Premature ejaculation refers to a sexual dysfunction in which men experience a short intravaginal ejaculation latency and a lack of control over ejaculation during sexual activity. The onset of this condition is often accompanied by anxiety and depression, which can seriously affect the quality of the patient′s sexual life and the relationship between partners. Based on the "integration of body and spirit" theory in traditional Chinese medicine, our team believes that this condition is a comorbidity of physical and spiritual factors. We propose that the core pathogenesis of this disease lies in the "loss of form and essence, impairment of spirit, and depression of the mind, "while the primary treatment principle involves "nourishing form and regulating spirit." As a result, a new diagnosis and treatment approach of "four-dimensional integration" is summarized in this study. The disease is treated through the four dimensions of shape, body, spirit, and emotion. Traditional Chinese medicine is used to adjust the shape in cases where the physical form is damaged. For individuals with depression of heart and liver qi, the treatment focuses on soothing the heart and smoothing liver qi, and the modified Wangyou Powder and Xuanzhi Decoction is used. In cases where the heart and kidney function are compromised, the treatment involves nourishing both the heart and kidney while restoring interaction between the heart and the kidney, and modified Jihuo Yansi Elixir is used. To reduce the sensitivity of the glans penis, the patient′s body is washed with a traditional Chinese medicine formula, and a delicate fumigation formula is decocted for external washing. For those who are not in tune with their god, psychological counseling can be used to regulate their spirit and advocate "self-partner" and psychotherapy. If there are issues with intimacy, partners should focus on cooperating during foreplay, sexual intercourse, and post-coital interactions. Overall, the treatment aims to harmonize the body and spirit, addressing both physical and psychological factors through a comprehensive, multi-dimensional approach. This method provides new perspectives and ideas for the clinical diagnosis and treatment of this condition.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To investigate the correlation between plasma Dickkopf-1 (DKK1) and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke.Methods:Consecutive patients with first-ever acute ischemic stroke admitted to the Department of Neurology, Nanjing Jiangbei Hospital from March 2023 to February 2024 were included prospectively. Enzyme-linked immunosorbent assay was used to detect plasma DKK1 within 24 hours of onset. The Montreal Cognitive Assessment Scale was used to evaluate cognitive function at 3 months after onset. A score ≤22 was defined as PSCI. Multivariate logistic regression analysis was used to determine the correlation between DKK1 and PSCI. The relationship between DKK1 and PSCI risks was evaluated through restrictive cubic spline analysis. Results:A total of 205 patients with acute ischemic stroke were enrolled, including 106 males (51.7%), aged 67.0±9.4 years; 61 patients (29.8%) experienced PSCI. Multivariate logistic regression analysis showed that after adjusting for age, gender, education level, and other confounding factors, there was a significant independent correlation between higher plasma DKK1 and PSCI (odds ratio 1.778, 95% confidence interval 1.313-2.408; P=0.001). Subgroup analysis showed that age, gender, etiological classification of stroke, and education level had no significant effect on the above correlation. Restrictive cubic spline analysis showed plasma DKK1 had a linear relationship with the risk of PSCI ( P=0.003). Conclusion:Higher plasma DKK1 level is significantly correlated with PSCI in patients with acute ischemic stroke at 90 days after onset.

Objective To investigate the effect of percutaneous balloon mitral valvuloplasty under echocardiographic guidance for patients with moderate to severe mitral stenosis during pregnancy. Methods A retrospective observational study was conducted to include pregnant women who were diagnosed with moderate to severe mitral stenosis and underwent percutaneous balloon mitral valvuloplasty under echocardiographic guidance in Fuwai Hospital from August 2018 to June 2022, and their baseline characteristics, surgical outcomes, echocardiographic results, and follow-up results were analyzed. Results A total of 3 pregnant women aged 30-35 years, with gestational age of 19-26 weeks, and New York Heart Association (NYHA) function class Ⅲ were included. All the procedures were successfully performed. The mitral valve orifice area increased from 0.9 cm2 preoperatively to 2.1 cm2 postoperatively. The mean transvalvular pressure gradient decreased from 15.0 mm Hg preoperatively to 6.7 mm Hg postoperatively. No perioperative adverse events occurred. The follow-up time ranged from 3 to 48 months. All patients delivered uneventfully and returned to normal life, with maternal-fetal safety. Conclusion Percutaneous balloon mitral valvuloplasty under echocardiographic guidance is a feasible and effective procedure for the treatment of patients with moderate to severe mitral stenosis in pregnancy, with satisfactory maternal-fetal outcomes.

Transcatheter left ventricular assist pump (LVAP) is widely used in cardiogenic shock, post-circulatory hypoperfusion syndrome and high-risk percutaneous coronary intervention (PCI), and its application scenarios cover various complex environments such as ICU, operating room, emergency department and catheterization room. It is important to quickly and accurately implant the transcatheter LVAP and monitor its position in real time. This paper reported 2 male patients with high-risk PCI, aged 47 and 45 years, both with triple coronary artery disease and reduced ejection fraction (<35%). The domestically produced transcatheter LVAP was implanted using an echocardiography guidance technology system, and PCI treatment was performed under the assistance of the interventional pump. The operation was smooth, and the interventional pump assisted for 1 h in 2 patients, and the pump was successfully removed. There were no obvious complications related to the pump and PCI after the operation, and the patients were discharged smoothly.

Objective:To use structural equation modeling to identify the indicator variables of intrinsic ability vitality among the elderly population.Methods:The study collected data on seven variables commonly used to measure vitality and mobility, including body mass index, weight loss, calf circumference, grip strength, gait speed at 4 m, up and go, and up and sit, from the comprehensive geriatric assessment(CGA)of patients admitted to the Department of Geriatrics of Beijing Hospital between May 2020 and May 2022.The study used a structural equation model to explore and verify the indicator variables of activity, utilizing exploratory factor analysis, confirmatory factor analysis, and correlation analysis.Results:The study conducted an exploratory factor analysis on seven variables, which resulted in two latent variables named vitality and locomotion.Body mass index, weight loss, and calf circumference were found to reflect vitality, while grip strength, 4 m-walking speed, time up and go test, and standing up and down test were found to reflect locomotion.Confirmatory factor analysis indicated that the measurement model was well-constructed and the indicator variables of vitality and locomotion were reasonably assigned[ χ2/ df=35/13, CFI=0.96, RMSEA(95% CI)=0.06(0.04, 0.08)].Correlation analysis showed that grip strength had a stronger correlation with locomotion-related variables than vitality-related variables( for grip strength and locomotion=0.33, for grip strength and vitality=0.21). Conclusions:The intrinsic ability and vitality of elderly individuals can be assessed through various means, including body mass index, weight loss, and calf circumference.However, grip strength is considered a more appropriate measure for reflecting locomotion rather than overall vitality.

The safety and efficacy of a compound endoscopic dissection knife were evaluated in animal models. The compound endoscopic dissection knife can readily switch between Dual knife mode and IT knife mode. Vitro experiments were done on 30 mucosal lesion models and 30 submucosal lesion models, respectively, of pig stomach tissue. In vivo experiments, mucosal lesion resection were performed on each 10 lesions of gastrointestinal tract in 6 porcine models. The compound endoscopic dissection knife were used in the experimental group, and Dual knife combined with IT knife were used in the control group. Dissection time were recorded. The wounds were biopsied to evaluate muscle damage. The results of vitro experiment showed the dissection time of mucosal and submucosal lesions in the experiment group was significantly shorter than that in the control group (17.93±2.52 min VS 21.07±3.58 min, t=-2.774, P=0.010; 25.73±2.66 min VS 31.80±3.78 min, t=-5.081, P<0.001). The results of vivo experiment showed the dissection time in the experiment group was significantly shorter than that in the control group (21.67±4.10 min VS 25.36±3.83 min, t=-3.602, P=0.001). The muscle damage rate was lower in the experimental group, but the difference was not statistically significant [3.3% (1/30) VS 10.0% (3/30), χ2=1.071, P=0.612]. The compound endoscopic dissection knife is both safe and effective in animal models.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Objective:To establish a multi-component exercise intervention program for the elderly with frailty, assess its effectiveness on improving the severity of frailty, and examine the effects of different intervention modes.Methods:174 elderly people in a community in Beijing were randomly divided into three groups.The control group did not receive special intervention.The health education group received lectures, demonstrations and pamphlets on basic knowledge about frailty and instructions about a multi-component sports program.The multi-component exercise training program group was trained for three months via regular videos delivered through a WeChat app.The severity of frailty and exercise adherence of subjects in the three groups were compared.Results:166 subjects completed the study.Frailty phenotype(FP)scores of the health education group and the WeChat app group were lower than those at baseline( P<0.05).After intervention, FP scores of the control group, the health education group and the WeChat app group were 1(1, 2), 1(0, 1)and 1(0, 1), respectively, and there were differences among the three groups after intervention( H=15.539, P<0.05).There were 10 subjects(17.2%)in the control group, 15(25.9%)in the health education group and 28(48.3%)in the WeChat app group who experienced reversal from frailty or pre-frailty to no frailty( χ2=12.770, P=0.002).The number of people who reversed to no frailty in the WeChat app group was higher than in the control group( χ2=11.536, P=0.001)and the health education group( χ2=5.659, P=0.014).The numbers of people with frailty in the control group, health education group and WeChat app group were 9(15.5%), 1(1.7%)and 1(1.7%), respectively( χ2=13.040, P=0.001), with the numbers of frailty cases in the health education group and the WeChat app group lower than in the control group( χ2=7.552, 7.210, P=0.006, 0.007).The percentage of people completing the exercise program in the WeChat app group was higher than in the control group( χ2=49.366, P<0.001)and also in the health education group( χ2=26.481, P<0.001), while the percentage of people completing the exercise program in the health education group was higher than in the control group( χ2=6.171, P=0.013). Conclusions:The multi-component exercise program can improve the frailty state of the elderly, and the intervention method based on the WeChat app has clear advantages in improving frailty and enhancing exercise adherence.

Objective:To investigate the ideal body mass index(BMI)range for hospitalized older adults with good functional ability.Methods:Data on inpatients thorough comprehensive geriatric assessment, including sex, age, BMI, ethnicity, and 9 functional indicators(basic daily mobility, instrumental daily mobility, frailty, cognition, depression, sleep, swallowing function, somatic activity, and grip strength)were collected in the geriatric department between January 2020 and November 2022.To determine the ideal BMI range, Logistic regression was used to analyze the dose-response relationships between BMI and functional ability.The findings were then validated by looking at the 5%-95% range of BMI among elderly people with normal functional ability.Results:A total of 1 950 hospitalized elderly adults were included in the study, with the age ranging from 60-103(77.2±8.9)years and women making up 50.8% of the participants.The average BMI was(23.4±3.6)kg/m 2; 8.9%(n=174)of the participants were low body weight and 8.7%(n=171)obese.Between 12.1%-66.0% of patients showed deterioration in the indicators of functional ability.With a higher BMI, there was a trend of decreasing functional ability in the elderly.Compared with people with a BMI between 20.0-24.9 kg/m 2, a BMI<20.0 kg/m 2 was a risk factor for bodily functional abnormality( OR: 1.49-2.06, all P<0.01). There was no clear risk for functional abnormality if the BMI was between 28.0-29.9 kg/m 2.In fact, in this BMI range, there was even a protective effect for grip strength and cognitive ability( OR=0.42, 0.25, both P<0.01). Of 214 elderly participants with normal values in all parameters, the 95% confidence interval of BMI ranged from 19.8 to 28.8 kg/m 2. Conclusions:To maintain appropriate functional ability for elderly inpatients, the optimal BMI range is between 20.0 kg/m 2 and 29.9 kg/m 2.