Wound healing process in beagles after vaporization of the prostate with a novel 200W 450-nm laser.

In comparison to other commercially used lasers, the coagulation layer of the novel 450-nm laser is thinner, and this coagulation layer's thickness is a key factor influencing wound healing. In this study, we investigated whether the novel 200W 450-nm laser system (BR6800, Blueray Medical Ltd., Shaanxi, China) is superior to classic transurethral resection of the prostate (TURP) for wound healing in beagles. Twenty-two 6-to 8-year-old male beagles were treated with TURP or blue laser vaporization of the prostate (BLVP). Prostate wounds were observed via cystoscopy at 3 h and at 1, 2, 3, and 5 weeks post-operation (two beagles per group). Additionally, two elderly beagles without surgery served as normal controls. After cystoscopy examination, prostate samples were collected and fixed for hematoxylin and eosin (H&E) and immunofluorescence staining to observe wound healing progression under microscopy. The urethras of prostates under cystoscopy in BLVP groups were healed three weeks after surgery, while in the TURP group, they were healed five weeks after surgery. H&E staining confirmed that the coagulation necrosis layer in the TURP group was thicker than that in the BLVP group and it took longer to remove coagulation necrosis after surgery. Macrophage polarity transformation was also earlier in the BLVP group. The new 200W 450-nm laser was superior to TURP for wound healing. The thinner coagulation layer of the 450-nm laser was the primary reason for this process.

DAB2IP regulates intratumoral testosterone synthesis and CRPC tumor growth by ETS1/AKR1C3 signaling.

The intratumoral androgen synthesis is one of the mechanisms by which androgen receptor (AR) is aberrantly re-activated in castration-resistant prostate cancer (CRPC) after androgen ablation. However, pathways controlling steroidogenic enzyme expression and de novo androgen synthesis in prostate cancer (PCa) cells are largely unknown. In this study, we explored the potential roles of DAB2IP in testosterone synthesis and CRPC tumor growth. Indeed, DAB2IP loss could maintain AR transcriptional activity, PSA re-expression and tumor growth under castrated condition in vitro and in vivo, and reprogram the expression profiles of steroidogenic enzymes, including AKR1C3. Mechanistically, DAB2IP could dramatically inhibit the AKR1C3 promoter activity and the conversion from androgen precursors (i.e., DHEA) to testosterone through PI3K/AKT/mTOR/ETS1 signaling. Consistently, there was a high co-expression of ETS1 and AKR1C3 in PCa tissues and xenografts, and their expression in prostate tissues could also restore AR nuclear staining in castrated DAB2IP-/- mice after DHEA supplement. Together, this study reveals a novel regulation of intratumoral de novo androgen synthesis in CRPC, and provides the DAB2IP/ETS1/AKR1C3 signaling as a potential therapeutic target.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.

Nitrogen-Doped Multiwalled Carbon Nanotubes Enhance Bone Remodeling through Immunomodulatory Functions.

It has been reported that multiwalled carbon nanotubes (MWCNTs) can reportedly positively affect growth and differentiation of bone-related cells and therefore offer great potential in biomedical applications. To overcome negative immune responses that limit their application, specific doping and functionalization can improve their biocompatibility. Here, we demonstrated that nitrogen-doped carboxylate-functionalized MWCNTs (N-MWCNTs) enhance bone remodeling both in vitro and in vivo with excellent biocompatibility, via stimulation of both bone resorption and formation. We revealed that 0.2 µg/mL N-MWCNTs not only increase the transcription of osteoblastogenic and osteoclastogenic genes but also up-regulate the activities of both TRAP and AKP in the differentiation of bone marrow stromal cells (BMSCs). Additionally, intramuscular administration of N-MWCNTs at a dosage of 1.0 mg/kg body weight enhances bone mineral density and bone mass content in mice, as well as induces potentiated degree of TRAP- and ARS-positive staining in the femur. The positive regulation of N-MWCNTs on bone remodeling is initiated by macrophage phagocytosis, which induces altered production of inflammatory cytokines by immune response pathways, and consequently up-regulates IL1α, IL10, and IL16. These cytokines collectively regulate the central osteoclastogenic transcription factor NFATc1 and osteoblastogenic BMP signaling, the suppression of which confirmed that these factors respectively participate in N-MWCNT-mediated regulation of osteoclastic and osteoblastic bone marrow stem cell activities. These results suggest that N-MWCNTs can be readily generalized for use as biomaterials in bone tissue engineering for metabolic bone disorders.

Efficacy of sorafenib adjuvant therapy in northwestern Chinese patients with non-metastatic renal-cell carcinoma after nephrectomy: A multicenter retrospective study.

Recent studies have confirmed the efficacy of sorafenib for patients with advanced renal cell carcinoma; however, its efficacy and safety as an adjuvant therapy in patients with non-metastatic and loco-regional renal cell carcinoma after surgery remains controversial. Thus, the aim of the present retrospective study was to evaluate the efficacy of adjuvant sorafenib therapy in such patients from 8 centers in northwestern China that were treated from August 2009 to December 2016.After surgery, the patients (n = 48) received oral sorafenib for 3 months. The control group (n = 48) comprised patients that underwent the same surgery from December 2009 to June 2016 but without adjuvant therapy who were matched 1:1 with the sorafenib group with respect to sex, age, pathological findings, disease stage and grade, operation time, and surgical procedure. The primary outcome compared between the groups was disease-free survival. Adverse events were also recorded to evaluate the safety of sorafenib. The influence of patients' characteristics and laboratory tests on recurrence was analyzed using unconditional logistic regression.Overall, the demographic characteristics of the 2 groups were similar. There was no significant difference in the rate of recurrence (8.3% for sorafenib patients and 6.2% for the matched patients, P = .66) or median disease-free survival between the 2 groups (hazard ratio = 1.561, 95% confidence interval = 0.349-6.987, P = .56). In multiple logistic regression analysis, increased blood urea nitrogen (BUN) emerged as an independent predictor of recurrence risk (P = .02).These results indicate that postoperative sorafenib adjuvant therapy did not achieve the expected beneficial effect, pointing to the need for further studies to evaluate its utility in such cases.

Targeting 3-phosphoinositide-dependent protein kinase 1 associated with drug-resistant renal cell carcinoma using new oridonin analogs.

The current agents used for renal cell carcinoma (RCC) only exhibit the moderate response rate among patients. Development of drug resistance eventually fuels the need of either more potent drugs or new drugs to target the resistant pathways. Oridonin is a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens and has been shown to have antitumor activities in many cancers. We previously developed new synthetic methodologies to modify structurally diversified diterpenoids and designed a series of nitrogen-enriched oridonin analogs. In this study, we screened a variety of oridonin analogs based on their cytotoxicity using MTT assay and identify the most potent candidate, namely, CYD-6-17. CYD-6-17 exhibited a high potency to inhibit the in vitro growth of several drug-resistant RCC cells as well as endothelial cells stimulated by tumor cells at nanomolar range. Delivery of CYD-6-17 significantly inhibited RCC tumor growth using xenograft model. Mechanistically, it targeted the 3-phosphoinositide-dependent protein kinase 1 gene that appeared to be a potent regulator of AKT and was associated with patient survival after targeted therapies. This offers a new rational therapeutic regimen of CYD-6-17 to drug-resistant RCC based on its novel mechanism of action.

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling.

Renal cell carcinoma (RCC) is known as one of the most lethal malignancies in the urological system because of its high incidence of metastasis. Tetrandrine (Tet), a traditional Chinese herbal medicine, exerts a potent anti-cancer effect in a variety of cancer cells. However, the anti-metastatic effect of Tet and its possible mechanism in RCC is still unclear. The present study revealed that Tet significantly suppressed the migration and invasion of RCC 786-O and 769-P cells in vitro. Mechanistically, the protein levels of matrix metalloproteinases 9 (MMP-9), phosphorylated PI3K, PDK1, Akt and NF-κB were markedly reduced after Tet treatment. Moreover, co-treatment with LY294002 (PI3K inhibitor) could further enhance the Tet-inhibited migration and invasion, and the NF-κB and MMP-9 protein levels were further decreased. Similar results were observed after PDTC (NF-κB inhibitor) co-treatment. Conversely, SC79, an Akt activator, could partially reverse the anti-metastatic effects of Tet, accompanied by the restoration of NF-κB and MMP-9 protein levels. In conclusion, the current results indicated that Tet inhibited migration and invasion of RCC partially by regulating Akt/NF-κB/MMP-9 signaling pathway, suggesting that Tet may be a potential therapeutic candidate against metastatic RCC.

Tetrandrine suppresses proliferation, induces apoptosis, and inhibits migration and invasion in human prostate cancer cells.

Tetrandrine (TET), a traditional Chinese medicine, exerts remarkable anticancer activity on various cancer cells. However, little is known about the effect of TET on human prostate cancer cells, and the mechanism of function of TET on prostate cancer has not yet been elucidated. To investigate the effects of TET on the suppression of proliferation, induction of apoptosis, and inhibition of migration and invasion in human prostate cancer cell lines, DU145 and PC-3. Inhibition of growth was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and clone formation assay, and flow cytometry analysis was performed to detect the induction of apoptosis. Activation of poly (ADP-ribose) polymerase, caspase-3, Akt, phospho-Akt, Bcl-2, and Bax was analyzed by Western blotting. Wound healing assay and transwell migration assay were used to evaluate the effect of TET on migration and invasion of cancer cells. TET inhibited the growth of DU145 and PC-3 cells in a dose- and time-dependent manner. Cell cloning was inhibited in the presence of TET in DU145 and PC-3 cells. TET suppressed the migration of DU145 and PC-3 cells. Transwell invasion assay showed that TET significantly weakened invasion capacity of DU145 and PC-3 cells. TET exhibited strong inhibitory effect on proliferation, migration, and invasion of prostate cancer cells. In addition, TET induced apoptosis in a dose-dependent manner by activating the caspase cascade and inhibiting phosphoinositide 3-kinase-Akt signal pathway. The accumulating evidence suggests that TET could be a potential therapeutic candidate against prostate cancer in a clinical setting.

Silibinin inhibits ß-catenin/ZEB1 signaling and suppresses bladder cancer metastasis via dual-blocking epithelial-mesenchymal transition and stemness.

Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3ß (GSK3ß) phosphorylation, ß-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of ß-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness.

The protective effects of the traditional Chinese herbs against renal damage induced by extracorporeal shock wave lithotripsy: a clinical study.

Extracorporeal shock wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms. We have reported previously that Astragalus membranaceus, Salvia miltiorrhiza, a decoction of six drugs containing rhizoma Rehmanniae preparata and supplements of a few traditional Chinese medicinal herbs for invigorating the kidney and excreting calculus, have a protective effect on renal injury induced by high-energy shock waves (HESW) in rabbits. In this clinical study we further investigate the protective effects of these traditional Chinese herbs against renal damage induced by ESWL. Sixty consenting patients with renal calculus who underwent ESWL treatment were included and randomly assigned to the medication group or control group. Post-ESWL plasma nitric oxide (NO), endothelin-1 (ET-1), malondialdehyde (MDA), and serum tumor necrosis factor α (TNF-α) increased significantly in the controls (P < 0.05), while in the medication group, slightly but not significantly elevated levels of plasma ET-1, NO, and serum TNF-α were found. The difference between the groups was statistically significant (P < 0.05). The levels of superoxide dismutase (SOD) decreased gradually in the controls, reaching a trough 72 h after ESWL (P < 0.05), while in the treated group it was unchanged, and remained at a level higher versus the controls (P < 0.05). Plasma NO peaked twice by 72 h and at 1 week in the controls (P < 0.05). Urinary enzymes and ß(2)-microglobulin increased significantly and peaked by 24 h and immediately after ESWL (P < 0.05). These values were greater in the controls, and the difference was statistically significant (P < 0.05). This study demonstrates that the preparations of traditional Chinese medicines for invigorating the kidney and excreting calculus can reduce renal tubular damage induced by ESWL, and can shorten the recovery time of renal tubules in human subjects.

Targeting silibinin in the antiproliferative pathway.

IMPORTANCE OF THE FIELD: Due to the failure and severe toxicity of cancer chemotherapy, silibinin, a natural flavonoid from the seeds of milk thistle, has recently received more attention for its potential anticancer and nontoxic roles in animals and humans. Silibinin has clearly demonstrated inhibition of multiple cancer cell signaling pathways, including growth inhibition, inhibition of angiogenesis, chemosensitization, and inhibition of invasion and metastasis. Cumulative evidence implicates that silibinin is a potential agent for cancer chemoprevention and chemotherapy. AREAS COVERED IN THIS REVIEW: Our aim is to discuss the recent progress of silibinin in regulating multiple anticancer proliferative signaling pathways; the review covers literature mainly from the past 3 - 5 years. WHAT THE READER WILL GAIN: One of the strategies for tumor therapy is eradication of cancer cells through targeting specific cell-proliferative pathways. This review highlights the current knowledge of silibinin in regulating multiple cellular proliferative pathways in cancer cells, including receptor tyrosine kinases, androgen receptor, STATs, NF-kappaB, cell cycle regulatory and apoptotic signaling pathways. TAKE HOME MESSAGE: The molecular mechanisms of silibinin-mediated antiproliferative effects are mainly via receptor tyrosine kinases, androgen receptor, STATs, NF-kappaB, cell cycle regulatory and apoptotic signaling pathways in various cancer cells. Targeting inhibition of proliferative pathways through silibinin treatment may provide a new approach for improving chemopreventive and chemotherapeutic effects.

Silibinin inhibits prostate cancer invasion, motility and migration by suppressing vimentin and MMP-2 expression.

AIM: Silibinin is known to exert growth inhibition and cell death together with cell cycle arrest and apoptosis in human prostate cancer cells. Whether silibinin could inhibit the invasion, motility and migration of prostate cancer cells remains largely unknown. This study was designed to evaluate this efficacy and possible mechanisms using a novel highly bone metastatic ARCaP(M) cell model. METHODS: Four prostate cancer cell lines, LNCaP, PC-3, DU145, and ARCaP(M), were used in this study. These cells were treated with increasing concentrations of silibinin (50, 100, and 200 micromol/L) for different periods of time. After treatment, cell viabilities of four prostate cancer cells were compared by MTT assay. Alterations of ARCaP(M) cell invasion, motility and migration were assessed by cell invasion, motility and wound healing assays. The changes of vimentin expression were observed by Western blotting and immunofluorescence staining, and the expression of MMP-2, MMP-9, and uPA was analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: ARCaP(M) cells showed less sensitivity to the growth inhibition of pharmacological doses of silibinin than LNCaP, PC-3, and DU145 cells. However, silibinin exerted significant dose- and time-dependent inhibitory effects on the invasion, motility and migration of ARCaP(M) cells. Furthermore, the expression of vimentin and MMP-2, but not MMP-9 or uPA, was down-regulated in a dose- and time-dependent manner after treatment of silibinin. CONCLUSION: This study shows that silibinin could inhibit the invasion, motility and migration of ARCaP(M) cells via down-regulation of vimentin and MMP-2 and therefore may be a promising agent against prostate cancer bone metastasis.

[The protective effect of Chinese herbs for supplementing shen to eliminate stone on renal injury induced by extracorporeal shockwave lithotripsy in patients with renal calculus].

OBJECTIVE: To study the protective effect of Chinese herbs for supplementing Shen to eliminate stone on renal injury induced by extracorporeal shockwave lithotripsy (ESWL) in patients with renal calculus. METHODS: Sixty patients with diagnosis of renal calculus confirmed by X-ray film or CT combined with abdominal B ultrasonography but showing no obvious symptoms, were randomized into the treated group and the control group. They all were scheduled to receive ESWL treatment. To the patients in the treated group, prescribed Chinese herbs was orally administered in the three days before and after ESWL, patients in the control group ate and drank as usual. Changes of blood levels of nitric oxide (NO), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-alpha), urinary levels of N-acetyl-D-glucosaminidase (NAG), gamma-glutamyltransferase (gamma-GT) and beta 2-microglobulin (beta 2-MG) before and after ESWL were observed. RESULTS: Blood levels of NO, ET-1, MDA and TNF-alpha significantly increased after ESWL in the control group, higher than the levels in the treated group (P < 0.05); and level of SOD decreased gradually in the control group reaching the valley 72 h after ESWL (P < 0.05), while in the treated group it was unchanged and remained at the level higher than that in the control group (P < 0.05). As for the urinary levels of NAG, gamma-GT and beta2-MG, after ESWL, they were all higher in the control group than those in the treated group, showing statistical significance (P <0. 05). CONCLUSION: ESWL could induce renal damage in patients with renal calculus and the Chinese herbs for supplementing Shen to eliminate stone can reduce the renal tubular damage by way of anti-oxidation and regulating the renal hemorrheologic disorder and the release of inflammatory mediators.

[Clinical trials of combined therapy of an oral Chinese medicine with massage for chronic nonbacterial prostatitis].

OBJECTIVE: To evaluate the clinical effect of an oral Chinese medicine combined with massage of the prostate in treating chronic nonbacterial prostatitis (CNP). METHODS: Seventy-two CNP patients were randomly divided into an experimental group (oral Chinese medicine with massage) and a control group (oral Chinese medicine only). The main parameters were compared before and two months after the treatment. RESULTS: Total efficacy rates of the experimental and control groups were 90.0% and 68.6%, respectively. Compared with the controls, patients in the experiment group had a lower score on NIH-CPSI, and the difference was significant statistically (P < 0.05). CONCLUSION: The combined therapy is more effective than oral Chinese medicine alone for the treatment of CNP.

A novel antioxidant agent, astragalosides, prevents shock wave-induced renal oxidative injury in rabbits.

Extracorporeal shock-wave lithotripsy (ESWL)-induced renal damage can occur as a result of multiple mechanisms, including small vessel injury and free radical formation. Our previous studies have demonstrated that Astragalus membranaceus (AM), a traditional Chinese herb, could significantly alleviate shock wave-induced renal oxidative injury, and its renoprotective effects were superior to those of varapamil, a calcium antagonist, which were considered to be a powerful agent in treating renal damage during ESWL. However, the effective antioxidant ingredient of this herb in the setting of lithotripsy remains unclear. Astragalosides, the major components of AM, was demonstrated to have superior antioxidation properties both in vitro and in vivo. Therefore, in this study we further investigate the potential effects of astragalosides on the shock wave-induced oxidative stress in rabbit kidney. Thirty male rabbits were randomly assigned to two groups, each consisting of 15 rabbits: (1) control group, (2) astragaloside-treated group. Each group of animals underwent 1,500 shock waves to the right kidney. Peripheral blood, urine and kidney tissue samples were collected pre- and post-ESWL. The level of urinary N-acetyl-beta-glucosaminidase (NAG), serum creatinine, serum or homogenates malondialdehyde (MDA) and superoxide dismutase (SOD), respectively, were detected. Histological alterations were also examined through light microcopy and transmission electron microscopy. In the control group, shock wave significantly increased the level of MDA and decreased SOD activity in both blood and renal homogenates (P<0.05, respectively). The comparison between the control and astragalosides group demonstrated that astragalosides could significantly decrease the level of MDA (P<0.05) and inhibit the decline of SOD activity (P<0.05). After exposure to shock waves, the activity of urinary NAG increased significantly in the control group (P<0.05). However, the concentration of serum creatinine did not change significantly. The comparison between the control and astragalosides group demonstrated that astragalosides significantly reduced the shock wave-induced leakage of NAG into the urine (P<0.05). Histological examination also showed that renal morphological impairments were much milder in astragaloside-treated rabbits than those of the control group. Our results indicated that astragaloside treatment provided significant protection against shock wave-induced renal oxidative injury.

[The protective effects of three components isolated from Astragalus membranaceus on shock wave lithotripsy induced kidney injury in rabbit model].

OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) is has been shown to reduce renal parenchymal injury subject to application of shock wave lithotripsy in our pervious study. To investigate the protective action of three main components from Astragalus membranaceus, including total saponins of astragalus (TSA), total flavonoids of astragalus (TFA) total polysaccharide of astragalus (TPA) in alleviating shock wave induced kidney damage. METHODS: Sixty four male rabbits were randomly assigned to a control group or to 3 groups that were premedicated with TSA TFA and TPA respectively prior to application of ESWL. Each group of animals underwent shock wave lithotripsy (18 kV) to the right kidneys and received a total of 1500 shocks. Peripheral blood samples were collected to evaluate the levels of plasma endothelin-1 (ET-1), plasma nitric oxide (NO) and serum malondialdehyde (MDA) before and after shock wave treatment. The concentrations of these markers in the treated kidney tissues were also detected 3 days, 7 days and 14 days after application of ESWL. The changes of histopathology and cells ultrastructure were observed through light microscope and electron microscope. Untreated contralateral kidneys were evaluated as controls. RESULTS: In control serials the levels of ET-1 and MDA were elevated significantly while the level of NO was significantly decreased after application of shock wave lithotripsy (P < 0.05). The comparison between the controls and premedicated groups demonstrated that all these three components especially TSA and TFA significantly inhibited shock wave induced increasing of ET-1 and MDA (P < 0.05). TSA also significantly suppressed the decrease of NO and made the recovery time earlier compare to the results of controls (P < 0.05). However, TFA and TPA had almost no effects on the change of NO. (P > 0.05). The results in histopathology showed noticeably damage of glomerular and tubular epithelial cells in the treated kidneys in the controls. The histological alterations in the TPA group were similar to those of the controls. These alterations were significantly milder in the TSA and TFA particular the TSA group. CONCLUSION: TFA and TSA, especially TSA seemed to play the key role in alleviating ESWL induced kidney damage.

[Etiology and treatment of bladder spasm associated with benign prostatic hyperplasia].

OBJECTIVE: To investigate the etiology and treatment of bladder spasm associated with benign prostatic hyperplasia (BPH). METHODS: Urodynamic tests were performed in 102 cases of BPH before operation. The correlation of bladder spasm with aging, international prostate symptom score (IPSS), quality of life, prostatic volume, operation methods and urodynamic indexes was studied by t and chi2 tests. RESULTS: The incidences of bladder spasm in the lower compliant bladder and unstable bladder were 32.1% (9/28) and 42.5% (13/20), and those after suprapubic prostatectomy and transurethral resection of the prostate (TURP) were 50.9% (26/51) and 23.3% (12/51). There was significant difference between operation methods (P < 0.05). CONCLUSION: Bladder spasm easily develops in the lower compliant bladder and unstable bladder, especially after suprapubic prostatectomy. TURP might decrease the incidence of bladder spasm after BPH operation.

Transfection of promyelocytic leukemia in retrovirus vector inhibits growth of human bladder cancer cells.

AIM: To construct a recombinant retrovirus vector carrying human promyelocytic leukemia (PML) cDNA and identify its expression and biology role in bladder cancer UM-UC-2 cells for future gene therapy. METHODS: PML full-length cDNA was inserted into the EcoR I and BamH I site of pLXSN vector containing the long terminal repeat (LTR) promoter. The vector was identified by restriction enzyme digestion and then transfected into PA317 packaging cell line by calcium phosphate coprecipitation. PML cDNA was detected by polymerase chain reaction (PCR) and the protein was identified by laser confocal microscopy and Western blot in bladder cancer cells, respectively. The morphology was observed by inverted phase contrast microscope, and MTT assay determined growth curve of the bladder cancer cells. RESULTS: Restriction enzyme digestion proved that a 2.1 kb PML cDNA was inserted into the pLXSN vector. PCR assay demonstrated that 304 bp fragments were found in UM-UC-2/pLPMLSN transfects. Laser confocal microscopy showed speck dots fluorescence in the UM-UC-2/pLPMLSN nucleus. A 90 kD specific brand was found by Western blot. MTT assay demonstrated the UM-UC-2/pLPMLSN bladder cancer growth inhibition. CONCLUSION: The retrovirus pLPMLSN vector was successfully constructed and could generate high effective expression of human PML in bladder cancer cell UM-UC-2, suggesting that PML recombinant retrovirus have potential utility in the gene therapy for bladder cancer.

Astragalus membranaceus reduces free radical-mediated injury to renal tubules in rabbits receiving high-energy shock waves.

BACKGROUND: Recent studies have revealed the important role of free radicals in renal damage induced by high-energy shock waves (HESW). This study aimed at investigating the effects of Astragalus membranaceus, a traditional Chinese medicinal herb, on free radical-mediated HESW-induced damage to renal tubules in a live rabbit model. METHODS: Forty-five healthy male New Zealand white rabbits were randomly divided into three groups: control group (n = 15), sham group (n = 15), and herb-treated group (n = 15). Three days prior to HESW application, the controls received verapamil (0.4 mg/kg), the shams received physiological saline (20 ml), and the herb-treated animals received Astragalus membranaceus (2.4 g/kg) intravenously. HESW (1500 shocks, 18 kV) was applied to the right kidneys of all anesthetized rabbits. We measured superoxide dismutase (SOD) and malondialdehyde (MDA) levels before and after shock treatment in blood and kidney homogenates. Histopathological changes were also observed. RESULTS: MDA levels increased and SOD activity decreased significantly in the sham group (P < 0.05 for both) after shock treatment. MDA levels showed a much less increase in the controls (P < 0.05) and did not increase to statistically significant levels in the group receiving Astragalus membranaceus (P > 0.05). SOD values were significantly higher in the controls than in the shams (P < 0.05). By contrast, SOD levels recovered rapidly in the rabbits receiving Astragalus membranaceus, reaching a nadir within 24 hours, and returning to baseline more quickly than in control and sham rabbits (P < 0.05). Histopathological examinations showed that renal tubular damage in the controls was less severe than in the shams, while damage in the Astragalus membranaceus group was even more mild, with rapid recovery in comparison with the controls. CONCLUSION: This study provides preliminary evidence indicating that Astragalus membranaceus has strong protective effects on free radical-mediated renal tubular damage induced by HESW and that these effects are superior to the effects of verapamil.

[Effects of components isolated from Astragalus mongholicus on expression of p-selectin in shock wave induced kidney injury in rabbit model].

OBJECTIVE: To investigate the effective components of Astragalus mongholicus and their mechanisms in alleviating extracorporeal shock wave lithotripsy (ESWL) induced kidney injury. METHOD: 69 male rabbits were randomly assigned into control group, sham treatment group, Total Saponins of Astragalus (TSA) group, Total Flavonoids of Astragalus (TFA) group, and Total Polysaccharide of Astragalus group (TPA). The shock wave treated kidneys were observed for the expression of p-selectin and the change of cells ultrastructure pre and post ESWL. The concentration of Maleic Dialdehyde (MDA) as well as activity of superoxide dismutase (SOD) in the kidney tissues was also analyzed. RESULT: After application of shock wave treatment, p-selectin was expressed extensively in renal glomerulus, renal tubules and renal interstitium of the treated kidneys. It showed a significant increase of MDA levels and decrease of SOD activity in control group (P < 0.05) after ESWL. The comparison between controls and TSA group demonstrated that TSA could significantly reduce the positive rate of p-selectin P < 0.05) and alleviate the injuries of cells ultrastructure. The results also showed a significant decrease of MDA levels and increase of SOD activity in TSA group compared to controls (P < 0.05). The protective effects of TFA and TPA in alleviating kidney injury induced by shock wave were lower than those of TSA; they had no effects of the expression of P-selectin. CONCLUSION: TSA is the main components of A. mongholicus in alleviating shock wave induced kidney injury not only by scavenging oxygen free radicals but also inhibiting the expression of p-selectin.