Chronic chemogenetic inhibition of TRPV1 bladder afferent promotes micturition recovery post SCI.

Spinal cord injury often results in chronic loss of micturition control, which is featured by bladder hyperreflexia and detrusor sphincter dyssynergia. Previous studies showed that treatment of capsaicin reduces non-voiding bladder contractions in multiple animal injury models and human patients. However, its underlying neural mechanisms remain largely unknown. Here, by injecting a RetroAAV into the bladder wall, we specifically targeted TRPV1+, a capsaicin receptor, bladder afferent neurons. Morphometric analysis revealed borderline increase of the soma size and significant spinal axon sprouting of TRPV1+ bladder afferent neurons post a complete T8 spinal cord crush. We further demonstrated that chronic chemogenetic inhibition of these DRG neurons improved micturition recovery after SCI by increasing voiding efficiency and alleviating bladder hyperreflexia, along with reduced morphological changes caused by injury. Our study provided novel insights into the structural and functional changes of TRPV1+ bladder afferent post SCI and further supports the clinical use of capsaicin as an effective treatment to improve bladder functions in patients with SCI.

[Changes in Secondary Inorganic Ions in PM2.5 at Different Pollution Stages Before and After COVID-19 Control].

To investigate the change characteristics of secondary inorganic ions in PM2.5 at different pollution stages before and after COVID-19, the online monitoring of winter meteorological and atmospheric pollutant concentrations in Zhengzhou from December 15, 2019 to February 15, 2020 was conducted using a high-resolution (1 h) online instrument. This study analyzed the causes of the haze process of COVID-19, the diurnal variation characteristics of air pollutants, and the distribution characteristics of air pollutants at different stages of haze.The results showed that Zhengzhou was mainly controlled by the high-pressure ridge during the haze process, and the weather situation was stable, which was conducive to the accumulation of air pollutants. SNA was the main component of water-soluble ions, accounting for more than 90%. Home isolation measures during COVID-19 had different impacts on the distribution characteristics of air pollutants in different haze stages. After COVID-19, the concentration of PM2.5 in the clean, occurrence, and dissipation stages increased compared with that before COVID-19 but significantly decreased in the development stage. The home isolation policy significantly reduced the high value of PM2.5. The concentrations of NO2, SO2, NH3, and CO were the highest in the haze development stage, showing a trend of first increasing and then decreasing. The concentration of O3 was lowest in the pre-COVID-19 development stage but highest in the post-COVID-19 development stage. The linear correlation between[NH4+]/[SO42-] and[NO3-]/[SO42-] at different time periods before and after COVID-19 was strong, indicating that the home isolation policy of COVID-19 did not change the generation mode of NO3-, and the corresponding reaction was always the main generation mode of NO3-. The correlation between[excess-NH4+] and[NO3-] was high in different periods before COVID-19, and NO3- generation was related to the increase in NH3 or NH4+ in the process of PM2.5 pollution in Zhengzhou.

Specific Biomarkers of Prostate Cancer-Associated Ischemic Stroke: A Case-Control Study.

BACKGROUND Ischemic stroke in cancer patients is associated with poor prognosis. However, the specific biomarkers of cancer-associated ischemic stroke (CaIS) have not been well defined. MATERIAL AND METHODS A retrospective study was conducted on PCaIS patients. Clinical data and laboratory and imaging findings were collected. Multivariable logistic regression analysis was used to analyze the independent risk factors for PCaIS. A multiple model combining the independent risk factors of PCaIS was developed using the receiver operating characteristic (ROC) and area under the ROC curve (AUC). RESULTS A total of 83 PCaIS patients and 83 prostate cancer (PCa) patients were included. PCaIS patients had higher levels of D-dimer, neutrophil-to-lymphocyte ratio (NLR), and total prostate-specific antigen (T-PSA). In the multivariate analysis, D-dimer [OR=1.001, 95% CI: 1.00,1.00, P=0.002], NLR [OR=1.12, 95% CI: 1.04,1.22, P=0.005], and T-PSA [OR=6.275, 95% CI: 2.57,15.31, P<0.001] were independent risk factors of PCaIS. Additionally, the AUC of the multiple model of PCaIS was 0.815 (95% CI, 0.750-0.869), with sensitivity of 81.71% and specificity of 70.21%. CONCLUSIONS Elevated levels of D-dimer and T-PSA and increased NLR are independent risk factors of PCaIS. The multiple model of PCaIS can be a specific biomarker and is a reliable predictor of development of PCaIS.

Biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke.

AIM: To investigate the specific biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke (CRCIS). METHODS: A retrospective study was conducted on CRCIS patients (colorectal cancer patients with ischemic stroke without conventional stroke risk factors) registered at seven centers between January 2007 and December 2017. Clinical data and laboratory and imaging findings were compared with age- and sex- matched patients with colorectal cancer (CRC) without ischemic stroke that were admitted to the same hospital during the same period. Univariate and multivariate analyses were performed to analyze the independent risk factors for CRCIS. A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the products of the independent risk factors for CRCIS. RESULTS: A total of 114 CRCIS patients and 114 CRC patients were included. Multiple lesions in multiple vascular territories were common in CRCIS patients (71, 62.28%). The levels of plasma D-dimer, carcinoembryonic antigen (CEA), cancer antigen 125, and neutrophil count were significantly higher in CRCIS patients than in CRC patients. Multiple logistic regression analysis revealed that plasma D-dimer levels [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.001-1.003, P < 0.001], CEA levels (OR = 1.011, 95%CI: 1.006-1.015, P < 0.001), and neutrophil count levels (OR = 1.626, 95%CI: 1.268-2.087, P < 0.001) were independent risk factors for CRCIS. In addition, receiver operator characteristic curve revealed that the area under curve for the products of plasma D-dimer, CEA, and neutrophil count was 0.889 ± 0.022 (95%CI: 0.847-0.932, P < 0.001), and the optimal cut-off value for the product was 252.06, which was called the CRCIS Index, with a sensitivity of 86.0% and specificity of 79.8%. CONCLUSION: Hypercoagulability induced by elevated CEA and neutrophils may be an important cause of CRCIS. The CRCIS index, which serves as a biomarker of CRCIS, needs further study.

[Design, synthesis and antiproliferative activity in cancer cells of novel dihydropyrazolyl and pyrazolyl artemisinin-phenyl ethers].

To explore potent anticancer agent based on artemisinin scaffold, a series of 10-O-phenyl ethers derivatives containing dihydropyrazolyl or pyrazolyl moiety have been designed and synthesized. Their structures were determined by LC-MS and ¹H-NMR date. Inhibitory effects of the target compounds in human breast cancer MCF-7, MCF/Adr, MDA-MB-231 cells and prostate cell line PC-3 were determined by MTT assay. Those derivatives displayed good antiproliferative activity against the tested cancer cells. Particularly, target compounds exhibited significant cytotoxicity against drug-resistance cells MCF/Adr, which was worthy for further investigation.

[Updated treatments of castration-resistant prostate cancer].

The diagnosis and treatment of prostate cancer are being improved due to the popularized screening of prostate specific antigen. Advanced prostate cancer, in spite of its response to androgen deprivation therapy, may finally develop into castration-resistant prostate cancer (CRPC) and shorten the overall survival of the patients. Many efforts have been made by worldwide researchers for new approaches to the management of CRPC, including new hormonal therapy, cytotoxic chemotherapy, immunotherapy, and bone metastasis-targeted therapy. This paper reviews the emerging agents undergoing clinical evaluation and drugs that have received approval for the treatment of CRPC in order to provide doctors and patients with more treatment options for CRPC and improve the overall survival rate and quality of life of the patients.

[Transurethral transumbilical laparoendoscopic single-site surgery for radical prostatectomy].

OBJECTIVE: To investigate the feasibility and advantages of transurethral transumbilical laparoendoscopic single-site surgery (TU-LESS) for radical prostatectomy. METHODS: Five patients with prostate cancer underwent TU-LESS for radical prostatectomy, with a four-channel single-port device inserted into a 2. 5 cm periumbilical incision and another placed through the urethra, followed by analysis of the perioperative data. RESULTS: All the operations were successfully accomplished, with neither conversion to open surgery nor additional channel. The mean operation time, intraoperative blood loss, and postoperative hospital stay were 168 min, 120 ml, and 15 d, respectively. No severe perioperative complications were observed. TNM stage classification manifested T2cN0M0 in 2 cases and T2bN0M0 in the other 3. Postoperative pathology showed no negative surgical margins in any of the cases. CONCLUSION: TU-LESS is safe and feasible for radical prostatectomy and can reduce the complication of low urinary tract surgery by single-site laparoendoscopy.

[Indirubin inhibits the proliferation of prostate cancer PC-3 cells].

OBJECTIVE: To explore the antitumoral effect of indirubin on androgen-independent prostate cancer PC-3 cells and its possible mechanisms. METHODS: We measured the inhibitory effect of indirubin on the proliferation of prostate cancer PC-3 cells using MTT assay, detected their cell cycles by flow cytometry, and determined the expressions of the cell cycle regulatory protein cyclin D1 and its related downstream gene c-myc by Western blot. RESULTS: The viability of the PC-3 cells was significantly decreased by indirubin in a concentration-dependent manner, reduced to 52. 2% and 13. 6% at 5 and 10 µmol/L, respectively. The cell cycle of the PC-3 cells was markedly inhibited by indirubin at 5 µmol/L, with the cells remarkably increased in the G0 and G1 phases and decreased in the S and G2/M phases. Meanwhile, indirubin also inhibited the expressions of cyclin D1 and c-myc in the Wnt signaling pathway. CONCLUSION: Indirubin can suppress the proliferation of androgen-independent prostate cancer PC-3 cells, which may be associated with its inhibitory effect on the cell cycle and Wnt signaling pathway.

Differential expression of the Wnt/ß-catenin pathway in the genital tubercle (GT) of fetal male rat following maternal exposure to di-n-butyl phthalate (DBP).

Di-n-butyl phthalate (DBP) is one of the most abundantly produced endocrine disruptors that leaches out from polyvinyl chloride plastics and can cause hypospadias in male rats during maternal exposure. The objective of this study was to first explore the roles of Wnt/ß-catenin pathway in the fetal rat genital tubercle (GT) following in-utero exposure to DBP. Timed-pregnant rats were given DBP by gastric intubation at a dose of 750 mg/kg body weight (bw)/day from gestation day (GD) 14 to GD18 to establish a rat model of hypospadias. On GD19, genital tubercle down-regulation of ß-catenin, Phospho-GSK-3ß, and up-regulation of GSK-3ß (glycogen synthase kinase-3ß), NFκB in fetal male rats was observed by western blot analysis. ß-catenin was located in the urethral plate epithelium (UPE). Immunochemistry showed that the relative expression of ß-catenin decreased in the DBP-treated fetal rat GT compared to the normal control. These findings, for the first time, indicate that DBP may affect the development of GT by down-regulating the Wnt/ß-catenin pathway in fetal male rats.

[Proteomic analysis of the testis and differential expression of Annexin A3 in hypospadiac rats].

OBJECTIVE: To investigate the effect of in utero exposure to di-n-butyl phthalate (DBP) on the protein expression in the penile tissue of hypospadiac rats, isolate and identify differentially expressed proteins, and determine the role of the differential expression of Annexin A3 in the development of hypospadia in the rat offspring after maternal exposure to DBP. METHODS: Twenty pregnant SD rats were randomly assigned to an experimental group, intragastrically administered DBP at 800 mg/kg, and a control group, given soybean oil at 5 ml/kg, both for 5 days. Three days after birth, the penises of the newborn rats were removed, and the total protein extracted for 2D-electrophoretic separation and image analysis. Differentially expressed protein spots were screened and identified by mass spectrometry, and the changes in the expression of Annexin A3 detected by Western blotting and immunohistochemistry. RESULTS: Thirty-one differentially expressed protein spots were screened, of which 17 were identified by mass spectrometry and the SwissProt database, including pyruvate kinase M2, alpha-enolase, and Annexin A3. Western blot showed that Annexin A3 was mainly located in the urethral epithelia and had a lower expression in the hypospadiac rats (1.851 +/- 0.014, n = 10) than in the controls (2.603 +/- 0.012, n = 10) (P < 0.05). CONCLUSION: A pedigree of differentially expressed proteins in the penises of DBP-induced hypospadia and normal rats was established by the proteomic method. The differential expression of Annexin A3 may play an important role in the development of hypospadia.