Treatment and surveillance for non-muscle-invasive bladder cancer: a clinical practice guideline (2021 edition).

Non-muscle invasive bladder cancer (NMIBC) is a major type of bladder cancer with a high incidence worldwide, resulting in a great disease burden. Treatment and surveillance are the most important part of NIMBC management. In 2018, we issued "Treatment and surveillance for non-muscle-invasive bladder cancer in China: an evidence-based clinical practice guideline". Since then, various studies on the treatment and surveillance of NMIBC have been published. There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China. Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated. We formed a working group of clinical experts and methodologists. Through questionnaire investigation of clinicians including primary medical institutions, 24 clinically concerned issues, involving transurethral resection of bladder tumor (TURBT), intravesical chemotherapy and intravesical immunotherapy of NMIBC, and follow-up and surveillance of the NMIBC patients, were determined for this guideline. Researches and recommendations on the management of NMIBC in databases, guideline development professional societies and monographs were referred to, and the European Association of Urology was used to assess the certainty of generated recommendations. Finally, we issued 29 statements, among which 22 were strong recommendations, and 7 were weak recommendations. These recommendations cover the topics of TURBT, postoperative chemotherapy after TURBT, Bacillus Calmette-Guérin (BCG) immunotherapy after TURBT, combination treatment of BCG and chemotherapy after TURBT, treatment of carcinoma in situ, radical cystectomy, treatment of NMIBC recurrence, and follow-up and surveillance. We hope these recommendations can help promote the treatment and surveillance of NMIBC in China, especially for the primary medical institutions.

[Exposure of the scrotum to 4G cellphone radiofrequency electromagnetic radiation affects the spermatogenesis and blood-testis barrier of adult male rats].

OBJECTIVE: To investigate the direct impact of exposure of the scrotum to 4G cellphone radiofrequency electromagnetic radiation (RF-EMR) on the testis of adult rats. METHODS: We equally randomized 30 adult male SD rats into a control and an exposure group, the latter exposed to 4G cellphone RF-EMR 6 hours a day for 150 days. Then, we analyzed the changes in semen quality and seminiferous epithelia, and measured the levels antioxidant enzyme-peroxide and the expressions of blood-testis barrier proteins in the testis of the rats. RESULTS: Compared with the controls, the rats in the exposure group showed significantly decreased sperm concentration (ï¼»6.39 ± 0.82ï¼½ vs ï¼»4.74 ± 0.87ï¼½ ×107/ml, P < 0.05), viability (ï¼»62.11 ± 8.82ï¼½% vs ï¼»41.44 ± 7.33ï¼½%, P < 0.05), motility (ï¼»55.71 ± 7.39ï¼½ vs ï¼»36.22 ± 6.36ï¼½%, P < 0.05), the percentage of morphologically normal sperm (ï¼»84.89 ± 5.11ï¼½% vs ï¼»70.78 ± 8.11ï¼½%, P < 0.05) and Johnsen's score (8.38 ± 0.98 vs 6.11 ± 1.56, P < 0.05), increased Coentino's score (1.36 ± 0.21 vs 1.81 ± 0.34, P < 0.05) and MDA level (P < 0.05), reduced levels of SOD, GSH and CAT (P < 0.05), and down-regulated expressions of occludin, ZO-1, CAR and N-Cadherin (P < 0.05). CONCLUSIONS: Exposure of the scrotum to 4G cellphone RF-EMR directly causes injury of the testis, disorder of the blood-testis barrier, reduction of semen quality and consequently decline in the fertility of male rats.

Androgen receptor suppresses prostate cancer cell invasion via altering the miR-4496/ß-catenin signals.

Previous study found that AR in prostate may act as both a proliferator and a suppressor to promote or suppress the metastasis of prostate cancer (PCa). In current work, we demonstrated that AR could suppress PCa cell invasion through altering the miR-4496/ß-catenin signals. And mechanisms dissection found that AR could negatively regulate the expression of ß-catenin through enhancing the miR-4496 expression via directly binding to the AR-response-elements (AREs) of miR-4496 promoter, subsequently, the miRNA could directly target the 3' UTR of the ß-catenin-mRNA to reduce its expression. To conclude, our work suggests that AR might play an important role to suppress PCa cell invasion, targeting the newly identified AR/miR-4496/ß-catenin signaling with small molecules may help us to build up new therapeutic approaches to better suppress the metastasis of PCa.

Is testicular dysgenesis syndrome a genetic, endocrine, or environmental disease, or an unexplained reproductive disorder?

Progressive increases in the incidence of male reproductive disorders inclusive of hypospadias, cryptorchidism, poor semen quality, and testicular germ cell cancer (TGCC) have been observed in recent times. The central hypothesis of this study asserted that these disorders may all collectively signify testicular dysgenesis syndrome (TDS). This review aimed to provide evidence verifying the reality of TDS based on four key aspects: environmental endocrine-disrupting chemicals (EDCs), genetic factors, intrauterine growth disorders and lifestyle factors. Although TDS might result from genetic polymorphisms or aberration, recent evidence has highlighted links indicating the conditions associations to both environmental and lifestyle factors due to the rapid temporal changes in the clinical symptoms observed over recent decades. Based on our review of genetic and environmental factors, a key observation of our study suggested that there is an urgent need to prioritize research in reproductive physiology and pathophysiology, particularly in highly industrialized countries facing decreasing populations. At present, current research has yet to elucidate the mechanisms of TDS, in addition to the lack of genuine consideration of a variety of potentially key factors and TDS mechanisms. In conclusion, our study revealed that environmental exposures owing to modern lifestyles are primary factors involved in the associated trends of the syndrome, which are capable of affecting the adult endocrine system via direct means or through epigenetic mechanisms.

Salidroside reduces renal cell carcinoma proliferation by inhibiting JAK2/STAT3 signaling.

Salidroside has been reported to exhibit anticancer properties. This study aimed to investigate the effects of salidroside on renal cell carcinoma growth. Cell viability and proliferation was assessed by Cell Counting Kit-8 and colony formation assays in A498 and 786-0 cells. The effects of salidroside on in vivo tumor growth were also assessed in a mouse xenograft model of renal cell carcinoma. Flow cytometry was used to analyze cell cycle and apoptosis and protein levels were determined by western blotting. Salidroside reduced cell viability and colony formation in both cell lines in a concentration- and time-dependent manner. Tumor growth was also suppressed in the mouse model. Furthermore, salidroside induced significant G1 phase cell cycle arrest and induced apoptosis in both A498 and 786-0 cells. Higher concentrations of salidroside reduced the levels of phosphorylated signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2). These results suggested that salidroside produced potent anticancer properties in renal cell carcinoma by modulating JAK2/STAT3 signaling. Administration of salidroside to patients with renal cell carcinoma might provide a promising therapeutic strategy for this malignancy.

[Expressions of Cx26, Cx32 and Cx43 in prostate cancer and their implications].

OBJECTIVE: To investigate the expressions of Cx26, Cx32 and Cx43 in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their roles in the development and progression of PCa in order to provide some novel evidence for the diagnosis and treatment of PCa. METHODS: We determined the expressions of Cx26, Cx32 and Cx43 in the paraffin samples from 31 cases of PCa and 23 cases of BPH by SABC immunohistochemical staining, and analyzed the relationship of their expressions with the clinical and pathological parameters of PCa and BPH using the semiquantitative method. RESULTS: The positive expressions of Cx26 in BPH and PCa were 82.6% and 74.2%, respectively (chi2 = 0.541, P > 0.05), those of Cx32 were 78.3% and 61.3% (chi2 = 1.763, P > 0.05), and those of Cx43 were 87.0% and 38.7% (chi2 = 12.730, P < 0.01). The staining intensities of Cx26 and Cx43 were negatively correlated with the malignant phenotype of PCa (rCx26 = -0.476, P < 0.01; rCx43 = -0.484, P < 0.01), but not the expression of Cx32 (r = -0.242, P > 0.05). The three Cxs exhibited no correlation with the age and serum PSA level of the patients (P > 0.05), nor among their expressions (P > 0.05). CONCLUSION: Cx26, Cx32 and Cx43 are expressed in different degrees in BPH and PCa tissues. Cx43 plays a role in the occurrence and progression of PCa, and may serve as a new marker of PCa besides PSA as well as a new target in the biotherapy of PCa. Cx26 may be partially involved in the progression of PCa, but its mechanisms need to be further studied.

Arterially transplanted mesenchymal stem cells in a mouse reversible unilateral ureteral obstruction model: in vivo bioluminescence imaging and effects on renal fibrosis.

BACKGROUND: Chronic kidney disease (CDK) is a worldwide health problem, but there is currently no effective treatment that can completely cure this disease. Recently, studies with mesenchymal stem cells (MSCs) on treating various renal diseases have shown breakthroughs. This study is to observe the homing features of MSCs transplanted via kidney artery and effects on renal fibrosis in a reversible unilateral ureteral obstruction (R-UUO) model. METHODS: Thirty-six Balb/c mice were divided into UUO group, UUO-MSC group, and sham group randomly, with 12 mice in each group. The MSCs had been infected by a lentiviral vector to express stably the luciferase reporter gene and green fluorescence protein genes (Luc-GFP-MSC). Homing of MSCs was tracked using in vivo imaging system (IVIS) 1, 3, 14, and 28 days after transplantation. Imaging results were verified by detecting GFP expression in frozen section under a fluorescence microscope. E-cadherin, α-SMA, TGF-ß1, and TNF-α mRNA expression in all groups at 1 and 4 weeks after transplantation were analyzed by quantitative PCR. RESULTS: Transplanted Luc-GFP-MSCs showed increased Luciferase expression 3 days after transplantation. The expression decreased from 7 days, weakened thereafter and could not be detected 14 days after transplantation. Quantitative PCR results showed that all gene expressions in UUO group and UUO-MSC group at 1 week had no statistical difference, while at 4 weeks, except TGF-ß expression (P > 0.05), the expression of E-cadherin, α-SMA, and TNF-α in the above two groups have statistical difference (P < 0.01). CONCLUSION: IVIS enables fast, noninvasive, and intuitive tracking of MSC homing in vivo. MSCs can be taken home to kidney tissues of the diseased side in R-UUO model, and renal interstitial fibrosis can be improved as well.

A glass microfluidic chip for continuous blood cell sorting by a magnetic gradient without labeling.

This paper presents a microfluidic chip for highly efficient separation of red blood cells (RBCs) from whole blood on the basis of their native magnetic properties. The glass chip was fabricated by photolithography and thermal bonding. It consisted of one inlet and three outlets, and a nickel wire of 69-microm diameter was positioned in the center of a separation channel with 149-microm top width and 73-microm depth by two parallel ridges (about 10 microm high). The two ridges were formed simultaneously during the wet etching of the channels. The nickel wire for generating the magnetic gradient inside the separation channel was introduced from the side of the chip through a guide channel. The external magnetic field was applied by a permanent magnet of 0.3 T placed by the side of the chip and parallel to the main separation channel. The RBCs were separated continuously from the 1:40 (v/v) diluted blood sample at a flow rate in the range 0.12-0.92 microL/min (9-74 mm/min) with the chip, and up to 93.7% of the RBCs were collected in the middle outlet under a flow rate of 0.23 microL/min. The cell sedimentation was alleviated by adjusting the specific density of the supporting media with bovine serum albumin. Quantum dot labeling was introduced for visual fluorescence tracking of the separation process. The uneven distribution phenomenon of the blood cells around the nickel wire was reported and discussed.

[Prevalence survey on Cyclospora cayetanensis and Cryptosporidium ssp. in diarrhea cases in Yunnan Province].

OBJECTIVE: To investigate the prevalence and distribution characteristics of Cyclospora cayetanensis and Cryptosporidium ssp. infection in diarrhea cases of Yunnan Province. METHODS: To collect fresh faeces from diarrhea cases in 7 counties/cities, examine the specimens by direct smear with iodine staining and modified acid-fast staining. RESULTS: The infection rate of C. cayetanensis and Cryptosporidium ssp. was 3.97% and 5.29%, respectively. The infection rate of the two pathogenic coccidians was as high as 10.64% and 8.51% in preschool children. C. cayetanensis was found in 3 counties and Cryptosporidium in 6 counties. CONCLUSION: Both C. cayetanensis and Cryptosporidium ssp. are prevalent in Yunnan Province with the latter distributed more widely, and the two pathogens are more prevalent in preschool children.