[Influencing factors analysis on live birth outcome of D3 cleavage stage frozen-thawed embryo after overnight culture and development of nomogram prediction model].

Objective: To analyze the factors affecting the live birth outcome of D3 cleavage stage frozen-thawed embryos after overnight culture, and establish a nomogram model to predict the live birth probability. Methods: The clinical data of assisted reproductive patients treated with D3 cleavage stage frozen-thawed embryo transfer in the First Affiliated Hospital of Zhengzhou University from January 2017 to July 2020 were analyzed retrospectively. A total of 5 456 patients were divided into modeling group and validation group according to the ratio of 7∶3. The modeling group [3 831 patients with average age of (33±6) years] was used to evaluate the independent risk factors of the patient's live birth outcome through multivariate logistic regression analysis and construct the nomogram prediction model. The validation group [1 625 patients with average age of (33±6) years] was used to verify and calibrate the performance of the model. Results: The results of multivariate logistic regression analysis showed that the risk factors related to live birth outcome of D3 frozen-thawed embryos after overnight culture included: female age (OR=0.901,95%CI:0.889-0.914,P<0.001), body mass index (BMI) (OR=0.979,95%CI:0.957-1.002,P=0.072), endometrial thickness on the transfer day (OR=1.121,95%CI:1.080-1.164,P<0.001), the number of transferred embryos (OR=2.192,95%CI:1.867-2.579,P<0.001) and embryo division resumed after overnight culture (OR=1.405,95%CI:1.213-1.627,P<0.001). The area under the curve (AUC) of the nomogram model in the modeling group was 0.716 and that in the validation group was 0.739.Both sets of calibration curves fited well with the ideal curve, which illustrated that the model had good predictive ability. Conclusions: The female age, BMI endometrial thickness on the transfer day, the number of transferred embryos and the embryo division resumed after overnight culture are risk factors for the live birth outcome of frozen-thawed embryos after overnight culture. The nomogram established based on the above factors can help predict the probability of live birth after frozen-thawed embryo transfer.

Preconditioning with sodium arsenite inhibits apoptotic cell death in rat kidney with ischemia/reperfusion or cyclosporine-induced Injuries. The possible role of heat-shock protein 70 as a mediator of ischemic tolerance.

This study was performed to evaluate the effect of heat-shock protein (HSP)70 induction with sodium arsenite (SA) on ischemia/reperfusion (I/R) or cyclosporin A (CsA)-induced injuries in rat kidney. Rats were classified into five groups (sham, I/R, SA+I/R, I/R+CsA and SA+I/R+CsA groups) according to both the status of SA pretreatment and treatment with CsA. SA (6 mg/kg, i.v.) pretreatment was accomplished 12 h before I/R injury, and CsA (20 mg/kg, s.c.) was given subsequent to I/R injury. The effect of SA pretreatment on I/R injury was evaluated using measurements of renal function, the histopathology score, and assays for apoptosis (DNA fragmentation analysis, TUNEL staining, mRNA expressions of the pro-apoptotic genes and caspase activities). In addition, mitochondrial morphology was examined by electron microscopy. Induction of HSP70 with SA improved both renal function and the histopathology score as compared to the group without HSP70 induction. The assays for apoptosis revealed that SA pretreatment decreased the DNA laddering pattern, TUNEL-positive cells, mRNAs expression of pro-apoptotic genes and caspase activities as compared with the group without SA pretreatment. In addition, the mitochondrial morphology was well preserved in the groups with SA pretreatment. In conclusion, SA pretreatment prevents subsequent I/R or CsA-induced injuries in the rat kidney, and this renoprotective effect appears to be mediated by induction of HSP70.

Clinical significance of anti-endothelial cell antibody in renal transplant recipients.

In order to evaluate the role of anti-endothelial cell antibody (AECA) in acute rejection in renal transplantation, serum AECA IgG titers were measured in 68 healthy controls, 111 chronic hemodialysis (HD) patients and 58 first renal transplant recipients. The AECA titer in hemodialysis patients was higher than in healthy controls (13.9 +/- 5.0 vs. 4.8 +/- 2.3 U/mL, p < 0.01). In transplant recipients, AECA titers were not affected by dialysis mode (HD vs. CAPD vs. non-dialysis; 9.6 +/- 7.6 vs. 7.9 +/- 3.9 vs. 11.9 +/- 3.1 U/mL, p > 0.05). After renal transplantation, AECA titer was decreased significantly (vs. 4.7 +/- 3.6 U/mL. p < 0.01). The serum AECA IgG titers increased significantly in recipients with acute rejection (6.9 +/- 3.1 vs. 13.5 +/- 9.9 U/mL, p < 0.01), but decreased to 5.6 +/- 3.0 U/mL (p < 0.01) after formal rejection therapy. In the recipients with acute rejection (n = 27), the pre-renal transplant AECA titer was higher than in that without acute rejection (14.0 +/- 8.6 vs. 7.7 +/- 3.8 U/mL, p < 0.01). The results of this study lead us to conclude that pre- and post-renal transplant AECA titer might be a useful predictor for acute rejection and useful for monitoring acute rejection in renal transplant recipients.

Activation of PLC and PI 3 kinase by PDGF receptor alpha is not sufficient for mitogenesis and migration in mesangial cells.

BACKGROUND: Platelet-derived growth factor (PDGF) isoforms act through two distinct cell surface alpha and beta receptors. Glomerular mesangial cells express both receptors. PDGF BB and AB are potent mitogens for glomerular mesangial cells, and PDGF BB stimulates cell migration in a phosphatidylinositol 3 (PI 3) kinase-dependent manner. In this study, we investigated the effect of PDGF AA on cell migration, PI 3 kinase and phospholipase C (PLC) activation, and the role of these two enzymes in mediating biological responses in these cells in response to all three isoforms. METHODS: 3H-thymidine incorporation and modified Boyden chamber assay were used to determine DNA synthesis and directed migration, respectively, in response to all three PDGF isoforms. Differential activation of alpha and beta receptors was studied by immunecomplex tyrosine kinase assay of corresponding receptor immunoprecipitates. PLC gamma 1 activity was determined by measuring total inositol phosphates in response to different PDGF isoforms. PI 3 kinase activity was determined in antiphosphotyrosine or PDGF receptor immunoprecipitates. RESULTS: Both PDGF BB and AB resulted in stimulation of DNA synthesis and directed migration of mesangial cells. AA was neither chemotactic nor mitogenic. However, all three isoforms increased tyrosine phosphorylation of a 180 kD protein in antiphosphotyrosine immunoprecipitates, suggesting activation of respective receptors. Direct immunecomplex tyrosine kinase assay of alpha and beta receptors demonstrated significant activation of both of these receptors when cells are treated with PDGF BB or AB. PDGF AA increased tyrosine kinase activity of the alpha receptor but not the beta receptor. All three isoforms significantly stimulated the production of inositol phosphates with order of potency being BB > AB > AA. PDGF AA also dose dependently stimulated PI 3 kinase activity measured in antiphosphotyrosine immunoprecipitates of treated cells. A comparison of PI 3 kinase activity in antiphosphotyrosine immunoprecipitates from mesangial cells stimulated with three different PDGF isoforms showed significant activation of this enzyme with a decreasing order of activity: BB > AB > AA. CONCLUSION: Taken together, these data demonstrate that all three isoforms of PDGF significantly stimulate PLC gamma 1 and PI 3 kinase, two enzymes necessary for both DNA synthesis and directed migration. However, activation of alpha receptor by PDGF AA with a subsequent increase in PLC and PI 3 kinase activities is not sufficient to induce these biological responses in mesangial cells. These data indicate that the extent of activation of signal transduction pathways may be a major determinant of the biological activity of different PDGF isoforms in mesangial cells.

The possible role of c-fos protein in hypothalamus in sleep disturbance in chronic uremic rats.

Sleep disturbance is very common in patients with chronic renal failure, but its mechanism is not clear. The activity of c-fos protein (FOS) in ventrolateral preoptic neurons (VLPO) is associated with the sleep pattern. The purpose of this study was to evaluate the relationship between sleep disturbance and the expression of FOS in VLPO of chronic uremic rats. Chronic uremia was induced by the 5/6 nephrectomized model. The movements of the rats were measured with infrared monitoring during the daytime (8.00-20.00) and nighttime (20.00-8.00). Rats were killed at 10.00 or 16.00 h for the daytime (uremic rats 7, control 8) and at 22.00 h for the nighttime (uremic rats 7, control 9). The expression of FOS in VLPO was examined with the immunohistochemical method. The number of recorded daytime movements in uremic rats was significantly higher than in control rats (458 +/- 185 vs. 222 +/- 41, p < 0.001), but the number of recorded nighttime movements in uremic rats was lower than in control rats (949 +/- 430 vs. 1,618 +/- 261, p < 0.001). In the daytime, the number of FOS immunoreactive cells in uremic rats was lower than in control rats (18.4 +/- 5.3 vs. 42.8 +/- 6.3, p < 0. 001), but there was no difference between two groups in the nighttime (10.8 +/- 8.4 vs. 12.5 +/- 5.1, p = 0.62). There was a strong negative correlation between the number of recorded movements and the number of FOS immunoreactive cells in VLPO (r = -0.700, p < 0.001). This finding suggests that sleep disturbances in chronic uremic rats might be related to the decreased expression of FOS in VLPO.

Bone morphogenetic protein-2 inhibits MAPK-dependent Elk-1 transactivation and DNA synthesis induced by EGF in mesangial cells.

Bone morphogenetic protein-2 (BMP-2) is a member of the TGFbeta superfamily of growth and differentiation factors. We investigated the effect of BMP-2 on epidermal growth factor (EGF)-induced mitogenic signaling in kidney glomerular mesangial cells. BMP-2 dose-dependently inhibits EGF-induced DNA synthesis. Maximum effect was obtained at a concentration of 100 ng/ml. BMP-2 had no inhibitory effect on the EGF receptor (EGFR)-associated tyrosine kinase activity indicating that inhibition of DNA synthesis is due to regulation of post-receptor signaling event(s). EGF stimulates MAPK activity in mesangial cells in a time-dependent manner. Inhibition of MAPK by the MEK inhibitor PD098059 blocks EGF-induced DNA synthesis indicating the requirement of this enzyme activity in EGF-mediated mitogenic signaling. Furthermore, we show that exposure of mesangial cells to BMP-2 blocks EGF-induced MAPK activity which leads to phosphorylattion of Elk-1 transcription factor. Using a GAL-4 DNA binding-domain-Elk-1 transactivation domain fusion protein-based reporter assay, we demonstrate that BMP-2 inhibits EGF-induced Elk-1-mediated transcription. These data provide the first evidence that BMP-2 signaling in mesangial cells initiates a negative regulatory cross-talk with MAPK-based transcription to inhibit EGF-induced DNA synthesis.

Factors on graft survival of living donor kidney transplantation in a single center.

We analyzed the potential factors that could influence the survival of graft, focused on primary graft living-donor kidney transplantation with cyclosporine (CsA) therapy. 680 cases were enrolled in this study. Patients and graft survival rates were calculated by a Kaplan-Meier product limit estimate with a 1-day time interval. The analyzed variables were donor relationship, HLA matching, recipient age and sex, donor age and sex, ABO blood type compatibility, diabetic status, hepatitis virus infection, donor specific or non-specific blood transfusion and acute rejection episode. The results suggested that acute rejection episode was the most prognostic factor in graft survival. An HLA-matched donor and a young male donor, i.e. a greater donor nephron mass for less recipient body mass, will show better long-term survival. Diabetes and hepatitis B infection have some negative effects on the long-term survival of graft kidney, but age of recipient, donor-specific transfusion and donor-recipient relationship have little effect.

Comparison of peritoneal catheter survival with fistula survival in hemodialysis.

OBJECTIVE: To compare continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) with regard to long-term maintenance of access. DESIGN: Retrospective study of a four- to six-year time period at one center. PATIENTS: One hundred and twenty-two CAPD patients between December 1988 and December 1992, and 172 HD patients between May 1986 and December 1992. MAIN OUTCOME MEASURE: Cumulative survival rate of peritoneal catheters and arteriovenous fistulas (AVF) was the main outcome measure. Variables affecting the survival rate including sex, age, presence or absence of diabetes, and type of AVF (autogenous or prosthetic graft) were assessed. The causes of peritoneal catheter failures were analyzed. RESULTS: The cumulative survival rate of all peritoneal catheters was significantly longer than the AVF survival rate (84% vs 74% at one year; 73% vs 61% at two years; and 63% vs 48% at three years) (p = 0.029). There were no differences in peritoneal catheter survival according to sex, age, or diabetes. Compared with AVF survival, peritoneal catheter survival was significantly longer in male (p = 0.0492), elderly (p = 0.0082), and diabetic (p = 0.0022) patients. Prosthetic graft and old age were risk factors for AVF survival. Of all peritoneal catheter failures, infectious complications were responsible for 75% (33/44) and mechanical complications for 25% (11/44). Peritonitis was the leading infectious complication (21/33) and outflow obstruction was the leading mechanical complication (9/11). CONCLUSION: In terms of long-term maintenance of access, CAPD is superior to HD, especially in the elderly or diabetics. Prevention and proper management of peritonitis may prolong the peritoneal catheter survival.

Effect of long-term administration of somatostatin analogue on renal enlargement in uninephrectomized-diabetic rats.

Recent study has demonstrated that the long-acting somatostatin analogue administration effectively prevented initial renal growth in diabetic and uninephrectomized rats. In the present study we examined long-term effect of somatostatin analogue (Sandostatin) on renal enlargement in uninephrectomized-diabetic rat5. Animals were divided into 4 groups: (1) normal control rats (C) (n = 7), (2) uninephrectomized rats (NPX) (n = 7), (3) uninephrectomized-diabetic rats (NPX + DM) (n = 7) and (4) NPX + DM rats treated with Sandostatin (NPX + DM + Tx) (n = 9). All animals had free access to diet (50% protein) and water during the experimental period. To the NPX + DM + Tx rats, 2.5 micrograms of Sandostatin was given subcutaneously twice a day for 8 weeks. Periodic observations were done at 0, 4 and 8 weeks. After 8 weeks. NPX rats (0.540 +/- 0.017 (SEM)) had higher fractional kidney weights (FKW) (wet kidney wt/body wt) compared to C rats (0.410 +/- 0.014) (p < 0.0005), and both NPX + DM rats (0.983 +/- 0.098) and NPX + DM + Tx rats (1.091 +/- 0.042) had higher FKW compared to C rats (p < 0.0001) and NPX rats (p < 0.005), respectively. But no significant change of FKW was observed between NPX + DM rats and NPX + DM + Tx rats. Systolic blood pressure, BUN, serum creatinine, glomerular filtration rate and 24 hour urine protein excretion in NPX + DM rats were not different from those in NPX + DM + Tx rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of HLA mismatching on graft survival in living-donor kidney transplants: Catholic Medical Center, 1984 to 1993.

This study focuses on the beneficial effect of HLA matching on long-term graft survival rates in CsA-treated living primary kidney transplants at Catholic Medical Center, 1984 to 1993. 1. An impressive 26% difference in kidney graft survival was observed at 5 years between recipients who received 0 and 2 HLA-DR mismatches (79% vs 53%). 2. Five-year kidney graft survival rates in the 0, 1, 2, and 3-HLA-B+DR mismatches were 87%, 76%, 77%, and 74%, respectively, which was significantly different from 54% survival rates in the 4-HLA-B+DR mismatch group. 3. The 5-year kidney graft survivals in the 0, 1, 2, HLA-DR-mismatched living-nonrelated donor group were 84%, 76%, and 39%, respectively, which were significant differences. 4. The 5-year kidney graft survivals in the 0, 1, 2, HLA-DR-mismatched living-related donor group were 75%, 79%, and 72%, respectively, which were not significant. 5. The effect of HLA-A, B, A+B, A+DR, and A+B+DR mismatches showed little difference among the groups with different mismatch numbers. In conclusion, better matching for the HLA-DR, B+DR antigens significantly improved kidney graft survivals in our CsA-treated primary living-donor transplant recipients.

Factors influencing long-term outcome of living-donor kidney transplantation in the cyclosporine era.

To evaluate the effect that CsA has had on the weight of some factors previously considered influential on kidney graft survival rates in conventionally immunosuppressed recipients, we analyzed patient and graft survival rates for 524 consecutive living-donor first kidney transplants. All patients were transplanted at the Catholic Medical Center between 1984 and 1991 and treated with CsA. The data were stratified to reflect differences in a) HLA matching; b) acute graft rejection within 3 months posttransplant; c) donor sources; d) age; e) sex; f) graft number; g) diabetics; h) HBV status; i) DST; and j) number of pretransplant transfusions. Overall actuarial 5-year patient and graft survival rates were 86% and 77%. The actuarial 5-year graft survival rates for the HLA-identical, haploidentical, and mismatched groups were 93%, 75% and 80% (p = 0.3858), respectively. The actuarial 5-year graft survival rates in recipients with acute graft rejection (< 3 months) and without acute graft rejection were 55% and 80% (p = 0.0001). The actuarial 5-year graft survival rates for the HBV-positive and -negative groups were 55% and 80% (p = 0.0048). The actuarial 5-year graft survival rates according to the number of pretransplant blood transfusions--0, 1-4, and over 5 units groups--were 65%, 80%, and 81% (p = 0.0026), respectively. We conclude that a) acute graft rejection within 3 months, b) HBV-positive, and c) pretransplant nontransfusion had a significant negative influence on long-term graft survival, whereas little or no effect was attributable to HLA matching, donor source, age, sex, graft number, diabetes, and DST.