.Rapamycin obviously reduced the high expression level of uPAR and the increase in the migration ability of podocytes caused by AGE-BSA treatment.CONCLUSION: AGE-BSA might cause the high migration of podocytes through the mTORC1/uPAR signaling pathway.

Objective To investigate the effect and adverse reactions of intravenous cyclophosphamide (CTX) pulse therapy on refractory nephrotic syndrome (RNS) in children. Methods Retrospective study was carried on 102 patients with RNS treated with high dose CTX impact treatment in The First Hospital Affiliated to Guangxi Medical University from August 2006 to August 2016. Clinical data and follow-up records were analyzed. Results Biochemical indicators significantly improved after treatment ,and the difference was statistically signifi-cant(P < 0.05). Fifty-six patients achieved complete remission,and 21 patients achieved partial remission,with an effective percentage of 75.5%,and adverse drug reactions incidence rate of 19.6%. There was not significant difference in the remission rate of different clinical types. Conclusions High dose of CTX shock treatment on children refractory nephrotic syndrome is effective ,with low adverse reactions incidence.

Objective Pulmonary hypertension (PH) was an independent predictor of mortality and new onset cardiovascular events in maintenance hemodialysis (MHD) patients. Recent studies revealed PH complicated by pericardial effusion (PE) increased mortality in non-CKD (chronic kidney disease) population. No such evidence existed in MHD patients. Methods We enrolled 108 MHD patients with diagnosed PH by echocardiography (61 with PE) between 2009 and 2011. All patients had been followed-up for 2 years. The endpoints were all-cause mor-tality, cardiovascular (CV) mortality and new onset CV events. Results The mean age was (60.2 ± 14.1) years, 55.6% were males and SPAP was (53.0 ± 15.4) mmHg. 12.0% were severe PH and 1.9% were moderate-to-severe PE. The overall mortality, cardiovascular mortality and new on-set cardiovascular events in PE and non-PE group were 34.4% vs. 21.3%、 23.0% vs. 12.8% and 54.1% vs. 42.6%, respectively (P > 0.05). Kaplan-Meier curve showed there was no difference on all-cause mortality , CV mortality nor new-onset CV events between PE and non-PE group (Log Rank P > 0.05). Conclusions Compared with patients without PE, the presence of PE in patients with PH did not increase the mortality and worsen the cardiovascular outcome in MHD patients.

Objective To investigate the related risk factors of contrast-induced acute kidney injury (CI-AKI)after cerebrovascular intervention. Methods The clinical data of 5423 patients performed cerebrovascular angiography and intervention at the Departments of Neurology and Neurosurgery,Guangdong People′s Hospital from January 2005 to December 2013 were analyzed retrospectively. The patients who underwent cerebrovascular angiography and intervention were evaluated and screened. A clinical history database was established. All the selected patients used iodixanol,an isotonic contrast agent. The occurrence of CI-AKI was used as an endpoint. The patients were divided into either a CI-AKI group or a non CI-AKI group. A multivariate Logistic regression model was used to analyze the risk factors associated with the occurrence of CI-AKI. Results A total of 4164 patients were finally enrolled,including 137 had CI-AKI. The incidence of CI-AKI was 3. 3%. The results of multivariate Logistic regression showed that age >60 years (OR,1. 965,95%CI 1. 244-3. 136),baseline estimated glomerular filtration rate (eGFR)<60mL/(min·1. 73 m2)(OR,4. 163,95%CI 2. 422-5. 873),diabetes (OR,3. 140,95%CI 1. 983-3. 902),and anemia (OR,1. 524,95%CI 1. 226 -3. 253)were the influencing factors for occurring CI-AKI after cerebrovascular angiography and intervention. Conclusion Chronic kidney disease (eGFR<60 mL/[min·1. 73 m2 ]),diabetes,anemia,and old age (age >60 years)are the independent risk factors for occurring CI-AKI after cerebrovascular angiography and intervention.

Objective We aimed to investigate the clinical values of combination of blood creatinine and cystatin C for acute kidney injury(AKI)diagnosi. Methods Total 7 627 patients were studied retrospectively. The AKI was classified by creatinine or cystatin C according to the Kidney Disease:Improving Global Outcomes criteria. Results The maximum levels of cystatin C and creatinine were correlated(Spearman′s rank coefficient 0.699,P < 0.001). The area under a receiver operating characteristic curve of maximum cystatin C value for pre-dicting in-hospital death was 0.761(95% confidence interval 0.693 ~ 0.828). Total 1 004 and 173 patients were classified into AKI by blood creatinine or by cystatin C(13.2% vs.2.3%,P<0.001),respectively.The total inci-dence of AKI was 14.7% diagnosed by the combination of the two markers.In multivariable logistic model,the cre-atinine negative plus cystatin C positive group was associated with a higher in-hospital death compared with the cre-atinine and cystatin C double negative group(OR 15.524,95% confidence interval 5.110 ~ 47.166,P < 0.001). Conclusion Combination of cystatin C increased sensitivity of creatinine for AKI diagnosis and facilitated to iden-tify in-hospital patients with high risk.

OBJECTIVETo investigate the impact of pre-operative uric acid on acute kidney injury (AKI) after cardiac surgery in elderly patients.

METHODSClinical data were collected from 936 elderly patients (age ≥ 60 years) undergoing cardiac surgery with cardiopulmonary bypass in Guangdong General Hospital between January 2005 and May 2011. The baseline serum creatinine was defined as the latest serum creatinine before surgery, and AKI was diagnosed according to RIFLE criteria. Patients were divided into three groups according to the sex-specific cutoff values of serum uric acid tertiles (group A: ≤ 384.65 µmol/L in men, and ≤ 354.00 µmol/L in women; group B:384.66-476.99 µmol/L in men and 354.01-437.96 µmol/L in women; group C: ≥ 477.00 µmol/L in men and ≥ 437.97 µmol/L in women). Multivariate logistic regression analysis was used to analyze the independent risk factors for AKI.

RESULTSAmong 936 elderly patients, 576 cases (61.5%) developed AKI. Mean uric acid concentration was higher in AKI patients than in Non-AKI patients ( (436.6 ± 119.1) µmol/L vs. (398.0 ± 107.2) µmol/L, P < 0.001). The incidence of AKI was 56.1% (175/312) in group A, 56.3% (175/311) in group B, 72.2% (226/313) in group C (P < 0.001). Multiple logistic regression analysis showed that, after adjusted for age, gender, co-morbidities(hypertension, diabetes mellitus, cerebrovascular disease, chronic obstructive pulmonary disease), previous cardiac surgery, eGFR<60 ml×min(-1) ×1.73 m(-2), heart function ≥ 3 (NYHA), positive urine protein, combination of coronary artery bypass grafting and valvular surgery, cardiopulmonary bypass operation time, aortic cross-clamping time, pre-operative angiotensin converting enzyme inhibitor or angiotensin II receptor blockers and lipid-lowering drugs use, early postoperative angiotensin converting enzyme inhibitor or angiotensin II receptor blockers, diuretics and digoxin use, post-operation central venous pressure, risk of post operative AKI was significantly higher in group C than in group A (OR:1.897, 95%CI: 1.270-2.833, P = 0.002).

CONCLUSIONPre-operative elevated uric acid is an independent risk factor of AKI after cardiac surgery in elderly patients.

Acute Kidney Injury ; etiology ; Aged ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Cardiac Surgical Procedures ; adverse effects ; Cardiopulmonary Bypass ; Coronary Artery Bypass ; Female ; Humans ; Incidence ; Kidney Function Tests ; Male ; Middle Aged ; Predictive Value of Tests ; Risk Factors ; Uric Acid ; blood