Sleep duration and testosterone levels in community older men: results from the West China Health and Aging Trend study

To the Editor:Testosterone is a fundamental male sex hormone produced by the testicular Leydig cells.Testosterone levels are affected by age,peaking in the 20s and 30s and gradually declining thereafter.[1]Low testosterone level may predispose men,especially older men,to a poor prognosis or death in coronavirus disease 2019(COVID-19).[2]Therefore,testosterone levels have a significant impact on the health status of older men.The identification of modifiable non-drug factors affecting testosterone levels in older men is important for improving their health.

Rational Fabrication and Biomedical Application of Biomolecule-Conjugated AIEgens through Click Reaction

Recently,the issue of cancer has attracted extensive attention.Early diagnosis and timely therapy are important for cancer treatment.And lots of advanced fluorescent probes have been applied to cancer theranostics.However,the further development of these probes is limited by the disadvantages of poor targeting,weak sensitivity and photobleaching.Fortunately,the emergence of biomolecule-conjugated fluorescent probes with aggregationinduced emission properties has taken innovative impetus to the cancer theranostics.This review summarizes the rational fabrication and biomedical applications of biomolecule-conjugated A1E luminogens(AIEgens)based on"click reaction"over the past decade.In the meantime,the challenges of biomolecule-conjugated AIEgens in the field of biomedicine are also discussed.

Complete androgen blockade vs.medical castration alone as adjuvant androgen deprivation therapy for prostate cancer patients following radical prostatectomy:a retrospective cohort study

Background:Till date,the optimal treatment strategy for delivering adjuvant androgen deprivation therapy(ADT)in localized and locally advanced prostate cancer(PCa),as a lower stage in PCa progression compared with metastatic PCa,is still unclear.This study compares the efficacy of castration alone with complete androgen blockade(CAB)as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy(RP).Methods:Patients diagnosed with PCa,without lymph node or distant metastasis,who received RP in West China Hospital between January 2009 and April 2019,were enrolled in this study.We performed survival,multivariable Cox proportional hazard regression,and subgroup analyses.Results:A total of 262 patients were enrolled,including 107 patients who received castration alone and 155 patients who received CAB.The survival analysis revealed that there was no significant difference between the two groups(hazard ratios[HR]=1.07,95%confidence intervals[95%CI]=0.60-1.90,P=0.8195).Moreover,the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant.Similarly,there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models.Furthermore,our subgroup analysis showed that CAB achieved better biochemical recurrence(BCR)outcomes than medical castration alone as adjuvant ADT for locally advanced PCa(P for interaction=0.0247,HR=0.37,95%CI=0.14-1.00,P=0.0497).Conclusion:Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Blockade of integrin signaling reduces chemotherapy-induced premature senescence in collagen cultured bladder cancer cells

Background:Diminished sensitivity towards chemotherapy remains the major impediment to the clinical treatment of bladder cancer.However,the critical elements in control of chemotherapy resistance remain obscure.Methods:We adopted improved collagen gels and performed cytotoxicity analysis of doxorubicin(DOX)and mitomycin C(MMC)of bladder cancer cells in a 3D culture system.We then detected the expression of multidrug resistant gene ABCB1,dormancy-associated functional protein chicken ovalbumin upstream-transcription factor 1(COUPTF1),cell proliferation marker Ki-67,and cellular senescence marker senescence-associatedβ-galactosidase(SA-β-Gal)in these cells.We further tested the effects of integrin blockade or protein kinase B(AKT)inhibitor on the senescent state of bladder cancer.Also,we examined the tumor growth and survival time of bladder cancer mouse models given the combination treatment of chemotherapeutic agents and integrinα2β1 ligand peptide TFA(TFA).Results:Collagen gels played a repressive role in bladder cancer cell apoptosis induced by DOX and MMC.In mechanism,collagen activated the integrinβ1/AKT cascade to drive bladder cancer cells into a premature senescence state via the p21/p53 pathway,thus attenuating chemotherapy-induced apoptosis.In addition,TFA had the ability to mediate the switch from senescence to apoptosis of bladder cancer cells in xenograft mice.Meanwhile,TFA combined with chemotherapeutic drugs produced a substantial suppression of tumor growth as well as an extension of survival time in vivo.Conclusions:Based on our finding that integrinβ1/AKT acted primarily to impart premature senescence to bladder cancer cells cultured in collagen gel,we suggest that integrinβ1 might be a feasible target for bladder cancer eradication.

Recent advances in stimuli-responsive theranostic systems with aggregation-induced emission characteristics

Theranostic systems by integrating the tumor imaging and tumor therapeutic capabilities into one platform have attracted numerous attentions from worldwide researchers.Despite the great developments,their clinical application is still in the nascent stage,owing to the unsatisfied imaging quality and limited therapeutic efficacy.Fortunately,the emerging of aggregation-induced emission(AIE)molecules with unique fluorescence property offers an opportunity to solve the imaging problem.Besides,further utilizing the tumor microenvironments and external triggers to design the stimuli-responsive imaging-guided therapy could enhance the therapeutic efficacy and reduce the side effects.In this review,the advancements in stimuli-responsive theranostic systems with AIE characteristics are summarized.Theranostic systems are first classified according to their treatment modes,and then subdivided based on various stimuli,including pH,redox,enzyme,and light.In each section,the design strategies and application examples are introduced.At last,the current state of the art,limitations,as well as prospects are also discussed.