Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption.

The aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when SGLT2 is inhibited. The PBPK-UGE model was developed using physicochemical and biochemical properties, renal physiological parameters, binding kinetics, glucose, and Na+ reabsorption kinetics by SGLT1/2. For area under the plasma concentration-time curve, maximum plasma concentration, and cumulative EMP excretion in urine, the predicted values fell within a range of 0.5-2.0 when compared to observed data. Additionally, the simulated UGE data also matched well with the clinical data, further validating the accuracy of the model. According to the simulations, SGLT1 and SGLT2 contributed approximately 13% and 87%, respectively, to RGR in the absence of EMP. However, in the presence of EMP at doses of 2.5 and 10 mg, the contribution of SGLT1 to RGR significantly increased to approximately 76%-82% and 89%-93%, respectively, in patients with type 2 diabetes mellitus. Furthermore, the model supported the understanding that the compensatory effect of SGLT1 is the underlying mechanism behind the moderate inhibition observed in total RGR. The PBPK-UGE model has the capability to accurately predict the PK and UGE time profiles in humans. Furthermore, it provides a comprehensive analysis of the specific contributions of SGLT1 and SGLT2 to RGR in the presence or absence of EMP.

Genomic prediction of pig growth traits based on machine learning.

This study aimed to assess and compare the performance of different machine learning models in predicting selected pig growth traits and genomic estimated breeding values (GEBV) using automated machine learning, with the goal of optimizing whole-genome evaluation methods in pig breeding. The research employed genomic information, pedigree matrices, fixed effects, and phenotype data from 9968 pigs across multiple companies to derive four optimal machine learning models: deep learning (DL), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGB). Through 10-fold cross-validation, predictions were made for GEBV and phenotypes of pigs reaching weight milestones (100 kg and 115 kg) with adjustments for backfat and days to weight. The findings indicated that machine learning models exhibited higher accuracy in predicting GEBV compared to phenotypic traits. Notably, GBM demonstrated superior GEBV prediction accuracy, with values of 0.683, 0.710, 0.866, and 0.871 for B100, B115, D100, and D115, respectively, slightly outperforming other methods. In phenotype prediction, GBM emerged as the best-performing model for pigs with B100, B115, D100, and D115 traits, achieving prediction accuracies of 0.547, followed by DL at 0.547, and then XGB with accuracies of 0.672 and 0.670. In terms of model training time, RF required the most time, while GBM and DL fell in between, and XGB demonstrated the shortest training time. In summary, machine learning models obtained through automated techniques exhibited higher GEBV prediction accuracy compared to phenotypic traits. GBM emerged as the overall top performer in terms of prediction accuracy and training time efficiency, while XGB demonstrated the ability to train accurate prediction models within a short timeframe. RF, on the other hand, had longer training times and insufficient accuracy, rendering it unsuitable for predicting pig growth traits and GEBV.

LDOC1 regulates Wnt5a expression and osteosarcoma cell metastasis and is correlated with the survival of osteosarcoma patients.

Osteosarcomas are common bone malignancies in children and adolescents. LDOC1 (leucine zipper, down-regulated in cancer 1), a tumor suppressor, is down-regulated in many cancers. In this study, we investigated the role of LDOC1 in tumor metastasis and its prognostic significance in osteosarcomas. We established osteosarcoma cells stably expressing LDOC1, driven by an HIV-based lentiviral system. We investigated the impact of LDOC1 on migration and invasion abilities in these cells using a transwell assay. LDOC1-associated changes in expression of metastasis-promoting genes were analyzed with a quantitative real-time polymerase chain reaction primer array. A xenograft tumor model (n = 7 mice/group) was used to assess the effect of LDOC1 on osteosarcoma metastasis in vivo. The overall survival and disease-free survival of osteosarcoma patients (n = 74) were analyzed retrospectively based on immunohistochemical analysis of LDOC1 levels in tumors and Kaplan-Meier analysis. LDOC1-expressing osteosarcoma cells displayed decreased migration and invasion in vitro. The quantitative real-time polymerase chain reaction primer array data showed that increased LDOC1 expression up-regulated many metastasis-suppressor genes. In the xenograft model, micro-computed tomography imaging data indicated that increased LDOC1 expression is associated with weaker lung metastasis ability. The Wnt5a signaling pathway promotes osteosarcoma metastasis; LDOC1 expression decreased Wnt5a levels in osteosarcoma cells. Kaplan-Meier analysis showed that higher LDOC1 expression was associated with improved osteosarcoma patient overall survival and disease free survival (p = 0.022). Our data show that LDOC1 is a tumor suppressor in osteosarcoma, and that it regulates metastasis of osteosarcoma cells. Furthermore, LDOC1 might be a valuable prognostic marker in osteosarcomas.

Engineering P450 Peroxygenase to Catalyze Highly Enantioselective Epoxidation of cis-ß-Methylstyrenes.

P450 119 peroxygenase and its site-directed mutants are discovered to catalyze the enantioselective epoxidation of methyl-substituted styrenes. Two new site-directed P450 119 mutants, namely T213Y and T213M, which were designed to improve the enantioselectivity and activity for the epoxidation of styrene and its methyl substituted derivatives, were studied. The T213M mutant is found to be the first engineered P450 peroxygenase that shows highly enantioselective epoxidation of cis-ß-methylstyrenes, with up to 91 % ee. Molecular modeling studies provide insights into the different catalytic activity of the T213M mutant and the T213Y mutant in the epoxidation of cis-ß-methylstyrene. The results of the calculations also contribute to a better understanding of the substrate specificity and configuration control for the regio- and stereoselective peroxygenation catalyzed by the T213M mutant.

Total Synthesis of Chiral Falcarindiol Analogues Using BINOL-Promoted Alkyne Addition to Aldehydes.

An enantioselective total synthesis of chiral falcarindiol analogues from buta-1,3-diyn-1-yltriisopropylsilane is reported. The key step in this synthesis is BINOL-promoted asymmetric diacetylene addition to aldehydes. The two chiral centers of the falcarindiol analogues can be produced by using the same kind of catalyst with high selectivity, and the final product can be obtained in only six steps.

[Effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension].

OBJECTIVE: To investigate the effect of atorvastatin on exercise tolerance in patients with diastolic dysfunction and exercise-induced hypertension. METHODS: A randomized, double-blind, placebo-controlled prospective study was performed. Sixty patients with diastolic dysfunction (mitral flow velocity E/A <1) and exercise-induced hypertension (SBP>200 mm Hg) treated with atorvastatin (20 mg q.d) or placebo for 1 year. Cardiopulmonary exercise test and exercise blood pressure measurement were performed. Plasma B-natriuretic peptide (BNP) concentration at rest and at peak exercise, plasma high sensitive-C reaction protein (hs-CRP) and endothelin (ET) concentration were determined at baseline and after treatment. RESULTS: After treatment by atorvastatin, the resting SBP, pulse pressure, the peak exercise SBP and BNP were significantly decreased; and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were increased. All of these parameters had significant differences with baseline levels (P<0.05) and the rest pulse pressure, the peak exercise SBP and BNP, and the exercise time had significant differences compared with placebo treatment (P<0.05). Plasma concentrations of hs-CRP and ET were markedly reduced by atorvastatin treatment compared with baseline and placebo (P<0.05). No difference in above parameters was found before and after placebo treatment (P>0.05). CONCLUSION: In patients with diastolic dysfunction at rest and exercise-induced hypertension, atorvastatin can effectively reduce plasma hs-CRP and ET level, lower blood pressure and peak exercise SBP, decrease peak exercise plasma BNP concentration, and ultimately improve exercise tolerance.

Osteopontin knockdown inhibits αv,ß3 integrin-induced cell migration and invasion and promotes apoptosis of breast cancer cells by inducing autophagy and inactivating the PI3K/Akt/mTOR pathway.

BACKGROUND: Osteopontin (OPN) is associated with tumor formation, progression and metastasis, and increased OPN levels have been associated with poor survival in breast cancer. We investigated the mechanisms responsible for OPN activity, and the relationships between OPN expression and clinical parameters in breast cancer. METHODS: OPN mRNA and protein levels were compared in malignant and benign breast tumors by polymerase chain reaction (PCR) and immunohistochemistry, respectively, and levels in breast cancer cells were determined by PCR and western blotting. The effects of lentiviral-mediated knockdown of OPN on OPN and αv,ß3 integrin expression, cell invasion and migration, autophagy and apoptosis were analyzed in MDA-MB-231 cells. RESULTS: OPN expression increased with aggressiveness of breast cancer phenotype. OPN knockdown inhibited αv,ß3 integrin expression in MDA-MB-231 cells, with subsequent inhibition of cell migration and invasion. Knockdown also inhibited the PI3K/Akt/mTOR pathway, promoted expression of the autophagy-related gene products LC3 and Beclin 1, and increased apoptosis. OPN expression was positively associated with tumor grade and lymph node metastasis. CONCLUSION: These results suggest that knockdown of OPN may inhibit breast cancer metastasis by regulating αv,ß3 integrin expression and inducing autophagy and subsequent inhibition of PI3K/Akt/mTOR signaling, thus providing further insights into the complex mechanisms regulating tumor growth and metastasis.

A sensitive immunosorbent bio-barcode assay based on real-time immuno-PCR for detecting 3,4,3',4'-tetrachlorobiphenyl.

A functionalized gold-nanoparticle bio-barcode assay, based on real-time immuno-PCR (IPCR), was designed for the determination of 3,4,3',4'-tetrachlorobiphenyl (PCB77). 15 nm gold nanoparticles were synthesized, and modified with thiol-capped DNA and goat anti-rabbit IgG. The nanoparticle probes were used to replace antibody-DNA conjugate in the IPCR, and were fixed on the PCR tube wall via the immune reaction. Real-time PCR was performed to quantify the DNA signal directly. Under optimized conditions, the new method was used to detect PCB77 with a linearity range from 5 pg L(-1) to 10 ng L(-1), and the limit of detection (LOD) was 1.72 pg L(-1). Real samples of Larimichthys polyactis, collected from the East China Sea, were analyzed. Recovery was from 82 % to 112 %, and the coefficient of variation (CV) was acceptable. The results were compared with GC-ECD, revealing that the method would be acceptable for providing rapid, semi-quantitative, and reliable test results for making environmental decisions.

The glycogen synthase kinase-3ß/nuclear factor-kappa B pathway is involved in cinobufagin-induced apoptosis in cultured osteosarcoma cells.

Cinobufagin, a major component of cinobufacini (huachansu), is an important cardenolidal steroid. Several studies have suggested that cinobufagin has potent anti-cancer effects. The present study examines the apoptosis-inducing activity and the underlying mechanism of action of cinobufagin in osteosarcoma (OS) cells. Our results showed that cinobufagin potently inhibited the proliferation of U2OS, MG63 and SaOS-2 cells. Significant increases in G2/M cell-cycle arrest and apoptosis in OS cells were also observed. The expression levels of several apoptotic proteins were assessed after cinobufagin treatment in U2OS cells. Among them, xIAP, cIAP-1, survivin and Bcl-2 levels decreased remarkably, while the levels of Bax and cleaved-PARP increased. Furthermore, we validated the inhibition of GSK-3ß/NF-κB signaling following cinobufagin treatment. Western blots showed a decrease in nuclear p65 protein expression after exposure to different concentrations of cinobufagin, while the phosphorylation of GSK-3ß was simultaneously increased. Transduction with constitutively active forms of GSK-3ß could protect against the downregulation of p65 and upregulation of cleaved-PARP that are induced by cinobufagin treatment. However, combined treatment with cinobufagin and SB216367 resulted in a significant reduction in p65 and an increase in cleaved-PARP in U2OS cells. Altogether, these results show that cinobufagin is a promising agent for the treatment of OS. These studies are the first to reveal the involvement of the GSK-3ß/NF-κB pathway in cinobufagin-induced apoptosis.

[Effect of modified Badenoch operation on the treatment of posterior urethral stricture].

OBJECTIVE: To determine the effects of modified pull-through operation (Badenoch operation) on the treatment of posterior urethral stricture. METHODS: From September 2001 to December 2010 traditional pull-through operation was Modified for two times in our center. A total of 129 patients with posttraumatic posterior urethral stricture resulting from pelvic fracture injury underwent the modified urethral pull-through operation. Stricture length was 1.5 to 5.3 cm (mean 2.9 cm). Of the patients 43 had undergone at least 1 previous failed management for stricture. In phase 1 (from September 2001 to January 2008), the improving items include: (1) The distal urethral end was stitched and tied to the catheter. (2) As catheter was inserted into bladder and 20 ml water was injected into catheter balloon, the distal urethral end was fixed in the proximal urethra and an overlaying of 1.5 cm was formed between the two ends. (3) Three weeks later, it was tried to insert the catheter to bladder. After the urethral stump necrosis and the catheter separating from the urethra, the catheter was removed. In phase 2 (from February 2008 to December 2010), based on the above, irrigating catheter was used. After the surgery, urethra was irrigated with 0.02% furacillin solution through the catheter 3 times a day. All patients were followed up for at least 6 months. If patients had no conscious dysuria and maximum urinary flow rate (Qmax) > 15 ml/s, the treatment was considered successful. All complications were recorded. RESULTS: In phase 1, the 96 patients (101 times) underwent the procedure. The treatment was successful in 88 patients (success rate 92%). Within 1 to 13 days after removal of the catheter, urethral stricture was recurred in 8 patients. They had to undergo cystostomy once more for 3 to 11 months before reoperation (the 3 patients' reoperation was in phase 2). The 8 cases were treated successfully. In phase 2, 33 patients (total 36 times) underwent the procedure. One patient was failed (success rate 97%). The actual follow-up time is 7 to 93 months (An average of 37.6 months). Qmax is (22 ± 5) ml/s. No complications such as urinary incontinence, erectile pain, urinary shortening happened. CONCLUSIONS: The modified urethral pull-through operation is effective for the surgical treatment of posttraumatic posterior urethral stricture. It has a high success rate with durable long-term results. Complications are few. The procedure is simple, less demanding and especially suitable in patients who had previously undergone failed surgical treatments.

Renal vein lengthening using gonadal vein reduces surgical difficulty in living-donor kidney transplantation.

BACKGROUND: During living-donor kidney transplantation, to maximally decrease donor injury, the right kidney with lower glomerular filtration rate often is selected as the donor kidney. However, the renal vein of the right kidney is relatively short for transplantation. The gonadal vein is essentially useless and is easily accessed during the donor nephrectomy. METHODS: Seventeen live kidney donors received right kidney nephrectomy for living-donor kidney transplantation. Short renal veins were lengthened by circular anastomosis or spiral anastomosis of longitudinally cut gonadal veins. The renal function of receivers was evaluated using creatinine clearance. RESULTS: The renal veins were extended by 2.0-2.7 cm with circular anastomosis and 4.1-4.5 cm with spiral anastomosis with an average of 2.5 ± 0.7 cm. Lengthening of renal veins averaged 20.4 ± 4.2 min. All surgeries were successful, significantly reducing difficulty of vascular anastomosis during transplantation. No poor early graft function occurred. No side effects were observed in donors. CONCLUSIONS: When donor renal veins are too short for effective kidney transplantation and may affect reliability of vascular anastomosis, they can be lengthened by using gonadal veins without increasing injury to the donor. Successful extension of donor kidney renal veins expands the indication for right donor kidneys.

[Treatment of displaced humeral supracondylar fractures in children with external fixation using plaster or splint].

OBJECTIVE: To investigate the therapeutic effects of closed reduction and external fixation (plaster or splint) for the treatment of displaced humeral supracondylar fractures in children. METHODS: From March 2007 to September 2009,33 children (15 female and 18 male) with humeral supracondylar fractures treated in our hospital, ranging from 3 to 12 years old with an average of 6.4 years old. All the fractures were extension-type injuries, the flexion injures were excluded in our study. The humeral supracondylar fractures were classified according to Gartland classification. There were 21 Type H and 12 type III. In the initial treatment, all the patients were treated with closed reduction and external immobilization. The blood supply of the damaged upper extremity was evaluated before and after treatment. Clinical assessment was obtained at final follow-up using Flynn criteria, and radiologic assessment was obtained using Baumann and lateral humerocapitellar angles. RESULTS: All the children were treated successfully with closed reduction in the initial time; 24 children maintained limb alignment by external immobilization. Nine patients lost position due to the swelling around the elbow which affected unstable external fixation during the follow-up, 5 of which were treated with a repeated closed reduction and internal fixation with Kirschner wires, 4 of which were treated with traction. Thirty-one patients had a satisfactory outcome and 2 patients had an unsatisfactory outcome according to the Flynn criteria at the latest follows-up. CONCLUSION: Closed reduction and external stabilization is an important method for the treatment of displaced humeral supracondylar fractures in children. Making regular follow-up visits after closed reduction and casting is important for patients to maintain acceptable alignment, avoid complications and diagnose any loss of reduction.

Tetra-imidazolium piperazinediium bis-(benzene-1,3,5-tricarboxyl-ate) dihydrate.

During the crystallization of the title compound, 4C(3)H(5)N(2) (+)·C(4)H(12)N(2) (+)·2C(9)H(3)O(6) (3-)·2H(2)O, the acidic protons were transferred to the imidazole and piperazine N atoms, forming the final 4:1:2:2 hydrated mixed salt. The mean planes of the three carboxyl-ate groups in the anion are twisted with respect to the the central benzene ring, making dihedral angles of 13.5 (1), 14.5 (1) and 16.9 (1)°. In the crystal, the component ions are linked into a three-dimensional network by a combination of inter-molecular N-H⋯O, O-H⋯O and weak C-H⋯O hydrogen bonds. Further stabilization is provided by π-π stacking inter-actions with centroid-centroid distances of 3.393 (2) Šand weak C=O⋯π inter-actions [O-centroid = 3.363 (2) Å].

[Reduced cardiopulmonary exercise capacity in patients with essential hypertension: impact of left ventricular hypertrophy].

OBJECTIVE: To evaluate the cardiopulmonary exercise capacity in patients with essential hypertension (EH) complicating with or without left ventricular hypertrophy (LVH). METHODS: Graded maximal exercise test on the bicycle ergometer with respiratory gas analysis were performed in 30 gender and age matched normotensive controls, 40 EH patients without LVH and 30 EH patients with LVH (LVMI>125 g/m2 in males and > 120 g/m2 in females). Metabolic equivalents (METs), oxygen uptake (VO2), oxygen uptake to body mass ratio (VO2/kg) and oxygen uptake to heart beat ratio (VO2/HR) at time of reaching anaerobic threshold (AT) and at maximal oxygen uptake (VO2max) were measured and compared. RESULTS: METs and VO2/kg were significantly reduced in EH patients with or without LVH compared with controls [at AT, METs: 3.57 +/- 0.8 and 4.34 +/- 1.47 vs. 5.21 +/- 1.45; VO2/kg: 12.38 +/- 2.85 and 14.42 +/- 4.33 vs. 18.48 +/- 4.52, all P < 0.01; at VO2max, METs: 4.94 +/- 1.24 and 5.90 +/- 1.51 vs. 6.96 +/- 1.85; VO(2)/kg: (17.20 +/- 4.34) mlxmin(-1)xkg(-1) and (20.41 +/- 4.59) mlxmin(-1)xkg(-1) vs. (24.04 +/- 5.21) mlxmin(-1)xkg(-1), all P < 0.01]. METs and VO2/kg at both time points were also significantly reduced in EH patients with LVH compared EH patients without LVH (all P < 0.05). The lower VO2/kg in hypertensive patients was significantly correlated to higher LVMI (P < 0.05). CONCLUSIONS: Cardiopulmonary exercise capacity was reduced in hypertensive patients, especially in hypertensive patients with LVH.

[Purification function and ecological services value of Crassostrea sp. in Yangtze River estuary].

Oyster reef ecosystem is a natural decontamination plant of estuarine environment. This paper analyzed the bioaccumulation of heavy metals by Crassostrea sp. population at the dams of Yangtze River estuary, with its purification capacity and ecological services value assessed. The results indicated that Crassostrea sp. had a high capacity in bio-accumulating Cu, Zn and Cd, with the bio-concentration factor (BCF) and biota-sediment accumulation factor (BSAF) being (14.28 +/- 2.41) x 10(3), (12.75 +/- 2.02) x 10(3) and (14.51 +/- 3.71) x 10(3), and 26.78 +/- 4.53, 23.24 +/- 3.69 and 16.62 +/- 4.25, respectively. The bioaccumulation capacity decreased in the order of Cu > Zn > Cd > As > Pb > Hg. The total weight and fresh meat weight of the oyster at the dams of Yangtze River estuary were about 1.07 x 10(6) t and 1.75 x 10(5) t, respectively, and the total storage of nutrients and heavy metals were 1.462 x 10(6) kg N, 1 x 10(5) kg P, 24 745 kg Cu, 58 257 kg Zn, 609 kg Pb, 254 kg Cd, 0.18 kg Hg and 329 kg As. The total ecological services value of the oyster reef was estimated at about 8.27 x 10(6) RMB x a(-1), including habitat value of about 5.10 x 10(6) RMB x a(-1) and environmental value of about 3.17 x 10(6) RMB x a(-1). Such an environmental value was equivalent to the value of treating about 7.31 x 10(6) t combined sewage each year, and corresponded to a large municipal sewage plant with a treatment capacity about 20 000 t d(-1).

[Influence of transforming growth factor beta1 on long-term renal allograft function].

OBJECTIVE: To determine the association between urine transforming growth factor beta(1) (TGF-beta(1)) concentration and long-term renal allograft function. METHODS: Patients undergoing kidney transplantation between August 1, 1999 and June 30, 2001 and survived for one year with normal renal functions were investigated. The blood and urine TGF-beta(1) concentrations were tested at an interval of at least 6 months. Totally 134 patients completed the 3-year follow up investigation. Correlation between their renal functions (creatinine clearance rates) and their urine relative TGF-beta(1) concentrations 1 year after renal transplantation were determined. Of the 134 renal recipients, 16 were diagnosed to have chronic allograft nephropathy (CAN), and their blood and urine TGF-beta(1) concentrations 1 year after renal transplantation were compared with those of the recipients free of CAN. RESULTS: There was a positive correlation between long-term renal functions (loss of creatinine clearance rates) and in relative concentration of TGF-beta(1) urine 1 year after renal transplantation. The urine TGF-beta(1) concentrations of CAN and CAN-free recipients 1 year after transplantation were 182.7-/+40.2 and 398-/+33.5 pg/mg.Cr, respectively, showing significant differences. The blood TGF-beta(1) concentrations of CAN and CAN-free recipients were comparable (32.1-/+4.7 and 31.9-/+4.8 ng/ml, respectively). CONCLUSION: Urine TGF-beta(1) is significantly elevated even before the onset of renal dysfunction in patients with CAN, and urine TGF-beta(1) level in early stage after renal transplantation can help predict long-term renal function.

[Comparison percutaneous cervical disc nucleoplasty and cervical discectomy for the treatment of cervical disc herniation].

OBJECTIVE: To compare the therapeutic effect of percutaneous cervical disc nucleoplasty (PCN group) and percutaneous cervical discectomy (PCD group) for the treatment of cervical disc herniation. METHODS: A retrospective study was carried out from July of 2002 to December of 2004, and there were 80 cervical disc herniation cases who were operated by PCN (42 cases) or PCD (38 cases). The time of operation, clinical result and the stability of cervical spine after operation were evaluated and compared between 2 groups. RESULTS: All cases had been followed up from 6 months to 26 months, average (12 +/- 5) months on the PCN group and (12 +/- 4) months on the PCD group, and there was no significant difference on 2 groups (t = -0.06, P = 0.953). All cases had been successfully operated. There was significant difference in the operation time between 2 groups (t = -21.70, P = 0.000). There was significant difference in the pre- and post-operation scores of each group (PCN group: t = 14.05, P = 0.000; PCD group: t = -14.79, P = 0.000). There was no significant difference in 2 groups of the clinical outcomes (z = -0.377, P = 0.706, > 0.05). There was no instability of cervical spine cases in 2 groups after operation (P > 0.05), and the cervical spine stability was no significant difference in pre- and-operation in each group. CONCLUSIONS: PCN and PCD for the treatment of cervical disc herniation achieves good outcomes and no difference on the stability of cervical spine. PCN and PCD is a safe, minimally invasive, short time of operation, less traumatic operation and excellent clinical outcome.

[Association between TGF-Beta1 in allograft and chronic allograft nephropathy].

OBJECTIVE: To investigate the relation between TGF-beta1 in allograft and chronic allograft nephropathy (CAN). METHODS: The levels of urine TGF-beta1 were tested in 146 recipients whose renal function were normal from September 1, 2000 to January 31, 2001. Twenty recipients with the highest level of urine TGF-beta1 were classified in group A, while 20 other recipients with the lowest level of urine TGF-beta1 were classified in group B. In these two groups biopsies were carried out in 14 cases and 12 cases respectively, and TGF-beta1 mRNA in the biopsies was measured by RT-PCR. The levels of TGF-beta1 in the blood were also measured in the two groups. Three years later, the renal function was compared between the two groups. Biopsies were carried out in renal recipients whose creatinine is higher than normal. RESULTS: The level of TGF-beta1 in the blood showed no significant difference between the two groups; 3 years after transplantation, the loss of renal function in group A was severer than that in group B. The number levels of CAN cases in group A was larger than that in group B. The expression levels of TGF-beta1 and TGF-beta1 mRNA of the allografts were higher in group A than in group B; there were statistically significant differences between the two groups. CONCLUSION: The findings suggest that there is an association between TGF-beta1 in kidneys and CAN. The level of urine TGF-beta1 after renal transplantation may predict future renal function.

Effect of losartan on slowing progression of chronic allograft nephropathy.

OBJECTIVE: To investigate the effects of losartan, a specific angiotensin II receptor blocker, on slowing progression of renal insufficiency in patients with biopsy-proven chronic allograft nephropathy (CAN) and the molecular mechanism of the therapy. METHODS: Twenty-two renal transplant recipients with biopsy-proven CAN (group A) were treated with losartan within two months after renal dysfunction for at least one year. Losartan was administered at a dose of 50 mg/d. Twenty-four recipients in the same fashion (group B) who never received angiotensin II receptor antagonist were studied as control. The investigation time for each patient lasted one year. Renal functions and concentrations of plasma and urine transforming growth factor-beta1 (TGF-beta1) were compared between the two groups at the initiation and end of the study. In group A, expressions of TGF-betal mRNA and immunofluorescence intensity of TGF-betal protein and pathological alterations in renal biopsy specimens were compared between before losartan therapy and after one year of the therapy. RESULTS: At the initiation of the investigation, no significant differences were found between group A and group B in clinical data such as donor age, cold-ischemia time, HLA mismatch, levels of creatinine clearance (Ccr), plasma and urine TGF-beta1 concentrations. One year later, 14 of 22 (63.6%) patients showed stable or improved graft functions in group A, and 4 of 24 (16.7%) in group B. The difference was significant (P < 0.05). At the end of the study, urine TGF-betal concentration was 273.8 +/- 84.1 pg/mg x Cr in group A and 457.2 +/- 78.9 pg/mg x Cr in group B. During one year study period, loss of Ccr was 6.6 +/- 5.4 mL/min in group A and 16.2 +/- 9.1 mL/min in group B. Both of the differences were significant between the two groups (P < 0.01). No significant differences were found in plasma TGF-betal concentrations between the four values determined at the initiation and end of the study in the two groups (F = 2.56, P > 0.05). After one year losartan therapy, group A showed a significant decrease in expressions of TGF-beta1 mRNA and TGF-betal protein in renal biopsy specimens [from 1.59 +/- 0.35 to 0.96 +/- 0.27 and from (10.83 +/- 2.33) x l0(6) to (6.41 +/- 1.53) x 10(6), respectively; both P < 0.01], but in light microscopy the histological changes were similar to the first renal biopsy. Losartan was excellently tolerated in all patients in group A. No cases with losartan therapy showed too low blood pressure and other side effects. CONCLUSION: This study suggests that losartan have an effect on slowing progression of CAN. Reducing production of intrarenal TGF-betal may play a decisive role in the efficacy of losartan.

[TGF-beta1 in allograft and long-term renal function].

OBJECTIVE: To determine the relation between transforming growth factor beta1 (TGF-beta1) in allograft and long-term renal function. METHODS: Urine TGF-beta1 relative concentration (divided by urine creatinine) was tested in 168 recipients whose renal function was normal between August 1, 2000 and March 31, 2001. Twenty patients with higher urine TGF-beta1 relative concentrations formed Group A, and another 20 patients with lower urine TGF-beta1 formed Group B. In both groups biopsies were carried out in 15 cases and 12 cases respectively, and TGF-beta1 in the biopsis was tested by immunofluorescence. Blood TGF-beta1 concentrations in the 2 groups were also tested. Three years later, the renal function was compared between the 2 groups. Biopsies were carried out in renal recipients whose creatinine was higher than that of the normal. RESULTS: Blood TGF-beta1 concentrations in the 2 groups were not different significantly; 3 years after the transplantation, there was more loss of renal function and more chronic allograft nephropathy (CAN) cases in Group A than in Group B. Expression of TGF-beta1 in the allografts was higher in Group A than in Group B. The differences in the 2 groups were significant. CONCLUSION: The findings suggest that the higher expression of TGF-beta1 in the allografts is associated with the lower long-term survival rate of kidney graft. The level of urine TGF-beta1 after the renal transplantation can predict the long-term renal function.