Genetic proxies for antihypertensive drugs and mental disorders: Mendelian randomization study in European and East Asian populations.

BACKGROUND: Mental disorders are among the top causes of disease burden worldwide. Existing evidence regarding the repurposing of antihypertensives for mental disorders treatment is conflicting and cannot establish causation. METHODS: We used Mendelian randomization to assess the effects of angiotensin-converting-enzyme inhibitors (ACEIs), beta blockers (BBs), and calcium channel blockers (CCBs) on risk of bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ). We used published genetic variants which are in antihypertensive drugs target genes and correspond to systolic blood pressure (SBP) in Europeans and East Asians, and applied them to summary statistics of BD (cases = 41,917; controls = 371,549 in Europeans), MDD (cases = 170,756; controls = 329,443 in Europeans and cases = 15,771; controls = 178,777 in East Asians), and SCZ (cases = 53,386; controls = 77,258 in Europeans and cases = 22,778; controls = 35,362 in East Asians) from the Psychiatric Genomics Consortium. We used inverse variance weighting with MR-Egger, weighted median, weighted mode, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. We performed gene-specific analysis and utilized various methods to address potential pleiotropy. RESULTS: After multiple testing correction, genetically proxied ACEIs were associated with an increased risk of SCZ in Europeans (odds ratio (OR) per 5 mmHg lower in SBP 2.10, 95% CI 1.54 to 2.87) and East Asians (OR per 5 mmHg lower in SBP 2.51, 95% CI 1.38 to 4.58). Genetically proxied BBs were not associated with any mental disorders in both populations. Genetically proxied CCBs showed no benefits on mental disorders. CONCLUSIONS: Antihypertensive drugs have no protection for mental disorders but potential harm. Their long-term use among hypertensive patients with, or with high susceptibility to, psychiatric illness needs careful evaluation.

Using genetics to examine the overall and sex-specific associations of branch-chain amino acids and the valine metabolite, 3-hydroxyisobutyrate, with ischemic heart disease and diabetes: A two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Branch-chain amino acids (BCAAs) are linked to higher risk of diabetes, whilst the evidence on ischemic heart disease (IHD) is limited. Valine metabolite, 3-hydroxyisobutyrate (3-HIB), also plays an important role in metabolism, whilst its effect has been rarely examined. At the situation of no evidence from large trials, we assessed the role of BCAAs and 3-HIB in IHD and diabetes using Mendelian randomization to minimize confounding. Given their potential role in sex hormones, we also examined sex-specific associations. METHODS: We used genetic variants to predict BCAAs and 3-HIB, and obtained their associations with IHD and diabetes in large consortia and cohorts, as well as sex-specific association in the UK Biobank and DIAGRAM. We obtained and combined the Wald estimates using inverse variance weighting, and different analytic methods robust to pleiotropy. RESULTS: Genetically predicted BCAAs were associated with higher risk of IHD (odds ratio (OR) 1.19 per standard deviation (SD) increase in BCAAs, 95% confidence interval (CI) 1.05 to 1.35) and diabetes (OR 1.20, 95% CI 1.08 to 1.34). The associations with IHD were stronger in women (OR 1.23, 95% CI 1.03 to 1.48) than men (OR 0.96, 95% CI 0.83 to 1.10). 3-HIB was associated with higher risk of IHD (OR 1.43, 95% CI 1.17 to 1.73) but not diabetes, with no sex disparity. CONCLUSION: BCAAs and 3-HIB are potential targets for prevention in IHD and/or diabetes. BCAAs may exert a sex-specific role in IHD. Consideration of the sex disparity and exploration of the underlying pathways would be worthwhile.

Environment- and epigenome-wide association study of obesity in 'Children of 1997' birth cohort.

Background: Increasing childhood obesity is a global issue requiring potentially local solutions to ensure it does not continue into adulthood. We systematically identified potentially modifiable targets of obesity at the onset and end of puberty in Hong Kong, the most economically developed major Chinese city. Methods: We conducted an environment-wide association study (EWAS) and an epigenome-wide association study of obesity to systematically assess associations with body mass index (BMI) and waist-hip ratio (WHR) in Hong Kong's population-representative 'Children of 1997' birth cohort. Univariable linear regression was used to select exposures related to obesity at ~11.5 years (BMI and obesity risk n ≤ 7119, WHR n = 5691) and ~17.6 years (n = 3618) at Bonferroni-corrected significance, and multivariable regression to adjust for potential confounders followed by replicated multivariable regression (n = 308) and CpG by CpG analysis (n = 286) at ~23 years. Findings were compared with evidence from published randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. Results: At ~11.5 and~17.6 years the EWAS identified 14 and 37 exposures associated with BMI, as well as 7 and 12 associated with WHR, respectively. Most exposures had directionally consistent associations at ~23 years. Maternal second-hand smoking, maternal weight, and birth weight were consistently associated with obesity. Diet (including dairy intake and artificially sweetened beverages), physical activity, snoring, binge eating, and earlier puberty were positively associated with BMI at ~17.6 years, while eating before sleep was inversely associated with BMI at ~17.6 years. Findings for birth weight, dairy intake, and binge eating are consistent with available evidence from RCTs or MR studies. We found 17 CpGs related to BMI and 17 to WHR. Conclusions: These novel insights into potentially modifiable factors associated with obesity at the outset and the end of puberty could, if causal, inform future interventions to improve population health in Hong Kong and similar Chinese settings. Funding: This study including the follow-up survey and epigenetics testing was supported by the Health and Medical Research Fund Research Fellowship, Food and Health Bureau, Hong Kong SAR Government (#04180097). The DNA extraction of the samples used for epigenetic testing was supported by CFS-HKU1.

Genetic proxies for calcium channel blockers and cancer: a Mendelian randomization study.

Calcium channel blockers (CCBs) are commonly prescribed antihypertensives. However, concerns exist about potential off-target effects on cancer. This Mendelian randomization (MR) study examined the associations of genetic proxies for CCBs with the risk of cancer. We used published genetic proxies in the target genes of CCBs as instruments, and obtained MR estimates by applying them to large studies of 17 site-specific cancers (non-Hodgkin lymphoma, melanoma, leukemia, thyroid, rectal, pancreatic, oral cavity/pharyngeal, kidney, esophagus/stomach, colon, bladder, endometrial, cervical and breast, prostate, lung and ovarian cancer) from the Pan-Cancer study, with replication for breast cancer (133,384 cases, 113,789 controls from the Breast Cancer Association Consortium), prostate cancer (79,148 cases, 61,106 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium), lung cancer (11,348 cases, 15,861 controls from the International Lung Cancer Consortium), and ovarian cancer (25,509 cases, 40,941 controls from the Ovarian Cancer Association Consortium). We used inverse variance weighting for the main analysis and the weighted median, MR-Egger and Mendelian Randomization Pleiotropy Residual Sum and Outlier as sensitivity analyses. Genetic proxies for CCBs were not associated with any cancer after Bonferroni-correction (at the threshold of p < 0.003). Associations were robust to different MR methods. In conclusion, our study suggests no association of genetic proxies for CCBs with 17 different cancers. While the findings add some support to the safety profile of CCBs in long-term use, future replication is necessary to provide definitive evidence.

Predicting prognosis and clinical efficacy of immune checkpoint blockade therapy via interferon-alpha response in muscle-invasive bladder cancer.

Background: Immune checkpoint blockade (ICB) can prompt durable and robust responses in multiple cancers, involving muscle-invasive bladder cancer (MIBC). However, only a limited fraction of patients received clinical benefit. Clarifying the determinants of response and exploring corresponding predictive biomarkers is key to improving outcomes. Methods: Four independent formerly published cohorts consisting of 641 MIBC patients were enrolled in this study. We first analyzed the associations between various cancer hallmarks and ICB therapy response in two immunotherapeutic cohorts to identify the leading prognostic hallmark in MIBC. Furthermore, advanced machine learning methods were performed to select robust and promising predictors from genes functioning in the above leading pathway. The predictive ability of selected genes was also validated in multiple MIBC cohorts. Results: We identified and verified IFNα response as the leading cancer hallmark indicating better treatment responses, favorable overall survival, and an inflamed tumor microenvironment with higher infiltration of immune effector cells in MIBC patients treated with ICB therapy. Subsequently, two commonly selected genes, CXCL10 and LAMP3, implied better therapy response and the CXCL10highLAMP3high patients would benefit more from ICB therapy, which was comprehensively validated from the perspective of gene expression, clinical response, patient survival and immune features. Conclusion: Higher IFNα response primarily predicted better ICB therapeutic responses and reflected an inflamed microenvironment in MIBC. A composite of CXCL10 and LAMP3 expression could serve as promising predictive biomarkers for ICB therapeutic responses and be beneficial for clinical decision-making in MIBC.

Exploration of Metabolic Biomarkers Linking Red Meat Consumption to Ischemic Heart Disease Mortality in the UK Biobank.

Growing evidence suggests that red meat consumption is a risk factor for cardiovascular health, with potential sex disparity. The metabolic mechanisms have not been fully understood. Using the UK Biobank, first we examined the associations of unprocessed red meat and processed meat with ischemic heart disease (IHD) mortality overall and by sex using logistic regression. Then, we examined the overall and sex-specific associations of red meat consumption with metabolites using multivariable regression, as well as the associations of selected metabolites with IHD mortality using logistic regression. We further selected metabolic biomarkers that are linked to both red meat consumption and IHD, with concordant directions. Unprocessed red meat and processed meat consumption was associated with higher IHD mortality overall and in men. Thirteen metabolites were associated with both unprocessed red meat and IHD mortality overall and showed a consistent direction, including triglycerides in different lipoproteins, phospholipids in very small very-low-density lipoprotein (VLDL), docosahexaenoic acid, tyrosine, creatinine, glucose, and glycoprotein acetyls. Ten metabolites related to triglycerides and VLDL were positively associated with both unprocessed red meat consumption and IHD mortality in men, but not in women. Processed meat consumption showed similar results with unprocessed red meat. Triglycerides in lipoproteins, fatty acids, and some nonlipid metabolites may play a role linking meat consumption to IHD. Triglycerides and VLDL-related lipid metabolism may contribute to the sex-specific associations. Sex differences should be considered in dietary recommendations.

Sex-Specific Associations of Red Meat and Processed Meat Consumption with Serum Metabolites in the UK Biobank.

Red meat consumption has been found to closely related to cardiometabolic health, with sex disparity. However, the specific metabolic factors corresponding to red meat consumption in men and women have not been examined previously. We analyzed the sex-specific associations of meat consumption, with 167 metabolites using multivariable regression, controlling for age, ethnicity, Townsend deprivation index, education, physical activity, smoking, and drinking status among ~79,644 UK Biobank participants. We also compared the sex differences using an established formula. After accounting for multiple testing with false discovery rate < 5% and controlling for confounders, the positive associations of unprocessed red meat consumption with branched-chain amino acids and several lipoproteins, and the inverse association with glycine were stronger in women, while the positive associations with apolipoprotein A1, creatinine, and monounsaturated fatty acids were more obvious in men. For processed meat, the positive associations with branched-chain amino acids, several lipoproteins, tyrosine, lactate, glycoprotein acetyls and inverse associations with glutamine, and glycine were stronger in women than in men. The study suggests that meat consumption has sex-specific associations with several metabolites. This has important implication to provide dietary suggestions for individuals with or at high risk of cardiometabolic disease, with consideration of sex difference.

Study of mirabegron and solifenacin in the improvement of catheter-related bladder discomfort in patients undergoing transurethral resection: A case-control study.

BACKGROUND: The goal of this study was to see if using mirabegron, solifenacin, or placebo may help patients with transurethral resection avoid catheter-related bladder discomfort (CRBD). METHODS: Patients who underwent transurethral surgery and were given a catheter for 3 days after surgery were chosen for this study. The enrolled patients were separated into 3 groups: mirabegron (M), solifenacin (S), and a blank control group (C). All patients had their overactive bladder symptoms score (OABSS) and blood pressure checked before surgery. The CRBD, blood pressure, and heart rate were measured at 6, 24, 48, and 72 hours after surgery. The OABSS and side effects were documented on the 7th day. RESULTS: The 104 patients in this trial were randomized into 3 groups at random: M, S, and C. The ultimate follow-up was completed by 99 patients, including 33 in group M, 33 in group S, and 33 in group C. The OABSS, CRBD, and blood pressure in groups M and S were similar before and after surgery (P > .05). Groups M and S performed much better on the OABSS and CRBD than group C (P < .05). There were no significant differences in blood pressure between the 3 groups (P > .05). There were no significant differences in the occurrences of new onset dry mouth (P = .84) or constipation (P = .64) among the 3 groups. CONCLUSION: Mirabegron is comparable to solifenacin as an alternative for the prevention of CRBD, making it a viable option for CRBD prevention.

Artificial Intelligence Algorithm-Based MRI in the Diagnosis of Complications after Renal Transplantation.

This study was to explore the diagnostic value of magnetic resonance imaging (MRI) optimized by residual segmentation attention dual channel network (DRSA-U-Net) in the diagnosis of complications after renal transplantation and to provide a more effective examination method for clinic. 89 patients with renal transplantation were selected retrospectively, and all underwent MRI. The patients were divided into control group (conventional MRI image diagnosis) and observation group (MRI image diagnosis based on DRSA-U-Net). The accuracy of MRI images in the two groups was evaluated according to the comprehensive diagnostic results. The root mean square error (RMSE) and peak signal-to-noise ratio (PSNR) of DRSA-U-Net on T1WI and T2WI sequences were better than those of U-Net and dense U-Net (P < 0.05); comprehensive examination showed that 39 patients had obstruction between ureter and bladder anastomosis, 13 cases had rejection, 10 cases had perirenal hematoma, 5 cases had renal infarction, and 22 cases had no complications; the diagnostic sensitivity, specificity, accuracy, and consistency of the observation group were higher than those of the control group (P < 0.05). In the control group, the sensitivity, specificity, and accuracy in the diagnosis of complications after renal transplantation were 66.5%, 84.1%, and 78.32%, respectively; in the observation group, the sensitivity, specificity, and accuracy in the diagnosis were 67.8%, 86.7%, and 80.6%, respectively. DRSA-U-Net denoising algorithm can clearly display the information of MRI images on the kidney, ureter, and surrounding tissues, improve its diagnostic accuracy in complications after renal transplantation, and has good clinical application value.

Hydroamination of Unactivated Alkenes with Aliphatic Azides.

We report here an efficient and highly diastereoselective intermolecular anti-Markovnikov hydroamination of unactivated alkenes with aliphatic azides in the presence of silane. The system tolerates a wide range of azides and alkenes and operates with alkene as limiting reagent. Mechanistic studies suggest a radical chain pathway that involves aminium radical formation, radical addition to alkenes and HAT from silane to ß-aminium alkyl radical. The use of sterically bulky silane is proposed to contribute to the excellent diastereoselectivity for HAT. Computational analysis uncovers the reaction pathway of aliphatic azide activation with silyl radical for aminyl radical formation.

L-carnitine, a friend or foe for cardiovascular disease? A Mendelian randomization study.

BACKGROUND: L-carnitine is emerging as an item of interest for cardiovascular disease (CVD) prevention and treatment, but controversy exists. To examine the effectiveness and safety of L-carnitine, we assessed how genetically different levels of L-carnitine are associated with CVD risk and its risk factors. Given higher CVD incidence and L-carnitine in men, we also examined sex-specific associations. METHODS: We used Mendelian randomization to obtain unconfounded estimates. Specifically, we used genetic variants to predict L-carnitine, and obtained their associations with coronary artery disease (CAD), ischemic stroke, heart failure, and atrial fibrillation, as well as CVD risk factors (type 2 diabetes, glucose, HbA1c, insulin, lipid profile, blood pressure and body mass index) in large consortia and established cohorts, as well as sex-specific association in the UK Biobank. We obtained the Wald estimates (genetic association with CVD and its risk factors divided by the genetic association with L-carnitine) and combined them using inverse variance weighting. In sensitivity analysis, we used different analysis methods robust to pleiotropy and replicated using an L-carnitine isoform, acetyl-carnitine. RESULTS: Genetically predicted L-carnitine was nominally associated with higher risk of CAD overall (OR 1.07 per standard deviation (SD) increase in L-carnitine, 95% CI 1.02 to 1.11) and in men (OR 1.09, 95% CI 1.02 to 1.16) but had a null association in women (OR 1.00, 95% CI 0.92 to 1.09). These associations were also robust to different methods and evident for acetyl-carnitine. CONCLUSIONS: Our findings do not support a beneficial association of L-carnitine with CVD and its risk factors but suggest potential harm. L-carnitine may also exert a sex-specific role in CAD. Consideration of the possible sex disparity and exploration of the underlying pathways would be worthwhile.

A Novel Angiogenesis-Related Gene Signature to Predict Biochemical Recurrence of Patients with Prostate Cancer following Radical Therapy.

Background: Prostate cancer (PCa) is one of the most common malignancies in males; we aim to establish a novel angiogenesis-related gene signature for biochemical recurrence (BCR) prediction in PCa patients following radical therapy. Methods: Gene expression profiles and corresponding clinicopathological data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We quantified the levels of various cancer hallmarks and identified angiogenesis as the primary risk factor for BCR. Then machine learning methods combined with Cox regression analysis were used to screen prognostic genes and construct an angiogenesis-related gene signature, which was further verified in external cohorts. Furthermore, estimation of immune cell abundance and prediction of drug responses were also conducted to detect potential mechanisms. Results: Angiogenesis was regarded as the leading risk factor for BCR in PCa patients (HR = 1.58, 95% CI: 1.38-1.81), and a novel prognostic signature based on three genes (NRP1, JAG2, and VCAN) was developed in the training cohort and successfully validated in another three independent cohorts. In all datasets, this signature was identified as a prognostic factor with promising and robust predictive values. Moreover, it also predicted higher infiltration of regulatory T cells and M2-polarized macrophages and increased drug sensitivity of angiogenesis inhibitors in high-risk patients. Conclusions: The angiogenesis-related three-gene signature may serve as an independent prognostic factor for BCR, which would contribute to risk stratification and personalized management of PCa patients after radical therapy in clinical practice.

Epstein-Barr virus-positive post-transplant lymphoproliferative disordepresenting as hematochezia and enterobrosis in renal transplant recipients in China: A report of two cases.

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is a rare severe complication after renal transplantation, with an incidence of approximately 0.3%-2.0% in patients undergoing renal transplantation. The clinical manifestations of PTLD are often nonspecific, leading to tremendous challenges in the clinical diagnosis and treatment of PTLD. CASE SUMMARY: We report two Epstein-Barr virus (EBV)-positive PTLD cases whose main clinical manifestations were digestive tract symptoms. Both of them admitted to our hospital because of extranodal infiltration symptoms and we did not suspect of PTLD until the pathology confirmation. Luckily, they responded well to the treatment of rituximab. We also discuss the virological monitoring, clinical characteristics, diagnosis, and treatment of PTLD. CONCLUSION: PTLD is a deceptive disease and difficult to diagnose. Once patients are confirmed with PTLD, immune suppressant dosage should be immediately reduced and rituximab should be used as first-line therapy.

Prograf produces more benefits for CYP3A5 low expression patients in early stage after kidney transplantation.

OBJECTIVE: This study is to analyze concentration changes of the prolonged-release and shorter-acting formulation of tacrolimus in patients with different CYP3A5 genotypes after kidney transplantation. METHODS: A single-factor retrospective analysis was performed in patients underwent allogeneic kidney transplantation with postoperative administration of Advagraf or Prograf in our hospital from May 2013 to June 2014. The CYP3A5 genotypes were determined, and tacrolimus trough concentrations in whole blood were measured within 28days after transplantation. The rates of acute rejection rate, chronic rejection and infection were recorded and compared after one year follow-up after surgery. RESULTS: The study included 106 patients administered Advagraf (45 cases) or Prograf (61 cases). The low expression genotype of CYP3A5 was detected in 40 (37.7%) patients. A higher dose of Advagraf was required to increase the tacrolimus trough concentrations within 21days after transplantation. Moreover, a higher dose for Advagraf than Prograf was required to increase the tacrolimus trough concentrations in low expression patients. In the low expression patients, Prograf more frequently achieved the target tacrolimus trough concentrations within seven days after transplantation (five days: 7.14% vs. 84%, P=0.001; seven days: 33.33% vs. 77.78%, P=0.001). The patient and kidney graft survival rates one year after transplantation both were 100%. The estimated glomerular filtration rate showed no significant difference between different CYP3A5 phenotypes or formulations of tacrolimus (P>0.05). However, the incidence of infections was higher in the Advagraf group in low expression patients (P<0.05). CONCLUSION: Tacrolimus of different formulations had different impact on patients with different CYP3A5 genotypes after kidney transplantation.

miR­19a­3p targets PMEPA1 and induces prostate cancer cell proliferation, migration and invasion.

Prostate cancer (PCa) is one of the most common malignant tumors in men. Studies have observed that microRNA (miR)­19a­3p expression levels are downregulated in several types of cancer, and yet the biological function and its underlying mechanisms in the pathogenesis of PCa remain unclear. In the current study, the expression pattern of miR­19a­3p in PCa tissues and cell lines was detected by reverse transcription­quantitative polymerase chain reaction. The proliferative, migratory and invasive capacity of PCa cells were determined using EdU and Transwell assays following transfection with miR­19a­3p mimics. Additionally, the current study investigated the biological impact and regulation of prostate transmembrane protein androgen induced 1 (PMEPA1) in PCa cells by transfection with PMEPA1 small interfering (si)RNA. It was observed that miR­19a­3p was upregulated in PCa tissue samples and cell lines in vitro. Functional analysis also confirmed that miR­19a­3p overexpression promoted the proliferation, migration and invasion of PCa cells. Furthermore, PMEPA1 was identified as a direct target of miR­19a­3p, and siRNA knockdown of PMEPA1 resulted in increased proliferation, migration and invasion of PCa cells, which partially accounts for the effect of miR­19a­3p in tumor metastasis. In conclusion, the findings of the present study suggest that the upregulation of miR­19a­3p expression levels contributes to tumor progression and that one of its underlying mechanisms involves inhibition of PMEPA1 expression.

Meta-analysis of female stress urinary incontinence treatments with adjustable single-incision mini-slings and transobturator tension-free vaginal tape surgeries.

BACKGROUND: The study on SIMS and SMUS as a whole by Alyaa Mostafa et al showed that after excluding the TVT-S sling, there is no significant difference in patient-reported cure rate and objective cure rate between these two methods. In this paper, we systematically evaluate the relevant data on SIMS-Ajust and TVT-O/TOT and further confirm their safety and effectiveness, providing reliable clinical evidence. METHODS: By searching the Medline, Embase, Scopus, and Web of Science databases and the Cochrane Database of Systematic Reviews combined with manual searches, all reports on randomized controlled trials (RCTs) of single-incision mini-sling (SIMS-Ajust) and transobturator tension-free vaginal tape (TVT-O/TOT) surgeries were collected. Using RevMan 5.2 statistical software, the patient-reported cure rate, objective cure rate, operative time, postoperative pain, lower urinary tract injuries, groin pain, postoperative voiding difficulties, de novo urgency and/or worsening of preexisting surgery, vaginal tape erosion, repeated continence surgery, and other related data on both surgical methods were evaluated. RESULTS: A total of 154 relevant research reports were retrieved, and five randomized controlled trials were included in this study, involving a total of 678 patients. The meta-analysis results show no significant difference in the patient-reported cure rate and objective cure rate between SIMS-Ajust and TVT-O/TOT [RR = 0.95, 95% CI (0.87 to 1.04), P > 0.05; RR = 0.97, 95% CI (0.90-1.05), P > 0.05]. With respect to operation time and groin pain, SIMS-Ajust outperforms TVT-O/TOT [MD = -1.61, 95% CI (-2.48 to 0.74), P < 0.05; RR = 0.30, 95% CI (0.11 to 0.85), P < 0.05]. In terms of postoperative pain, lower urinary tract injuries, postoperative voiding difficulties, de novo urgency and/or worsening of preexisting surgery, vaginal tape erosion, and repetition of continence surgery, there is no significant difference between SIMS-Ajust and TVT-O/TOT [RR = 0.50, 95% CI(0.18-1.43), P > 0.05; RR = 2.82, 95% CI(0.14-57.76), P > 0.05; RR = 0.64, 95% CI(0.28-1.45), P > 0.05; RR = 1.06, 95% CI(0.66-1.71), P > 0.05; RR = 1.04, 95% CI(0.24-4.45), P > 0.05; RR = 1.64, 95% CI(0.41-6.61), P > 0.05]. CONCLUSIONS: SIMS-Ajust is safe and effective in the treatment of female stress urinary incontinence. Compared with TVT-O/TOT surgery, SIMS-Ajust surgery has the same high objective cure rate and patient-reported cure rate and low incidence of perioperative complications, in addition to its short operative time and low incidence of groin pain. Its long-term efficacy needs further observation.

[Application of NGAL and Cys c in predicting graft function during early period after kidney transplantation].

OBJECTIVE: To assess the diagnostic values of novel biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin c (Cys c), in the diagnosis of delayed graft function (DGF). METHODS: A total of 114 patients undergoing kidney transplantation from deceased donors from October 2012 to October 2013 were enrolled. Recipients on dialysis during the first postoperative week were included into DGF group while those without DGF into early graft function (EGF) group. sNGAL, sCys c and serum creatinine (sCr) were measured pre-operation, as well as at 4, 12, 24, 72 and 168 h post-operation. Furthermore, uNGAL leveks were measured at 4, 12 and 24 h post-transplantation. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the predictive value of DGF. RESULTS: Among 114 recipients enrolled, 23 presented DGF and 91 EGF. In EGF group, within 4 h post-transplantation sNGAL and sCys c decreased more significantly than sCr (51.31% (40.30%, 62.31%), 56.39% (50.02%, 68.40%) vs 21.40% (6.77%, 27.44%), P = 0.009 and 0.029 respectively). Between two groups, differences of sequential decrease were observed earlier in sNGAL and sCys c than uNGAL and sCr. It demonstrated better performance in predicting DGF. The AUC of sCr was between uNGAL and sNGAL, sCys c. Combination of both sNGAL and sCys c yielded a ROC-AUC of 1.000. CONCLUSIONS: sNGAL and sCys are ideal for predicting the recovery of graft function during early period after kidney transplantation. And a combination of both biomarkers may dramatically improve the specificity and sensitivity of diagnosing DGF.