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Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel chemotherapy

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Asian Journal of Andrology 2023年第4期25卷 520-527页

作者： Jun-Hong Li xing-ming zhang Xiao-Jie Bian Wei-Jie Gu Fang-Ning Wan Bo Dai Ding-Wei Ye Department of Urology Fudan University Shanghai Cancer CenterShanghai 200032China Shanghai Genitourinary Cancer Institute Shanghai 200032China

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival(PFS)and overall survival(OS)in metastatic castration-resistant prostate cancer(mCRPC)patients receiving docetaxel.The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center(Shanghai,China)were reviewed.The following body composition parameters were calculated using computed tomography:skeletal muscle index(SMI),visceral adipose tissue index(VATI),and subcutaneous adipose tissue index(SATI).Pretreatment serum adipocytokine levels,including interleukin 6,insulin,leptin,monocyte chemoattractant protein-1,adiponectin,and resistin,were measured using the multiplex bead-based immunoassays.Cox regression and Kaplan–Meier methods were used for survival analyses.Of the 453 mCRPC patients initially identified,105 were included in the analysis.High VATI group patients had longer PFS(median,10 months vs 7 months,P=0.008)and OS(median,24 months vs 15 months,P=0.017),compared with low VATI group patients.SMI and SATI were not significantly associated with PFS or OS.Of the six detected adipocytokines,only leptin was associated with mCRPC prognosis.High leptin group patients had shorter PFS(median,7 months vs 12 months,P=0.0018)and OS(median,17 months vs 22 months,P=0.042),compared with low leptin group patients.Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS,while a high leptin level was an independent risk factor for PFS and OS.Therefore,VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

关键词： adipocytokines body composition castration-resistant prostate cancer chemotherapy prognosis

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The safety of radium-223 combined with new-generation hormonal agents in bone metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

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Asian Journal of Andrology 2023年第4期25卷 441-447页

作者： ming-Hao Wang Jin-Dong Dai xing-ming zhang Jin-Ge Zhao Guang-Xi Sun Yu-Hao Zeng Hong Zeng Nan-Wei Xu Hao Zeng Peng-Fei Shen Department of Urology West China Hospital of Sichuan UniversityChengdu 610041China

Patients with bone metastatic castration-resistant prostate cancer (mCRPC) might benefit from radium-223 (^(223)Ra) combined withnew-generation hormonal agents (NHAs) in terms of survival and quality of life (QoL). However, the safety of combination therapiesremains unclear. Therefore, we aimed to perform a network meta-analysis by reviewing the literature about the combination of^(223)Ra with abiraterone acetate plus prednisone (AAP) or enzalutamide and to evaluate the safety of combination therapy in bonemCRPC patients. Ultimately, ten studies (2835 patients) were selected, including four randomized controlled trials (RCTs), fiveretrospective cohort studies, and one single-arm study. Overall, there was no difference in the incidence of fracture between the^(223)Ra+NHA combination group and the ^(223)Ra monotherapy group (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.91–2.34,P = 0.66), but the incidences in both the ^(223)Ra+NHA combination group (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01) and the ^(223)Ramonotherapy group (OR: 2.24, 95% CI: 1.23–4.08, P < 0.01) were higher than that in the NHA monotherapy group. However, inthe meta-analysis involving only RCTs, there was no difference between the ^(223)Ra monotherapy group and the NHA monotherapygroup (OR: 1.14, 95% CI: 0.22–5.95, P = 0.88), while the difference between the ^(223)Ra+NHA combination group and the NHAmonotherapy group remained significant (OR: 3.22, 95% CI: 2.24–4.63, P < 0.01). Symptomatic skeletal events (SSEs), SSE-freesurvival (SSE-FS), all grades of common adverse events (AEs), and ≥grade 3 AEs among all groups did not show any significantdifference. Our results indicate that the combination of ^(223)Ra with NHAs was well tolerated in bone mCRPC patients compared to ^(223)Ra monotherapy, even though the incidence of fracture was higher in patients who received ^(223)Ra than that among those whoreceived NHA monotherapy. More evidence is needed to explore the safety and efficiency of ^(223)Ra combination therapies.

关键词： meta-analysis metastatic castration-resistant prostate cancer new-generation hormonal agents radium-223 safety

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Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer

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Asian Journal of Andrology 2022年第2期24卷 154-160页

作者： Yu-Chao Ni Jin-Ge Zhao Meng-Ni zhang Yi-Jun zhang Zhen-Yu Yang Ni Chen Jun-Ru Chen Peng-Fei Shen Guang-Xi Sun xing-ming zhang Yong-Hong Li Hao Zeng Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu 610041China Department of Pathology West China HospitalSichuan UniversityChengdu 610041China Department of Pathology Sun Yat-Sen University Cancer CenterGuangzhou 510060China Department of Urology Sun Yat-Sen University Cancer CenterGuangzhou 510060China

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer(mCRPC).Here,we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate(AA).We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018.All cases received AA plus prednisone as first-line therapy during mCRPC.Primary end points were biochemical progression-free survival(bPFS)and overall survival(OS).The risk groups were defined based on multivariate analysis.A total of 42(41.6%)and 25(24.8%)patients achieved 30%and 50%decline in prostate-specific antigen(PSA),respectively,after corticosteroid switching.The median bPFS and median OS on AA plus dexamethasone were 4.9(95%confidence interval[CI]:3.7–6.0)months and 18.8(95%CI:16.2–30.2)months,respectively.Aldo-keto reductase family 1 member C3(AKR1C3)expression(hazard ratio[HR]:2.15,95%Cl:1.22–3.80,P=0.008)and baseline serum alkaline phosphatase(ALP;HR:4.95,95%Cl:2.40–10.19,P160 IU l−1(HR:3.41,95%Cl:1.57–7.38,P=0.002)together with PSA level at switch≥50 ng ml−1(HR:2.59,95%Cl:1.22–5.47,P=0.013)independently predicted poorer OS.Based on the predictive factors in multivariate analysis,we developed two risk stratification tools to select candidates for corticosteroid switching.Detection of serum ALP level,PSA level,and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

关键词： abiraterone acetate alkaline phosphatase corticosteroid switching dexamethasone metastatic castration-resistant prostate cancer

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Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer

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Asian Journal of Andrology 2023年第4期25卷 462-467页

作者： Zhi-Peng Wang Jun-Ru Chen Jin-Ge Zhao Sha Zhu xing-ming zhang Jia-Yu Liang Ben He Yu-Chao Ni Guang-Xi Sun Peng-Fei Shen Hao Zeng Department of Urology Institute of UrologyWest China HospitalSichuan UniversityChengdu 610041China Department of Urology The Third People’s Hospital of ChengduChengdu 610031China

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases inmen with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients betweenNovember 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classifiedinto 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymphnode (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and livermetastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane(below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostatecancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showedthat patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, andpatients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those inG5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015;medianOS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC,and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicatethat the farther the NRLNs are located, the more aggressive the disease is.

关键词： lymph node metastases metastatic hormone-sensitive prostate cancer metastatic pattern metastatic site nonregional lymph node metastases staging

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Prior switching to a second-line nonsteroidal antiandrogen does not impact the therapeutic efficacy of abiraterone acetate in patients with metastatic castration-resistant prostate cancer： a real-world retrospective study

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Asian Journal of Andrology 2018年第6期20卷 545-550页

作者： Jin-G Zhao Jian-Dong Liu Peng-Fei Shen Xin Tang Guang-Xi Sun xing-ming zhang Jun-Ru Chen Kun-Peng Shu ming Shi Hao Zeng Department of Urology Institute of Urology West China Hospital Sichuan University Chengdu 610041 China Department of Oncology West China Hospital Sichuan University Chengdu 610041 China

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen （NSAA） is still widely used in treating metastatic castration-resistant prostate cancer （mCRPC）, especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate （Abi） remains uncertain, in the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA （from bicalutamide to flutamide） before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival （PSA-PFS, 5.5 vs 5.6 months, P = 0.967）, radiographic progression-free survival （rPFS, 12.8 vs 13.4 months, P = 0.508）, overall survival （OS, not reached vs 30.6 months, P = 0.606）, or PSA-response rate （71.4% [15121] vs 60.6% [40166], P = 0.370）. This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors＇ decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.

关键词： abiraterone antiandrogen castration-resistant prostate cancer flutamide

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Laser powder b e d fusion of copper matrix iron particle reinforced nanocomposite with high strength and high conductivity

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Journal of Materials Science & Technology 2023年第3期134卷 50-59页

作者： Yingang Liu Jingqi zhang Qiang Sun Meng Li ming Yan b xing Cheng Miaoquan Li ming-xing zhang School of Mechanical and Mining Engineering The University of QueenslandSt.LuciaQLD 4072Australia Department of Materials Science and Engineering and Shenzhen Key Laboratory for Additive Manufacturing of High-performance Materials Southern University of Science and TechnologyShenzhen 518055China School of Materials Science and Engineering Northwestern Polytechnical UniversityXi’an 710072China

Liquid-liquid phase separation,and the resulted solute segregation,during conventional solidification have been a long-term challenge to produce copper(Cu)-iron(Fe)immiscible composites with high strength and high conductivity.The present work reports an effective solution to this issue through laser powder bed fusion(L-PBF)in-situ alloying of Cu-8 wt.%Fe.Microstructure observation showed that the fast cooling within micron-scale melt pools fully eliminated the Fe segregation and therefore the L-PBF fabricated nanocomposite achieved the homogeneous microstructure,which featured equiaxed fine grains around 1μm in size.Ageing of the nanocomposite at 600℃for 1 h enabled precipitation of two types of nanoparticles.One is coarser Fe nanoprecipitates with body-centered cubic(BCC)structure and diam-eter of 100-300 nm,mainly distributing along grain boundaries.The other is smaller Fe nanoprecipitates with face-centered cubic(FCC)structure and diameter of 10-35 nm,being observed within the grains and having coherent interfaces with the Cu matrix.As a result,the aged Cu-Fe nanocomposite achieved tensile strength of 462.9±6.6 MPa with 30.4%±1.7%elongation to failure and 74.5%IACS(International Annealed Copper Standard)electrical conductivity.The formation mechanisms of the nanoprecipitates and the strengthening mechanisms of the nanocomposite are discussed.

关键词： Immiscible alloy Copper Laser powder bed fusion Ageing Nanocomposite

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Light-and Heat-Controlled Formation of Osmanaphthalenes and Osmanaphthalynes

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Chinese Journal of Chemistry 2022年第24期40卷 2853-2860页

作者： ming-xing zhang Xiaofei Yang Zhiqiang Xu Jun Yin Sheng Hua Liu Key Laboratory of Pesticide and Chemical Biology Ministry of EducationCollege of ChemistryCentral China Normal UniversityWuhanHubei430079 China Hubei Key Laboratory of Purification and Application of Plant Anti-cancer Active Ingredients College of Chemistry and Life ScienceHubei University of EducationWuhanHubei430205 China Key Laboratory for Green Chemical Process of Ministry of Education School of Chemical Engineering and PharmacyWuhan Institute of TechnologyWuhanHubei430205 China

mple and efficient synthesis of metalla-aromatics with tailored distinctive optical,magnetic,redox,and light-emitting properties is attractive yet challenging.We have now successfully synthesized three paramagnetic osmanaphthalenes bearing different electron-donating groups as well as the first osmabenzo[b]carbazole containing an osmanaphthalene unit with four fused rings in good yields by subjecting suitable osmium carbyne precursors to a visible-light-induced protocol.In contrast,the four corresponding diamagnetic cyclic metal carbynes containing an osmanaphthalyne unit were obtained from the same osmium carbyne precursors by a heating method.The lowest-energy absorptions of the paramagnetic osmanaphthalenes are red-shifted compared to the corresponding osmanaphthalynes.Additionally,experimental observations including X-ray analysis as well as nucleus-independent chemical shift(NICS),anisotropy of the current-induced density(AICD)calculations revealed these novel osmapolycycles bearing phosphonium substituents to be of aromatic character.

关键词： Metallacycles Aromaticity Osmanaphthalyne Osmanaphthalene Photolysis

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Predictive efficacy of the 2014 International Society of Urological Pathology Gleason grading system in initially diagnosed metastatic prostate cancer

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Asian Journal of Andrology 2017年第5期19卷 573-578页

作者： Guang-Xi Sun Peng-Fei Shen xing-ming zhang Jing Gong Hao-Jun Gui Kun-Peng Shu Jiang-Dong Liu Jinge Zhao Yao-Jing Yang xue-Qin Chen Ni Chen Hao Zeng Department of Urology Institute of Urology West China Hospital Sichuan University Chengdu 610041 Sichuan China Department of Pathology West China Hospital Sichuan University Chengdu 610041 Sichuan China

We compared the predictive ability of the 2014 and 2005 Gleason grading systems in 568 patients initially diagnosed with metastatic prostate cancer （PCa）. Outcomes included the duration of castration-resistant prostate cancer-free survival （CFS） and overall survival （OS）. Univariate analyses and log-rank tests were used to identify prognosis indicators and assess univariable differences in CFS and OS in Gleason score （GS） groups. Cox proportional hazards and area under the curves of receiver operator characteristics methods were used to evaluate the predictive efficacy of the 2005 and 2014 ISUP grading systems. Univariate analyses showed that the 2005 and 2014 grading systems were prognosticators for CFS and OS; both systems could distinguish the clinical outcome of patients with GS 6, GS 7, and GS 8-10. Using the 2014 criteria, no statistical differences in patient survival were observed between GS 3 ＋ 4 and GS 4 ＋ 3 or GS 8 and GS 9-10. The predictive ability of the 2014 and 2005 grading systems was comparable for CFS and OS （P = 0.321）. However, the 2014 grading system did not exhibit superior predictive efficacy in patients initially diagnosed with PCa and bone metastasis; trials using larger cohorts are required to confirm its predictive value. To the best of our knowledge, ours is the first study to compare the 2005 and 2014 grading systems in initially diagnosed PCa with bone metastasis. At present, we recommend that both systems should be used to predict the prognosis of patients with metastatic PCa.

关键词： castration-resistance prostate cancer-free survival International Society of Urological Pathology grading system metastasis overall survival prostate cancer

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Heterogeneous lamella design to tune the mechanical behaviour of a new cost-effective compositionally complicated alloy

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Journal of Materials Science & Technology 2022年第1期96卷 113-125页

作者： Yu Yin Qiyang Tan Qiang Sun Wangrui Ren Jingqi zhang Shiyang Liu Yingang Liu Michael Bermingham Houwen Chen ming-xing zhang School of Mechanical and Mining Engineering University of QueenslandQLD 4072Australia College of Materials Science and Engineering Chongqing UniversityChongqing 400044China

A heterogeneous lamella(HL)design strategy was applied to manipulate mechanical properties of a new cost-effective Fe_(35)Ni_(35)Cr_(25)Mo_(5)compositionally complicated alloy(CCA).The HL structure was produced by single-step heat treatment(800℃for 1 h)after cold rolling.This HL structure consists of alternative lamellae regions of coarse-grained FCC matrix(5-20μm),and regions containing ultra-fine grains or subgrains(200-500 nm)together with nanoprecipitates(20-500 nm)and annealing twins.As compared with other cost-effective CCAs,the 800℃annealed sample with HL structure demonstrated a comparable tensile property,with yield strength over 1.0 GPa and total elongation of~13%.Formation of the annealing twins and nanoprecipitates decorated HL structure was a result of the concurrent partial recrystallization and precipitation ofσphase at the shear bands with a high density of lattice defects(e.***.high-density dislocation walls and deformation twins).The latter restricted the growth of recrystallized grains,leading to the formation of ultrafine subgrains within the HL structure.The high yield strength resulted from the multistage hetero-deformation induced(HDI)strengthening and precipitation strengthening associated with heterogeneous lamella structures containing nanoprecipitates.The ductility was originated from the coexistence of multiple deformation mechanisms,which started with dislocation slip and formation of stacking faults at the initial stage,followed by nano-twinning at the higher strain level.This HL design strategy,comprising composition and thermomechanical process designs,and the resultant microstructure tuning,open a broader window for the development of cost-effective CCAs with enhanced performance.

关键词： High entropy alloys Compositionally complicated alloys Heterogeneous lamella structure Nanoprecipitates Recrystallization Mechanical properties

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Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 230-242页

作者： WANG Yi CHEN ming-qi DAI Lin-feng zhang Hai-dong WANG xing Department of Critical Care Medicine Changzhou Hospital of Traditional of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineChangzhouJiangsu Province213000China Department of Critical Care Medicine Jiangsu Province Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing210029China

Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments.Methods:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell model.Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis.Through ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was analyzed.Results:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(P<0.05).Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis.As confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(P<0.05).Furthermore,FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(P<0.05).Conclusion:FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.

关键词： sepsis Fangji Fuling Decoction mitogen-activated protein kinase 14/Forkhead Box O 3A signaling pathway inflammatory response apoptosis lung injury Chinese medicine

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