Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To investigate the prevalence of hyperuricemia (HUA) in Bozidun Kirghiz township of Xinjiang Aksu region, and to explore the risk factors for the occurrence of HUA in the local area.Methods:A cross-sectional survey study was conducted by randomly selecting 9 villages in Bozidun Kirgiz Township by the whole-group sampling method and questionnaire were distributed to the households. The questionnaire included: demographic information, history of past illness, personal history, and all subjects were measured for height, weight, blood pressure, abdominal circumference, etc. The diagnostic of HUA if the serum uric acid (SUA) level >420 μmol/L in men or >360 μmol/L in women. The incidences of HUA in different age, sex, food type and life style behavior were analyzed. T test, non-parametric test and Chi-square test were used to analyze the differences among the groups, and logistic regression was used to analyze the risk factors. Results:①A total of 2 138 subjects were surveyed, among which 68 patients were with HUA, the prevalence of HUA in Bozidun Kirghiz township, Aksu region in the general population was 3.18%(68/2 138); the prevalence rate in men was 4.60%(45/978), 45 patients were identified; and the prevalence rate in women was 1.98%(23/1 160), 23 patients were identified. The peak age of HUA in male and female patients was 51~60 years old. ②The prevalence of HUA was lower in those who consumed dairy products ( χ2=6.91, P=0.017), nuts ( χ2=8.43, P=0.038) and eggs ( χ2=7.38, P=0.023), and lower in those who consumed more. Different intake of cereals ( χ2=0.87, P=0.647), meat( χ2=0.82, P=0.662), vegetables and fruits( χ2=5.22, P=0.073) had no effect on the prevalence of HUA.③In terms of different life behaviors, the prevalence of HUA in men who had been smoking was higher than those who had never smoked (57.78%, 28.89%, 13.33%, χ2=8.16, P=0.017). In the relationship between drinking and HUA, the prevalence rates of male always drinking, ever drinking and never drinking were 80.00%, 11.11% and 3.89%, respectively, the difference was statistically significant ( χ2=6.67, P=0.038). ④Multi-factor logistic regression analysis showed that high BMI, old age, high TG, increased Cr and increased WBC were risk factors for the occurrence of HUA [ OR(95% CI)=1.13(1.04, 1.23), 1.03(1.00,1.05),1.39(1.00, 1.93), 1.03(1.02, 1.05), 1.27(1.07, 1.49), all P<0.05]. Conclusion:The prevalence of HUA in Bozidun Kirgiz township in Aksu prefecture of Xinjiang is lower than that in other areas with continental climate. High BMI, old age, high TG, increased Cr and increased WBC count are risk factors for the development of HUA .

Objective To understand the current status of nurses'health promotion lifestyle in tertiary comprehensive hospitals,explore the category characteristics of nurses'health promotion lifestyle,and analyze the influencing factors under different categories.Methods From March to April 2023,a multi-stage sampling method was used to select 1326 nurses from 10 tertiary comprehensive hospitals in Hunan Province as the research subjects.A cross-sectional survey was conducted by General Information Questionnaire,Health Promotion Lifestyle Profile Scale,Self-Rated Abilities for Health Practices Scale,Health Behavior Self-Efficacy Assessment Scale,and Nursing Work Environment Scale.Latent profile analysis(LPA)of nurses'health promotion lifestyle was conducted,and the influencing factors of different profiles were explored through univariate analysis and logistic regression analysis.Results A total of 1220 nurses were included,and the score of Health Promotion Lifestyle Profile Scale was(62.61±18.67)points.Nurses'health promotion lifestyle in tertiary comprehensive hospitals can be divided into 3 profiles,namely survival type(25.41％),vitality type(21.97％)and normal type(52.62％).The results of logistic regression analysis showed that coping strategies for stress,non-occupational physical activity,perceived health status,health behavior self-efficacy,and nursing work environment are the influencing factors of nurses'health promotion lifestyle in tertiary comprehensive hospitals(P＜0.05).Conclusion Nurses'health promotion lifestyle in tertiary comprehensive hospitals exhibit significant heterogeneity.It is recommended that nursing managers carry out individualized interventions based on the characteristics of nurses in different categories.Health behavior self-efficacy can be used as the core of intervention to improve nurses'health promotion lifestyles.

AIM To investigate the protective effects of Didang Decoction-containing serum on rat glomerular endothelial cells(RGECs)following high glucose injury.METHODS Rats were given distilled water or Didang Decoction by gavage to prepare the blank serum or Didang Decoction-containing serum.CCK8 method was used to screen the glucose concentration for the modeling and serum concentration of the drug.The RGECs were divided into the blank group,the model group,Didang Decoction group(10%Didang Decoction medicated serum),Dapagliflozin group(normal serum+2 μmol/L Dapagliflozin)and Didang Decoction+Dapagliflozin group(10%Didang Decoction medicated serum+2 μmol/L Dapagliflozin).24 hrs after the drug treatment,the RGECs had their mRNA and protein expressions of Nrf2,HO-1 and NQO-1 detected by RT-qPCR method and Western blot method;their Nrf2 fluorescence expression detected by immunofluorescence method;and their SOD activity and MDA level detected by colorimetric method.RESULTS Compared with the blank group,the model group displayed decreased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P＜0.01),and increased MDA level(P＜0.01).Compared with the model group,the groups intervened with the drugs showed increased mRNA and protein expressions of Nrf2,HO-1 and NQO-1 as well as the activity of SOD(P＜0.05,P＜0.01),and decreased MDA level(P＜0.01).CONCLUSION Didang Decoction-containing serum can protect RGECs from high glucose injury through activating the Nrf2 signaling pathway.

Objective:To explore the association between triglyceride-glucose (TyG) index and carotid artery plaque in patients with type 2 diabetic kidney disease (DKD).Methods:Clinical data of 620 DKD patients admitted in the Department of Endocrinology, the Affiliated Huai′an First People′s Hospital of Nanjing Medical University from August 2018 to August 2022 were retrospectively analyzed, including 366 cases with carotid artery plaque and 254 cases without carotid plaque. According to TyG index quartile patients were divided into Q 1,Q 2, Q 3 and Q 4 groups with TyG index<8.94,≥8.94 and<9.44,≥9.44 and<9.96, and≥9.96, respectively. The prevalence of carotid plaque in DKD patients with different TyG index levels was analyzed. The relationship between TyG index and carotid plaque occurrence in DKD patients were analyzed with Logistic regression analysis and restricted cubic lines (RCS). Results:The age, course of disease, smoking rate, SBP, HbA1c, TG, BUN, eGFR and TyG indexes in carotid plaque group were significantly higher than those in non-carotid plaque group (all P<0.05). Binary logistic regression analysis showed that age, disease course, smoking rate, SBP, HbA1c, TG, BUN, low eGFR and TyG index were independent influencing factors for carotid plaque ( OR=1.05, 1.05, 1.88, 1.01, 1.09, 1.11, 1.09, 0.99 and 1.28, all P<0.05). The risk of carotid plaque in DKD patients in Q 3 and Q 4 groups was 2.20 and 2.50 times higher than that in Q 1 group. After adjusting for age, sex, course of disease, smoking, BMI, blood pressure (SBP and DBP), blood lipids (TC, HDL and LDL) and renal function, the risk of carotid plaque in DKD patients in Q 3 and Q 4 groups was higher than that in Q 1 group ( OR=1.95 and 2.24). RCS analysis showed that the correlation between TyG index and the risk of carotid plaque in DKD patients was linear(χ 2=0.40, P=0.527), and DKD patients with TyG index>9.95 had a higher risk of carotid plaque. Conclusions:TyG index is significantly elevated in DKD patients with carotid plaque, and TyG index is an independent risk factor for the occurrence of carotid plaques in DKD patients.

Intracellular neurofibrillary tangles resulting from abnormal hyperphosphorylation of Tau protein constitute one of the principal pathological markers of Alzheimer′s disease. Existing studies have indicated that BSc3094 is an efficacious inhibitor of Tau protein aggregation, capable of binding to Tau protein, inhibiting Tau protein phosphorylation, and enhancing cell viability concurrently, holding significant potential in treating Alzheimer′s disease. Nevertheless, due to the presence of the blood-brain barrier, it is challenging for drugs to penetrate the brain and exert their effects, and whether BSc3094 can treat Alzheimer′s disease by inhibiting Tau protein aggregation has not been profoundly investigated. Hence, in this study, small-sized (PLGA) nanoparticles were fabricated through the stirring method. BSc3094 was loaded into the nanoparticles (PLGA@BSc). To further enhance the brain entry efficiency of PLGA nanoparticles, a pathological BBB-targeting peptide was modified on the surface to obtain PLGA@BSc@K. In this study, the stability, cytotoxicity, and pathological targeting of the nanosystem were characterized. The particle size of the nanosystem was about 90 nm, which was negatively charged. The results demonstrated that the particle size of the nanoparticles did not fluctuate conspicuously within 168 h, and the stability was favorable. PLGA and BSc3094 had no notable impact on cell viability and displayed low cytotoxicity. At 1 and 4 h, it was observed that the uptake of targeted modified nanoparticles by cells in pathological states augmented, suggesting that PLGA@BSc@K had an excellent pathological blood-brain barrier targeting effect. This study provides a novel concept for the targeting of BSc3094 nanoparticles in the brain and the treatment of Alzheimer′s disease.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly desmoplastic tumor with poor prognosis even after curative resection. We investigated the associations between the composition of the ICC stroma and immune cell infiltration and aimed to develop a stromal-immune signature to predict prognosis in surgically treated ICC. Patients and methods: We recruited 359 ICC patients and performed immunohistochemistry to detect α-smooth muscle actin (α-SMA), CD3, CD4, CD8, Foxp3, CD68, and CD66b. Aniline was used to stain collagen deposition. Survival analyses were performed to detect prognostic values of these markers. Recursive partitioning for a discrete-time survival tree was applied to define a stromal-immune signature with distinct prognostic value. We delineated an integrated stromal-immune signature based on immune cell subpopulations and stromal composition to distinguish subgroups with different recurrence-free survival (RFS) and overall survival (OS) time. Results: We defined four major patterns of ICC stroma composition according to the distributions of α-SMA and collagen: dormant (α-SMAlow/collagenhigh), fibrogenic (α-SMAhigh/collagenhigh), inert (α-SMAlow/collagenlow), and fibrolytic (α-SMAhigh/collagenlow). The stroma types were characterized by distinct patterns of infiltration by immune cells. We divided patients into six classes. Class I, characterized by high CD8 expression and dormant stroma, displayed the longest RFS and OS, whereas Class VI, characterized by low CD8 expression and high CD66b expression, displayed the shortest RFS and OS. The integrated stromal-immune signature was consolidated in a validation cohort. Conclusion We developed and validated a stromal-immune signature to predict prognosis in surgically treated ICC. These findings provide new insights into the stromal-immune response to ICC.

Objective:To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis.Methods:In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed.Results:The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome.Conclusions:Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*