Britannin inhibits cell proliferation, migration and glycolysis by downregulating KLF5 in lung cancer.

Lung cancer is a harmful type of malignancy and the leading cause of cancer-associated mortality. It is therefore imperative to develop novel drugs effective for treating this cancer. The Traditional Chinese Medicine compound Britannin has been previously reported to inhibit the development of certain cancers, such as pancreatic, breast and liver cancer. Moreover, Kruppel-like factor 5 (KLF5) has been identified an on oncogene in lung cancer. In the present study, the possible regulatory effects and underlying mechanism of Britannin in lung cancer were investigated. A549 and 16HBE cells were treated with different concentrations of Britannin. Subsequently, Cell counting kit-8, EdU staining and colony formation assays were used to detect the proliferative ability of these cells. Cell migration was detected by wound healing and Transwell assays, respectively. XF96 extracellular flux analyzer was used to analyze the extent of extracellular acidification and oxygen consumption rate in cells, whereas assay kits were used to detect glucose and lactic acid levels in the cell supernatant. The targeting effect between Britannin and the KLF5 protein was investigated using molecular docking technology. The protein expression levels of KLF5 in cells challenged with Britannin was detected by western blotting. Finally, overexpression of KLF5 in A549 cells was performed before cell proliferation, migration and the glycolysis rate were measured to explore the regulatory effects of Britannin. Britannin was found to inhibit the proliferation, migration and glycolysis of lung cancer cells, during which the protein expression levels of KLF5 were decreased. This suggests that Britannin regulated the expression of KLF5 in A549 cells. Overexpression of KLF5 reversed the inhibitory effects of Britannin on the proliferation, migration and glycolysis in lung cancer cells. In conclusion, these results suggest that Britannin can inhibit cell proliferation, migration and glycolysis by downregulating KLF5 expression in lung cancer cells.

Vitamin D3 improved erectile function recovery by regulating autophagy and apoptosis in a rat model of cavernous nerve injury.

Vitamin D3 is an important element in improving erectile function. However, the mechanisms of vitamin D3 remain unknown. Thus, we explored the effect of vitamin D3 on erectile function recovery after nerve injury in a rat model and investigated its possible molecular mechanisms. Eighteen male Sprague-Dawley rats were used in this study. The rats were randomly divided into three groups: the control, bilateral cavernous nerve crush (BCNC), and BCNC + vitamin D3 groups. BCNC model was established in rats by surgery. The intracavernosal pressure and the ratio of intracavernosal pressure to mean arterial pressure were utilized to evaluate erectile function. Masson trichrome staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and western blot analysis were performed on penile tissues to elucidate the molecular mechanism. The results indicated that vitamin D3 alleviated hypoxia and suppressed the fibrosis signalling pathway by upregulating the expression of eNOS (p = 0.001), nNOS (p = 0.018) and α-SMA (p = 0.025) and downregulating the expression of HIF-1α (p = 0.048) and TGF-ß1 (p = 0.034) in BCNC rats. Vitamin D3 promoted erectile function restoration by enhancing the autophagy process through decreases in the p-mTOR/mTOR ratio (p = 0.02) and p62 (p = 0.001) expression and increases in Beclin1 expression (p = 0.001) and the LC3B/LC3A ratio (p = 0.041). Vitamin D3 application improved erectile function rehabilitation by suppressing the apoptotic process through decreases in the expression of Bax (p = 0.002) and caspase-3 (p = 0.046) and an increase in the expression of Bcl2 (p = 0.004). Therefore, We concluded that vitamin D3 improved the erectile function recovery in BCNC rats by alleviating hypoxia and fibrosis, enhancing autophagy and inhibiting apoptosis in the corpus cavernosum.

An Anomalous Electron Configuration Among 3d Transition Metal Atoms.

Physical properties of materials are mainly determined by valence electron configurations, where different valence shells would induce divergent phenomena. In compounds containing Sc2+ , 3d electron occupancy is expected, the same as other transition metal atoms like Ti3+ . But this situation still awaits experimental verification in inorganic materials. Here, we selected ScS to measure the valence electron density and orbital population of Sc2+ through delicate quantitative convergent-beam electron diffraction. With the absence of 3d orbital features around Sc-atom sites and the nearly bare population of t2g orbital, the unintuitive occupation of 4s orbital in Sc2+ is concluded. It should be the first time to report such a special electron configuration in a transition metal compound, in which 4s rather than 3d orbital is preferred. Our findings reveal the distinct behavior of Sc and probable ways to modulate material properties by controlling electron orbitals.

Risk of cardiovascular disease among cancer survivors: Protocol of a pooled analysis of population-based cohort studies.

Introduction: Cancer and cardiovascular disease remain leading causes of death and disability worldwide, which places a heavy burden on public health systems and causes widespread suffering. Because these entities have highly overlapping risk factors, including hyperlipidemia, hypertension, diabetes, obesity, smoking and other lifestyle factors, many studies have reported that they have similar etiological mechanisms. Accumulating evidence indicates that there is an increased risk of cardiovascular disease among cancer survivors compared with the general population. However, whether cancer is associated with an increased risk of cardiovascular disease remains controversial. Methods and analysis: We will conduct and report the meta-analysis strictly based on the Cochrane Handbook for Systematic Reviews and the Meta-analysis of Observational Studies in Epidemiology guidelines combined with the Preferred Reporting Items for Systematic Reviews and Meta-analysis for Protocols (PRISM-P). This meta-analysis was registered with PROSPERO (registration number CRD42022307056). We will search for studies published from database inception to December 1, 2021, regardless of language or date, in three electronic databases (PubMed, EMBASE, and Cochrane Library) to identify and appraise cohort studies examining the relationship between cancer and subsequent cardiovascular disease risk. The literature screening, inclusion and data extraction will be conducted independently by two investigators using pre-designed standardized data extraction forms. A senior investigator will be consulted in cases of disagreement. We will assess risk of bias in the included cohort studies using the Newcastle-Ottawa Scale (NOS). Quantitative synthesis will be conducted using a random-effects model. To explore potential sources of heterogeneity, we will carry out multiple sensitivity analysis, meta-regression and subgroup analysis according to baseline characteristics. Publication bias will be evaluated through visual inspection of funnel plot asymmetry as well as by Begg's rank correlation test and Egger's weighted linear regression test.

Spatio-temporal evolution and trend prediction of the incidence of Class B notifiable infectious diseases in China: a sample of statistical data from 2007 to 2020.

BACKGROUND: With the accelerated global integration and the impact of climatic, ecological and social environmental changes, China will continue to face the challenge of the outbreak and spread of emerging infectious diseases and traditional ones. This study aims to explore the spatial and temporal evolutionary characteristics of the incidence of Class B notifiable infectious diseases in China from 2007 to 2020, and to forecast the trend of it as well. Hopefully, it will provide a reference for the formulation of infectious disease prevention and control strategies. METHODS: Data on the incidence rates of Class B notifiable infectious diseases in 31 provinces, municipalities and autonomous regions of China from 2007 to 2020 were collected for the prediction of the spatio-temporal evolution and spatial correlation as well as the incidence of Class B notifiable infectious diseases in China based on global spatial autocorrelation and Autoregressive Integrated Moving Average (ARIMA). RESULTS: From 2007 to 2020, the national incidence rate of Class B notifiable infectious diseases (from 272.37 per 100,000 in 2007 to 190.35 per 100,000 in 2020) decreases year by year, and the spatial distribution shows an "east-central-west" stepwise increase. From 2007 to 2020, the spatial clustering of the incidence of Class B notifiable infectious diseases is significant and increasing year by year (Moran's I index values range from 0.189 to 0.332, p < 0.05). The forecasted incidence rates of Class B notifiable infectious diseases nationwide from 2021 to 2024 (205.26/100,000, 199.95/100,000, 194.74/100,000 and 189.62/100,000) as well as the forecasted values for most regions show a downward trend, with only some regions (Guangdong, Hunan, Hainan, Tibet, Guangxi and Guizhou) showing an increasing trend year by year. CONCLUSIONS: The current study found that since there were significant regional disparities in the prevention and control of infectious diseases in China between 2007 and 2020, the reduction of the incidence of Class B notifiable infectious diseases requires the joint efforts of the surrounding provinces. Besides, special attention should be paid to provinces with an increasing trend in the incidence of Class B notifiable infectious diseases to prevent the re-emergence of certain traditional infectious diseases in a particular province or even the whole country, as well as the outbreak and spread of emerging infectious diseases.

Prolonged isoflurane anesthesia-induced acidosis decreases penile intracavernous pressure in rats.

BACKGROUND: Intracavernous pressure measurement following cavernous nerve electrostimulation has been extensively adopted for the evaluation of erectile function in animals. However, the effect of measurement time and acidosis during anesthesia is still lacking. OBJECTIVE: To explore the effect of measurement time and acidosis during anesthesia. MATERIALS AND METHODS: Fifty-six male Sprague-Dawley rats were used and anesthetized by a spontaneous inhalation of isoflurane. In the first step, rats were randomly divided into four groups: a control group and three time-delayed measurement groups (intracavernous pressure measurement beginning at 15, 30, and 45 min after cavernous nerve exposure). In the second step, rats were randomly divided into three groups: a control group and two time-delayed measurement groups. Two intravenous fluid support strategies were used in time-delayed measurement groups: a normal saline solution and an isotonic Na2 CO3 solution. RESULTS: Isoflurane-anesthetized rats developed systemic acidosis that worsens with time during intracavernous pressure measurement, which results in a significant decrease in the maximum intracavernous pressure value, intracavernous pressure/mean arterial pressure ratio, and total intracavernous pressure measured. The Na2 CO3 infusion could effectively correct acidosis. The decrease in intracavernous pressure was related to the reduced nitric oxide synthase activity, decreased cyclic guanosine monophosphate concentration, and reactive oxygen species activation in rat penis under acidosis conditions. DISCUSSION AND CONCLUSION: Prolonged isoflurane anesthesia-induced acidosis markedly depresses the erectile response to cavernous nerve electrostimulation in rats. In this situation, it is recommended to supplement with a Na2 CO3 infusion to maintain a normal acid-base balance.

The Effect of MaxiK Channel on Regulating the Activation of NLRP3 Inflammasome in Rats of Blast-induced Traumatic Brain Injury.

Abundant findings including our previous work proved that the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome exerts a key role in the process of neuroinflammation following blast-induced traumatic brain injury (bTBI). The opening of potassium channels leads to low K+ environment in cells, which appears to be an essential requirement for NLRP3 inflammasome activation. Notably, MaxiK (BK) channel is significant for K+ transport. The present study is aim to investigate the potential role of MaxiK in the activation of NLRP3 and to evaluate whether MaxiK channel blocker paxilline could confer beneficial effects on attenuating the severity of bTBI in rats. Rats were randomly assigned into five groups (n = 8). MaxiK channel expression was measured in bTBI rats. The effect of paxilline on the expression of NLRP3 inflammasome, the level of inflammatory cytokines, brain injury biomarkers in serum and brain edema were also evaluated in bTBI rats. The results showed that the expression of MaxiK was elevated significantly in the cerebral cortex of bTBI rats. The treatment of MaxiK channel blocker paxilline suppressed the NLRP3 inflammasome expression substantially. In addition, paxilline could also decrease the level of pro-inflammatory cytokines and the biomarkers of brain injury and alleviate brain edema of bTBI rats. Our findings have revealed that MaxiK channel might be involved in the process of neuroinflammation of bTBI. Paxilline could depress neuro-inflammation response and alleviate brain injury by blocking MaxiK channel and subsequently inhibition of NLRP3 inflammasome activation.

Long non-coding RNA MIAT is involved in the regulation of pyroptosis in diabetic cardiomyopathy via targeting miR-214-3p.

Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes without effective treatment options. Its pathogenesis is complex and remains unclear. Long non-coding RNA (lncRNA) MIAT allele has been reported to be enriched in DCM patients and activate a pyroptosis program in hypoxia-induced H9c2 cells. Thus, whether MIAT played a role in DCM pyroptosis remains to be clarified. In the study, the expression of MIAT was found elevated in the serum of diabetic patients, as well as in high-glucose induced cardiomyocytes and diabetic mice. Further, the expression levels of CASP1 and pyroptosis correlation factors (IL-1 and IL-18) were downregulated after silencing MIAT. Through modeling and validation experiments, we then confirmed that the MIAT-miR-214-3p-CASP1 axis serves as an essential point in pyroptosis of DCM mice. These results suggested that silencing MIAT would be a potential treatment strategy for DCM.

Predictive Value of CT Perfusion Imaging on the Basis of Automatic Segmentation Algorithm to Evaluate the Collateral Blood Flow Status on the Outcome of Reperfusion Therapy for Ischemic Stroke.

Our objective was to study the predictive value of CT perfusion imaging based on automatic segmentation algorithm for evaluating collateral blood flow status in the outcome of reperfusion therapy for ischemic stroke. All data of 30 patients with ischemic stroke reperfusion in our hospital were collected and examined by CT perfusion imaging. Convolutional neural network (CNN) algorithm was used to segment perfusion imaging map and evaluate the results. The patients were grouped by regional leptomeningeal collateral score (rLMCs). Binary logistic regression was used to analyze the independent influencing factors of collateral blood flow on brain CT perfusion. The modified Scandinavian Stroke Scale was used to evaluate the prognosis of patients, and the effects of different collateral flow conditions on prognosis were obtained. The accuracy of CNN segmentation image is 62.61%, the sensitivity is 87.42%, the similarity coefficient is 93.76%, and the segmentation result quality is higher. Blood glucose (95% CI = 0.943, P=0.028) and ischemic stroke history (95% CI = 0.855, P=0.003) were independent factors affecting the collateral blood flow status of stroke patients. CBF (95% CI = 0.818, P=0.008) and CBV (95% CI = 0.796, P=0.016) were independent influencing factors of CT perfusion parameters. After 3 weeks of onset, the prognostic function defect score of the good collateral flow group (11.11%) was lower than that of the poor group (41.67%) (P < 0.05). The automatic segmentation algorithm has more accurate segmentation ability for stroke CT perfusion imaging and plays a good auxiliary role in the diagnosis of clinical stroke reperfusion therapy. The collateral blood flow state based on CT perfusion imaging is helpful to predict the treatment outcome of patients with ischemic stroke and further predict the prognosis of patients.

A study of self-precaution against the background of the COVID-19 pandemic from the perspective of risk perception attitude theory and social support.

BACKGROUND: In this research, the factors that influence the self-precautionary behavior during the pandemic are explored with the combination of social support and a risk perception attitude framework. METHODS: An online survey was conducted among 429 members to collect information on demographic data, social support, perceptions of outbreak risk, health self-efficacy, and self-precautionary behaviors with the guide of the Social Support Scale, the COVID-19 Risk Perception Scale, the Health Self-Efficacy Scale and the Self-precautionary Behavior Scale. RESULTS: The research shows that among the three dimensions of social support, both objective support and support utilization negatively predict risk perception, while subjective support positively predicts health self-efficacy; health self-efficacy and risk perception significantly predict self-precautionary behavior; the relationship between risk perception and self-precautionary behavior is significantly moderated by health self-efficacy. CONCLUSIONS: The combined influence of social capital and risk perception attitudinal frameworks on self-precautionary behavior is highlighted in this study, with the relationship between the public's risk perception, health self-efficacy, and self-precautionary behavior intentions examined against the background of coronavirus disease 2019 (COVID-19). These findings contribute to understanding the impact of social capital factors on risk perception and health self-efficacy, which provides insight into the current status and influencing factors of the public's precautionary behavior and facilitates early intervention during a pandemic.

Using Search Trends to Analyze Web-Based Interest in Lower Urinary Tract Symptoms-Related Inquiries, Diagnoses, and Treatments in Mainland China: Infodemiology Study of Baidu Index Data.

BACKGROUND: Lower urinary tract symptoms (LUTS) are one of the most commonly described urination disorders worldwide. Previous investigations have focused predominantly on the prospective identification of cases that meet the researchers' criteria; thus, the genuine demands regarding LUTS from patients and related issues may be neglected. OBJECTIVE: We aimed to examine web-based search trends and behaviors related to LUTS on a national and regional scale by using the dominant, major search engine in mainland China. METHODS: Baidu Index was queried by using LUTS-related terms for the period of January 2011 to September 2020. The search volume for each term was recorded to analyze search trends and demographic distributions. For user interest, user demand graph data and trend data were collected and analyzed. RESULTS: Of the 13 LUTS domains, 11 domains are available in the Baidu Index database. The Baidu search index for each LUTS domain varied from 37.78% to 1.47%. The search trends for urinary frequency (2011-2018: annual percent change APC=7.82%; P<.001), incomplete emptying (2011-2014: APC=17.74%; P<.001), nocturia (2011-2018: APC=11.54%; P<.001), dysuria (2017-2020: APC=20.77%; P<.001), and incontinence (2011-2016: APC=13.39%; P<.001) exhibited fluctuations over time. The search index trends for weak stream (2011-2017: APC=-4.68%; P<.001; 2017-2020: APC=9.32%; P=.23), split stream (2011-2013: APC=9.50%; P=.44; 2013-2020: APC=2.05%; P=.71), urgency (2011-2018: APC=-2.63%; P=.03; 2018-2020: APC=8.58%; P=.19), and nocturnal enuresis (2011-2018: APC=-3.20%; P=.001; 2018-2020: APC=-4.21%; P=.04) remained relatively stable and consistent. The age distribution of the population for all LUTS-related inquiries showed that individuals aged 20 to 40 years made 73.86% (49,218,123/66,635,247) of the total search inquiries. Further, individuals aged 40 to 49 years made 12.29% (8,193,922/66,635,247) of the total search inquiries for all LUTS-related terms. People from the east part of China made 67.79% (45,172,031/66,635,247) of the total search queries. Additionally, most of the searches for LUTS-related terms were related to those for urinary diseases to varying degrees. CONCLUSIONS: Web-based interest in LUTS-related terms fluctuated wildly and was reflected timely by Baidu Index in mainland China. The web-based search popularity of each LUTS-related term varied significantly and differed based on personal interests, the population's concerns, regional variations, and gender. These data can be used by care providers to track the prevalence of LUTS and the population's interests, guide the establishment of disease-specific health care policies, and optimize physician-patient health care sessions.

Optimal vacuum erectile device therapy regimen for penile rehabilitation in a bilateral cavernous nerve crush rat model.

BACKGROUND: Vacuum erectile device (VED) therapy has been widely used in penile rehabilitation after radical prostatectomy; however, there is no consensus on the best regimen. OBJECTIVES: To explore an optimal VED therapy regimen in bilateral cavernous nerve crush (BCNC) rat model. MATERIALS AND METHODS: Adult male rats were used to measure the effects of different durations (1-30 min) of VED treatment on penile length, penile blood gas analysis, and adverse effects. Forty-eight adult male rats were randomly divided into Sham, BCNC, and VED treatment groups (2-3-2-3 min, 4-3-3 min, 5-5 min, and 10 min). Penile length, erectile function, and side effects were detected after VED treatment. Histopathological staining and Western blotting were performed to explore the cellular and molecular changes. RESULTS: Prolongation of the duration of VED treatment significantly decreased the penile oxygen saturation, partial oxygen pressure, and arterial blood ratio (P < 0.05). Compared with the BCNC group, all VED treatment regimens partially reversed BCNC-induced penile shortening and erectile dysfunction (P < 0.0001), with the 4-3-3-min and 5-5-min treatment groups exhibiting more significant improvement than the 10-min and 2-3-2-3-min treatment groups (P < 0.0001). The mechanism may be related to the up-regulation of the smooth muscle cell/collagen ratio, endothelial nitric oxide synthase, and α-smooth muscle actin (all P < 0.0001); and the down-regulation of hypoxia-inducible factor-1α, transforming growth factor-ß1, and apoptosis (all P < 0.0001). The incidence of adverse effects in the 2-3-2-3-min treatment group was the highest. DISCUSSION: The commonly used VED therapy regimens maintained erectile function and penile length of BCNC rat by relieving hypoxia and fibrosis, and no further benefits were observed with increased treatment frequency or prolonged treatment duration. CONCLUSION: Two consecutive 5-min treatments with a short interval is the optimal VED therapy regimen for penile rehabilitation in BCNC rat model.

Vacuum therapy ameliorates erectile dysfunction in bilateral cavernous nerve crush rats by inhibiting apoptosis and activating autophagy.

Postprostatectomy erectile dysfunction (pPED) remains a current problem despite improvements in surgical techniques. Vacuum therapy is clinically confirmed as a type of pPED rehabilitation. However, its underlying mechanisms are incompletely understood. Recently, autophagy and apoptosis were extensively studied in erectile dysfunction resulting from diabetes, senescence, and androgen deprivation but not in the context of pPED and vacuum therapy. Therefore, this study was designed to investigate the roles of autophagy and apoptosis in pPED and vacuum therapy. Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: the control group, bilateral cavernous nerve crush (BCNC) group, and BCNC + vacuum group. After 4 weeks of treatment, intracavernosal pressure was used to evaluate erectile function. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry were used to measure the molecular expression. TdT-mediated dUTP nick-end labeling staining was used to assess apoptosis. Transmission electron microscopy was used to observe autophagosomes. After treatment, compared with those of the BCNC group, erectile function and cavernosal hypoxia had statistically significantly improved (P < 0.05). Apoptosis and the relative protein expression of B-cell lymphoma-2-associated X and cleaved Caspase3 were decreased (P < 0.05). Autophagy-related molecules such as phosphorylated unc-51-like autophagy-activating kinase 1 (Ser757) and p62 were decreased. Beclin1, microtubule-associated protein 1 light chain 3 A/B, and autophagosomes were increased (P < 0.05). Besides, the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, as a negative regulator of autophagy to some degree, was inhibited. This study revealed that vacuum therapy ameliorated pPED in BCNC rats by inhibiting apoptosis and activating autophagy.

Mangiferin loaded magnetic PCEC microspheres: preparation, characterization and antitumor activity studies in vitro.

Mangiferin is a promising effective chemopreventive agent against various tumors. However, its clinical use is limited by poor water solubility and low bioavailability. In this article, mangiferin loaded magnetic PCEC microspheres (MG-MS) were designed, characterized and the antitumor activity of MG-MS was evaluated in vitro. The magnetic nanoparticles (MNP) were synthesized via the high-temperature reaction of iron acetylacetonate in phenyl ether in the presence of oleic acid and oleylamine. Poly (ε-caprolactone)-poly (ethyleneglycol)-poly (ε-caprolactone) (PCL-PEG-PCL, PCEC) copolymers were formed by ring-opening copolymerization of ε-CL initiated by PEG-diol using Sn(Oct)2 as a catalyst and MG-MS were prepared by solvent diffusion method. MNP, PCEC copolymer, and MG-MS were characterized by GPC, TEM, XRD, FT-IR, 1H-NMP and Malvern Laser Particle Sizer. Meanwhile, the antiproliferative activity in vitro and in vitro release behavior of this microspheres were studied in detail. The results indicate that the obtained magnetic microspheres might have great potential as an effective carrier for mangiferin used in cancer chemotherapy.

N-acetylcysteine maintains penile length and erectile function in bilateral cavernous nerve crush rat model by reducing penile fibrosis.

Penile length shortening and erectile dysfunction are common complications after radical prostatectomy. Various methods have been used to maintain erectile function, but less attention has been paid to preserving penis length. N-acetylcysteine (NAC) has the effect of antioxidation and antifibrotic, which may be beneficial to improve those postoperative complications. This study investigated the effect of NAC on maintaining the penile length and the erectile function after bilateral cavernous nerve crush (BCNC) and its underlying mechanism. Twenty-four male rats were randomly divided into three groups: control group, BCNC group, and BCNC + NAC group. NAC or equal volume of saline was daily administrated by intragastric gavage for 4 weeks. The initial and end penile lengths were measured. Intracavernosal pressure/mean arterial pressure (ICP/MAP) ratio was calculated to assess erectile function. Hematoxylin-eosin staining, Masson's trichrome staining, immunohistochemistry, and Western blot were performed to explore cellular and molecular changes of the penis. Compared to the BCNC group, the penile length, ICP/MAP ratio and smooth muscle/collagen ratio in the BCNC + NAC group were improved significantly (all P < 0.05), and the expressions of endothelial nitric oxide synthase, α-smooth muscle actin, glutathione, and glutathione peroxidase 1 were significantly increased after NAC treated (all P < 0.05), along with the decreased expressions of hypoxia-inducible factor-1α, transforming growth factor-ß1, collagen I, collagen III, collagen IV, malonaldehyde, and lysine oxidase (all P < 0.05). This study demonstrated that NAC could maintain penile length and partly improve erectile function. Possible mechanism is directly and/or indirectly related to antihypoxic and antifibrosis.

Current approaches to the diagnosis of vascular erectile dysfunction.

Vascular erectile dysfunction (ED) is closely related to cardiovascular events, and early diagnosis of vascular ED may be helpful to predict the occurrence of cardiovascular events and improve prognosis. At present, there are many approaches to diagnose ED, but each method has its advantages and limitations. This study retrospectively reviewed all available literature focusing on the diagnosis of vascular ED through a systematic PubMed and EMBASE search. According to the different application scenarios, the main methods for the diagnosis of vascular ED are divided into four categories. Intra-cavernous injection of vasoactive drugs is the earliest method used in the diagnosis of vascular ED and is a basic test. For the diagnosis of arterial ED, color duplex Doppler ultrasound, selective penile angiography, magnetic resonance imaging, and computed tomography are more commonly used. While for the diagnosis of venous ED, shear wave elastography, dynamic infusion cavernosometry and cavernosography are more accurate. Endo-peripheral arterial tonometry (PAT) has also been used to detect vascular endothelial function. Although various existing examinations are widely used for the evaluation of vascular ED, they still have some shortcomings, such as invasiveness, contingency, high false positive (negative) rate. New methods of long-term dynamic detection are needed.

Advantages and limitations of current premature ejaculation assessment and diagnostic methods: a review.

Premature ejaculation (PE) is the most common male sexual dysfunction worldwide. Characteristic symptoms of PE are unexpected, rapid, complete ejaculation, which negatively impacts the sexual act for both sexual partners. Despite the existence of a definitive PE classification system and various diagnostic tools, diagnosing PE is still challenging due to the limitations associated with the assessment of this condition. Hence, it is necessary to review the diagnostic methods and processes of the physical examination that are currently performed in the medical setting. It is also important to analyze any controversial results of each main PE assessment method and propose novel diagnostic and assessment methods. To date, it is important to verify the accuracy of the PE evaluation method due to the ambiguity of previous definitions and proven invalidity of current examining techniques. Clinical diagnosis is based mainly on the patient history, patient-reported outcome scores, and diagnostic tools. Introduction of intravaginal ejaculatory latency time, penile biothesiometry, and the electrophysiological test provided objective means of evaluating PE. Due to the controversial and inconclusive findings in PE psychogenic and neurogenic etiology, utilizing a single parameter to describe and qualify PE using the aforementioned diagnostic methods provides valuable, but insufficient information for PE diagnosis. There is still a lack of a feasible and plausible means of objective measurement to evaluate the ejaculatory latency and control over ejaculation. Consequently, a comprehensive penile stimulation that simulates sexual intercourse could be useful to record intensity and duration parameters before the ejaculatory threshold, providing a more accurate method of describing and diagnosing PE versus a single chronological observation.

Advances in Gene Therapy for Erectile Dysfunction: Promises and Challenges.

Erectile Dysfunction (ED) is one of the most common conditions affecting middle-aged and older men. Over the past few decades, oral phosphodiesterase type 5 inhibitors have been used to treat ED. However, these oral medications require on-demand access and are not effective in some hard-totreat populations. Moreover, there are no effective alternative treatments for ED. Based on results from preclinical models designed to provide long-term improvement of ED and other related conditions, gene therapy has shown great potential as a novel therapy for clinical management of ED. Gene therapy refers to the use of viral and non-viral vectors to deliver therapeutic genes to tissues via direct or transduced cell-mediated approaches. With the growing knowledge on the molecular mechanisms involved in the pathophysiology of ED, a number of therapeutic gene strategies have been extensively tested and proven to be effective in many animal models. However, only a few of them have been evaluated in clinical trials. This is due to safety concerns that need to be addressed before the clinical application can be considered. In this review, we summarize the key advancements in gene therapy for ED treatment, with an emphasis on the emerging stem cell-based approaches as well as other combinational strategies. The challenges facing the clinical application of gene therapy for ED treatment are also discussed.