A phase 3,double-blind,randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapynaı¨ve patients with mCRPC in China,Malaysia,Thailand and Russia

Objective:This double-blind,placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate+prednisone(abiraterone)to prednisone alone in chemotherapy-naı¨ve,asymptomatic or mildly symptomatic metastatic castrationresistant prostate cancer(mCRPC)patients from China,Malaysia,Thailand and Russia.Methods:Adult chemotherapy-naı¨ve patients with confirmed prostate adenocarcinoma,Eastern Cooperative Oncology Group(ECOG)performance status(PS)grade 0e1,ongoing androgen deprivation(serum testosterone<50 ng/dL)with prostate specific antigen(PSA)or radiographic progression were randomized to receive abiraterone acetate(1000 mg,QD)t prednisone(5 mg,BID)or placebo t prednisone(5 mg,BID),until disease progression,unacceptable toxicity or consent withdrawal.Primary endpoint was improvements in time to PSA progression(TTPP).Results:Totally,313 patients were randomized(abiraterone:n Z 157;prednisone:n Z 156);and baseline characteristics were balanced.At clinical cut-off(median follow-up time:3.9 months),80% patients received treatment(abiraterone:n Z 138,prednisone:n Z 112).Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone,attaining 58%reduction in PSA progression risk(HR=0.418;p<0.0001).Abirateronetreated patients had higher confirmed PSA response rate(50%vs.21%;relative odds=2.4;p<0.0001)and were 5 times more likely to achieve radiographic response than prednisonetreated patients(22.9%vs.4.8%,p=0.0369).Median survival was not reached.Most common(≥10% abiraterone vs.prednisone-treated)adverse events:bone pain(7%vs.14%),pain in extremity(6%vs.12%),arthralgia(10%vs.8%),back pain(7%vs.11%),and hypertension(15%vs.14%).Conclusion:Interim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naı¨ve men with mCRPC,consistent with global study,thus supporting use of abiraterone in this patient population.

Do medullary thyroid carcinoma patients with high calcitonin require bilateral neck lymph node clearance?A case report

BACKGROUND In clinical work,85%-90%of malignant thyroid diseases are papillary thyroid cancer(PTC);thus,clinicians neglect other types of thyroid cancer,such as medullary thyroid carcinoma(MTC).CASE SUMMARY We report a 53-year-old female patient with a preoperative calcitonin level of 345 pg/mL.There was no definitive diagnosis of MTC by preoperative fine-needle aspiration cytology or intraoperative frozen pathology,but the presence of PTC and MTC was confirmed by postoperative paraffin pathology.The patient underwent total thyroidectomy and bilateral central lymph node dissection.Close follow-up at 1.5 years after surgery revealed no signs of recurrence or metastasis.CONCLUSION The issue in clinical work-up regarding types of thyroid cancer provides a novel and challenging idea for the surgical treatment of MTC.In the absence of central lymph node metastasis,it is worth addressing whether patients with high calcitonin can undergo total thyroidectomy and bilateral central lymph node dissection without bilateral lateral neck lymph node dissection.

CsABF3-activated CsSUT1 pathway is implicated in pre-harvest water deficit inducing sucrose accumulation in citrus fruit

Pre-harvest water deficit(PHWD)plays an important role in sugar accumulation of citrus fruit.However,the mechanism is not known well.Here,it was confirmed that PHWD promoted sucrose accumulation of citrus fruit,but had limited effect on fructose,glucose and total acid.A sucrose transporter,Cs SUT1,which localizes to the plasma membrane,was demonstrated to function in sucrose transport induced by PHWD.Compared to wild-type,Cs SUT1 overexpression in citrus calli stimulated sucrose,fructose and glucose accumulation,while its silencing in juice sacs reduced sucrose accumulation.Increased sugar accumulation in transgenic lines enhanced plant drought tolerance,and resulted in decreased electrolyte leakage,malondialdehyde and hydrogen peroxide contents,as well as increased superoxide dismutase activity and proline contents.An abscisic acid(ABA)-responsive transcription factor,Cs ABF3,was found with a same expression pattern with Cs SUT1 under PHWD.Yeast one-hybrid,electrophoretic mobility shift assay and dual-luciferase assays all revealed that Cs ABF3 directly bound with the Cs SUT1 promoter by ABA responsive elements.When Cs ABF3 was overexpressed in citrus calli,the sucrose,fructose and glucose concentration increased correspondingly.Further,transgenic studies demonstrated that Cs ABF3 could affect sucrose accumulation by regulating Cs SUT1.Overall,this study revealed a regulation of Cs ABF3 promoting Cs SUT1 expression and sucrose accumulation in response to PHWD.Our results provide a detail insight into the quality formation of citrus fruit.

Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL:Results from the Chinese Prostate Cancer Consortium

Objective:To test the diagnostic performance of percent free prostate-specific antigen(%fPSA)in predicting any prostate cancer(PCa)and high-grade prostate cancer(HGPCa)in a retrospective multi-center biopsy cohort with a PSA level of 4.0e10.0 ng/mL in China.Methods:Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st,2010 to December 31st,2013.Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization(WHO)standard.The diagnostic accuracy of PSA,%fPSA,and %fPSA in combination with PSA(%fPSA t PSA)was determined using the area under the receiver operating characteristic(ROC)curve(AUC).Results:A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included,and the detection rate of PCa was 25.1%.The AUC of%fPSA and %fPSA t PSA in predicting any PCa was superior to PSA alone in men aged≥60 years(0.623 vs.0.534,p<0.0001)but not in men aged 40e59 years(0.517 vs.0.518,p=0.939).Similar result was yield in predicting HGPCa.Conclusion:In a clinical setting of Chinese men with 4.0e10.0 ng/mL PSA undergoing initial prostate biopsy,adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients≥60 but not in patients aged 40-59 years.

Scientific publications in andrology journals from Chinese authors in various parts of East Asia： a 10-year survey of the literature

Dear Editor, Diseases of the genitourinary system were the fifth most common disease of inpatients in Chinese city hospitals in 2011 （6.0%）.1 Andrology in China has grown rapidly within the last decade, however, little is known about the scientific publications by Chinese authors in andrology. We, therefore, sought to reveal the contributions of Chinese authors in three major regions of China-the Mainland （ML）, Taiwan （TW）, and Hong Kong （HK）-to the research in the fields of andrology.

Magnetization-direction-dependent inverse spin Hall effect observed in IrMn/NiFe/Cu/YIG multilayer structure

The magnetization-direction-dependent inverse spin Hall effect(ISHE) has been observed in NiFe film during spin Seebeck measurement in IrMn/NiFe/Cu/yttrium iron garnet(YIG) multilayer structure, where the YIG and NiFe layers act as the spin injector and spin current detector, respectively. By using the NiFe/IrMn exchange bias structure, the magnetization direction of YIG(MYIG) can be rotated with respect to that of NiFe(MNiFe) with a small magnetic field, thus allowing us to observe the magnetization-direction-dependent inverse spin Hall effect voltage in NiFe layer. Compared with the situation that polarization direction of spin current(σs) is perpendicular to MNiFe, the spin Seebeck voltage is about 30% larger than that when σs and MNiFe are parallel to each other. This phenomenon may originate from either or both of stronger interface or bulk scattering to spin current when σs and MNiFe are perpendicular to each other. Our work provides a way to control the voltage induced by ISHE in ferromagnets.

Life-threatening hemorrhage after liver radiofrequency ablation successfully controlled by transarterial embolization

A 59-year-old man underwent liver radiofrequency ablation under laparotomy for recurrent hepatic carcinoma located in the caudate lobe,however,near-fatal bleeding occurred 1 wk after the operation.The intraoperative ultrasound study during laparotomy revealed left hepatic artery pseudoaneurysm.Suture and packing with ribbon gauze was used to obtain hemostasis.A secondary hemorrhage followed 11 h later and hepatic angiography was performed immediately.Bleeding from the pseudoaneurysm in a branch of the left hepatic artery was found and the artery branch was embolized with coils.Other than slight bile leakage,post-embolization continued satisfactorily.Bleeding did not reoccur.The follow up visit 1 mo later found the pseudoaneurysm disappearing and no tumor recurrence.

Revised Super-long Down-regulation Protocol Improves the Outcome of Infertile Patients with Repeated Implantation Failure in IVF/ICSI-ET

Objective To investigate the outcome of revised super-long down-regulation protocol （RSDP） for in vitro fertilization / intracytoplasmic sperm injection-embryo transfer （1VF/1CS1-ET） in the special infertile patients with repeated implantation failure （RIF）. Methods Patients with RIF were divided into RSDP group and routine long downregulation protocol （RLDP） group. In RSDP group, gonadotropin releasing hormone agonist （GnRHa） was injected intramuscularly by 2.5 mg in mid-luteal phase for the ftrst time and 1.25 mg after 28 d; gonadotropin （Gn） was started 14 d later after the second GnRHa dose. IVF/ICSI-ET was performed according to the routine procedure. The clinical outcomes of RSDP group were compared with those of RLDP group. Results In RSDP group, the number of retrieved oocytes and valid embryos was significantly lower （P〈0.05）; there were no significant differences about fertilization rate （P〉0. 05）; both good-quality embryo rate and implantation rate were significantly increased （P〈0. 005）; clinical pregnancy rate was obviously improved （P〈0. 05）, as compared with RLDP group.Conclusion RSDP can improve the IVF outcomes significantly in RIF patients.

Transurethral seminal vesiculoscopy for recurrent hemospermia： experience from 419 cases

We summarized our experience in transurethral seminal vesiculoscopy （TSV） for recurrent hemospermia by introducing surgical techniques, intraoperative findings, and treatment outcomes. TSV was performed in 419 patients with an initial diagnosis of persistent hemospermia at Shanghai Changhai Hospital （Shanghai, China） from May 2007 to November 2015. TSV was successfully performed in 381 cases （90.9%）. Hemospermia was alleviated or disappeared in 324 （85.0%） patients by 3 months after surgery. Common intraoperative manifestations were bleeding, obstruction or stenosis, mucosal lesions, and calculus. Endoscopic presentation of the ejaculatory duct orifice and the verumontanum was categorized into four types, including 8 （1.9%）, 32 （7.6%）, 341 （81.4%）, and 38 （9.1%） cases in Types A, B, C, and D, respectively. TSV is an effective and safe procedure in the management of seminal tract disorders. This study may help other surgeons to become familiar with and improve this procedure. However, further multicentric clinical trials are warranted to validate these findings.

Identification of proteinaceous binding media for the polychrome terracotta army of Emperor Qin Shihuang by MALDI-TOF-MS

A proteinaceous binding media for the polychrome terracotta army of Emperor Qin Shihuang has been identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).Methods for the preparation of the model samples and the elimination of interferences have been evaluated,as well as ageing processes.A method involving the complexation of EDTA in combination with dialysis was used to eliminate any interference in the polychrome layers taken from the historical samples.The model samples were aged by being buried in loess to replicate the ageing process of the historical samples as closely as possible.The optimum conditions for the extraction and subsequent enzymatic hydrolysis of the extracted protein were investigated.Under the optimized conditions,the‘‘peptide mass fingerprints’’of the proteinaceous binding media from the historical and model samples were determined by MALDITOF-MS.The results revealed that animal glue was used as the binding media for the polychrome layers of Emperor Qin Shihuang’s terracotta army.It also shows that animal glue used as binding media has a long history in China.

Indirect comparison between abiraterone acetate and enzalutamide for the treatment of metastatic castration-resistant prostate cancer： a systematic review

This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate （AA） and enzalutamide （Enz） for metastatic castration-resistant prostate cancer （mCRPC）. A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA （active comparator） and Enz （true placebo） randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings （HR. 0.90, 95% CI, 0.73-1.11; HR： 0.85, 95% CI, 0.68-1.07）. Compared with AA, Enz may better outperform control arms in treating mCRPC both before and after chemotherapy regarding secondary endpoints based on indirect comparisons： time to prostate-specific antigen （PSA） progression （HR. 0.34, 95% CI, 0.28-0.42; HR： 0.40, 95% CI, 0.30-0.53）, radiographic progression-free survival （HR： 0.37, 95% CI, 0.28-0.48; HR： 0.61, 95% CI, 0.50-0.74）, and PSA response rate （OR： 18.29, 95% CI, 11.20-29.88; OR： 10.69, 95% CI, 3.92-29.20）. With regard to the effectiveness of Enz following AA or AA following Enz, recent retrospective case series reported overall survival and secondary endpoints for patients with mCRPC progression after chemotherapy. However, confirmatory head-to-head trials are necessary to determine the optimal sequencing of these agents.

Effect of varicocelectomy on testis volume and semen parameters in adolescents： a meta-analysis

Varicocele repair in adolescent remains controversial. Our aim is to identify and combine clinical trials results published thus far to ascertain the efficacy of varicocelectomy in improving testis volume and semen parameters compared with nontreatment control. A literature search was performed using Medline, Embase and Web of Science, which included results obtained from meta-analysis, randomized and nonrandomized controlled studies. The study population was adolescents with clinically palpable varicocele with or without the testicular asymmetry or abnormal semen parameters. Cases were allocated to treatment and observation groups, and testis volume or semen parameters were adopted as outcome measures. As a result, seven randomized controlled trials （RCTs） and nonrandomized controlled trials studying bilateral testis volume or semen parameters in both treatment and observation groups were identified. Using a random effect model, mean difference of testis volume between the treatment group and the observation group was 2.9 ml （95% confidence interval [CI]： 0.6, 5.2; P 〈 0.05） for the varicocele side and 1.5 ml （95% CI- 0.3, 2.7; P 〈 0.05） for the healthy side. The random effect model analysis demonstrated that the mean difference of semen concentration, total semen motility, and normal morphology between the two groups was 13.7 x 106 ml-1 （95% CI： -1.4, 28.8; P= 0.075）, 2.5% （95% CI：-3.6, 8.6; P= 0.424）, and 2.9% （95% CI： -3.0, 8.7; P= 0.336） respectively. In conclusion, although varicocelectomy significantly improved bilateral testis volume in adolescents with varicocele compared with observation cases, semen parameters did not have any statistically significant difference between two groups. Well-planned, properly conducted RCTs are needed in order to confirm the above-mentioned conclusion further and to explore whether varicocele repair in adolescents could improve subsequently spontaneous pregnancy rates.

Upregulation of erythropoietin and erythropoietin receptor in castration-resistant progression of prostate cancer

Hypoxia-induced erythropoietin signaling plays an important role in tumor growth and invasion.In the present study,we investigated the contribution of erythropoietin signaling pathway to castration-resistant prostate cancer and the development of a neuroendocrine phenotype.Immunohistochemical staining showed that the erythropoietin and erythropoietin receptor scores in castration-resistant prostate cancer and androgen-dependent prostate cancer were 7.55 versus 4.5 and 7.45 versus 5.9,respectively(P<0.001).Furthermore,a cell proliferation assay was conducted,and the differential expression of erythropoietin and erythropoietin receptor in LNCaP cells and hypoxia-induced LNCaP cells was evaluated using western blot and quantitative real-time PCR.The proliferation capacity of hypoxia-induced LNCaP cells was similar in cultures of both fetal bovine serum and charcoal-stripped fetal bovine serum,suggesting that LNCaP cells acquired hypoxia-induced androgen-independent growth.After 2 weeks of hypoxic culture,LNCaP cells showed a neuroendocrine cell change and increased expression of neuron-specific enolase,erythropoietin,and erythropoietin receptor;knockdown of erythropoietin receptor reversed the hypoxia-induced upregulation of neuron-specific enolase in the LNCaP cells.In conclusion,the concurrent upregulation of erythropoietin and erythropoietin receptor in castration-resistant prostate cancer suggests that the erythropoietin/erythropoietin receptor autocrine loop plays an important role in the progression of castration resistance and is responsible for the development of a neuroendocrine phenotype.

LOCAL CONVERGENCE OF AN EM-LIKE IMAGE RECONSTRUCTION METHOD FOR DIFFUSE OPTICAL TOMOGRAPHY

In this paper, an EM-like image reconstruction iterative formula specifically developed for stable external sources is rewritten as a map towards a fixed point iteration. Eocal con- vergence of the image reconstruction method is then proved. Finally a three-dimensional numerical image reconstruction example is presented.

Amorphous nonstoichiometric oxides with tunable room-temperature ferromagnetism and electrical transport

Material functionalities strongly depend on the stoichiometry,crystal structure,and homogeneity.Here we demonstrate an approach of amorphous nonstoichiometric inhomogeneous oxides to realize tunable ferromagnetism and electrical transport at room temperature.In order to verify the origin of the ferromagnetism,we employed a series of structural,chemical,and electronic state characterizations.Combined with electron microscopy and transport measurements,synchrotron-based grazing incident wide angle X-ray scattering,soft X-ray absorption and circular dichroism clearly reveal that the roomtemperature ferromagnetism originates from the In0.23Co0.77O1-v,amorphous phase with a large tunable range of oxygen vacancies.The room-temperature ferromagnetism is tunable from a high saturation magnetization of 500 emu cm-3 to below 25 emu cm-3,with the evolving electrical resistivity from5×103μΩ cm to above 2.5×105 μΩ cm.Inhomogeneous nano-crystallization emerges with decreasing oxygen vacancies,driving the system towards non-ferromagnetism and insulating regime.Our work unfolds the novel functionalities of amorphous nonstoichiometric inhomogeneous oxides,which opens up new opportunities for developing spintronic materials with superior magnetic and transport properties.