Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective To preliminarily evaluate the safety and effectiveness of a novel non-implantable atrial shunt device based on radiofrequency ablation for the treatment of chronic heart failure(CHF).Methods This was a prospective single-arm study.From January 2023 to December 2023,five eligible CHF patients were consecutively enrolled at Beijing Anzhen Hospital,Capital Medical University,and underwent inter-atrial shunt using Shenzhen Betterway atrial shunt device.Pulmonary capillary wedge pressure(PCWP),right atrial pressure(RAP),pulmonary artery pressure(PAP),total pulmonary resistance(TPR),pulmonary vascular resistance(PVR),and pulmonary/systemic blood flow ratio(Qp/Qs)were measured using right heart catheterization before and immediately after procedure.Patients were followed up for 90 days,and echocardiography,right heart catheterization,and cardiac functional indicators were evaluated.The primary endpoint was procedural success.Secondary endpoints included clinical success,echocardiographic changes,6-minute walk distance(6MWD)changes,New York Heart Association(NYHA)class changes,Kansas city cardiomyopathy questionnaire(KCCQ)score changes,and amino-terminal probrain natriuretic peptide(NT-proBNP)level changes at 90 days.The safety endpoint was major cardiovascular and cerebrovascular adverse events and device-related adverse events.Results All five patients successfully achieved left-to-right atrial shunt.Compared with baseline,PCWP decreased significantly immediately after procedure in all five patients,with a procedural success rate of 100％.There were no significant changes in RAP,PAP,TPR,and PVR before and immediately after procedure.After 90 days follow-up,four patients had persistent left-to-right atrial shunt,and PCWP was significantly lower than baseline,with a clinical success rate of 80％.Compared with baseline,LVEF increased,left ventricular end-diastolic diameter decreased,and tricuspid annular plane systolic excursion and right ventricular fractional area change were not impaired in all five patients at 90 days.KCCQ scores and 6MWT improved,NT-proBNP decreased,and NYHA class did not change significantly.There were no deaths,rehospitalizations for heart failure,stroke-related adverse events,or device-related adverse events during the follow-up.Conclusions The novel non-implantable atrial shunt catheter can safely and effectively improve hemodynamic,echocardiographic,and cardiac functional indicators in patients with heart failure.However,larger-scale clinical studies are still needed to validate its long-term clinical effectiveness.

OBJECTIVE: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. METHODS: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. RESULTS: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044). CONCLUSION In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19.
Adult ; Aged ; COVID-19/drug therapy* ; Female ; Humans ; Length of Stay ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Retrospective Studies ; SARS-CoV-2

Objective To investigate the effectiveness and cost of 50% and 80% wettable powder of niclosamide ethanolamine salt (NESWP) and 26% metaldehyde and niclosamide suspension concentrate (MNSC) in hilly schistosomiasis-endemic regions, so as to provide insights into the selection of chemical molluscicides in hilly regions. Methods In September 2020, a wasteland in Guanshanqiao Village, Yanrui Township, Yushan County of Jiangxi Province was selected as the experimental region, which was sectioned into five blocks and defined as four experimental groups (A₁, A₂, B, C) and a blank control group (D). 80% NESWP were given at doses of 1 g/m² and 1.5 g/m² in groups A₁ and A₂ using the spraying method, 50% NESWP was given at a dose of 2 g/m² in Group B using the spraying method, and 26% MNSC was at a dose of 4 g/m² in Group C using the spraying method, while no chemical treatment was given in Group D. Snail survey was performed using a systematic sampling method before chemical treatment and 1, 3, 7 d and 15 d post-treatment to examine the molluscicidal effect, and all molluscicidal costs were estimated to calculate the cost of chemical treatment per 1 m² and the cost of the reduction in the mean density of living snails per 1%. Results The highest mortality of snails was 78.95% and the lowest density of living snails was 0.2388 snails/0.1 m² in the experimental groups within 7 d of chemical treatment, and the highest mortality of snails was 94.74% and the lowest density of living snails was 0.058 0 snails/0.1 m² 7 d post-treatment. There were no significant differences in the snail mortality among the A₁, A₂, B and C groups 1 (χ² = 2.250, P > 0.05), 3 (χ² = 1.779, P > 0.05) or 15 d post-treatment (χ² = 2.286, P > 0.05), while a significant difference was detected in the snail mortality among the four groups 7 d post-treatment (χ² = 7.990, P = 0.046). In addition, there were no significant differences in the snail mortality between A₁ and A₂ groups 1 (χ² = 0.724, P > 0.05), 3 (χ² = 0.584, P > 0.05), 7 (χ² = 0.400, P > 0.05) or 15 d post-treatment (χ² = 0.251, P > 0.05). The costs of chemical treatment per 1 m² were 0.58, 0.60, 0.64 Yuan and 0.73 Yuan in groups A₁, A₂, B and C, and the costs of the mean density of living snail per 1% reduction were 19.29, 20.44, 21.68 Yuan and 23.53 Yuan in groups A₁, A₂, B and C, respectively. Conclusion 80% NESWP shows a high molluscicidal efficacy and low cost in hilly schistosomiasis-endemic regions.

OBJECTIVE: To investigate the effects of ALKBH5 on migration, invasion and epithelial-mesenchymal transition (EMT) of human trophoblast cells. METHODS: The expression plasmid of ALKBH5 or a negative control plasmid (ALKBH5-NC) was transfected in human trophoblast HTR-8 /SVneo cells, and the expressions of ALKBH5 mRNA and protein were detected by qRT-PCR and Western blotting. Transwell assay was used to assess the changes in migration and invasion abilities of the trophoblast cells after the transfection. Western blotting was performed to detect the expressions of EMT-related proteins in the cells including vimentin, fibronectin, E-cadherin, N-cadherin, MMP9 and MMP2. RESULTS: ALKBH5 mRNA and protein expressions were significantly higher in ALKBH5 group than in the control group ( CONCLUSIONS ALKBH5 is involved in the pathogenesis of preeclampsia by inhibiting EMT of trophoblast cells and hence reducing their migration and invasion abilities.
AlkB Homolog 5, RNA Demethylase ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Pre-Eclampsia ; Pregnancy ; Trophoblasts ; Vimentin/genetics*

OBJECTIVE: This work aims to investigate the effect of stripping of steep sheep maxillary sinus by using 0.012 or 0.014 model new-type memory elastic silk sleeve stripper and umbrella stripper. METHODS: Goats with sinus floor gradients of 60° to 90° were selected by computed tomography of sheep head. A total of 72 animal models were established and randomized into three groups (n=24): group A (0.012 model), B (0.014 model) and C (umbrella stripper). Alveolar and maxillary sinus mucosa were stripped after crowning, and stripping length was measured when the stripping limit was reached or mucosal perforation occurred. RESULTS: The average stripping length of mucosa in group A was 11.3 mm±4.6 mm, and three cases experienced perforation of sinus floor mucosa. The average stripping length of mucosa in group B was 17.5 mm±5.0 mm, and one case experienced perforation of sinus floor mucosa. The average stripping length of mucosa in group C was 4.2 mm±1.3 mm, and four cases experienced perforation of sinus floor mucosa. The difference among the three groups was statistically significant (P<0.01) according to variance analysis. Moreover, the comparison between any two means was also statistically significant according to Dunnett's T3 test (P<0.05). CONCLUSIONS The new-type memory elastic silk sleeve stripper effectively stripped steep maxillary sinus mucosa. The 0.014 model exhibited superior peeling effect and was relatively safe.
Animals ; Goats ; Maxillary Sinus ; Mucous Membrane ; Sheep ; Silk ; Sinus Floor Augmentation

The composition and potency of the high temperature (40℃) stress induced size variants of a recombinant humanized monoclonal antibody (rhumAb1) were characterized by means of SEC-HPLC, nonreduced CE-SDS, liquid chromatography coupled with mass spectrometry (LC-MS) and antibody dependent cell-mediated cytotoxicity (ADCC) assay. The molecular masses of the four size variants (SEC-1-SEC-4) separated by SEC-HPLC and seven size variants (NR-1-NR-7) detected by non-reduced CE-SDS were all characterized by LC-MS. The major low molecular weight variants were generated due to the hinge region fragmentation of heavy chain. The hinge region cleavage was found mainly in the Ser221-Cys-Asp-Lys-Thr-His-Thr-Cys228 sequence, in which C222-D223 and H226-T227 were the major cleavage sites. The size variants of rhumAb1, namely dimer and fragments, have significantly reduced ADCC activity in comparison with the intact rhumAb1 drug product. This study provided insights into the stability profiling for rhumAb1 drug product. The study protocols presented here may be applicable to the analytical characterization of other monoclonal antibody-based therapeutic products.

Fractional Flow Reserve, Myocardial ; Humans ; Male ; Middle Aged ; Tomography, X-Ray Computed ; methods

Antibodies, Monoclonal ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; metabolism ; Humans ; Immunohistochemistry ; methods ; In Situ Hybridization, Fluorescence ; Lung Neoplasms ; diagnosis ; genetics ; metabolism ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

BACKGROUNDDysregulated metallothionein 2A (MT2A) has been implicated in carcinogenesis. The purpose of this study was to investigate the expression of MT2A in gastric cancer (GC) and its correlation with prognosis.

METHODSReverse transcription-polymerase chain reaction and real-time polymerase chain reaction were used to detect the mRNA expression of MT2A in 12 GC cell lines, normal gastric epithelial GES-1 cells, and 36 GC and adjacent normal tissues. MT2A protein expression was determined in 258 GC tissues and 171 adjacent normal tissues by immunohistochemistry.

RESULTSMT2A mRNA expression was lower in GC cells and primary tumors than in GES-1 cells and adjacent normal tissues, respectively. High protein expression of MT2A was present in 130 of 171 normal tissues (76.0%) and in 56 of 258 GC tissues (21.7%; P < 0.001). MT2A protein expression was higher in well/moderately differentiated GC (22/54; 40.7%) than in poorly differentiated GC (34/204; 16.7%; P < 0.001). Moreover, the protein expression of MT2A was lower in diffuse-type GC (6/82; 7.3%) than in intestinal-type GC (50/176; 28.4%; P = 0.0001). Importantly, MT2A expression was an independent prognostic factor for GC, and decreased MT2A expression was associated with poor clinical outcome (P < 0.001). The expression status of MT2A could predict prognosis in intestinal and diffuse-type GCs.

CONCLUSIONExpression status of MT2A might be a useful prognostic biomarker for GC, especially when used in combination with Lauren's classification.

Adult ; Aged ; Cell Line, Tumor ; Female ; Humans ; Logistic Models ; Male ; Metallothionein ; analysis ; genetics ; MicroRNAs ; analysis ; Middle Aged ; Prognosis ; Proportional Hazards Models ; Stomach Neoplasms ; chemistry ; classification ; pathology