Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer

Objective:Real-word data on long-acting luteinizing hormone-releasing hormone(LHRH)agonists in Chinese patients with prostate cancer are limited.This study aimed to determine the real-world effectiveness and safety of the LHRH agonist,goserelin,particularly the long-acting 10.8-mg depot formulation,and the follow-up patterns among Chinese prostate cancer patients.Methods:This was a multicenter,prospective,observational study in hormone treatment-na?ve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen.The patients had follow-up evaluations for 26 weeks.The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen(PSA)levels.The secondary outcomes included testosterone and PSA levels,attainment of chemical castration(serum testosterone<50 ng/d L),and goserelin safety.The exploratory outcome was the monitoring pattern for serum testosterone and PSA.All analyses were descriptive.Results:Between September 2017 and December 2019,a total of 294 eligible patients received≥1 dose of goserelin;287 patients(97.6%)were treated with goserelin 10.8-mg depot.At week 24±2,the changes from baseline[standard deviation(95%confidence interval)]in serum testosterone(n=99)and PSA(n=131)were-401.0 ng/d L[308.4 ng/d L(-462.5,-339.5 ng/d L)]and-35.4 ng/m L[104.4 ng/m L(-53.5,-17.4 ng/m L)],respectively.Of 112 evaluable patients,100(90.2%)achieved a serum testosterone level<50 ng/d L.Treatment-emergent adverse events(TEAEs)and severe TEAEs occurred in 37.1%and 10.2%of patients,respectively.The mean testing frequency(standard deviation)was 1.6(1.5)for testosterone and 2.2(1.6)for PSA.Conclusions:Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

The application of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy with a new robotic system KangDuo Surgical Robot-01:Initial experience

Objective To assess the feasibility of internal suspension technique in retroperitoneal robot-assisted laparoscopic partial nephrectomy(rRAPN)with a new robotic platform called KangDuo Surgical Robot-01(KD-SR-01)system(Suzhou KangDuo Robot Co.,Ltd.,Suzhou,China)and discuss its surgical technique.Methods A 44-year-old male patient was admitted with a 2.5 cm tumor on dorsolateral upper pole of the left kidney.The R.E.N.A.L.nephrometry score of this patient was 4x.This patient underwent rRAPN with KD-SR-01.The perinephric fat between the tumor and Gerota's fascia was preserved,which was used for internal suspension traction during tumor resection.Postoperative follow-up data were collected.Results The surgery was successfully carried out with a duration of 127 min,in which the docking time was 6 min 25 s and console time was 60 min.The warm ischemia time was 19 min 53 s,and the estimated blood loss was 0 mL.The pathological histology showed a pathological tumor stage 1a clear cell renal cell carcinoma,with a negative surgical margin.The World Health Organization/International Society of Urological Pathology(WHO/ISUP)grade of this patient was Grade 2.No recurrence was observed during the 6-month follow-up.Conclusion Internal suspension in rRAPN is feasible and effective with use of the new robotic system KD-SR-01.

Prostate cancer in Asia:A collaborative report

The incidence of prostate cancer(PCa)within Asian population used to be much lower than in the Western population;however,in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly.This collaborative report summarized the latest epidemiology information,risk factors,and racial differences in PCa diagnosis,current status and new trends in surgery management and novel agents for castration-resistant prostate cancer.We believe such information would be helpful in clinical decision making for urologists and oncologists,health-care ministries and medical researchers.

Current status of diagnosis and treatment of bladder cancer in China-Analyses of Chinese Bladder Cancer Consortium database

Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.

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.

Application of fluorescence in situ hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population

Objective:To evaluate the diagnostic value of fluorescence in situ hybridization(FISH)in bladder cancer.Methods:We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008.Receiver operating characteristic(ROC)curve analysis was performed and the area under curve(AUC)values were calculated for both the FISH and urine cytology tests.Results:A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population.A total of 4807 patients with hematuria were prospectively,randomly enrolled for the simultaneous analysis of urine cytology,FISH testing,and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen.Overall,the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%,while that of cytology was 33.4%(p<0.001).The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7%and 89.6%,respectively(p=0.004).The sensitivity values of FISH for low and high grade bladder cancer were 82.6%and 90.1%,respectively(p=0.002).Conclusion:FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages.Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.

Vibration and sound radiation of a rotating train wheel subject to a vertical harmonic wheel–rail force

The rapid development of high-speed railway networks requires advanced methods for analysing vibration and sound radiation characteristics of a fast rotating train wheel subject to a vertical harmonic wheel-rail force. In order to consider the rotation of the wheel and at the same time increase the computational efficiency, a procedure is adapted in this paper taking advantage of the axial symmetry of the wheel. In this procedure, a recently developed 2.5D finite element method, which can consider wheel rotation but only requires a 2D mesh over a cross section containing the wheel axis, is used to calculate the vibration response of the wheel. Then, the vibration response of the wheel is taken as acoustic boundary condition and the 2.5D acoustic boundary element method, which only requires a 1D mesh over the boundary of the above cross section, is utilised to calculate the sound radiation of the wheel. These 2.5D methods and relevant programs are validated by comparing results from this procedure with those from conventional 3D analyses using commercial software. The comparison also demonstrates that these 2.5D methods have a much higher computational efficiency. Using the 2.5D methods, we study the wheel rotation speed influences on the factors including the vertical receptance of the wheel at wheel-rail contact point, sound pressure level at a pre-defined standard measurement point, radiated sound power level, directivity of the radia- tion, and contribution of each part of the wheel. It can be concluded that the wheel rotation speed splits most peaks of the vertical receptance at the wheel-rail contact point, sound pressure levels at the field, and the sound power level of the wheel into two peaks. The directivity and power contribution of the wheel are also significantly changed by the wheel rotation speed. Therefore, the rotation of a train wheel should be taken into account when calculating its vibration and sound radiation.

Analysis of Combined Natural Convection and Radiation Heat Transfer in a Partitioned Rectangular Enclosure with Semitransparent Walls

In this paper, we present a two-dimensional numerical analysis of the conjugate natural convection and radiation heat transfer in a double-space enclosure with two semitransparent walls. Two kinds of boundary conditions are considered, the rst being the isothermal process of the opaque wall, and the other the incidence of a constant radiation ux in the left semitransparent wall. The renormalization group k ε model is adopted to simulate the turbulent ow in the enclosure. To compute the radia- tion heat transfer in a semitransparent medium, the discrete ordinates model is used. We compare the behaviors of enclosures with single and double semitransparent walls and determine the di erence in the results obtained for semitransparent and opaque partitions. The results indicate that a semitransparent partition facilitates a reduction in the heat loss or obtains a higher temperature distribution. The transmittance of a semitransparent wall has a great e ect on the thermal and ow char- acteristics in an enclosure. The change of wall temperature is found to be signi cant when the thermal conductivity values range from 0.05 to 0.5 W/(m K), and to be small when ranging from 0.5 to 10 W/(m K). These conclusions are helpful for green design and energy saving in solar buildings.

Census report on Chinese urological surgeons

Objective:To grasp the general situation of Chinese urological surgeons and the status quo of their scientific research,work and training,thus providing valuable recommendations for urological talent team construction in future.Methods:The survey respondentswere the urological surgeons,who held the Certificate ofMedical Practitioner in the People’s Republic of China,whose scope of practice was confined to urological surgery.The urological surgeons involved in the project completed an online questionnaire survey.All the data were collected through the internet.Results:There were a total of 18981 urological surgeons in China in 2015,of whom 15875 from 2602 hospitals participated in this project,with a mean age of 39.64 years old.In 2015,1949631 cases of surgery were performed,including 493723 cases of open surgery,1146444 cases of endoscopic/laparoscopic surgery(robot-assisted laparoscopic surgery were excluded),6259 robot-assisted surgery and other types of urological surgery.Besides,Chinese urological surgeons published 1358 monographs as well as 14558 academic papers,and also obtained 2064 scientific funds in 2015.A total of 92122 person-time participated in academic conferences.Urological surgeons with higher educational degrees as well as higher academic titles and from Eastern China or higher-level hospitals hadmore opportunities to participate in further education and training.

Almost sure exponential stability of neutral stochastic delayed cellular neural networks

In this paper, almost sure exponential stability of neutral delayed cellular neural networks which are in the noised environment is studied by decomposing the state space to sub-regions in view of the saturation linearity of output functions of neurons of the cellular neural networks. Some algebraic criteria are obtained and easily verified. Some examples are given to illustrate the correctness of the results obtained.

An accurate diagnostic approach for urothelial carcinomas based on novel dual methylated DNA markers in small-volume urine

Diagnostic methods for urothelial carcinomas(UCs)are often invasive or have suboptimal accuracy.Methylation of exfoliated cell DNA or cell-free DNA in urine has shown great promise in the diagnosis of UCs.However,most current studies have focused on bladder cancer(BCa),and only a few high-plex methylated DNA panels based on large-volume urine have been reported to exhibit both high sensitivity and specificity.[1,2]The purpose of this study was to identify universal biomarkers for BCa and upper tract urothelial carcinoma(UTUC)using a small volume of urine.We developed a dual-target diagnostic panel comprising the novel marker AL021918.2 and the well-known BCa biomarker Vimentin(VIM).This panel can accurately detect UCs using only 1.8 mL of full-voided urine.

Stability analysis of proportional delayed projection neural network for quadratic programming problem

At present,projection neural network(PNN)with bounded time delay has been widely used for solving convex quadratic programming problem(QPP).However,there is little research concerning PNN with unbounded time delay.In this paper,we propose the proportional delayed PNN to solve QPP with equality constraints.By utilizing homeo morphism mapping principle,we prove the proportional delayed PNN exists with unique equilibrium point which is the optimal solution of QPP.Simultaneously,delay-dependent criteria about global exponential stability(GES)and global polynomial stability(GPS)are also acquired by applying the method of variation of constants and inequality techniques.On the other hand,when proportional delay factor q is equal to 1,the proportional delayed PNN becomes the one without time delay which still can be utilized for solving QPP.But in most situations,q is not equal to 1,and time delay is unpredictable and may be unbounded in the actual neural network,which causes instability of system.Therefore,it is necessary to consider proportional delayed PNN.A numerical example demonstrates that,compared with the proportional delayed Lagrange neural network,the proportional delayed PNN is faster in terms of convergence rate.The possible reason is that appropriate parameters make the model converge to the equilibrium point along the direction of gradient descent.

Robotic urologic surgery using the KangDuo-Surgical Robot-01 system:A single-center prospective analysis

Background:The KangDuo-Surgical Robot-01(KD-SR-01)system is a new surgical robot recently developed in China.The aim of this study was to present our single-center experience and mid-term outcomes of urological procedures using the KD-SR-01 system.Methods:From August 2020 to April 2023,consecutive urologic procedures were performed at Peking University First Hospital using the KD-SR-01 system.The clinical features,perioperative data,and follow-up outcomes were prospectively collected and analyzed.Results:A total of 110 consecutive patients were recruited.Among these patients,28 underwent partial nephrectomy(PN),41 underwent urinary tract reconstruction(26 underwent pyeloplasty,3 underwent ureteral reconstruction and 12 underwent ureterovesical reimplantation[UR]),and 41 underwent radical prostatectomy(RP).The median operative time for PN was 112.5 min,157.0 min for pyeloplasty,151.0 min for ureteral reconstruction,142.5 min for UR,and 138.0 min for RP.The median intraoperative blood loss was 10 mL for PN,10 mL for pyeloplasty,30 mL for ureteral reconstruction,20 mL for UR,and 50 mL for RP.All procedures were successfully completed without conversion,and there were no major complications in any patient.The median warm ischemia time of PN was 17.3 min,and positive surgical margin was not noted in any patient.The overall positive surgical margin rate of RP was 39%(16/41),and no biochemical recurrence was observed in any RP patient during the median follow-up of 11.0 months.The surgical success rates of pyeloplasty and UR were 96%(25/26)and 92%(11/12)during the median follow-up of 29.5 months and 11.5 months,respectively.Conclusion:The KD-SR-01 system appears feasible,safe,and effective for most urological procedures,based on our single-center experience.

Function and Cryo-EM structures of broadly potent bispecific antibodies against multiple SARS-CoV-2 Omicron sublineages

Dear Editor,SARS-CoV-2 rapidly evolves during the pandemic1 with many variants of concern(VoCs)lineages(Supplementary Fig.S1a).Omicron(B.1.1.529)and its sub-lineages led to multiple infection waves globally.2 Omicron subvariants harbored a high number of mutations,especially in the spike(S)glycoprotein,and clustered in the receptor-binding domain(RBD)(Supplementary Fig.S1b,c;Supplemental Discussion).These subvariants drastically decrease the efficacy of current vaccinations and monoclonal antibody therapies.

CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors

In the past decade,chimeric antigen receptor(CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers,demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients.CAR-natural killer(CAR-NK)cell complements CAR-T cell therapy by offering several distinct advantages.CAR-NK cells do not require HLA compatibility and exhibit low safety concerns.Moreover,CAR-NK cells are conducive to“off-the-shelf”therapeutics,providing significant logistic advantages over CAR-T cells.Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies.However,their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration,as well as an immuno-suppressive tumor microenvironment.In this review,we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies,with a specific focus on the obstacles to their application in solid tumors.We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization.Finally,we explore future perspectives of these adoptive immunotherapies,highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.

三级活塞推料离心机数值模拟与操作参数优化

针对新型三级活塞推料离心机的研发,在转鼓尺寸和物料增大情况下,操作参数对分离过程中转鼓内侵蚀现象和分离效率有重要影响。采用样机实验结合CFD数值模拟,对三级活塞推料离心机进行三维建模和仿真,并利用密集离散粒子模型(DDPM)模拟侵蚀过程。基于粒度分析可知,氯化钠颗粒粒径d_(m)为0.070~0.200 mm时,随颗粒粒径增加,固相对离心机转鼓内部的侵蚀越大。结合响应面分析法可知,响应模型各因素的交互影响明显,以更高分离率与更低侵蚀率作为评价指标,得出最优值为推料频率40次/min、转鼓转速1431 r/min、进料浓度60%。与实验数据进行对比,模拟结果的误差在可接受范围内。

Polynomial dissipativity of proportional delayed BAM neural networks

This paper pays close attention to the global polynomial dissipativity(GPD)for proportional delayed BAM neural networks(PDBAMNNs).The global exponential dissipativity(GED)and the global dissipativity(GD)are also talked about.Under the help of novel Lyapunov functionals and a generalized Halanay inequality,a set of dissipative criteria for such systems are led out,together with the global polynomial attracting set(GPAS)and the global attracting set(GAS).Further,the relationship among GPD,GED and GD is unveiled.Finally,a proposed theoretical condition is validated through a simulation experiment.

Status and strategies analysis on international standardization of auricular acupuncture points

OBJECTIVE： To supply literature for developing an international standard of auricular acupuncture points. METHODS： Electronic database searches were con- ducted in the Chinese National Knowledge Infra- structure and VlP, and the Western databases, Pubmed, the National Science and Technology Li- brary, and the German Journal of Acupuncture, from 1990 to April, 2012. We also searched the doc- uments of international symposiums for auricular acupuncture points （AAPs）. Keywords were ＂auricu- lar points＂, ＂auricular acupuncture points＂, ＂ear points＂, or ＂auriculotherapy＂ RESULTS： Basic and clinical research on AAPs was performed in China, the United States, France, andGermany. Clinical AAP research was done in Italy, Austria, Switzerland, Spain, the UK, Holland, Japan, Russia, and Africa. However, AAP research was not communicated internationally. The World Federa- tion of Acupuncture-Moxibustion Societies recom- mended international standard of auricular acu- puncture points （ISAAPs）. Standardized nomencla- ture and locations of AAPs would provide a solid basis to draft an international standard organiza- tion. CONCLUSION： Experts need to find common points from different countries or regions, provide evidence of different ideas, and list the proposal as a recommendation for an international standard.

Rapid antimicrobial susceptibility testing for mixed bacterial infection in urine by AI-stimulated Raman scattering metabolic imaging

Urinary tract infection with mixed microorganisms may lead to false-positive resistance detection.Current antimicrobial susceptibility testing(AST)performed in clinical laboratories is based on bacterial culture and takes a long time for mixed bacterial infections.Here,we propose a machine learning-based single-cell metabolism inactivation concentration(ML-MIC)model to achieve rapid AST for mixed bacterial infections.Using E.coli and S.aureus as a demonstration of mixed bacteria,we performed feature extraction and multi-feature analysis on stimulated Raman scattering(SRS)images of bacteria with the ML-MIC model to determine the subtypes and AST of the mixed bacteria.Furthermore,we assessed the AST of mixed bacteria in urine and obtained single-cell metabolism inactivation concentration in only 3 h.Collectively,we demonstrated that SRS imaging of bacterial metabolism can be extended to mixed bacterial infection cases for rapid AST.