Recent studies have revealed a significant relationship between erectile dysfunction(ED)and lower urinary tract symptoms(LUTS),both of which commonly affect middle-aged and older men.These conditions share underlying ...Recent studies have revealed a significant relationship between erectile dysfunction(ED)and lower urinary tract symptoms(LUTS),both of which commonly affect middle-aged and older men.These conditions share underlying causes,particularly endothelial dysfunction,atherosclerosis,and chronic pelvic ischemia(CPI).This study investigated the therapeutic potential of LDD175,a large-conductance Ca2+-activated K+channel(BKCa channel)opener,in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats.Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet.We assessed erectile and voiding functions by measuring intracavernosal pressure(ICP)and intraurethral pressure(IUP),respectively,after nerve stimulation.We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms.This study evaluated the effectiveness of LDD175 compared to standard treatments,such as sildenafil for ED and tamsulosin for LUTS.Therefore,the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP.Analysis revealed elevated levels of hypoxia-inducible factor-1α,transforming growth factor-β1 andβ2 in cavernous tissue,and increasedα1A-adrenoceptor expression in prostate tissue.LDD175 administration showed promising results,with dose-dependent improvements in ICP and IUP,and therapeutic effects comparable to those of established treatments.Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS,opening new possibilities for clinical application in the treatment of these interconnected conditions.展开更多
BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical r...BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.展开更多
Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the ha...Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.展开更多
Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyl...Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.展开更多
Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbl...Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to pr...As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.展开更多
BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This re...BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This review is to outline the pathomechanism,organ heterogeneity,biomarkers,and therapeutic implications of endothelial dysfunction in sepsis,off ering references and insights for the clinical management of sepsis.METHODS:A systematic search of Web of Science and PubMed from inception to June 10,2025,limited to English publications,was conducted.Two reviewers independently identifi ed studies on EC injury in patients with septic microcirculatory dysfunction.Duplicate articles based on multiple search criteria were excluded.RESULTS:Fifty-nine articles,including cell,animal,and clinical studies,were included.These studies reported the effects of EC injury on the microcirculation in sepsis,including changes in vascular permeability,coagulation dysfunction,vasomotor regulation,and infl ammatory responses.These pathways interact and ultimately lead to septic microcirculation disorders.CONCLUSION:Sepsis-induced endothelial dysfunction involves various interconnected mechanisms,which collectively compromise ECs and impede microcirculatory perfusion.Future research should enhance current understanding of endothelial injury mechanisms,develop synergistic multi-target strategies to disrupt this cycle,and facilitate the clinical application of endothelial markers for early intervention and dynamic assessment.展开更多
Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apop...Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.展开更多
Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significa...Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resu...Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.展开更多
AIM:To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.METHODS:Twenty male patients undergoing subtotal gastrectomy were enrolled in this study.Young and elderly patie...AIM:To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.METHODS:Twenty male patients undergoing subtotal gastrectomy were enrolled in this study.Young and elderly patient groups aged 25-40 years and 60-85 years,respectively,were included.Inclusion criteria were:no clinical evidence of cardiovascular,renal or diabetic diseases.Conventional clinical examinations were carried out.After surgery,gastric submucosal arteries were immediately dissected free of fat and connective tissue.Vascular responses to acetylcholine(ACh)and sodium nitroprusside(SNP)were measured by isolated vascular perfusion.Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin(HE)staining and Verhoeff van Gieson(EVG)staining.The expression of xanthine oxidase(XO)and manganese-superoxide dismutase(Mn-SOD)was assessed by Western blotting analysis.The malondialdehyde(MDA)and hydrogen peroxide(H2O2)content and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were determined according to commercial kits.RESULTS:The overall structure of vessel walls was shown by HE and EVG staining,respectively.Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients;however,cell layer number in the vessel wall increased significantly in the elderly group.Compared with submucosal arteries in young patients,the amount of vascular collagen fibers,lumen diameter and media cross-sectional area were significantly increased in elderly patients.Ach-and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients.Compared with the young group,the expression of XO and the contents of MDA and H2O2in gastric submucosal arterioles were increased in the elderly group.In addition,the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group.CONCLUSION:Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process.展开更多
Aim： To test the hypothesis that sildenafil （50 mg nightly for one year） can improve spontaneous erectile function （EF） in men with mild-to-moderate arteriogenic erectile dysfunction （ED） responsive to erectoge...Aim： To test the hypothesis that sildenafil （50 mg nightly for one year） can improve spontaneous erectile function （EF） in men with mild-to-moderate arteriogenic erectile dysfunction （ED） responsive to erectogenic treatment. Methods： In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function （IIEF EF） and the peak systolic velocity （PSV） of penile cavernous arteries were used to measure the efficacy. Results： After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 （60.4%, 95% confidence interval [CI]： 45.3-74.2%） of the nightly group vs. 4 of 49 （8.2%, 95% CI： 2.3-19.6%） of the as-needed group. PSV improved by 11.2 cm/s （95% CI： 4.7-21.4; P = 0.012） in the nightly group but only by 3.4 cm/s （-5.1- 14.7; P = 0.435） in the as-needed group. IIEF EF normalized in 1 of 18 （5.6%, 95% CI： 0.1-27.3%） non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most （28/29, 97%） nightly group men who had initially normalized. Conclusion： Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.展开更多
Penile hypersensitivity plays an important role in premature ejaculation （PE）, but differences in penile sensitivity among subtypes of PE are unknown. Therefore, we compared penile sensory thresholds in PE subtypes ...Penile hypersensitivity plays an important role in premature ejaculation （PE）, but differences in penile sensitivity among subtypes of PE are unknown. Therefore, we compared penile sensory thresholds in PE subtypes of lifelong and acquired PE, PE with and without erectile dysfunction （ED）, PE with an intravaginal ejaculation latency time 〈1 min and 〉1 min, and PE with and without orgasmic pleasure perceptual dysfunction. During August 2014 to January 2016, 136 patients with PE were included. Penile warm, cold, and vibratory thresholds were measured. Data of clinical characteristics, sexual life, Premature Ejaculation Diagnostic Tool （PEDT） score, and the 5-item version of the International Index of Erectile Function （IIEF-5） score were collected. Vibratory thresholds of the PE with ED group were higher in the right coronal sulcus （median amplitude： 4.92 vs 3.65 μm, P= 0.02） and the right penile shaft （median amplitude： 3.87 vs 3.30 μm, P = 0.03）, while differences in penile sensory thresholds between other subtypes were not significant. The median PEDT score was lower in the PE without ED group （12 vs 14, P 〈 0.001）. The IIEF-5 and PEDT scores were negatively correlated （r = -0.29, P 〈 0.001）. Patients with orgasmic pleasure perceptual dysfunction had a lower median IIEF-5 score （20 vs 21, P = 0.02）. Patients with PE and ED had lower penile sensitivity, and ED was associated with more severe symptoms and weaker orgasmic pleasure perception. In men with PE, management of comorbid ED is necessary. In case of side effects in erectile function, topical anesthetics should be cautiously used in men with PE and ED.展开更多
Sildenafil and tadalafil are efficacious and well tolerated in Chinese men with erectile dysfunction （ED）. Recent study results indicate that men with ED in China who were naive to phosphodiesterase inhibitor type 5...Sildenafil and tadalafil are efficacious and well tolerated in Chinese men with erectile dysfunction （ED）. Recent study results indicate that men with ED in China who were naive to phosphodiesterase inhibitor type 5 （PDE5） therapy prefer tadalafil 20-mg （on-demand） versus sildenafil 100-mg （on-demand）. Differences in psychosocial outcomes may help to explain treatment preference in favor of tadalafih This open-label, randomized, crossover study compared psychosocial outcomes and drug attribute choices between tadalafil and sildenafil in Chinese men with ED na＇（ve to PDE5 inhibitor therapy. Eligible patients were randomized to sequential 20-mg tadalafU/lOO-mg sildenafil （n = 190） or 100-mg sildenafil/20-mg tadalafil （n = 193） for 8 weeks each and were asked which treatment they preferred to take for the 8-week extension phase. Psychosocial outcomes were assessed using the Psychological and Interpersonal Relationship Scale （PAIRS）, Drug Attributes Questionnaire （DRAQ）, and Sexual Life Quality Questionnaire （SLQQ）. When taking tadalafil versus sildenafil, men had a higher mean endpoint score on the PAIRS Spontaneity Domain （tadalafil = 2.86 vs sildenafil = 2.72; P 〈 0.001）, and a lower mean endpoint score on the Time Concerns Domain （tadalafil = 2.41 vs sildenafil = 2.55; P 〈 0.001）. A numerical increase in the Sexual Self-Confidence Domain was observed when taking tadalafil versus sildenafil （tadalafil -- 2.76 vs sildenafil = 2.72; P= 0.102）. The most frequently chosen drug attributes explaining treatment preference were able to get an erection long after having drug, and ability to get an erection every time. SLQQ results were comparable between treatment groups. These psychosocial outcomes may explain why more Chinese men preferred tadalafil versus sildenafil for the treatment of ED in this clinical trial.展开更多
The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate （sildenafil） and tadalafil for treating erectile dysfunction （ED） in Chinese men na＇ive to phosphodiesterase 5 （PDE...The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate （sildenafil） and tadalafil for treating erectile dysfunction （ED） in Chinese men na＇ive to phosphodiesterase 5 （PDE5） inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire （PITPQ）. Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function （IIEF） erectile function （EF） domain, sexual encounter profile （SEP） Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men （91%） completed the randomized treatment phase. Two hundred and forty-two per 350 （69.1%） patients preferred 20-mg tadalafil, and 108/350 （30.9%） preferred lO0-mg sildenafil （P 〈 0.001） as their treatment in the 8 weeks extension. Ninety-two per 242 （38%） patients strongly preferred tadalafil and 37/108 （34.3%） strongly the preferred sildenafil. The SEP2 （penetration）, SEP3 （successful intercourse）, and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by 〉 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED na＇ive to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.展开更多
文摘Recent studies have revealed a significant relationship between erectile dysfunction(ED)and lower urinary tract symptoms(LUTS),both of which commonly affect middle-aged and older men.These conditions share underlying causes,particularly endothelial dysfunction,atherosclerosis,and chronic pelvic ischemia(CPI).This study investigated the therapeutic potential of LDD175,a large-conductance Ca2+-activated K+channel(BKCa channel)opener,in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats.Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet.We assessed erectile and voiding functions by measuring intracavernosal pressure(ICP)and intraurethral pressure(IUP),respectively,after nerve stimulation.We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms.This study evaluated the effectiveness of LDD175 compared to standard treatments,such as sildenafil for ED and tamsulosin for LUTS.Therefore,the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP.Analysis revealed elevated levels of hypoxia-inducible factor-1α,transforming growth factor-β1 andβ2 in cavernous tissue,and increasedα1A-adrenoceptor expression in prostate tissue.LDD175 administration showed promising results,with dose-dependent improvements in ICP and IUP,and therapeutic effects comparable to those of established treatments.Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS,opening new possibilities for clinical application in the treatment of these interconnected conditions.
文摘BACKGROUND To investigate whether seasonal differences in ambient temperature affect the incidence of early postoperative cognitive dysfunction(POCD)among elderly patients undergoing laparoscopic surgery in tropical regions.Additionally,it explored the perioperative risk factors associated with early POCD following abdominal laparoscopic surgery.AIM To investigate the influence of seasonal differences in ambient temperature on POCD of elderly patients METHODS A total of 125 patients aged≥65 years from Hainan Province,China,who underwent laparoscopic surgery under general anesthesia with tracheal intubation,were enrolled. All patients completed the Mini-Mental State Examination one day before surgery and onpostoperative days 1, 3, and 7. A decline of ≥ 2 points from baseline was considered indicative of cognitivedysfunction. Serum levels of S100 calcium binding protein B and neuron-specific enolase were measured usingenzyme-linked immunosorbent assay at three time points: Preoperatively, immediately after extubation, and 24hours postoperatively. Perioperative clinical data were collected to identify potential risk factors for POCD.Propensity score matching (PSM) was performed (1:1, caliper = 0.03), resulting in 41 matched patient pairs betweenwinter and summer groups.RESULTSAfter PSM, baseline characteristics including age, gender, body mass index, education level, comorbidities, andsurgical variables were well balanced between groups. There were no significant differences in the incidence ofPOCD on postoperative days 1, 3, and 7 between patients undergoing laparoscopic surgery in winter vs summer.However, multivariable logistic regression revealed that surgical duration (day 1, P value = 0.049), advanced ageand elevated creatinine (day 3, P value = 0.044, P value = 0.008), and hypoalbuminemia (day 3, P value = 0.042;day7, P value = 0.015) were independently associated with early POCD.CONCLUSIONAmbient temperature differences between winter and summer in tropical regions did not significantly affect theincidence of early POCD in elderly patients undergoing laparoscopic surgery. Nonetheless, age, longer surgicalduration, elevated creatinine, and hypoalbuminemia emerged as key risk factors. These findings underscore theimportance of perioperative optimization to reduce the risk of POCD in elderly patients, regardless of seasonaltemperature variations.
文摘Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.
基金supported by Swiss Center for Applied Human Toxicology(SCAHT AP22-01)(to RN).
文摘Alzheimer’s disease(AD)is the most common cause of dementia,characterized by progressive cognitive decline,and affects over 55 million people worldwide.AD is pathological featured by the aberrant accumulation of amyloid-βplaques,neurofibrillary tangles formed by hyperphosphorylated tau,synaptic loss,and dysfunction of neurotransmitter systems.Evidence from in vivo and autopsy studies has consistently shown that synaptic dysfunction and loss are strongly correlated with cognitive decline in AD,particularly in brain regions such as the hippocampus and cortex,which are critical for memory formation and processing.This perspective highlights recent histopathological findings related to synaptic dysfunction in AD,advancements in the development of imaging and fluid-based biomarkers for synaptic loss,and future studies.
基金supported by China Scholarship Council(No.202106380078 to HL)the Netherlands Cardiovascular Research Initiative:The Dutch Heart Foundation(CVON 2018-28 and 2012-06 Heart Brain Connection to AMT)。
文摘Cerebral small vessel disease(SVD)represents a range of pathological changes in the small blood vessels of the brain.SVD can be detected on MRI,which includes white matter hyperintensities,lacunes,and cerebral microbleeds(Duering et al.,2023).Patients with SVD exhibit significant clinical heterogeneity,often presenting with cognitive impairment,apathy,gait dysfunction,and lacunar stroke(Wardlaw et al.,2019).
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82430018 to Q.C.,82270361 and 82570402 to H.Z.)the Nanjing Medical University Undergraduate Innovation and Entrepreneurship Training Program Fund(Grant No.202410312138Y to C.Z.)the Basic Sciences of Jiangsu Higher Education Institutions(Grant No.22KJA310002 to H.Z.)。
文摘As the prevalence of obesity increases dramatically,obesity-associated cardiac dysfunction constitutes a considerable challenge to human health.This study aimed to identify more useful lipid/inflammatory markers to predict the risk of obesity-associated cardiac dysfunction.By retrospectively analyzing the clinical characteristics of 5648 cardiac disease patients,we found that both the plasma level of high-density lipoprotein cholesterol(HDLC)and the blood monocyte count were significantly associated with impairment of the left ventricular ejection fraction(LVEF).Univariate and multivariate regression analyses revealed that the monocyte to HDL-C ratio(MHR)was a more powerful predictor of the risk of LVEF decline than either HDL-C or monocyte alone.Mediation analysis further revealed a mediating effect of a high MHR on the decline in obesity-associated cardiac systolic function.Collectively,our results demonstrate a superior role of MHR in predicting the risk of an obesityassociated decline in cardiac systolic function among routine metabolic/inflammatory markers.
文摘BACKGROUND:Sepsis is a prevalent and severe condition,with microcirculation disruptions playing a crucial role in its progression.Endothelial cell(EC)injury is the primary factor behind microcirculatory issues.This review is to outline the pathomechanism,organ heterogeneity,biomarkers,and therapeutic implications of endothelial dysfunction in sepsis,off ering references and insights for the clinical management of sepsis.METHODS:A systematic search of Web of Science and PubMed from inception to June 10,2025,limited to English publications,was conducted.Two reviewers independently identifi ed studies on EC injury in patients with septic microcirculatory dysfunction.Duplicate articles based on multiple search criteria were excluded.RESULTS:Fifty-nine articles,including cell,animal,and clinical studies,were included.These studies reported the effects of EC injury on the microcirculation in sepsis,including changes in vascular permeability,coagulation dysfunction,vasomotor regulation,and infl ammatory responses.These pathways interact and ultimately lead to septic microcirculation disorders.CONCLUSION:Sepsis-induced endothelial dysfunction involves various interconnected mechanisms,which collectively compromise ECs and impede microcirculatory perfusion.Future research should enhance current understanding of endothelial injury mechanisms,develop synergistic multi-target strategies to disrupt this cycle,and facilitate the clinical application of endothelial markers for early intervention and dynamic assessment.
基金supported by the National Natural Science Foundation of China,No.82204663(to TZ)the Natural Science Foundation of Shandong Province,No.ZR2022QH058(to TZ).
文摘Modulations of mitochondrial dysfunction,which involve a series of dynamic processes such as mitochondrial biogenesis,mitochondrial fusion and fission,mitochondrial transport,mitochondrial autophagy,mitochondrial apoptosis,and oxidative stress,play an important role in the onset and progression of stroke.With a better understanding of the critical role of mitochondrial dysfunction modulations in post-stroke neurological injury,these modulations have emerged as a potential target for stroke prevention and treatment.Additionally,since effective treatments for stroke are extremely limited and natural products currently offer some outstanding advantages,we focused on the findings and mechanisms of action related to the use of natural products for targeting mitochondrial dysfunction in the treatment of stroke.Natural products achieve neuroprotective through multi-target regulation of mitochondrial dysfunction encompassing the following processes:(1)Mitochondrial biogenesis:Cordyceps and hydroxysafflor yellow A activate the peroxisome proliferator-activated receptor gamma coactivator 1-alpha/nuclear respiratory factor pathway,promote mitochondrial DNA replication and respiratory chain protein synthesis,and thereby restore energy supply in the ischemic penumbra.(2)Mitochondrial dynamics balance:Ginsenoside Rb3 promotes Opa1-mediated neural stem cell migration and diffusion for recovery of damaged brain tissue.(3)Mitochondrial autophagy:Gypenoside XVII selectively eliminates damaged mitochondria via the phosphatase and tensin homolog-induced kinase 1/Parkin pathway and blocks reactive oxygen species and the NOD-like receptor protein 3 inflammasome cascade,thereby alleviating blood-brain barrier damage.(4)Anti-apoptotic mechanisms:Ginkgolide K inhibits Bax mitochondrial translocation and downregulates caspase-3/9 activity,reducing neuronal programmed death induced by ischemia-reperfusion.(5)Oxidative stress regulation:Scutellarin exerts antioxidant properties and improves neurological function by modulating the extracellular signal-regulated kinase 5-Kruppel-like factor 2-endothelial nitric oxide synthase signaling pathway.(6)Intercellular mitochondrial transport:Neuroprotective effects of Chrysophanol are associated with accelerated mitochondrial transfer from astrocytes to neurons.Existing studies have confirmed that natural products exhibit neuroprotective effects through multidimensional interventions targeting mitochondrial dysfunction in both ischemic and hemorrhagic stroke models.However,their clinical translation still faces challenges,such as the difficulty in standardization due to component complexity,insufficient cross-regional clinical data,and the lack of long-term safety evaluations.Future research should aim to integrate new technologies,such as single-cell sequencing and organoid models,to deeply explore the mitochondria-targeting mechanisms of natural products and validate their efficacy through multicenter clinical trials,providing theoretical support and translational pathways for the development of novel anti-stroke drugs.
文摘Dengue fever is an acute infectious disease caused by the dengue virus and transmitted by mosquito vectors[1].Its clinical manifestations include high fever,headache,muscle and joint pain,and rash.It holds a significant position in global public health.In recent years,its incidence has continued to rise worldwide[2],making it one of the major diseases threatening human health.The disease course of dengue fever is divided into three typical phases:the acute febrile phase,the critical phase,and the recovery phase.While most patients experience mild symptoms,some may progress to severe dengue and potentially fatal outcomes if not promptly and effectively treated during the critical phase.
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
文摘Metabolic dysfunction-associated steatotic liver disease(MASLD),formerly known as nonalcoholic fatty liver disease,is a chronic liver disease characterized by hepatic lipid deposition and hepatocellular steatosis,resulting from nonalcoholic causes and closely linked to metabolic dysfunction[1].It is strongly associated with metabolic abnormalities,including type 2 diabetes,overweight,and obesity.The global prevalence of MASLD is estimated to be approximately 25%−33%,and its incidence is rising rapidly,particularly among younger populations,due to increasingly prevalent unhealthy lifestyle behaviors such as sleep deprivation,sedentary habits,and diets rich in calories.
基金Supported by The Natural Science Foundation of Jiangsu Province,China,No.BK2009088the Natural Science Fund for Colleges and Universities in Jiangsu Province,No.10KJB310015
文摘AIM:To evaluate human gastric submucosal vascular dysfunction and its mechanism during the aging process.METHODS:Twenty male patients undergoing subtotal gastrectomy were enrolled in this study.Young and elderly patient groups aged 25-40 years and 60-85 years,respectively,were included.Inclusion criteria were:no clinical evidence of cardiovascular,renal or diabetic diseases.Conventional clinical examinations were carried out.After surgery,gastric submucosal arteries were immediately dissected free of fat and connective tissue.Vascular responses to acetylcholine(ACh)and sodium nitroprusside(SNP)were measured by isolated vascular perfusion.Morphological changes in the gastric mucosal vessels were observed by hematoxylin and eosin(HE)staining and Verhoeff van Gieson(EVG)staining.The expression of xanthine oxidase(XO)and manganese-superoxide dismutase(Mn-SOD)was assessed by Western blotting analysis.The malondialdehyde(MDA)and hydrogen peroxide(H2O2)content and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were determined according to commercial kits.RESULTS:The overall structure of vessel walls was shown by HE and EVG staining,respectively.Disruption of the internal elastic lamina or neointimal layers was not observed in vessels from young or elderly patients;however,cell layer number in the vessel wall increased significantly in the elderly group.Compared with submucosal arteries in young patients,the amount of vascular collagen fibers,lumen diameter and media cross-sectional area were significantly increased in elderly patients.Ach-and SNP-induced vasodilatation in elderly arterioles was significantly decreased compared with that of gastric submucosal arterioles from young patients.Compared with the young group,the expression of XO and the contents of MDA and H2O2in gastric submucosal arterioles were increased in the elderly group.In addition,the expression of Mn-SOD and the activities of SOD and GSH-Px in the elderly group decreased significantly compared with those in the young group.CONCLUSION:Gastric vascular dysfunction and senescence may be associated with increased oxidative stress and decreased antioxidative defense in the aging process.
文摘Aim： To test the hypothesis that sildenafil （50 mg nightly for one year） can improve spontaneous erectile function （EF） in men with mild-to-moderate arteriogenic erectile dysfunction （ED） responsive to erectogenic treatment. Methods： In a prospective open-label trial, 112 men with ED were randomized to sildenafil 50 mg nightly or sildenafil 50 or 100 mg as needed for 12 months, followed by one-month and 6-month non-medicated periods. Non-randomized, non-medicated men with ED were also assessed. The EF domain of the International Index of Erectile Function （IIEF EF） and the peak systolic velocity （PSV） of penile cavernous arteries were used to measure the efficacy. Results： After sildenafil treatment and a subsequent non-medicated month, IIEF EF was normal in 29 of 48 （60.4%, 95% confidence interval [CI]： 45.3-74.2%） of the nightly group vs. 4 of 49 （8.2%, 95% CI： 2.3-19.6%） of the as-needed group. PSV improved by 11.2 cm/s （95% CI： 4.7-21.4; P = 0.012） in the nightly group but only by 3.4 cm/s （-5.1- 14.7; P = 0.435） in the as-needed group. IIEF EF normalized in 1 of 18 （5.6%, 95% CI： 0.1-27.3%） non-medicated men and the PSV declined slightly. Six months after treatment, the IIEF EF remained normal and PSV was stabilized in most （28/29, 97%） nightly group men who had initially normalized. Conclusion： Sildenafil nightly for one year resulted in ED regression that persisted well beyond the end of treatment, so that spontaneous EF was characterized as normal on the IIEF in most men. The results from this open-label, randomized trial warrant verification under double-blind, placebo-controlled conditions.
文摘Penile hypersensitivity plays an important role in premature ejaculation （PE）, but differences in penile sensitivity among subtypes of PE are unknown. Therefore, we compared penile sensory thresholds in PE subtypes of lifelong and acquired PE, PE with and without erectile dysfunction （ED）, PE with an intravaginal ejaculation latency time 〈1 min and 〉1 min, and PE with and without orgasmic pleasure perceptual dysfunction. During August 2014 to January 2016, 136 patients with PE were included. Penile warm, cold, and vibratory thresholds were measured. Data of clinical characteristics, sexual life, Premature Ejaculation Diagnostic Tool （PEDT） score, and the 5-item version of the International Index of Erectile Function （IIEF-5） score were collected. Vibratory thresholds of the PE with ED group were higher in the right coronal sulcus （median amplitude： 4.92 vs 3.65 μm, P= 0.02） and the right penile shaft （median amplitude： 3.87 vs 3.30 μm, P = 0.03）, while differences in penile sensory thresholds between other subtypes were not significant. The median PEDT score was lower in the PE without ED group （12 vs 14, P 〈 0.001）. The IIEF-5 and PEDT scores were negatively correlated （r = -0.29, P 〈 0.001）. Patients with orgasmic pleasure perceptual dysfunction had a lower median IIEF-5 score （20 vs 21, P = 0.02）. Patients with PE and ED had lower penile sensitivity, and ED was associated with more severe symptoms and weaker orgasmic pleasure perception. In men with PE, management of comorbid ED is necessary. In case of side effects in erectile function, topical anesthetics should be cautiously used in men with PE and ED.
文摘Sildenafil and tadalafil are efficacious and well tolerated in Chinese men with erectile dysfunction （ED）. Recent study results indicate that men with ED in China who were naive to phosphodiesterase inhibitor type 5 （PDE5） therapy prefer tadalafil 20-mg （on-demand） versus sildenafil 100-mg （on-demand）. Differences in psychosocial outcomes may help to explain treatment preference in favor of tadalafih This open-label, randomized, crossover study compared psychosocial outcomes and drug attribute choices between tadalafil and sildenafil in Chinese men with ED na＇（ve to PDE5 inhibitor therapy. Eligible patients were randomized to sequential 20-mg tadalafU/lOO-mg sildenafil （n = 190） or 100-mg sildenafil/20-mg tadalafil （n = 193） for 8 weeks each and were asked which treatment they preferred to take for the 8-week extension phase. Psychosocial outcomes were assessed using the Psychological and Interpersonal Relationship Scale （PAIRS）, Drug Attributes Questionnaire （DRAQ）, and Sexual Life Quality Questionnaire （SLQQ）. When taking tadalafil versus sildenafil, men had a higher mean endpoint score on the PAIRS Spontaneity Domain （tadalafil = 2.86 vs sildenafil = 2.72; P 〈 0.001）, and a lower mean endpoint score on the Time Concerns Domain （tadalafil = 2.41 vs sildenafil = 2.55; P 〈 0.001）. A numerical increase in the Sexual Self-Confidence Domain was observed when taking tadalafil versus sildenafil （tadalafil -- 2.76 vs sildenafil = 2.72; P= 0.102）. The most frequently chosen drug attributes explaining treatment preference were able to get an erection long after having drug, and ability to get an erection every time. SLQQ results were comparable between treatment groups. These psychosocial outcomes may explain why more Chinese men preferred tadalafil versus sildenafil for the treatment of ED in this clinical trial.
文摘The study was to compare treatment preference, efficacy, and tolerability of sildenafil citrate （sildenafil） and tadalafil for treating erectile dysfunction （ED） in Chinese men na＇ive to phosphodiesterase 5 （PDE5） inhibitor therapies. This multicenter, randomized, open-label, crossover study evaluated whether Chinese men with ED preferred 20-mg tadalafil or 100-mg sildenafil. After a 4 weeks baseline assessment, 383 eligible patients were randomized to sequential 20-mg tadalafil per 100-mg sildenafil or vice versa for 8 weeks respectively and then chose which treatment they preferred to take during the 8 weeks extension. Primary efficacy was measured by Question 1 of the PDE5 Inhibitor Treatment Preference Questionnaire （PITPQ）. Secondary efficacy was analyzed by PITPQ Question 2, the International Index of Erectile Function （IIEF） erectile function （EF） domain, sexual encounter profile （SEP） Questions 2 and 3, and the Drug Attributes Questionnaire. Three hundred and fifty men （91%） completed the randomized treatment phase. Two hundred and forty-two per 350 （69.1%） patients preferred 20-mg tadalafil, and 108/350 （30.9%） preferred lO0-mg sildenafil （P 〈 0.001） as their treatment in the 8 weeks extension. Ninety-two per 242 （38%） patients strongly preferred tadalafil and 37/108 （34.3%） strongly the preferred sildenafil. The SEP2 （penetration）, SEP3 （successful intercourse）, and IIEF-EF domain scores were improved in both tadalafil and sildenafil treatment groups. For patients who preferred tadalafil, getting an erection long after taking the medication was the most reported reason for tadalafil preference. The only treatment-emergent adverse event reported by 〉 2% of men was headache. After tadalafil and sildenafil treatments, more Chinese men with ED na＇ive to PDE5 inhibitor preferred tadalafil. Both sildenafil and tadalafil treatments were effective and safe.
