Blockade of Kv1.3 Potassium Channel Inhibits Microglia-Mediated Neuroinflammation in Epilepsy.

Epilepsy is a chronic neurological disorder whose pathophysiology relates to inflammation. The potassium channel Kv1.3 in microglia has been reported as a promising therapeutic target in neurological diseases in which neuroinflammation is involved, such as multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), and middle cerebral artery occlusion/reperfusion (MCAO/R). Currently, little is known about the relationship between Kv1.3 and epilepsy. In this study, we found that Kv1.3 was upregulated in microglia in the KA-induced mouse epilepsy model. Importantly, blocking Kv1.3 with its specific small-molecule blocker 5-(4-phenoxybutoxy)psoralen (PAP-1) reduced seizure severity, prolonged seizure latency, and decreased neuronal loss. Mechanistically, we further confirmed that blockade of Kv1.3 suppressed proinflammatory microglial activation and reduced proinflammatory cytokine production by inhibiting the Ca2+/NF-κB signaling pathway. These results shed light on the critical function of microglial Kv1.3 in epilepsy and provided a potential therapeutic target.

The effect of dipeptidyl peptidase IV on disease-associated microglia phenotypic transformation in epilepsy.

BACKGROUND: Accumulating evidence suggests that disease-associated microglia (DAM), a recently discovered subset of microglia, plays a protective role in neurological diseases. Targeting DAM phenotypic transformation may provide new therapeutic options. However, the relationship between DAM and epilepsy remains unknown. METHODS: Analysis of public RNA-sequencing data revealed predisposing factors (such as dipeptidyl peptidase IV; DPP4) for epilepsy related to DAM conversion. Anti-epileptic effect was assessed by electroencephalogram recordings and immunohistochemistry in a kainic acid (KA)-induced mouse model of epilepsy. The phenotype, morphology and function of microglia were assessed by qPCR, western blotting and microscopic imaging. RESULTS: Our results demonstrated that DPP4 participated in DAM conversion and epilepsy. The treatment of sitagliptin (a DPP4 inhibitor) attenuated KA-induced epilepsy and promoted the expression of DAM markers (Itgax and Axl) in both mouse epilepsy model in vivo and microglial inflammatory model in vitro. With sitagliptin treatment, microglial cells did not display an inflammatory activation state (enlarged cell bodies). Furthermore, these microglia exhibited complicated intersections, longer processes and wider coverage of parenchyma. In addition, sitagliptin reduced the activation of NF-κB signaling pathway and inhibited the expression of iNOS, IL-1ß, IL-6 and the proinflammatory DAM subset gene CD44. CONCLUSION: The present results highlight that the DPP4 inhibitor sitagliptin can attenuate epilepsy and promote DAM phenotypic transformation. These DAM exhibit unique morphological features, greater migration ability and better surveillance capability. The possible underlying mechanism is that sitagliptin can reduce the activation of NF-κB signaling pathway and suppress the inflammatory response mediated by microglia. Thus, we propose DPP4 may act as an attractive direction for DAM research and a potential therapeutic target for epilepsy.

Comprehensive role of prostate-specific antigen identified with proteomic analysis in prostate cancer.

Current treatments including androgen deprivation fail to prevent prostate cancer (PrCa) from progressing to castration-resistant PrCa (CRPC). Accumulating evidence highlights the relevance of prostate-specific antigen (PSA) in the development and progression of PrCa. The underlying mechanism whereby PSA functions in PrCa, however, has yet been elucidated. We demonstrated that PSA knockdown attenuated tumorigenesis and metastasis of PrCa C4-2 cells in vitro and in vivo, whereas promoted the apoptosis in vitro. To illuminate the comprehensive role of PSA in PrCa, we performed an isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to explore the proteomic change induced by PSA knockdown. Among 121 differentially expressed proteins, 67 proteins were up-regulated, while 54 proteins down-regulated. Bioinformatics analysis was used to explore the mechanism through which PSA exerts influence on PrCa. Protein-protein interaction analysis showed that PSA may mediate POTEF, EPHA3, RAD51C, HPGD and MCM4 to promote the initiation and progression of PrCa. We confirmed that PSA knockdown induced the up-regulation of MCM4 and RAD51C, while it down-regulated POTEF and EPHA3; meanwhile, MCM4 was higher in PrCa para-cancerous tissue than in cancerous tissue, suggesting that PSA may facilitate the tumorigenesis by mediating MCM4. Our findings suggest that PSA plays a comprehensive role in the development and progression of PrCa.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

A statistical study of postmortem heart weight in Chinese adults.

INTRODUCTION: Objective assessment of cardiac hypertrophy in forensic pathology practice is of great significance for forensic pathologists, for whom reference values for normal heart weights are needed. Developed regions such as Europe, the United States, and Japan recalculate the weight of human organs at regular intervals, but in China, there has been no systematic calculation of the weights of human organs since 2006. AIMS: To statistically analyse the heart weight of Chinese adults postmortem and obtain a reference range. MATERIALS AND METHODS: 4170 adult autopsy reports were collected from 12 forensic departments in 10 provinces in China. The causes of death were classified by sex, and heart weight and the heart weight/body height ratio reference values were further calculated according to different body mass index and body heights. Finally, the cutoff value of cardiac hypertrophy in Chinese adults was calculated. RESULTS: In the group of non-cardiovascular disease causes of death, the cardiac weight of the electric death group was higher, while the heart weight of the prolonged bed-rest group was significantly reduced. After the electric death and prolonged bed-rest groups were excluded, heart weight, the heart weight/body height ratio, and cutoff values for cardiac hypertrophy were further classified and analysed according to body mass index. The mean reference values for heart weight in men and women with normal weight status were 325.82 ± 41.60 g and 286.39 ± 44.84 g, and the heart weight/body height ratios were 1.95 ± 0.23 in men and 1.82 ± 0.27, respectively. The cutoff values for cardiac hypertrophy were 387.35 g for men and 346.80 g for women. CONCLUSION: The heart weight reference values of both sexes in this study were significantly higher than those in 2006, which is considered related to the development of China's economy and the improvement of people's living standards. This study also suggests the need for a new round of statistical surveys and updated data on the weight of other organs.

Fertility preservation in male adolescents with cancer (2011-2020): A retrospective study in China.

BACKGROUND: According to the studies, more than 80% of pediatric patients with cancer can achieve a survival rate greater than 5 years; however, long-term chemotherapy and/or radiation therapy may seriously affect their reproductive ability. Fertility preservation in adolescents with cancer in China was initiated late, and related research is lacking. Analyze data to understand the current situation and implement measures to improve current practices. METHODS: From 2011 to 2020, data on 275 male adolescents with cancer whose age ranged from 0 to 19 years old were collected from 16 human sperm banks for this retrospective study. Methods include comparing the basic situation of male adolescents with cancer, the distribution of cancer types, and semen quality to analyze the status of fertility preservation. RESULTS: The mean age was 17.39 ± 1.46 years, with 13 cases (4.7%) aged 13-14 years and 262 cases (95.3%) aged 15-19 years. Basic diagnoses included leukemia (55 patients), lymphomas (76), germ cell and gonadal tumors (65), epithelial tumors (37), soft tissue sarcomas (14), osteosarcoma (7), brain tumors (5), and other cancers (16). There are differences in tumor types in different age stages and regions. The tumor type often affects semen quality, while age affects semen volume. Significant differences were found in sperm concentration and progressive motility before and after treatment (p < 0.001). Moreover, 90.5% of patients had sperm in their semen and sperm were frozen successfully in 244 patients (88.7%). CONCLUSIONS: The aim of this study is to raise awareness of fertility preservation in male adolescents with cancer, to advocate for fertility preservation prior to gonadotoxic therapy or other procedures that may impair future fertility, and to improve the fertility status of future patients.

Overexpression of immunoglobulin G prompts cell proliferation and inhibits cell apoptosis in human urothelial carcinoma.

Only B lymphocytes can express immunoglobulins according to the traditional immunological theories, and the expression of immunoglobulin G (IgG) messenger RNA (mRNA) and protein was found in certain human cancer cells recently. However, the expression pattern of IgG and its possible role in human urothelial carcinoma are still elusive. In this study, we investigated the expression of IgG in two human urothelial carcinoma cell lines, T24 and BIU-87, and in 56 cases of clinical urothelial carcinoma tissues. The mRNA of IgG was positively detected by in situ hybridization and reverse transcription PCR; furthermore, IgG protein was also positively detected by immunohistochemistry and Western blot. Moreover, blockade of tumor-derived IgG by either antihuman IgG antibody or antisense oligonucleotides increased cell apoptosis and inhibited cell growth in bladder cancer cell lines in vitro, and antihuman IgG antibody could suppress the growth of xenotransplant tumor in vivo. In addition, either antihuman IgG antibody or antisense oligonucleotides enhanced the sensitivity to mitomycin C in bladder cancer cell line T24. Furthermore, blockade of IgG in bladder cancer cell T24 resulted in upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase. Our results indicated that bladder cancer cells were capable of expressing IgG, and blockade of IgG expression induced cell apoptosis through activation of caspase-dependent pathway. A novel potential targeted therapy for bladder cancer will be possibly developed based on these data.

AID-induced CXCL12 upregulation enhances castration-resistant prostate cancer cell metastasis by stabilizing ß-catenin expression.

Prostate cancer (PCa) is one of the most common malignant diseases of urinary system and has poor prognosis after progression to castration-resistant prostate cancer (CRPC), and increased cytosine methylation heterogeneity is associated with the more aggressive phenotype of PCa cell line. Activation-induced cytidine deaminase (AID) is a multifunctional enzyme and contributes to antibody diversification. However, the dysregulation of AID participates in the progression of multiple diseases and related with certain oncogenes through demethylation. Nevertheless, the role of AID in PCa remains elusive. We observed a significant upregulation of AID expression in PCa samples, which exhibited a negative correlation with E-cadherin expression. Furthermore, AID expression is remarkably higher in CRPC cells than that in HSPC cells, and AID induced the demethylation of CXCL12, which is required to stabilize the Wnt signaling pathway executor ß-catenin and EMT procedure. Our study suggests that AID drives CRPC metastasis by demethylation and can be a potential therapeutic target for CRPC.

Neurotoxic A1 astrocytes promote neuronal ferroptosis via CXCL10/CXCR3 axis in epilepsy.

Epilepsy is a common neurological disorder with a complex etiology. Ferroptosis, a new form of programmed cell death, is characterized by the accumulation of lipid peroxides and associated with seizures. However, the underlying mechanism of ferroptosis in epilepsy remains elusive. Here, we found that GPX4-GSH-dependent neuronal ferroptosis was detected in epileptic mice, which was attenuated with ferroptosis inhibitors. Moreover, activated neurotoxic A1 astrocytes facilitated seizure-related neuronal ferroptosis in epileptic brains. Inhibition of ferroptosis blocked A1 astrocyte-induced neurotoxicity. A1 astrocyte-secreted CXCL10 enhanced STAT3 phosphorylation but suppressed SLC7A11 in neurons via CXCR3, leading to ferroptosis-associated lipid peroxidation in a GPX4-dependent manner. This was in line with clinical findings, showing a significant correlation between neuronal ferroptosis and A1 astrocytes in epileptic patients. In summary, the present data show that A1 astrocyte-induced neuronal ferroptosis contributes to the pathogenesis of epilepsy, which offers a novel therapeutic target for precision medicine.

A randomized, active-controlled, multicentre clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated or complicated urinary tract infection.

PURPOSE: To evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated urinary tract infection (UTI) or complicated UTI. METHODS: In this randomized, active-controlled clinical trial, the patients with acute uncomplicated UTI were randomized to receive sitafloxacin 100-mg once-daily (qd) or levofloxacin 500-mg qd orally for 3-5 days. The patients with complicated UTI were randomized to receive sitafloxacin 100-mg twice daily or levofloxacin 500-mg qd orally for 10-14 days. The primary endpoint was the clinical efficacy at test-of-cure (TOC) visit. RESULTS: At TOC visit, the clinical cure rate was 89.2% (58/65) in sitafloxacin group and 97.1% (68/70) in levofloxacin group for the patients with acute uncomplicated UTI corresponding to the bacterial eradication rate of 97.1% (34/35) and 97.6% (41/42) (all p > .05), respectively. For the patients with complicated UTI, the clinical cure rate was 81.8% (27/33) in sitafloxacin group and 76.9% (20/26) in levofloxacin group corresponding to the bacterial eradication rate of 93.3% (14/15) and 63.6% (7/11) (all p > .05), respectively. Sitafloxacin and levofloxacin showed similar incidence of drug-related adverse events. CONCLUSIONS: Oral sitafloxacin is as effective and safe as levofloxacin in treating acute uncomplicated and complicated UTI. KEY MESSAGE: Oral sitafloxacin showed similar clinical cure rate and bacterial eradication rate as levofloxacin for treatment of complicated and uncomplicated urinary tract infections (UTIs) in a randomized, active-controlled, multicentre clinical trial. Oral sitafloxacin is safe and well-tolerated in treating acute uncomplicated and complicated UTIs in Chinese adults. Sitafloxacin is a promising alternative treatment option for UTIs in adults.

TRPV1 channel mediates NLRP3 inflammasome-dependent neuroinflammation in microglia.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease in the central nervous system (CNS). The NLRP3 inflammasome is considered an important regulator of immunity and inflammation, both of which play a critical role in MS. However, the underlying mechanism of NLRP3 inflammasome activation is not fully understood. Here we identified that the TRPV1 (transient receptor potential vanilloid type 1) channel in microglia, as a Ca2+ influx-regulating channel, played an important role in NLRP3 inflammasome activation. Deletion or pharmacological blockade of TRPV1 inhibited NLRP3 inflammasome activation in microglia in vitro. Further research revealed that TRPV1 channel regulated ATP-induced NLRP3 inflammasome activation through mediating Ca2+ influx and phosphorylation of phosphatase PP2A in microglia. In addition, TRPV1 deletion could alleviate mice experimental autoimmune encephalomyelitis (EAE) and reduce neuroinflammation by inhibiting NLRP3 inflammasome activation. These data suggested that the TRPV1 channel in microglia can regulate NLRP3 inflammasome activation and consequently mediate neuroinflammation. Meanwhile, our study indicated that TRPV1-Ca2+-PP2A pathway may be a novel regulator of NLRP3 inflammasome activation, pointing to TRPV1 as a potential target for CNS inflammatory diseases.

Effects of rhodioloside on the neurological functions of rats with total cerebral ischemia/reperfusion and cone neuron injury in the hippocampal CA1 region.

Rhodioloside, the main effective constituent of Rhodiola rosea, demonstrates antiaging and antioxidative stress functions and inhibits calcium overloading in cells. These functions imply that rhodioloside may exert protective effects on hippocampal neurons after total cerebral ischemia/reperfusion injury. In this study, male Wistar rat models of total cerebral ischemia were constructed and randomly divided into four groups: sham-operation, ischemia/reperfusion, low-dosage, and high-dosage groups. The result showed that rhodioloside treatment reduced the apoptosis rates of hippocampal neurons and the histological grades of cone cells in the hippocampal CA1 region, but neuronal density was significantly increased. Besides, the protein expressions of Bcl-2/Bax and p53 were measured and found Bcl-2/Bax was increased and p53 protein level was reduced. Therefore, rhodioloside might have protective effects on rats with ischemia/reperfusion brain injury.

Inhibition of the NLRP3-inflammasome prevents cognitive deficits in experimental autoimmune encephalomyelitis mice via the alteration of astrocyte phenotype.

Multiple sclerosis (MS) is a chronic disease that is characterized by demyelination and axonal damage in the central nervous system. Cognitive deficits are recognized as one of the features of MS, and these deficits affect the patients' quality of life. Increasing evidence from experimental autoimmune encephalomyelitis (EAE), the animal model of MS, has suggested that EAE mice exhibit hippocampal impairment and cognitive deficits. However, the underlying mechanisms are still unclear. The NLRP3 inflammasome is a key contributor to neuroinflammation and is involved in the development of MS and EAE. Activation of the NLRP3 inflammasome in microglia is fundamental for subsequent inflammatory events. Activated microglia can convert astrocytes to the neurotoxic A1 phenotype in a variety of neurological diseases. However, it remains unknown whether the NLRP3 inflammasome contributes to cognitive deficits and astrocyte phenotype alteration in EAE. In this study, we demonstrated that severe memory deficits occurred in the late phase of EAE, and cognitive deficits were ameliorated by treatment with MCC950, an inhibitor of the NLRP3 inflammasome. In addition, MCC950 alleviated hippocampal pathology and synapse loss. Astrocytes from EAE mice were converted to the neurotoxic A1 phenotype, and this conversion was prevented by MCC950 treatment. IL-18, which is the downstream of NLRP3 inflammasome, was sufficient to induce the conversion of astrocytes to the A1 phenotype through the NF-κB pathway. IL-18 induced A1 type reactive astrocytes impaired hippocampal neurons through the release of complement component 3 (C3). Altogether, our present data suggest that the NLRP3 inflammasome plays an important role in cognitive deficits in EAE, possibly via the alteration of astrocyte phenotypes. Our study provides a novel therapeutic strategy for hippocampal impairment in EAE and MS.

Activation-Induced Cytidine Deaminase Expression Facilitates the Malignant Phenotype and Epithelial-to-Mesenchymal Transition in Clear Cell Renal Cell Carcinoma.

Although advances have been made in the development of antiangiogenesis targeted therapy and surgery, metastatic clear cell renal cell carcinoma (ccRCC) is still incurable. Activation-induced cytidine deaminase (AID) is mainly expressed in a variety of germ and somatic cells, and induces somatic hypermutation and class-switch recombination, playing a vital role in antibody diversification. We confirmed that AID was expressed at a higher level in ccRCC tissues than in the corresponding nontumor renal tissues. We explored the impact of AID on ccRCC proliferation, invasion, and migration. In 769-p and 786-0 cells, expression of an AID-specific short hairpin RNA significantly reduced AID expression, which markedly inhibited tumor cell invasion, proliferation, and migration. Previous studies showed that AID is associated with Wnt ligand secretion mediator (WLS/GPR177), cyclin-dependent kinase 4 (CDK4), and stromal cell-derived factor-1 (SDF-1/CXCL12) regulation, which was further confirmed in human ccRCC tissues. Therefore, we studied the relationship between AID and these three molecules, and the impact of AID on epithelial-to-mesenchymal transition in ccRCC. WLS/GPR177, SDF-1/CXCL12, and CDK4 were sensitive to 5-azacytidine (a DNA demethylation agent), which reverted the inhibition of carcinogenesis caused by AID repression. In summary, AID is an oncogene that might induce tumorigenesis through DNA demethylation. Targeting AID may represent a novel therapeutic approach to treat metastatic ccRCC.

AID modulates carcinogenesis network via DNA demethylation in bladder urothelial cell carcinoma.

Bladder cancer is one of the most common malignant diseases in the urinary system, with poor survival after metastasis. Activation-induced cytidine deaminase (AID), a versatile enzyme involved in antibody diversification, is an oncogenic gene that induces somatic hypermutation and class-switch recombination (CSR). However, the contribution of AID-mediated DNA demethylation to bladder urothelial cell carcinoma (BUCC) remains unclear. Herein, we evaluated the impact on BUCC caused by AID and explored the gene network downstream of AID by using a proteomic approach. Lentiviral vector containing AID-specific shRNA significantly reduced AID expression in T24 and 5637 cells. Silencing AID expression remarkably inhibited tumour malignancies, including cell proliferation, invasion and migration. We used Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics analysis technology to study the underpinning mechanism in monoclonal T24 cells, with or without AID knockdown. Among the 6452 proteins identified, 99 and 142 proteins in shAICDA-T24 cells were significantly up- or downregulated, respectively (1.2-fold change) compared with the NC-T24 control. After a pipeline of bioinformatics analyses, we identified three tumour-associated factors, namely, matrix metallopeptidase 14 (MMP14), C-X-C motif chemokine ligand 12 and wntless Wnt ligand secretion mediator, which were further confirmed in human BUCC tissues. Nonetheless, only MMP14 was sensitive to the DNA demethylation molecule 5-aza-2'-deoxycytidine (5-azadC; 5 µM), which reversed the inhibition of carcinogenesis by AID silence in T24 and 5637 cells. Overall, AID is an oncogene that mediates tumourigenesis via DNA demethylation. Our findings provide novel insights into the clinical treatment for BUCC.

miR-124 regulates STAT3-mediated cell proliferation, migration and apoptosis in bladder cancer.

The etiology and pathogenesis of bladder cancer (BCa) is complex. MicroRNA (miRNA) has been implicated in BCa. Targeting of signal transducer and activator of transcription 3 (STAT3) by miR-124 to regulate tumorigenesis has been demonstrated in other types of cancer. In the present study, miR-124 levels were downregulated in the BCa T24 cell line and STAT3 was increased in BCa cell lines. Transfection of miR-124 mimics into T24 cells significantly inhibited STAT3 expression. A luciferase assay confirmed that miR-124 directly targeted the STAT3 3'untranslated region to inhibit STAT expression. Knockdown of STAT3 expression led to increased apoptosis of T24 cells and reduced tumor growth in vitro. The results demonstrated the molecular mechanisms and biological functions of the miR-124/STAT3 signal pathway at the cellular level and indicate the potential of miR-124 as a therapeutic target for BCa.

Efficacy and Safety of Tamsulosin in Medical Expulsive Therapy for Distal Ureteral Stones with Renal Colic: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Recent large high-quality trials have questioned the clinical effectiveness of medical expulsive therapy using tamsulosin for ureteral stones. OBJECTIVE: To evaluate the efficacy and safety of tamsulosin for distal ureteral stones compared with placebo. DESIGN, SETTING, AND PARTICIPANTS: We conducted a double-blind, placebo-controlled study of 3296 patients with distal ureteral stones, across 30 centers, to evaluate the efficacy and safety of tamsulosin. INTERVENTION: Participants were randomly assigned (1:1) into tamsulosin (0.4mg) or placebo groups for 4 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point of analysis was the overall stone expulsion rate, defined as stone expulsion, confirmed by negative findings on computed tomography, over a 28-d surveillance period. Secondary end points included time to stone expulsion, use of analgesics, and incidence of adverse events. RESULTS AND LIMITATIONS: Among 3450 patients randomized between September 1, 2011, and August 31, 2013, 3296 (96%) were included in the primary analysis. Tamsulosin benefits from a higher stone expulsion rate than the placebo (86% vs 79%; p<0.001) for distal ureteral stones. Subgroup analysis identified a specific benefit of tamsulosin for the treatment of large distal ureteral stones (>5mm). Considering the secondary end points, tamsulosin-treated patients reported a shorter time to expulsion (p<0.001), required lower use of analgesics compared with placebo (p<0.001), and significantly relieved renal colic (p<0.001). No differences in the incidence of adverse events were identified between the two groups. CONCLUSIONS: Our data suggest that tamsulosin use benefits distal ureteral stones in facilitating stone passage and relieving renal colic. Subgroup analyses find that tamsulosin provides a superior expulsion rate for stones >5mm, but no effect for stones ≤5mm. PATIENT SUMMARY: In this report, we looked at the efficacy and safety of tamsulosin for the treatment of distal ureteral stones. We find that tamsulosin significantly facilitates the passage of distal ureteral stones and relieves renal colic.

Identifying priority management intervals of discharge and TN/TP concentration with copula analysis for Miyun Reservoir inflows, North China.

The quantitative environmental management of reservoir inflows is challenging due to complex coexistence relationships between water quantity and water quality variables. Taking discharge as a representative water quantity indicator, as well as total nitrogen (TN) and total phosphorus (TP) as water quality indicators for the twin rivers (i.e., the Chaohe and Baihe rivers) which run into the Miyun Reservoir in North China, this study calculated marginal probability distributions of these indicators, and analyzed the joint probability distribution of discharge and TN/TP concentration by applying the Frank copula function. According to an analysis of various scenario combinations of discharge and TN/TP concentration, the quantitative management intervals including the priority control interval, the key attention interval and the daily maintenance interval, were identified. The results were as follows: (a) a fitting degree evaluation indicated that the Pearson-III distribution for the marginal probability distribution of discharge and the lognormal distribution for that of TN/TP concentration were feasible. Additionally, the Frank copula theory was applicable for their joint probability analysis according to the applicability analysis and goodness-of-fit test; (b) regarding to the water quality of the Miyun Reservoir inflows, it is more important to enhance the control of the Chaohe River and the monitoring of TP concentration; and (c) the TN concentration within division values of discharge (i.e., 16.59, 24.14m3/s) was tend to exceed the class III limitation of the Environmental Quality Standard for Surface Water in China, and the concentrations of TN and TP increased as the discharge increased for the two rivers. The quantitative management intervals based on copula analysis is an intuitive and effective solution for comprehensive risk management of reservoir inflows.

[Urethroplasty with oblique preputial island flap for the treating of hypospadia].

OBJECTIVE: To Explore the effect of oblique preputial island flap for the treating of hypospadias. METHODS: Fifty-one patients were performed one-stage urethroplasty with oblique preputial island flap to repair hypospadias. RESULTS: All cases resulted in a good contour of the penis without any redundancy and a normal anatomic position of slit-shaped urethral meatus. The urination was perfect. Six patients occurred complications (3 cases of urinary fistula, 3 cases of meatal stenosis). CONCLUSION: With extensive scope of materials, reliable blood supply of skin flap, satisfactory appearance of shaping penis and few complications, one-stage urethroplasty with oblique preputial island flap is an effective method to repair hypospadias of penile type and penile-scrotal type.