Prognostic factors in Chinese patients with metastatic castration-resistant prostate cancer treated with docetaxel-based chemotherapy

This study aims to evaluate the potential value of patient characteristics in predicting overall survival （OS） in patients with metastatic castration-resistant prostate cancer （mCRPC） treated with docetaxel-based thermotherapy. A total of 115 patients with mCRPC undergoing a docetaxel q3w regimen were enrolled in this study. A survival analysis was performed using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the prognostic value of all covariates for OS. OS was also analysed after stratifying patients according to the results of multivariate analysis. The median OS for the entire cohort was 17.0 months. The multivariate analysis showed that the prostate-specific antigen doubling time （PSADT）, baseline haemoglobin （Hb） concentration, alkaline phosphatase （ALP） concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS. According to the presence of PSADT 〈46.3 days and baseline ALP/〉 110 IU 1-1, all patients were divided into three risk groups： low-risk group （no risk factors）, intermediate-risk group （one risk factor） and high-risk group （two risk factors）. Median OSs for patients in low-, intermediate- and high-risk groups were 28.0 months （95% Ch 23.8-32.2）, 21.0 months （95% Ch 18.9-23.1） and 11.0 months （95% Ch 7.6-14.4）, respectively （P〈O.O01）. In conclusion, PSADT, baseline Hb concentration, ALP concentration, cycles of chemotherapy and time to castration resistance were independent prognostic factors of OS in Chinese patients with mCRPC treated with docetaxel. PSADT combined with the baseline ALP concentration could be a useful risk stratification parameter for evaluating survival outcomes.

Prostate-specific antigen half-life： a new predictor of progression- free survival and overall survival in Chinese prostate cancer patients

We investigated the potential value of prostate-specific antigen half-life （PSAHL） and decreasing velocity （PSAVd） to predict progression-free survival （PFS） and overall survival （OS） in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone- refractory prostate cancer （HRPC） and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen （PSA） concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL^-1 per month. The median PFS and OS were 22.7 months （95% confidence interval [CI], 22.0-29.6 months） and 43.5 months （95% CI, 37.9-48.4 months）, respectively. On univariate and multivariate analysis, long PSAHL （〉 0.5 months）, metastatic disease, high biopsy Gleason scores （〉 8） and high nadir PSA （〉 0.4 ng mL^-1） were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time （PSADT 〈 2.0 months） were significantly associated with short OS. There were no significant relationships between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent predictor of survival. Patients with long PSAHL were identified as those at high risk for a relatively short PFS and OS.

Influence of obesity on localized prostate cancer patients Ireated with radical prostatectomy

This study aimed to investigate the association between different anthropometric measures of obesity and clinicopathological characteristics in Chinese patients with clinically localized prostate cancer （PCa）. A total of 734 patients with clinically localized PCa who underwent radical prostatectomy （RP） were included in this study. Clinical and pathological data from each patient were collected. Anthropometric measures of abdominal adiposity were measured from T2-weighted sagittal Iocalisation images from magnetic resonance imaging （MRI） for 413 （56.3%） patients. Patient clinical and pathological characteristics were compared across body mass index （BMI） groups. Univariable and multivariable logistic regression models were used to address the influence of the preoperative total testosterone level and anthropometric measures of obesity on pathological outcomes. In the multivariate analysis, BMI was not significantly associated with any pathological outcomes. However, the percentage of visceral adipose tissue （VAT%） was an independent predictor of a pathological Gleason score ≥8 （P〈0.O01）, extracapsular extension （ECE; P=0.002） and seminal vesicle invasion （SVI; P=0.007）. More importantly, we found that the preoperative total testosterone level was significantly correlated with the VAT% （Pearson＇s correlation coefficient： -0.485, P〈0.001） and subcutaneous adipose tissue （SAT; Pearson＇s correlation coefficient： 0.413, P〈0.001）. In conclusion, the results of this study suggest that abdominal fat distribution, and particularly VAT%, is associated with a risk of advanced PCa. Moreover, our present study confirms a significant inverse correlation between visceral adiposity and testosterone. Further studies are warranted to elucidate the biological mechanisms underlying the relationship between abdominal adiposity and the aggressiveness of PCa.

Perioperative complications of radical retropubic prostatectomy in patients with locally advanced prostate cancer： a comparison with clinically localized prostate cancer

Radical prostatectomy （RP） continues to be an effective surgical therapy for prostate carcinoma, particularly for organ-confined prostate cancer （PCa）. Recently, RP has also been used in the treatment of locally advanced prostate cancer. However, little research has been performed to elucidate the perioperative complications associated with RP in patients with clinically localized or locally advanced PCa. We sought to analyse the incidence of complications in these two groups after radical retropubic prostatectomy （RRP）. From June 2002 to July 2010, we reviewed 379 PCa patients who underwent RRP in our hospital. Among these cases, 196 had clinically localized PCa （Tla-T2c group 1）, and 183 had locally advanced PCa （ ≥ T3,： group 2）. The overall complication incidence was 21.9%, which was lower than other studies have reported. Perioperative complications in patients with locally advanced PCa mirror those in patients with clinically localized PCa （26.2% vs. 17.8%, P=0.91）. Our results showed that perioperative complications could not be regarded as a factor to consider in regarding RP in patients with cT3 or greater.

民航招飞体检中视网膜周边退行性变性的调查研究

目的:调查民航招飞体检中视网膜周边退行性变性的患病情况,为民航招飞体检鉴定提供数据支持。方法:选取2018-02/2019-05在民航总医院空勤鉴定所眼科进行招飞初检的准飞行学生2450名4900眼为研究对象,复方托吡卡胺滴眼液充分散瞳后按屈光度将其分为三组:低度远视及正视组:等效球镜为+3.00~<-0.50D,共215名;轻度近视组:等效球镜为-0.50~<-3.00D,共1385名;中度近视组:等效球镜为-3.00^-4.50D,共850名。检查视网膜周边退行性变性患病情况,并对检查结果进行统计学分析。结果:所有受检招飞学生中共计575名存在不同类型视网膜周边退行性变性,患病率为23.5%;不同屈光度组视网膜周边退行性变性患病率比较有差异(χ^2=65.386,P<0.01);不同类型视网膜周边退行性变性患病率比较有差异(χ^2=351.276,P<0.01);不同部位视网膜周边退行性变性患病率比较有差异(χ^2=563.712,P<0.01)。结论:视网膜周边退行性变性在民航招飞中并不罕见,随近视程度加深患病率增加,且病变以颞侧周边多见,建议根据不同类型进行针对性鉴定。

External validation of nomograms for predicting cancer-specific mortality in penile cancer patients treated with definitive surgery

Using a population-based cancer registry,Thuret et al.developed 3 nomograms for estimating cancerspecific mortality in men with penile squamous cell carcinoma.In the initial cohort,only 23.0% of the patients were treated with inguinal lymphadenectomy and had pN stage.To generalize the prediction models in clinical practice,we evaluated the performance of the 3 nomograms in a series of penile cancer patients who were treated with definitive surgery.Clinicopathologic information was obtained from 160 M0 penile cancer patients who underwent primary tumor excision and regional lymphadenectomy between 1990 and 2008.The predicted probabilities of cancer-specific mortality were calculated from 3 nomograms that were based on different disease stage definitions and tumor grade.Discrimination,calibration,and clinical usefulness were assessed to compare model performance.The discrimination ability was similar in nomograms using the TNM classification or American Joint Committee on Cancer staging(Harrell's concordance index = 0.817 and 0.832,respectively),whereas it was inferior for the Surveillance,Epidemiology and End Results staging(Harrell's concordance index = 0.728).Better agreement with the observed cancer-specific mortality was shown for the model consisting of TNM classification and tumor grade,which also achieved favorable clinical net benefit,with a threshold probability in the range of 0 to 42%.The nomogram consisting of TNM classification and tumor grading was shown to have better performance for predicting cancer-specific mortality in penile cancer patients who underwent definitive surgery.Our data support the integration of this model in decision-making and trial design.

The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer： who can benefit from ketoconazole therapy？

We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer （mCRPC）. In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival （PFS） was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months （0.5-8.6 months） for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen （PSA） declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following： 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and 〈0.2 ng ml- 1, respectively （hazard rate （HR）=4.767, P〈0.001）; 3.1 and 1.6 months for a baseline testosterone of ≥0.1 and 〈0.1 ng m1-1, respectively （HR=2.865, P=0.012）; 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and 〈120 g 1-1, respectively （HR= 1.605, P〈0.001）; and 3.0 and 1.9 months for a PSA doubling time （PSADT） of ≥ 2.0 and 〈2.0 months, respectively （HR= 1.454, P=-0.017）. A risk model was constructed according to the four factors that divided patients into three subgroups of low risk （0-1 factors）, moderate risk （2 factors） and high risk （3-4 factors） with PFS values of 3.6, 3.0 and 1.4 months, respectively （HR=1.619, P〈0.001）. A nadir PSA of ≥0.2 ng m1-1, a baseline testosterone of 〈0.1 ng m1-1, a baseline haemoglobin of 〈 120 g I- 1 and a PSADT of 〈2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.

H-BONDING SELF-ASSEMBLED TEMPLATE-CONTROLLED SYNTHESIS OF A NOVEL SOLUBLE AND REACTIVE AMIDE-BRIDGED LADDERLIKE POLYHYDROSILOXANE

A novel soluble and reactive amide-bridged ladderlike polyhydrosiloxane （ALPHS） was first synthesized by an amido H-bonding self-assembled template. ALPHS with molecular weight M^-a = 18300 has very highly ordered ladderlike structure, which was confirmed by a sharp resonance absorption peak of [-Si（H）O2/2 ] moiety with the half peak width △1/2 〈 0.5 in^29Si-NMR spectrum. Presence of the reactive Si-H groups gives ALPHS an opportunity to further derive a variety of functional polymers by versatile Si-H reactions such as hydrosilylation, condensation, and so on.

Comparison of two adjuvant hormone therapy regimens in patients with high-risk localized prostate cancer after radical prostatectomy, primary results of study CU 1005

The role of adjuvant hormonal therapy and optimized regimens for high-risk localized prostate cancer after radical prostatectomy remains controversial. Herein, the clinical trial CU 1005 prospectively evaluated two regimens of maximum androgen blockage or bicalutamide 150 mg daily as immediate adjuvant therapy for high-risk localized prostate cancer. Overall, 209 consecutive patients were recruited in this study, 107 of whom received 9 months of adjuvant maximum androgen blockage, whereas 102 received 9 months of adjuvant bicalutamide 150 mg. The median postoperative follow-up time was 27.0 months. The primary endpoint was biochemical recurrence. Of the 209 patients, 59 patients developed biochemical recurrence. There was no difference between the two groups with respect to clinical characteristics, including age, pretreatment prostate-specific antigen, Gleason score, surgical margin status, or pathological stages. The maximum androgen blockage group experienced longer biochemical recurrence-free survival （P = 0.004） compared with the bicalutamide 150 mg group. Side-effects in the two groups were similar and could be moderately tolerated in all patients. In conclusion, immediate, 9-month maximum androgen blockage should be considered as an alternative to bicalutamide 150 mg as adjuvant treatment for high-risk localized prostate cancer patients after radical prostatectomy.

Serum lipid profiles： novel biomarkers predicting advanced prostate cancer in patients receiving radical prostatectomy

This study aimed to evaluate the role of serum lipid profiles as novel biomarkers in predicting pathological characteristics of prostate cancer （PCa）. We retrospectively analyzed 322 consecutive patients with clinically localized PCa receiving radical prostatectomy （RP） and extended pelvic lymphadenectomy. Unconditional logistic regression was used to estimate the prostatectomy Gleason score （pGS）, pathological stage and lymph node involvement （LNI） in RP specimens. Preoperative prostate-specific antigen （PSA） levels, biopsy GS （bGS）, and preoperative tumor, node, metastasis staging were used as basic variables to predict postoperative pathological characteristics. Preoperative serum lipid profiles were introduced as potential predictors. A receiver operating characteristic （ROC） curve was used to determine predictive efficacy. Significant differences in pathological characteristics were observed among patients with normal and abnormal total cholesterol （TC）, triglyceride （TG）, and low-density lipoprotein （LDL） levels, with the exception of pGS in the TG group. Multivariable regression analysis revealed that the odds ratio for high levels of TC for LNI compared with normal TC levels was 6.386 （95% confidence interval [Cl] 1.510-27.010）, 3.270 （95% CI. 1.470-7.278） for high levels of TG for pT3-4 disease, and 2.670 （95% Ch 1.134-6.287） for high levels of LDL for pGS. The area under the ROC curve of the models with dyslipidemia was larger than that in models without dyslipidemia, in predicting pathological characteristics. Abnormal TC, TG, and LDL levels are significantly associated with postoperative pathological status in PCa patients. Together with preoperative PSA levels, bGS, and clinical stage, dyslipidemia is more accurate in predicting pathological characteristics.

Fisl phosphorylation by Met promotes mitochondrial fission and hepatocellular carcinoma metastasis

Met tyrosine kinase,a receptor for a hepatocyte growth factor(HGF),plays a critical role in tumor growth,metastasis,and drug resistance.Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network.Dysregulated mitochondrial dynamics are responsible for the progression and metastasis of many cancers.Here,using structured illumination microscopy(SIM)and high spatial and temporal resolution live cell imaging,we identified mitochondrial trafficking of receptor tyrosine kinase Met.The ton tacts betwee n activated Met kinase and mitochondria formed dramatically,and an intact HGF/Met axis was necessary for dysregulated mitochondrial fission and cancer cell movements.Mechanically,we found that Met directly phosphorylated outer mitochondrial membrane protein Fis1 at Tyr38(Fisl pY38).Fisl pY38 promoted mitochondrial fission by recruiting the mitochondrial fission GTPase dynamin-related protein・1(Drp1)to mitochondria.Fragmented mitochondria fueled actin filament remodeling and lamellipodia or invadopodia formation to facilitate cell metastasis in hepatocellular carcinoma(HCC)cells both in vitro and in vivo.These findings reveal a novel and noncanonical pathway of Met receptor tyrosine kinase in the regulation of mitochondrial activities,which may provide a therapeutic target for metastatic HCC.

Multiple Effects Tailoring the Self-organization Behaviors of Triphenylene Side-chain Liquid Crystalline Polymers via Changing the Spacer Length

Long-alkyl tail triphenylene （TP） side-chain liquid crystalline polymers （SCLCPs） with different spacer length （P-m-TP, m = 2, 3, 4, 6, 8, which is the number of carbon atom in the flexible alkyl spacers） have been successfully synthesized via free radical polymerization. The differential scanning calorimetry （DSC）, polarized light microscopy （POM）, ultraviolet-visible spectroscopy （UV- Vis）, wide-angle X-ray diffraction （WAXD） and small-angle X-ray scattering （SAXS） measurements were performed to investigate the influence of multiple effects on the self-organization behaviors of P-m-TP, including steric effect, decoupling effect and π-π stacking effect. The experimental results revealed that P-m-TP （m = 2, 3, 4） formed the columnar phase which was developed by the TP moieties and the main chain as a whole, suggesting that the side-chains had strong steric effect even though the number of spacer length （m） exceeded 4. In addition, the clearing points （Tis） of the polymers were above 300 ℃. When m = 6 and 8, the polymers displayed hexagonal columnar phase and exhibited the low Tis （91 and 80 ℃ respectively）, originating from the self-assembly of triphenylene due to the decoupling effect and π-π stacking effect. This work offers a viable and inspiring pathway to control the phase transition temperature and phase structure ofTP SCLCPs via simply tailoring the spacer length and increasing the alkyl tail length of TP.

Uniform Lipschitz Estimates of Homogenization of Elliptic Systems in Divergence Form with Dini Conditions

The paper is devoted to the homogenization of elliptic systems in divergence form.We obtain uniform interior as well as boundary Lipschitz estimates in a bounded C1,γdomain when the coefficients are Dini continuous,inhomogeneous terms are divergence of Dini continuous functions and the boundary functions have Dini continuous derivatives.The results extend Avellaneda and Lin’s work[Comm.Pure Appl.Math.,40:803-847(1987)],where Holder continuity is the main assumption on smoothness of the data.

Synthesis and performance of Li_4Ti_5O_(12) anode materials using the PVP-assisted combustion method

Li4Ti5O12 was synthesized by a facile gel-combustion method（GCM） with polyvinylpyrrolidone（PVP） as the polymer chelating agent and fuel.The structural and electrochemical properties of the sample were compared with the one prepared by the conventional solid-state reaction（SSR） through X-ray diffraction（XRD）,scanning electron microscopy（SEM）,cyclic voltammetry（CV）,charge-discharge measurements,and electrochemical impedance spectroscopy（EIS）,respectively.The sub-microscale Li4Ti5O12 oxides,with a high phase purity and good stoichiometry,can be obtained by annealing at 800℃.The grain size is smaller than that of the samples that were power prepared by SSR.Lithium-ion batteries with a GCM Li4Ti5O12 anode exhibit excellent reversible capacities of 167.6,160.7,152.9,and 144.2 mAh/g,at the current densities of 0.5 C,1 C,3 C and 5 C,respectively.The excellent cycling and rate performance can be attributed to the smaller particle size,lower charge-transfer resistance and larger lithium ion diffusion coefficient.It is therefore concluded that GCM Li4Ti5O12 is a promising candidate for applications in highrate lithium ion batteries.

Large-Scale Proteomics Data Reveal Integrated Prognosis-Related Protein Signatures and Role of SMAD4 and RAD50 in Prognosis and Immune Infiltrations of Prostate Cancer Microenvironment

As prostate cancer(PCa)is one of the most commonly diagnosed cancer worldwide,identifying potential prognostic bio-markers is crucial.In this study,the survival information,gene expression,and protein expression data of 344 PCa cases were collected from the Cancer Proteome Atlas(TCPA)and the Cancer Genome Atlas(TCGA)to investigate the potential prognostic biomarkers.The integrated prognosis-related proteins(IPRPs)model was constructed based on the risk score of each patients using machine-learning algorithm.IPRPs model suggested that Elevated RAD50 expression(p=0.016)and down-regulated SMAD4 expression(p=0.017)were significantly correlated with unfavorable outcomes for PCa patients.Immunohistochemical(IHC)staining and western blot(WB)analysis revealed significant differential expression of SMAD4 and RAD50 protein between tumor and normal tissues in validation cohort.According to the overall IHC score,patients with low SMAD4(p<0.0001)expression and high RAD50 expression(p=0.0001)were significantly correlated with poor outcomes.Besides,expression of SMAD4 showed significantly negative correlation with most immune checkpoint molecules,and the low SMAD4 expression group exhibited significantly high levels of LAG3(p<0.05),TGFβ(p<0.001),and PD-L1(p<0.05)compared with the high SMAD4 expression group in the validation cohort.Patients with low SMAD4 expression had significantly higher infiltration of memory B cells(p=0.002),CD8+T cells(p<0.001),regulatory T cells(p=0.006),M2-type macrophages(p<0.001),and significantly lower infiltration of naïve B cells(p=0.002),plasma cells(p<0.001),resting memory CD4+T cells(p<0.001)and eosinophils(p=0.045).Candidate proteins were mainly involved in antigen processing and presentation,stem cell differentiation,and type I interferon pathways.

Hot corrosion behaviors of 921A alloy and HVAF-sprayed Fe-based amorphous coating covered with KCl-ZnCl_(2) salts

Hot corrosion behaviors of the 921A alloy and Fe-based amorphous coating induced by KCl-10% ZnCl_(2) and KCl-55% ZnCl_(2) salts at 450℃ in air for 40 h were investigated.Results show that the 921A alloy suffers more serious corrosion damage than the coating and KCl-55% ZnCl_(2) salts are more corrosive than KCl-10% ZnCl_(2) salts.In the two salts,an Fe_(2)O_(3) layer is formed on the 921A alloy surface,while an outer Fe-rich oxide layer and an inner Cr-rich oxide layer are formed on the surface of the coating.Moreover,a certain amount of metal chloride can be found at the oxide/alloy(coating)interface,which can be explained by "active oxidation".However,the corrosion resistance of the Fe-based amorphous coating did not achieve the desired results,probably because the intersplats in the coating serve as corrosion diffusing channels,which facilitate the corrosion damage rate.Nevertheless,the coating is still in amorphous state after hot corrosion exposure.