Risk Factors of New-onset Diabetes After Renal Transplantation and Prognostic Analysis.

Context: New-onset diabetes after transplantation (NODAT) is one of the most common complications after renal transplantation and in kidney-transplant recipients is closely related to long-term adverse outcomes for recipients and transplants. The risk factors for NODAT still require exploration. Objectives: The study intended to explore the risk factors for new-onset diabetes after transplantation (NODAT) for patients receiving a renal transplantation, to provide a theoretical basis for reducing the incidence rate of NODAT and promoting a better outcome for patients. Design: The research team designed a retrospective study using clinical data of patients receiving renal transplantation at a hospital. Setting: The study took place in the Department of Urology at Xuanwu Hospital at Capital Medical University in Beijing, China. Participants: Participants were 396 patients who had undergone renal transplantation at the hospital, of whom 28 had NODAT syndrome, the NODAT group, and 368 didn't meet the diagnostic criteria for NODAT, the N-NODAT group. Outcome Measures: The research team calculated the incidence rate of NODAT and determined the causes of the disease, evaluated participants' preoperative risk factors-gender, preoperative systolic blood pressure (SBP), preoperative diastolic blood pressure (DBP), height, family history of diabetes, weight, smoking habits, age, drinking habits, pretransplant body mass index (BMI), preoperative fasting blood glucose, triglycerides (TG), total cholesterol (TC)-and their postoperative risk factors-acute rejection, use of immunosuppressive agents, blood CsA concentration, blood FK506 concentration, and renal function. Additionally, the team subjected the data in the two groups to univariate, logistic regression analysis and to multivariate, unconditional, logistic regression analysis to discover risk factors for NODAT. Results: Among the 396 participants, 28 had NODAT (7.1%), and 368 didn't suffer NODAT (92.9%). Statistically significant differences existed between the groups in participants' ages (0.013), weights (P = .032), smoking habits (P = .034), drinking habits (P = .034), BMIs (P = .023), preoperative fasting blood glucose (P < .05), preoperative TG (P < .05), and preoperative TC (P < .01). In the univariate logistic regression analysis, significant associations existed between age (P = .016), weight (P = .033), BMI (P = .025), smoking habits (P = .035), drinking habits (P = .043), preoperative fasting blood glucose (P = .048), preoperative TG (P = .049), preoperative TC (P = .009), acute rejection (P = .009), and immunosuppressive agents (P = .012) and the occurrence of NODAT (P < .05). In the multivariate unconditional logistic stepwise regression analysis, acute rejection (P = .011) and use of FK506 in immunotherapy (P = .013) were independent risk factors for NODAT. Conclusions: The risk factors of NODAT include age, weight, BMI, smoking habits, drinking habits, preoperative fasting blood glucose, preoperative TG, preoperative TC, acute rejection and exposure to immunosuppressive agents. Among them, only acute rejection and immunosuppressive agents are modifiable factors. The application of CsA as an immunosuppressive agent after surgery may decrease the incidence rate of NODAT and prolong the longevity of patients receiving renal transplantation.

Evaluation of neurogenic bladder outlet obstruction mimicking sphincter bradykinesia in male patients with Parkinson's disease.

BACKGROUND: Lower urinary tract symptoms are one of the most common groups of non-movement symptoms in patients with Parkinson's disease (PD). Storage symptoms are well-acknowledged, but neurogenic voiding dysfunction caused by PD remains a knowledge gap. This study aimed to evaluate the neurogenic bladder outlet obstruction in male patients with PD and its clinical significance. METHODS: Male patients who were diagnosed with PD and underwent urodynamic studies were retrospectively reviewed. The patients with prostate size < 30 ml and bladder outlet obstruction index ≥40 were included in the study. Lower urinary tract symptoms were evaluated by International Prostate Symptom Score (IPSS). Free flowmetry was performed and post void residual (PVR) volume was measured by ultrasound at follow-up. RESULTS: Six patients were included in the final analysis. The mean age was 68.2 and the mean movement symptom duration was 70.7 months. The patients had a mean IPSS of 12.5 and mean PVR volume of 70.8 ml. All patients had slow stream but none of them reported significant voiding difficulty. Urodynamic studies showed the delayed urinary sphincter relaxation and the special trace pattern. After a mean follow-up of 20 months, they had a mean IPSS of 12.5 and mean PVR volume of 73.3 ml. None of them complained of significant voiding difficulty at follow-up. CONCLUSION: The delayed urinary sphincter relaxation is a rare but repeatable phenomenon in male patients with PD. It is unlikely to cause disturbing voiding dysfunction, as reported by the patients, and does not progress prominently during the course of PD. Further studies are needed to investigate the nature of this special type of neurogenic BOO and whether it is peculiar to PD in a larger patient cohort.

The Resonance and the Allium ureteral stents in the treatment of non-malignant refractory ureterostenosis.

BACKGROUND: Refractory non-malignant ureterostenosis is challenging to treat. The experience to treat the stenosis primarily cause by retroperitoneal fibrosis with the Resonance and Allium metallic stent is still limited. We aim to evaluate the efficacy and safety of these two stents and provide alternative treatment options. METHODS: A retrospective study was conducted for patients with non-malignant ureterostenosis and treated with the Resonance and Allium stents from March 2011 to September 2020 in our department. The efficacy was evaluated by the change of serum creatinine, glomerular filtration rate (GFR), the proportion of GFR of the affected side and hydronephrosis grade. The safety was evaluated by postoperative presence of moderate or severe overactive bladder (OAB), recurrent urinary infection, pain, stent displacement, encrustation and re-obstruction. RESULTS: 33 patients were eligible for the study, including 18 cases treated by the Resonance stents and 15 patients treated by the Allium stents. The patients of two groups had similar age and gender proportion. The cause of ureterostenosis was mainly retroperitoneal fibrosis in both groups but the Resonance group had more idiopathic cases. Follow-up time was significantly longer in the Resonance group than the Allium group (36.2 ± 24.0 vs 9.4 ± 5.0 months, p < 0.001). Both groups showed improvement or maintenance of serum creatinine level, GFR, the GFR proportion of the affected side and hydronephrosis grade after treatment. The Resonance group presented significant higher incidence of moderate or severe OAB, recurrent urinary infection and pain, while the Allium group showed significant more cases of re-obstruction. CONCLUSION: Both the Resonance and Allium stent can relieve the non-malignant refractory ureterostenosis effectively. The Resonance stent may cause more irritable symptoms while the Allium stent may have a higher rate of re-obstruction. The long term efficacy and safety of the Allium stent in treating non-malignant refractory ureterostenosis requires further study.

Neurogenic lower urinary tract dysfunction predicts prognosis in patients with multiple system atrophy.

PURPOSE: To evaluate whether neurogenic lower urinary tract dysfunction and urodynamic parameters predict the outcomes of patients with multiple system atrophy (MSA). METHODS: A retrospective study was performed in patients who were diagnosed with MSA and underwent urodynamic studies simultaneously from September 2014 to July 2018. The urodynamic traces were reviewed by urologists. Detrusor contractility was evaluated by the bladder contractility index (BCI) and Schäfer nomogram. Telephone follow-up was conducted in July 2019 to acquire survival data. Clinical and urodynamic parameters were analyzed for survival using Cox regression analysis. RESULTS: Overall, 70 MSA patients were eligible for analysis, and 61 of them underwent urodynamic study within 3 years of initial symptom onset. The parkinsonian subtype of MSA (MSA-P) had a smaller proportion of men as well as longer motor and lower urinary tract symptom durations than the cerebellar subtype (MSA-C). MSA-P also had a lower mean BCI than MSA-C (32.0 ± 27.0 versus 53.6 ± 33.4, p = 0.025). The mean MSA survival time was 5.4 [95% confidence interval (CI) 4.8-6.3] years. Cox regression analysis showed that survival from baseline was correlated only with BCI [hazard ratio (HR) 0.983, 95% CI 0.969-0.997, p = 0.020]. Overall survival was correlated with BCI (HR 0.982, 95% CI 0.966-0.999, p = 0.039) and the presence of urinary incontinence (HR 3.007, 95% CI 0.993-9.220, p = 0.052). CONCLUSION: Detrusor contractility can be a prognostic marker in MSA patients. A high BCI value is a protective factor for survival from baseline and overall survival. The presence of urinary incontinence predicts shortened overall survival.

Injecting RNA interference lentiviruses targeting the muscarinic 3 receptor gene into the bladder wall inhibits neurogenic detrusor overactivity in rats with spinal cord injury.

AIMS: To investigate the effects of injecting RNA interference (RNAi) lentiviruses targeting the muscarinic 3 (M3 ) receptor gene into the bladder wall on bladder activity in rats with spinal cord injury (SCI). METHODS: Four M3 RNAi lentiviruses were constructed and used to infect primary cultured bladder smooth muscle cells (BSMCs). Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were performed to determine the optimal RNAi lentivirus with the highest interference efficiency. Female Wistar rats were subjected spinal cord transection at T9-10 and randomly divided into three groups (n = 8), namely, blank control, negative control, and experimental groups, and injected into the bladder wall with saline, negative control shRNA, and M3 RNAi lentiviruses, respectively, 1 week after spinal cord transection. The normal rats were used as normal control group. Urodynamic parameters and bladder tissues were evaluated in the different groups. RESULTS: An M3 RNAi lentivirus with the highest interference efficiency (78.9%) was constructed and identified. Three weeks after injecting M3 RNAi lentiviruses into the bladder wall, Western blotting and qRT-PCR showed that the M3 receptor was significantly downregulated in the experimental group. Cystometric evaluation suggested that downregulating M3 receptor expression could substantially decrease basal pressure, residual volume, and non-voiding contraction number, increase intercontraction interval, and significantly improve bladder compliance in rats with SCI. CONCLUSION: Injecting RNAi lentiviruses targeting the M3 receptor gene into the bladder wall could effectively inhibit neurogenic detrusor overactivity (NDO) due to SCI. Thus, this approach may be a potential treatment for NDO in SCI.

Preliminary experience of laparoscopic renal artery aneurysm clipping surgery.

Developments in endovascular therapy and laparoscopy have led to the expansion of minimally invasive surgical techniques in the treatment of renal artery aneurysm (RAA). In this study, we introduced a new surgical technique that combined the clipping technique widely used in neurosurgery with laparoscopic surgery to clip the aneurysm. RAA clipping was performed by retroperitoneal laparoscopy, and the procedures were completed with no conversions to open surgery. In addition, no perioperative complications were recorded. Our preliminary experience suggests that laparoscopic RAA clipping surgery is feasible and appears to be safe. Laparoscopic RAA clipping surgery has advantages of a simplified surgical process, short warm ischemia time, and excellent cosmetic results.

Efficacy of medication for overactive bladder symptoms in 70 patients with Parkinson's disease.

Background: Managing overactive bladder (OAB) symptoms in Parkinson's disease (PD) is challenging. This study aimed to investigate the medical management of OAB symptoms in patients with PD. Methods: Patients with OAB symptoms who were newly treated with tolterodine and/or tamsulosin were screened from a database of 187 PD patients. Before treatment, the Hoehn-Yahr scale, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and urodynamic evaluation were evaluated. On day 21 of treatment, the IPSS and OABSS were re-evaluated. The changes of these scores and urinary symptoms were analyzed. Results: Seventy patients with a mean age of 62.2±7.9 years and median Hoehn-Yahr stage of 2 (IQR 2-3) were enrolled. Tolterodine, tamsulosin, and tolterodine + tamsulosin were used in 43, 20, and 7 patients, respectively. The IPSS storage symptoms (9.4±3 vs. 3.5±2.3) and OABSS (9±2.8 vs. 4.8±3.3) improved significantly after treatment (both P<0.01). However, 28 (40%) patients displayed moderate urinary symptoms, and nocturia and urgency still affected more than half of the patients after treatment. Conclusions: Tolterodine and/or tamsulosin can significantly improve OAB symptoms in PD patients. Nocturia and urgency remain common after treatment.

Risk factors for SARS-CoV-2 pneumonia among renal transplant recipients in Beijing Omicron wave.

The novel coronavirus disease-19 had become an unprecedented global health emergency, quickly expanding worldwide. Omicron (B.1.1.529), as a novel variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was initially identified in South Africa and Botswana. Renal transplant recipients (RTRs) are a special group and are more vulnerable to viral pneumonia. Thus, this study aimed to assess the incidence and risk factors of SARS-CoV-2 pneumonia that occurred in RTRs with Omicron infection. This single-center case-control study enrolled the RTRs who were diagnosed with SARS-CoV-2 infection by the SARS-CoV-2 nucleic acid test, which were divided into two groups according to the imaging features of SARS-CoV-2 pneumonia. The parameters were collected by questionnaires and analyzed using Statistical Product and Service Solutions. A total of 313 RTRs completed the questionnaires, and 131 were enrolled in this study with a mean age of 42.66 years. The incidence of SARS-CoV-2 pneumonia among the enrolled participants was 76.3%. The first symptoms included fever (89.3%), cough (93.1%), and expectoration (81.7%). From the comparison, the parameters such as age, gender, body mass index, lymphocyte count, and the percent of neutrophils and the basic serum creatinine before SARS-CoV-2 infection were significantly different between the two groups (P < 0.05). In multivariate analysis, age and the basic serum creatinine were independent risk factors for developing SARS-CoV-2 pneumonia (P < 0.05). Older RTRs with a high level of serum creatinine before SARS-CoV-2 infection were more at risk of developing SARS-CoV-2 pneumonia. More randomized controlled studies are needed.IMPORTANCEThis study aimed to assess the incidence and the risk factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia that occurred in renal transplant recipients (RTRs) with Omicron infection. In conclusion, older RTRs with a high level of serum creatinine before SARS-CoV-2 infection were more at risk of developing SARS-CoV-2 pneumonia and should be timely treated, in case of severe pneumonia.

Construction of aptamer-siRNA chimera and glutamine modified carboxymethyl-ß-cyclodextrin nanoparticles for the combination therapy against lung squamous cell carcinoma.

Combination therapy has become the most important treatment for advanced non-small cell lung cancer (NSCLC), which can significantly improve the prognosis of patients. However, poor targeting and adverse reactions limited its clinical application. Here, we constructed an AS1411 aptamer-programmed cell death ligand-1 (PD-L1) siRNA chimera/polyethylenimine/glutamine/ß-cyclodextrin/doxorubicin (Chimera/ PEI/Gln/ß-CD/DOX) nanoparticle for the combination therapy (chemotherapy combined with immunotherapy). Scanning electron microscopy showed that PEI/Gln/ß-CD/DOX nanoparticle was conical, with a diameter of about 250-500 nm. AS1411 aptamer-PD-L1 siRNA chimera can effectively bind NSCLC cells and inhibit PD-L1 expression, further activating T cells and CD8+T cells. Glutamine modification effectively promoted the doxorubicin uptake by cancer cells and induced their apoptosis. Animal experiments showed that our nanoparticles effectively treated the transplanted tumor, and the adverse reactions were reduced. Compared with the Aptamer/ß-CD/DOX group, the volume and ki-67 index of transplanted tumors in the Chimera/ß-CD/DOX group were significantly decreased, while the apoptosis ratio was increased. Immunohistochemical results showed that Compared with the Aptamer/ß-CD/DOX group, the number of T cells and CD8+T cells in the Chimera/ß-CD/DOX group was increased by 1.34 and 1.41 times. Glutamine modification enhanced the chemotherapeutic efficacy and anti-tumor immune response in vivo. Our study provided a new method for the combination therapy of lung squamous cell carcinoma.

Genetic and pharmacological targeting of XBP1 alleviates hepatic ischemia reperfusion injury by enhancing FoxO1-dependent mitophagy.

Hepatic ischemia reperfusion (I/R) injury is a common clinical complication. X-box binding protein 1 (XBP1), as a critical regulator of the endoplasmic reticulum stress, has been implicated in a variety of diseases. In this study, we aimed to investigate the effects and the underlying mechanism of XBP1 in the progression of hepatic I/R injury. Hepatocyte-specific XBP1 knockout mice, multiple viral delivery systems and specific pharmacological inhibitors were applied in vivo in a partial hepatic I/R injury mouse model and in vitro in a cell model of hypoxia-reoxygenation (H/R) injury. Mitophagy and autophagic flux were evaluated and fluorescence resonance energy transfer (FRET) as well as immunoprecipitation were performed. The results demonstrated that reperfusion for 6 h represented a critical timepoint in hepatic I/R injury and resulted in significant intracellular mitochondrial dysfunction; led to the breakdown of hepatocytes accompanied by the highest expression levels of XBP1. Hepatocyte-specific XBP1 knockout alleviated hepatic I/R injury via enhanced mitophagy, as demonstrated by the reduction in hepatocellular damage/necrosis and increased expression of mitophagy markers. Mechanistically, XBP1 interacted with FoxO1 directly and catalyzed the ubiquitination of FoxO1 for proteasomal degradation. Targeting XBP1 by genetic or pharmacological techniques potentiated the protein levels of FoxO1, further promoting the activity of the PINK1/Parkin signaling pathway, thus augmenting mitophagy and exerting hepatoprotective effects upon I/R injury. In conclusion, the inhibition of XBP1 potentiated FoxO1-mediated mitophagy in hepatic I/R injury. Specific genetic and pharmacological treatment targeting XBP1 in the perioperative 6 h prior to reperfusion exerted beneficial effects, thus providing a novel therapeutic approach.

Thulium laser vaporesection versus standard transurethral resection of the prostate: a randomized trial with transpulmonary thermodilution hemodynamic monitoring.

OBJECTIVES: To characterize the hemodynamics comparing thulium laser vaporesection of the prostate with traditional transurethral resection of the prostate. METHODS: A total of 80 consecutive patients with benign prostatic hyperplasia were randomly assigned into the thulium laser vaporesection of the prostate group or transurethral resection of the prostate group. Transpulmonary thermodilution hemodynamic monitoring was used before and 1 h after surgery to assess patient hemodynamics. Acute complications and treatment efficiency were evaluated after surgery. RESULTS: There were no statistical differences in age, prostate volume, anticoagulants and International Prostate Symptom Score between the two groups. The postoperative Stroke Volume Index was significantly higher in the thulium laser vaporesection of the prostate group (P = 0.007). The extravascular lung water and intrathoracic blood volume indices differed significantly pre- and postoperatively, and were similar in both groups. Decreases in serum sodium and hemoglobin concentrations after surgery were lower in the thulium laser vaporesection of the prostate group (P < 0.01). Acute complications, and improvements in International Prostate Symptom Score and maximum urinary flow rates, were similar in both groups. CONCLUSIONS: Transpulmonary thermodilution hemodynamic monitoring provides additional safety measures during surgical procedures. Thulium laser vaporesection of the prostate is associated with fewer hemodynamic changes and provides similar efficacy to transurethral resection of the prostate. Thus, it can be considered a safe and effective procedure.

Expression profiles of circular RNAs and interaction networks of competing endogenous RNAs in neurogenic bladder of rats following suprasacral spinal cord injury.

Background: Neurogenic bladder (NB) following suprasacral spinal cord injury (SSCI) is an interstitial disease with the structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs) are involved in fibrotic disease development through their post-transcriptional regulatory functions. This study aimed to use transcriptome high-throughput sequencing to investigate the process of NB and bladder fibrosis after SSCI. Methods: Spinal cord transection at the T10-T11 level was used to construct the SSCI model in rats (10-week-old female Wistar rats, weighing 200 ± 20 g). The bladders were collected without (sham group) and with (SSCI 1-3 groups) NB status. Morphological examination was conducted to assess the extent of bladder fibrosis. Additionally, RNA sequencing was utilized to determine mRNAs and circRNAs expression patterns. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different periods of SSCI were further analyzed. Results: Bladder weight, smooth muscle cell hypertrophy, and extracellular matrix gradually increased after SSCI. Compared with the sham group, 3,255 DEMs and 1,339 DECs, 3,449 DEMs and 1,324 DECs, 884 DEMs, and 1,151 DECs were detected in the SSCI 1-3 groups, respectively. Specifically, circRNA3621, circRNA0617, circRNA0586, and circRNA4426 were significant DECs common to SSCI 1-3 groups compared with the sham group. Moreover, Gene Ontology (GO) enrichment suggested that inflammatory and chronic inflammatory responses were the key events in NB progression following SSCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment associated with the "Chemokine signaling pathway", the "IL-17 signaling pathway", and the "TGF-beta signaling pathway" suggests their potential involvement in regulating biological processes. The circRNA-miRNA-mRNA interaction networks of DECs revealed rno-circ-2239 (micu2) as the largest node, indicating that the rno-circ-2239-miRNA-mRNA-mediated network may play a critical role in the pathogenesis of SSCI-induced NB. Conclusions: This study offers a comprehensive outlook on the possible roles of DEMs and DECs in bladder fibrosis and NB progression following SSCI. These findings have the potential to serve as novel biomarkers and therapeutic targets.

Retroperitoneoscopic enucleation adrenalectomy: a viable surgical option for small nonsecreting adrenal tumors with low potential of malignancy.

Laparoscopic total adrenalectomy has become the standard treatment for adrenal mass. Meanwhile, there has been a growing trend toward laparoscopic adrenal-sparing surgery worldwide to avoid the risk and potential complications of adrenal insufficiency. The objectives of this study were to describe a retroperitoneoscopic adrenal tumor enucleation technique, to assess the clinical outcomes of this technique in the treatment of 20-40 mm nonsecreting adrenal tumor (NAT) with low potential of malignancy, and to provide a feasible choice for patients who have preference on resection. This study was a retrospective analysis of 61 patients with low potential of malignancy in 20-40 mm NAT identified at the first imaging examination or during follow-up. All patients were scheduled for planned enucleation adrenalectomy by a single surgeon between July 2016 and December 2020 in Xuanwu Hospital, Beijing, China. In all patients, retroperitoneoscopic surgery was performed via a retroperitoneoscopic process for all the patients. The crucial techniques of enucleation are presented in the video. Safety and feasibility factors of enucleation technique were measured for this study. No blood transfusion or organ injury was registered during the operation. The median operation time was 75 min, and the median blood loss was 35 mL. All operations were successfully performed without open conversion. A total of 58 patients received successful enucleation surgery. Three cases were converted to retroperitoneoscopic total adrenalectomy. In this study, surgical outcomes of retroperitoneoscopic enucleation adrenalectomy as a method to remove adrenal tumors were assessed. This procedure is a feasible and safe technique with the added benefit of preserving the remaining functional adrenal tissue.

[Application of neoadjuvant hormonal therapy in (125)I permanent seed implantation for prostate cancer].

OBJECTIVE: To explore the therapeutic response and toxicity of neoadjuvant hormonal therapy in (125)I permanent seed implantation for prostate cancer and validate the clinical efficacy of neoadjuvant hormonal therapy. METHODS: A total of 165 patients with T1c-T3b prostate cancer received transperineal ultrasound-guided (125)I permanent seed implantation and neo-adjuvant hormonal therapy (NHT). Their median age was 79 years (range: 65 - 88). They were randomized into 2 groups: group A (n = 90, 3-month NHT before (125)I permanent seed implantation for prostate cancer 0 and group B (n = 75, (125)I permanent seed implantation). The prostate surface antigen (PSA) response rate, the change of prostate volume and the toxicities of urinary system and sexual function were observed. RESULTS: The median PSA decreased to 0.38 (0.01 - 6.56) µg/L from 26.50 (3.56 - 150.00) µg/L after a 3-month neoadjuvant hormonal therapy and the median prostate volume dropped from 29.33 (23.62 - 65.21) ml from 46.38 (19.28 - 128.10) ml during a follow-up period of 24 months. After brachytherapy, the PSA level was maintained at a relatively low level (median number of 0.62 µg/L and 2.56 µg/L in groups A and B respectively). And 6 and 9 patients suffered from acute urinary retention after brachytherapy in groups A and B respectively. CONCLUSION: Neoadjuvant hormonal therapy can reduce the volume of prostate before brachytherapy and serum PSA in a short time. The toxicities of urinary system, gastrointestinal tract and sexual function should be examined by further randomized control studies. A long-term observation is needed for the PSA-free survival rate.

KLF16 Downregulates the Expression of Tumor Suppressor Gene TGFBR3 to Promote Bladder Cancer Proliferation and Migration.

INTRODUCTION: Krüppel-like factors (KLFs), which comprise 17 family members, exert important functions during the development of cancer. The role of KLF16 seems controversial in carcinogenesis because both tumor suppressive and promoting effects have been reported. METHODS: The expression level of KLF16 was analyzed based on public data sets from The Cancer Genome Atlas (TCGA) and evaluated by immunohistochemical (IHC) staining. CCK8 assay, colony formation analysis, transwell assays and the PI/Annexin V-APC assay kit were performed to detect cell growth, colony formation, cell migration and apoptosis of BC cells. Xenograft tumorigenesis assay was performed to detect the KLF16 expression on BC growth in vivo. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay were performed to analyze the interaction between KLF16 and its target. RESULTS: In this study, we explored the role of KLF16 in bladder cancer (BC). We demonstrated that KLF16 was overexpressed in human BC tissues. The high expression of KLF16 was a potential predictor of a poor prognosis in patients with BC. Interference with KLF16 expression in 563 cells, having relatively higher levels of KLF16, repressed cell proliferation and migration. In contrast, upregulation of KLF16 in T24 cells enhanced cellular function, including cell growth and migration. KLF16 also suppressed the apoptosis of BC cells. Additionally, KLF16 inhibited the expression of the TGF-type III receptor (TGFBR3) by binding to its promoter sequence and reducing transcriptional activity. There was a negative correlation between KLF16 and TGFBR3 in human BC tissues. Furthermore, TGFBR3 was revealed to be a negative regulator of BC cell proliferation and migration. KLF16 also supported BC tumorigenesis by downregulating TGFBR3 expression in vivo. DISCUSSION: These results suggested that KLF16 acts as an oncogene in BC through transcriptional inactivation of TGFBR3. This study provides evidence that targeting the KLF16/TGFBR3 axis may be beneficial for BC patients.

Case Report: Acute Pancreatitis Associated With Tacrolimus in Kidney Transplantation and a Review of the Literature.

Background: Drug-induced pancreatitis is a rare cause of acute pancreatitis. Tacrolimus has been used as an immunosuppressant agent in patients after organ transplantation. However, only a few case reports of tacrolimus-induced acute pancreatitis in kidney transplantation have been reported. The purpose of this case report is to alert clinicians that tacrolimus-induced acute pancreatitis may occur during tacrolimus therapy in kidney transplant patients. Case Presentation: We present the case of a 38-year-old woman who underwent kidney transplantation and received immunosuppressive therapy with tacrolimus; on day 20 post-transplantation, she presented with acute abdominal pain in the middle and left areas of the abdomen accompanied by diarrhea, nausea, and vomiting. We excluded gallstone disease, alcohol, hypertriglyceridemia, and other possible causes, and speculated that tacrolimus was the probable cause of pancreatitis because of the extremely high blood concentration of tacrolimus. After tacrolimus was changed to cyclosporine, her symptoms were gradually improved, and she was discharged home without relapse. Conclusion: Tacrolimus is a rare cause of pancreatitis after kidney transplantation. It is important to note that tacrolimus-induced acute pancreatitis may occur during tacrolimus therapy in kidney transplantation patients.

Differential Circulating Fungal Microbiome in Prostate Cancer Patients Compared to Healthy Control Individuals.

BACKGROUNDS: Infection and inflammation play an important role in prostate cancer (PCa) etiology and pathogenesis. However, the environmental drivers for PCa are not fully understood. METHODS: In a cross-sectional study, we analyzed circulating fungal microbiome in plasma samples from age and race-matched healthy control men (n = 34) and preoperative PCa patients (n = 31). RESULTS: The fungal community in the plasma exhibited differences between individuals with PCa and healthy controls according to the beta diversity; there was no difference in the alpha diversity. Moreover, the relative abundance of several fungi differed between the two study groups from the class to species levels. The most significant differences were Filobasidiales family, Pyronemataceae family, and Cryptococcus ater species, which were enriched in PCa patients compared to controls. The increased Bipolaris genus was associated with low prostate-specific antigen (PSA) levels, increased Sordariomycetes class was associated with severe pathological stage, and decreased Phoma herbarum species was associated with disease relapse, compared to corresponding controls. Several fungi from class to species levels were increased in the controls compared to patients. CONCLUSION: This is the first study to show plasma distinct fungal microbiome and its associations with PSA levels, relapse, and pathology stages in PCa patients.

Expression profiles of long non-coding RNAs in neurogenic bladder of spinal cord injured rats: a transcriptomic analysis.

Background: Growing evidence has indicated that long non-coding RNAs (lncRNAs) are important regulators of pathological and physiological processes through various mechanisms. However, the signature of lncRNA expression and the possible roles of lncRNAs in spinal cord injury (SCI) rat neurogenic bladder (NB) have not been comprehensively explored. In this study, the expression profiles of lncRNAs and mRNAs were explored in the bladder tissue of SCI rats using next-generation sequencing (NGS). Methods: Twenty female Wistar rats were randomly divided into SCI 1-3 and normal control (NC) groups. The spinal cord was completely transected at the T9-T10 level to establish the SCI model. Bladder tissues were collected on days 7, 14, and 28 after the operation. The expression profiles of lncRNAs were detected by NGS. Differentially expressed lncRNAs (DELs) were chosen for qRT-PCR verification to validate the RNA sequencing results. The functions of the predicted target genes were then evaluated using Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: Compared with the NC group, the SCI 1-3 groups had 468, 117, and 408 DELs [fold change (FC) >2], including 247, 38, and 201 up-regulated and 163, 79, and 207 down-regulated lncRNAs, respectively. Likewise, 6,654, 2,133, and 5,706 mRNAs (FC >2) were differentially expressed between SCI 1-3 and NC rats, of which 4,821, 1,195, and 3,695 were up-regulated, and 1,833, 938, and 2,011 were down-regulated, respectively. Specifically, Miat, Mir155hg, and H19 were significant DELs in all SCI groups. Moreover, GO revealed that the DELs were related to several terms, including immune response, and KEGG was mainly enriched in 10 pathways, such as the transforming growth factor ß signaling pathway. Conclusions: The results revealed the expression profiles and possible roles of lncRNAs in SCI rat NB. This study may help identify possible NB mechanisms following SCI from the perspective of lncRNAs and provides new potential lncRNAs for the early diagnosis and treatment of human NB in the future.

Botulinum toxin A improves neurogenic bladder fibrosis by suppressing transforming growth factor ß1 expression in rats.

BACKGROUND: Intradetrusor botulinum toxin A injection is recommended for the treatment of refractory detrusor overactivity (DO) in patients with neurogenic bladder, however, whether it could inhibit neurogenic bladder fibrosis is uncertain. This study aimed to investigate the effect of botulinum toxin A on neurogenic bladder fibrosis and the underlying mechanism. METHODS: Forty eight Female Wistar rats were evenly randomized into 4 groups: Sham, T10 transection, Early and Late groups. The last three groups were subjected to T10 spinal cord transection, while the Sham group was treated with sham surgery. 0.9% saline was injected into the detrusor in the Sham and T10 transection groups simultaneously with the surgery, while 2 U/rat botulinum toxin A was injected into the detrusor simultaneously with the surgery in the Early group and 4 weeks following the surgery in the Late group. Body/bladder weight, cystometric parameters, bladder Hematoxylin-eosin staining were used to evaluate the bladder fibrosis. Western blot and quantitative Real-time PCR were used to evaluate the expression of bladder transforming growth factor ß1. RESULTS: Compared with the T10 transection group, the bladder/body weight was decreased significantly in the Early and Late groups (P<0.05), along with the significant inhibition of non-voiding contraction (NVC) frequency and amplitude (P<0.05), and the significant increase of bladder volume (P<0.05). The detrusor connective tissue percentage (P<0.05) and the expression of transforming growth factor ß1 (P<0.05) also decreased significantly in the Early and Late groups. Those changes were more obviously in the Early group than in the Late group. CONCLUSIONS: Intradetrusor botulinum toxin A injection reduced bladder fibrosis in rats with spinal cord injury (SCI), which was more obviously in the Early group than in the Late group. The mechanisms might be mediated by suppression of transforming growth factor ß1 (TGF-ß1) expression.