Targeting Adenosine A2b Receptor Promotes Penile Rehabilitation of Refractory Erectile Dysfunction.

The mechanisms of adenosine and specific adenosine receptor subtypes in promoting penile rehabilitation remain unclear. Single-cell RNA sequencing of human corpus cavernosum,  adenosine deaminase (ADA) and adenosine receptors knock-out mice (ADA-/-, A1-/-, A2a-/-, A2b-/-, and A3-/-), and primary corpus cavernosum smooth muscle cells are used to determine receptor subtypes responsible for adenosine-induced erection. Three rat models are established to characterize refractory erectile dysfunction (ED): age-related ED, bilateral cavernous nerve crush related ED (BCNC), and diabetes mellitus-induced ED. In single-cell RNA sequencing data, the corpus cavernosum of ED patients show a decrease in adenosine A1, A2a and A2b receptors. In vivo, A2b receptor knock-out abolishes adenosine-induced erection but not that of A1, A2a, or A3 receptor. Under hypoxic conditions in vitro, activating the A2b receptor increases HIF-1α and decreases PDE5 expression. In refractory ED models, activating the A2b receptor with Bay 60-6583 improves erectile function and down-regulates HIF-1α and TGF-ß. Administering Dipyridamole (40 mg Kg-1) to BCNC rats improve penile adenosine levels and erectile function. Our study reveals that the A2b receptor mediates adenosine-induced penile erection. Activating the A2b receptor promotes penile rehabilitation of refractory ED by alleviating hypoxia and fibrosis.

An Analysis of Public Perception and Concern Toward Electronic Cigarettes: Exploring Attitudes and Profiles.

Introduction The emergence of electronic cigarettes (e-cigarettes) poses a new challenge to tobacco control efforts. With their increasing popularity, particularly among youth, public concerns have been raised in Mainland China. Further investigation is necessary to fully understand the safety and potential adverse effects of e-cigarettes. Methods The Baidu search index (BSI) was employed using e-cigarette related terms from January 1, 2011, to April 4, 2022. The search volume for each term was recorded and analyzed for the search trend module, geodemographic module, search-demand module, regional preferences, demographic preferences, and user demand. Results According to our analysis, the total BSI for the 18 e-cigarette related search keywords was 39,027,819. The average annual percentage change of BSI indicated an upward trend for each of these categories, including health issues (p < 0.05), definition (p < 0.05), product and promotions (p < 0.05), and policy and regulations. Of all inquiries, 59.38% originated from females and 40.62% from males. The total valid BSI for e-cigarette related words was 165,076,588, and 11.59% of all search inquiries were from individuals aged 19 years and younger. Our analysis also revealed that the public's primary concerns regarding e-cigarettes were related to their quality and potential health issues. Conclusions E-cigarettes enjoy great popularity nationwide, but product quality and safety are major public concerns. Regulation of e-cigarettes for their standard production, quality control, advertisement, and target customers should be implemented promptly, and the public needs to have a clear perception of e-cigarettes, especially adolescents. E-cigarette related health damages or consequences require further investigation, and advertisements and promotions for e-cigarettes should be strictly controlled by the government.

Implications of Human Antimicrobial Peptide Defensin Beta-1 in Clinical Oral Squamous Cell Carcinoma Patients via an Integrated Bioinformatics Approach.

BACKGROUND: The human antimicrobial peptide defensin beta 1 (DEFB1) has been found to play antimicrobial and anti-inflammatory roles in oral diseases; however, its tumor-regulating role in oral squamous cell carcinoma (OSCC) has not yet been researched by using an integrative bioinformatics approach. OBJECTIVE: To investigate the regulating mechanisms of the DEFB1 gene in OSCC in terms of its expression patterns, prognostic values, biological functions, and implication for tumor immunity. METHODS: The DEFB1 gene expression pattern and regulatory involvement in OSCC were investigated using publically accessible data from TCGA database. R software tools and public web servers were utilized to conduct statistical analysis of data from cancer and noncancerous samples. RESULTS: DEFB1 was found to be significantly downregulated in OSCC tumor samples compared with healthy control oral samples. The DEFB1 gene was found associated with the prognostic outcomes of OSCC, and its upregulation represented better survival outcome. Gene set enrichment analysis (GSEA) results showed that DEFB1-significantly correlated genes were mainly enriched in four signaling pathways mediating the antitumor role of DEFB1 in OSCC, including extracellular matrix-related pathway, RTK/PI3K/AKT/mTOR pathway, keratinization, and cytokine-related pathway. The gene-gene interaction network showed that DEFB1 was closely correlated with several genes, for example, CCR6 (C-C motif chemokine receptor 6), CXCL1 (C-X-C motif chemokine ligand 1), MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2), PTGER3 (prostaglandin E receptor 3), and MMP7 (matrix metallopeptidase 7). Moreover, DEFB1 was found to be involved in the tumor immunity of OSCC by regulating the function of tumor macrophage cells, mast cells, T cells, and NK cells. CONCLUSIONS: Given the dysregulation, prognostic value, and tumor progression-related biological pathway alteration, indicating the tumor immune-modulatory role of DEFB1 in OSCC, the DEFB1 gene should be regarded as a potential therapeutic target for treating oral cancer.

Online Public Attention of COVID-19 Vaccination in Mainland China.

With the approval of the vaccine in mainland China, concerns over its safety and efficacy emerged. Since the Chinese vaccine has been promoted by the Chinese government for months and got emergency approval from the World Health Organization. The Chinese vaccination program is yet to be identified from the perspective of local populations. The COVID-19 vaccine-related keywords for the period from January 2019 to April 2021 were examined and queried from the Baidu search index. The searching popularity, searching trend, demographic distributions and users' demand were analyzed. The first vaccine enquiry emerged on 25th January 2020, and 17 vaccination keywords were retrieved and with a total BSI value of 13,708,853. The average monthly searching trend growth is 21.05% (p < 0.05) and was led by people aged 20-29 (39.22%) years old. Over 54.93% of the demand term search were pandemic relevant, and the summed vaccine demand ratio was 44.79%. With the rising search population in COVID-19 vaccination, education programs and materials should be designed for teens and people above the 40 s. Also, vaccine-related birth safety should be alerted and further investigated.

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.

Online Public Attention Toward Premature Ejaculation in Mainland China: Infodemiology Study Using the Baidu Index.

BACKGROUND: Premature ejaculation (PE) is one of the most described psychosocial stress and sexual complaints worldwide. Previous investigations have focused predominantly on the prospective identification of cases that meet researchers' specific criteria. The genuine demand from patients with regard to information on PE and related issues may thus be neglected. OBJECTIVE: This study aims to examine the online search trend and user demand related to PE on a national and regional scale using the dominant major search engine in mainland China. METHODS: The Baidu Index was queried using the PE-related terms for the period of January 2011 to December 2020. The search volume for each term was recorded to analyze the search trend and demographic distributions. For user interest, the demand and trend data were collected and analyzed. RESULTS: Of the 36 available PE search keywords, 4 PE searching topics were identified. The Baidu Search Index for each PE topic varied from 46.30% (86,840,487/187,558,154) to 6.40% (12,009,307/187,558,154). The annual percent change (APC) for the complaint topic was 48.80% (P<.001) for 2011 to 2014 and -16.82% (P<.001) for 2014 to 2020. The APC for the inquiry topic was 16.21% (P=.41) for 2011 to 2014 and -11.00% (P<.001) for 2014 to 2020. For the prognosis topic, the annual APC was 11.18% (P<.001) for 2011 to 2017 and -19.86% (P<.001) for 2017 to 2020. For the treatment topic, the annual APC was 14.04% (P<.001) for 2011 to 2016 and -38.83% (P<.001) for 2016 to 2020. The age distribution of those searching for topics related to PE showed that the population aged 20 to 40 years comprised nearly 70% of the total search inquiries (second was 17.95% in the age group younger than 19 years). People from East China made over 50% of the total search queries. CONCLUSIONS: The fluctuating online popularity of PE searches reflects the real-time population demands. It may help medical professionals better understand population interest, population concerns, regional variations, and gender differences on a nationwide scale and make disease-specific health care policies. The internet search data could be more reliable when the insufficient and lagging registry data are completed.

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.

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.

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.

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.

Day Surgery Program at West China Hospital: Exploring the Initial Experience.

Healthcare facilities in China are facing increasing demands as the country has the fastest aging populations in the world. Day surgery can be utilized to address some of these demands. Benefits of day surgery include shortened hospital stay, decreased risk of hospital-associated infections, and increased cost efficiency. We present a retrospective study of eight years of day surgery data from West China Hospital, one of the largest hospitals in China, with an emphasis on an examination of the growth in day surgeries. We examined patterns of utilization of day surgery versus inpatient surgery (including types of surgeries performed in the Day Surgery Center and the ratio of day surgery versus elective surgery), as well as unplanned readmission and return to inpatient department rates, and a comparison of average costs and length of stay for day surgery versus hospital surgery. Day surgery has a safe and cost-effective way to alleviate the soaring healthcare demands in West China. There is potential opportunity to further address the ever-increasing demands on the healthcare system in this area by performing more complex surgeries as day surgeries. This article presents an effective organizational protocol and proposes a reliable medical quality assurance system, which prioritizes safety of the growing day surgery program; furthermore, it describes the factors and lessons learned from the successful implementation of a day surgery system.

Role of the lysyl oxidase family in organ development (Review).

Lysyl oxidase proteins (LOXs) are amine oxidases, which are mainly located in smooth muscle cells and fibroblasts and serve an important role in the formation of the extracellular matrix (ECM) in a copper-dependent manner. Owing to the ability of LOX proteins to modulate crosslinking between collagens and to promote the deposition of other fibers, they serve crucially in organogenesis and the subsequent organ development, as well as disease initiation and progression. In addition, ECM formation significantly influences organ morphological formation in both cancer- and non-tumor-related diseases, in addition to cellular epigenetic transformation and migration, under the influence of LOXs. A number of different signaling pathways regulate the LOXs expression and their enzymatic activation. The tissue remodeling and transformation process shares some resemblance between oncogenesis and embryogenesis. Additionally the roles that LOXs serve appeared to be stressed during oncogenesis and tumor metastasis. It has also been indicated LOXs have a noteworthy role in non-tumor diseases. Nonetheless, the role of LOXs in systemic or local organ development and disease control remains unknown. In the present study, the essential roles that LOXs play in embryogenesis were unveiled partially, whereas the role of LOXs in organ or systematic development requires further investigations. The present review aimed to discuss the roles of members of the LOX family in the context of the remodeling of organogenesis and organ development. In addition, the consequences of the malfunction of these proteins related to the development of abnormalities and resulting diseases is discussed.

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.