Objective To investigate the effect of the polymorphisms of multidrug resistance 1 (MDR1) C3435T and G2677T on Tacrolimus (Tac) individualized treatment and prognosis of grafts in the renal transplantation recipients (RTRs).Methods One hundred and twenty-seven RTRs who treated with Tac regimen and had a stable graft function were enrolled,and were divided into adjuvant treatment group and non-adjuvant treatment group according to whether given adjuvant drugs to raise Tac trough concentrations. MDR1 C3435T and G2677T SNPs were detected by using sequence specific primers PCR.Tac trough concentrations of whole blood were measured by using enzymelabeled immunosorbent assay.Tac concentration-to-dose ratio (C/D) standardized by body weight was compared according to the various genotypes and haplotypes of MDR1 C3435T and G2677TA SNPs.Results Adjuvant treatment group including 36 recipients had a higher frequency of C genotype of C3435T than un-adjuvant treatment group (68.05％ vs 48.35％,P ＜ 0.01 ). The frequency of G2677TA polymorphisms was of no significant difference between the two group recipients (P＞ 0.05).As to non-adjuvant treatment recipients,the mean Tac DD required and C/D were not significantly different among various polymorphisms of MDR1 G2677T/A and C3435T or various haplotypes (P＞0.05).During A follow-up period of 4 years,13 recipients suffered graft dysfunction in which 84.6％ (11/13) carried 3435C genotype (P＞0.05).Conclusion The frequency of MDR1 C3435T polymorphisms in RTRs is high in the recipients given adjuvant treatment to raise Tac concentrations.Recipients with 3435C genotype were prone to graft dysfunction.

Background Researches showed that the incidence rate of cataract is high in the nickel mining area. Nickel sulphate can apparently inhibit the metabolism and proliferation of human lens epithelium cells. But the study on the injury mechanism of nickel on lens is still seldom. Objective Present study was to investigate the effect of nickel sulphate on the lens of SD rats. Methods Forty-five SPF SD rats aged from 7 to 14 days were grouped randomly into subcutaneous injection group, intraperitoneal injection group and blank group. Nickel sulphate of 2 g/L ( 10 mg/kg) was subcutaneously or intraperitonealy injected for 45 days. The opacity of rat lens was examined under the slit lamp at two-week interval and scored based on the criteria of LOCS II and LOCS III. The rats were sacrificed in 45 days after experiment and the lens were obtained for the pathological examination. Result The mean score of the anterior subcapsule opacity of rat lens was obviously higher in subcutaneous injection group compared with blank control group with a significant difference between them (t= 14. 311, P < 0. 05 ) , but no significant difference in the anterior subcapsule opacity between intraperitoneal injection group and blank control group (t = 4. 355 , P>0. 05 ). The score of posterior subcapsule opacity of lens were evidently higher in both subcutaneous injection group and intraperitoneal injection group than the blank control group (t = 9. 316,P = 0. 004;t = 7. 464, P = 0. 009) ,so was the mean score of the anterior +posterior subcapsule opacities(t = 23. 387,P=0. 000;t= 10. 533,P = 0. 002) and the total score of rat lens opacity ( t = 12. 358 , P = 0. 001; t = 10. 188 , P = 0. 003 ) . No significant differences were found in cortex opacity score and nuclear opacity score among three groups ( P > 0.05 ). Histopathology examination revealed that the degeneration of lens collagen protein was more serious in subcutaneous injection group and intraperitoneal injection group than the blank control group,and the injury degree of lens collagen protein was more dominant in subcutaneous injection group. Conclusion System administration of nickel sulphate induced the injury of anterior and posterior subcapsule of lens in SD rat.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

ObjectiveTo investigate the relationship between the degenerative mechanisms of lumbar intervertebral disc (LID) and apoptosis.MethodsThe total RNAs were isolated from human LID tissues. Both the mRNAs from the degeneration and normal LID were reversely transcribed to the cDNAs. The cDNAs were labeled with the incorporations of fluorescent dUTP, for preparing the hybridization probes. The mixed probes were then hybridized to the cDNA microarray. After high-stringent washing, the cDNA microarray was scanned for the fluorescent signals and analyzed by computer image analysis. The apoptotic status and the expression of Bcl-2 and Bax in 12 cases of degenerative LID and 10 cases of normal LID were detected with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunohistochemistry methods.ResultsAmong the 4096 targets, there were 10 genes related to apoptosis. The expression related to Bax protein gene was up-regulated and it was down-regulated for Bcl-2 protein. In group of normal LID, the average apoptotic index (AI) was (24.897±3.620); percentage of Bcl-2 positive cells was (31.440±4.150)%; percentage of Bax positive cells was (29.372±2.588)%, average optical density (OD) values of positive particles were (0.183± 0.010 ), ( 0.203 ±0.012) and (0.169±0.005) respectively. In group of degenerative LID, the average AI was (49.232±3.440); percentage of Bcl-2 positive cells was (18.239±2.470)%; percentage of Bax positive cells was (52.349±3.764)%; average OD values of positive particles were (0.152±0.003), (0.310±0.008) and (0.262±0.014) respectively. There were significantly differences in AI and expressions of Bcl-2 and Bax proteins between normal LID and degenerative LID (P<0.05).ConclusionCell apoptosis plays an important role in the process of LID degeneration. Both Bcl-2 and Bax take part in the occurrence and progression of LID.

BACKGROUND:Pulmonary infection is the main complication after kidney transplantation, and its onset and morbidity may be related to conventional oral drugs after kidney transplantation.
OBJECTIVE:To analyze the effect of methylprednisolone instead of prednisone on severe pulmonary infection after kidney transplantation.
METHODS:Clinical data of 58 patients with severe pulmonary infection after kidney transplantation were retrospectively analyzed. First, according to the characteristics of post-onset patients and lung CT findings, broad-spectrum antibiotics and anti-fungal treatment were adopted, and subsequently targeted therapy, that is, withdrawal or adjustment of dosage and combination regimen of immunosuppressive agents, was employed depending on etiology, fungi and virus detection results. Among the 58 patients, 28 patients were injected methylprednisolone, and 30 patients took oral prednisone. Hyoxemia correction, support therapy and immune replacement therapy were applied.
RESULTS AND CONCLUSION:Thirty-nine of 58 patients (67.2%) were positive for pathogens, including 7 cases of simple bacterial pneumonia, 4 cases of fungal pneumonia, 3 cases of simple cytomegalovirus infection, and 25 cases of mixed infections (5 cases of multiple bacterial infections, 17 cases of fungal and bacterial co-infections, and 3 cases of fungi, bacteria and cytomegalovirus co-infections). Patients subjected to methylprednisolone treatment spent shorter time to recover their temperature than those undergoing oral prednisone (P<0.05). In addition, creatinine fluctuation range in the methylprednisolone group was less than that in the prednisone group (P<0.05). The results showed that intravenous injection of methylprednisolone may accelerate absorption of inflammatory exudate in the lung and shorten treatment time.

A total of 1 100 patients underwent renal transplantation in the Organ Transplantation Center,Second Affiliated Department of General Hospital of Chinese PLA between 1988 and 2008 were collected,and retrospective analysis was performed in five female patients with malignant tumor,which appeared at 68 months (20-132 months) following renal transplantation,including 2 with renipelvic and uretal cancer and 3 with bladder cancer. Two of the 3 patients with bladder cancer presented homolateral renipelvic and uretal metastasis. Three cases and 1 case of upper uretal cacer were observed at the homolateral or heterolateral of kidney grafts respectively. The main characteristic of sign was iterative and painless gross hematuria. The 5 patients underwent renal transplantation with intravesical instillation therapy and nephrectomy. All patients were survived without rejection in the 1-62 months follow-up. The incidence of malignancy in renal allograft recipients is much higher than that in normal ones,which is related to the long term use of immunosuppressants. Urinary epithelial cancer is the main complicating carcinoma and the first choice of treatment is surgical operation. Based on the normal renal grafts function,the dose of immunosuppressants should be as low as possible,Moreover,radiotherapy or chemiotherapy should be adopted according to the types and stages of tumor complicating renal transplantation.

Objective To investigate whether the donor's glomerular filtration rate (GFR) to recipient's weight ratio (Dg/Rw) is a useful tool to predict early clinical outcome in living-related do-nor transplantation.Methods A total number of 108 living donor transplant recipients in the Chinese Military 309th Hospital from Jan.2014 to July 2015 were enrolled in this study.The patients who had multi-organ transplantation or developed grafts rejection,delayed graft function,hydronephrosis or renal vascular stenosis were excluded.The 90 qualified recipients were divided into G1 group (Dg/Rw ≤0.81),G2 group (Dg/Rw 0.81～1.11),and G3 group (Dg/Rw≥1.12).We respectively analyzed the relationship between recipient's serum creatinine Scr and Dg/Rw at 3-,7-,30-day and 1 year after transplantation.Results Scr at 3-,7-,30-day and 1 year after transplantation had linear correlation with Dg/Rw.As compared with G1 and G2 groups,Scr level was significantly reduced in G3 group at different time points (P＜0.05).Conclusion Dg/Rw has a negative relationship with Scr level after renal transplantation.Pre-transplant Dg/Rw is a potential index to predict the early clinical outcome in living-related donor transplantation.

Objective To investigate the correlation between de nove anti-endothelial cell antibodies (AECA) and adverse events after renal transplantation and the effect of transplanted renal function within six months after operation.Methods The expression of AECA in serum of 85 renal transplant recipients was detected by indirect immunofluorescence assay (ⅡF) before and 1 day,3 days,7 days,15 days and 1 month after renal transplantation.The patients were divided into double positive group (AECA positive before and after surgery),single positive group (postoperative de nove AECA positive) and negative group (preoperative and postoperative AECA negative) according to AECA test results.The occurrence of adverse events in each group such as DGF,rejection,infection and so on,as well as the serum creatinine levels were recorded at each time point within six months.Results Of the 85 recipients,29 were positive for AECA,including 19 in the double positive group,10 in the single positive group,and 56 in the negative group.The incidence of rejection in single positive group (30％) was higher than that in the rest two groups (5.3％ for double positive group,and 17.9％ for negative group),but there was no statistically significant difference (P =0.21).The incidence of DGF in the single positive group,double positive group and negative group was 70.0％,26.3 ％ and 32.1 ％ respectively.The positive rate of the single positive group was significantly higher than that of the rest two groups (P =0.04),and the duration of DGF was significantly longer in the single positive group than that of the rest two groups (P＜0.01).The incidence of infection in the single positive group,double positive group and negative group was 20.0％,21.1％ and 8.9％respectively,and there was no significant difference among the three groups (P =0.31).As compared with the double positive group and the negative group,the serum creatinine level was significantly increased in the single positive group at 1st week,1st month,3rd month and 6th month after operation (P =0.02,P =0.04,P =0.04 and P =0.02 respectively).Conclusion Postoperative AECA can increase the risk of DGF,prolong the duration of DGF,and affect the recovery of renal function within 6 months after renal transplantation.

BACKGROUND: Removal of immunosuppressants in patients with recurrent tumor in long-term following organ transplantation is always a hot controversial point in academic circles. To further elevate clinical efficiency, people began to invent new immunosuppressant and studied immune efficiency of various immunosuppressant component. They tried to reduce the application of cyclosporin A (CsA).OBJECTIVE: To analyze the CsA safe withdrawal of a case of kidney recipients, at 18 years after renal transplantation, who developed bladder carcinoma and renal pelvic carcinoma at 11 years and 18 years after transplantation, respectively. METHODS: After identified diagnosis, we performed transurethral resection of bladder tumor (TURBt) and total nephroureterectomy merobladder excision. Pathologic examination revealed grade Ⅰ-Ⅱ of bladder and renal pelvic transitional cell carcinoma. After the operation, patient was treated with immune suppression program of CsA withdrawal gradually in 12 days.Within 12 days, 5 mg CsA was decreased every 3 days, and complete withdrawal was done at 12 days. The dosage of azathioprine tablets and prednisone acetate tablets was not changed. Serum creatinine levels were rechecked every 3 days during drug withdrawal, and blood pressure, urine volume, physical symptom of patients and ultrasound of transplanted kidney were observed.RESULTS AND CONCLUSION: During the three months of CsA withdrawal, the blood creatinine levels were from 65 to indicated that the CsA gradually withdrawal of a case of kidney recipients after renal transplantation, who developed transitional cell carcinoma and was performed transurethral resection of bladder tumor (TURBt) and total nephro- ureterectomy merobladder excision, was safe. No tumor relapse or diversion was found.

BACKGROUND: Early reperfusion can effectively treat acute myocardial infarction (AMI) and reduce the mortality significantly. This study aimed to compare the role of plasma microRNA-1 (miR-1) and cardiac troponin T (cTnT) in early diagnosis of AMI patients. METHODS: From May 2011 to May 2012, plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student'st test or Fisher's exact test. The Mann-WhitneyU test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic (ROC) curve was established to discriminate the AMI patients from the controls. RESULTS: In the present study, the expression of plasma miR-1 was significantly increased in the AMI patients compared with the healthy controls (P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days (P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population (P>0.05). ROC curve analyses demonstrated that miR-1 was specific and sensitive for the early diagnosis of AMI, but not superior to cTnT. CONCLUSION: Plasma miR-1 could be used in the early diagnosis of AMI, but it is similar to cTnT.