Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

Objective:To evaluate the application potential of the bimodal ultrasound/near-infrared (NIR) composite nanoscale probe Arg-Gly-Asp (RGD)/Ag 2Te/perfluoropentane (PFP) @ mesoporous silica nanoparticles (MSN) in the diagnosis and treatment of microvascular diseases. Methods:Nanoprobes loaded with RGD, PFP and Ag 2Te were prepared by ultrasound sonication and carbodiimide method. The characterization of the nanoprobes was determined. The imaging performance, photothermal response, and target-seeking ability of the nanoprobes under NIR irradiation were verified. The biosafety of the nanoprobes was examined, and the thrombolytic ability of the nanoprobes was evaluated. The mice were observed to visualize microvessels of the abdominal wall under the NIR-Ⅱ imaging, and the microvascular visualization ability of the nanoprobes was evaluated. Results:The particle size of nanoprobes was (205.3±2.9) nm and the potential was (2.05±0.58) mV. The coupling rate of the RGD was (82.27±0.36)%, the encapsulation rate of the quantum dots was (80.80±3.26)%, and the photostability of the quantum dots was good. The fluorescence intensity was enhanced with the increase of the mass concentration of RGD/Ag 2Te/PFP@MSN, and the warming effect was more obvious. After ultrasound and NIR irradiation, the thrombolysis rate was significantly increased. RGD/Ag 2Te/PFP@MSN successfully realized NIR-Ⅱ fluorescence imaging of mice microvessels. The cytotoxicity assay and hemolysis assay showed that the probe had a good biosafety. Conclusion:The RGD/Ag 2Te/PFP@MSN nanoprobe is a potential strategy for targeted therapy of thrombotic diseases, combining dual-modality therapy of ultrasound and NIR to offer new possibilities for non-invasive and visual diagnosis and treatment of microvascular embolism.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Objective To study the plasma metabolomics of mice poisoned by different dosage of the combination of diazepam and ethanol,and to reveal the toxicological mechanisms of combined poisoning of diazepam and ethanol.Methods Female Kunming mice were randomly divided into blank group,single and combined poisoning group(n=6),Based on the LD50 of diazepam co-administered with graded ethanol doses,mice in the single-drug and combined groups received oral gavage at 1/2,1,and 2 × LD50.Retro-orbital blood samples(～500 μL)were collected within 24 hours post-administration and analyzed by UPLC-QE-MS technology.Principal component analysis and orthogonal partial least squares discriminant analysis were used to identify differential metabolites and associated metabolic pathways.Results A total of 387 differential metabolites were identified in the combined poisoning group of diazepam and ethanol implicating the key pathways including tryptophan metabolism,phenylalanine metabolism,arginine and proline metabolism,Glycerophospholipid metabolism,phenylalanine,tyrosine and tryptophan biosynthesis.Conclusion Combined diazepam and ethanol poisoning exerts significant systemic effects by disrupting neurotransmitters conduction,exacerbating oxidative stress response and dysregulating energy metabolism.

Objective To establish a high-throughput non-targeted screening and prioritization method for emerging pollutants(EPs)in sewage using direct injection high-resolution mass spectrometry(HRMS).Methods The sewage samples were filtered by membrane filter and directly subjected to the liquid chromatography-time-of-flight mass spectrometer based on a method modified from our previous study.A C18 chromatographic column was applied for a gradient elution separation,and accurate mass and mass spectral fragment information were obtained through the MS full scan mode and MS/MS DIA data collection mode.After peak detection and alignment,the features from the raw data through open source software MZmine 3,and then high-throughput screening strategies such as MassBank and PubChem databases were used for compound annotation.Finally,the candidate features were confirmed with chemical standards by compared their retention time and mass spectrum fragmentation ion peaks.Results 13 EPs were identified,including 7 industrial chemicals,4 pharmaceuticals,1 pesticide and 1 metabolite.High detection rates were observed for metformin(86.2％),2-hydroxybenzothiazole(79.3％),1,2-benzisothiazole-3-one(72.4％),and 1,2-benzisothiazole-3-one(72.4％).The quantitative concentration range of EPs was 1.37～19.05 ng/mL,with the high concentrations observed for melamine(19.05 ng/mL)and furosemide(18.49 ng/mL).Ecological risk assessment identified 1,2-benzisothiazol-3-one,4-aminoacetophenone,creatinine,2-hydroxybenzothiazole,and furosemide as key pollutants.Conclusion This direct injection coupled with HRMS workflow enables efficient non-targeted screening and prioritization of emerging EPs in sewage samples,highlighting five ecotoxicologically critical EPs.The methodology enhances environmental monitoring capabilities and provide critical technical support for interdisciplinary research such as environmental forensics and health risk assessment.

Objective:To compare the efficacy and safety of LY01011,a recombinant anti-RANKL fully human monoclonal antibody injection,versus denosumab in the treatment of bone metastases from solid tumors.Methods:A randomized,double-blind,positive drug parallel-controlled,multicenter clinical trial was conducted.A total of 850 subjects were randomly assigned(1:1)to either the experimental group(424 subjects)or the control group(426 subjects).The experimental group received 13 doses of LY01011,while the control group received 3 doses of denosumab followed by 10 doses of LY01011.Results:The primary efficacy endpoint was the natural logarithmic change from baseline in urinary N-terminal telopeptide of type I collagen corrected by urinary creatinine(uNTX/uCr)at week 13.The change was-1.740(0.042 0)in the experimental group and-1.745(0.042 1)in the control group.The least-squares mean difference between groups was 0.005(90%CI:-0.088 to 0.097),indicating no statistically significant difference(P>0.05).Safety profiles,including treatment-emergent adverse events,laboratory tests,vital signs,physical examinations,and electrocardiograms,were comparable between groups(P>0.05).Conclusions:LY01011 demonstrated biosimilarity to denosumab,with favorable safety profile,tolerability,and potential for clinical application.

Objective:To evaluate the application potential of the bimodal ultrasound/near-infrared (NIR) composite nanoscale probe Arg-Gly-Asp (RGD)/Ag 2Te/perfluoropentane (PFP) @ mesoporous silica nanoparticles (MSN) in the diagnosis and treatment of microvascular diseases. Methods:Nanoprobes loaded with RGD, PFP and Ag 2Te were prepared by ultrasound sonication and carbodiimide method. The characterization of the nanoprobes was determined. The imaging performance, photothermal response, and target-seeking ability of the nanoprobes under NIR irradiation were verified. The biosafety of the nanoprobes was examined, and the thrombolytic ability of the nanoprobes was evaluated. The mice were observed to visualize microvessels of the abdominal wall under the NIR-Ⅱ imaging, and the microvascular visualization ability of the nanoprobes was evaluated. Results:The particle size of nanoprobes was (205.3±2.9) nm and the potential was (2.05±0.58) mV. The coupling rate of the RGD was (82.27±0.36)%, the encapsulation rate of the quantum dots was (80.80±3.26)%, and the photostability of the quantum dots was good. The fluorescence intensity was enhanced with the increase of the mass concentration of RGD/Ag 2Te/PFP@MSN, and the warming effect was more obvious. After ultrasound and NIR irradiation, the thrombolysis rate was significantly increased. RGD/Ag 2Te/PFP@MSN successfully realized NIR-Ⅱ fluorescence imaging of mice microvessels. The cytotoxicity assay and hemolysis assay showed that the probe had a good biosafety. Conclusion:The RGD/Ag 2Te/PFP@MSN nanoprobe is a potential strategy for targeted therapy of thrombotic diseases, combining dual-modality therapy of ultrasound and NIR to offer new possibilities for non-invasive and visual diagnosis and treatment of microvascular embolism.

Objective To establish a simultaneous detection approach for 34 emerging contaminants(ECs)in tap water by liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Human health risk assessment was performed according to the detection results from 43 tap water samples.Methods Tap water samples were concentrated and extracted by solid phase extraction,and then blown to near dry by nitrogen at 40℃.The sample extracts were dissolved in methanol-water solution(95:5,VN)to 0.5 mL for analyzing.Agilent Jet Stream Electrospray Ionization(AJS ESI)and the multiple reaction monitoring(MRM)mode were performed for MS to acquire the data of 34 ECs.A database including precursor ion,product ion and retention times was established accordingly.Results The average linear correlation coefficients(r)of 34 kinds of ECs was 0.995 9.The limits of detection were 0.01～0.60 ng/L and the recoveries were between 60.7％and 119.8％.The intra-group precisions were between 0.05％～9.89％and the intra-day precisions were between 0.20％～14.40％for the spiked samples.The method was applied to analyze 43 tap water samples and a total of 15 ECs were detected.According to the results,the detection rate of caffeine was the highest(84％),and the concentration range was ND～74.42 ng/L.Among all the ECs detected,1,2,3-benzotriazole had the highest concentration(ND～361.15 ng/L),where detection rate was 44％.Humans may be exposed to these ECs by drinking the tap water.The human health risk assessments of 12 kinds of ECs were carried out,however,the estimated risk was negligible(risk quotient＜0.01).Conclusion The method is simple,highly sensitive and selective,and could meet the detection needs of ECs at trace level in tap water.There was no human health risk posed for ECs identified in 43 tap water samples analyzed by this method.