Objective:To understand the epidemiological characteristics and trends of injury in older adults in Jiangsu Province from 2006 to 2022 and provide a scientific basis for developing prevention and control measures.Methods:The data on injury cases aged 60 and older were collected from 12 sentinel hospitals in Jiangsu Province during 2006-2022. The study analyzed the proportion of injury cases among the elderly in the overall population and calculated the annual percent change and average annual percent change (AAPC). A pairwise comparison between groups was performed, and the differences were judged according to the adjusted standardized residuals.Results:From 2006 to 2022, there were 218 426 injury cases among individuals aged 60 and older in Jiangsu Province, which accounted for an increasing proportion of injury cases within the entire population (AAPC=3.17%, P<0.001). The first five causes of elderly injury were falls (42.06%), road traffic injuries (20.20%), animal injuries (11.45%), knife/sharp injuries (9.43%), and blunt injuries (8.13%). From 2006 to 2022, the proportion of falls, animal injuries, and knife/sharp injuries among the elderly aged ≥60 showed an increasing trend, while the proportion of road traffic injuries and blunt injuries decreased (all P<0.001). The incidence of injury was highest in October, with a daily incidence peak between 8:00 and 10:00. Leisure activities (40.34%) were the major activity leading to injury. The injury occurred mainly at home (53.74%), and the injury intention was mainly unintentional (97.41%), all of which showed an increasing trend ( P<0.001). The injuries were mainly bruises (36.00%), and the most common injured positions of the body were low limbs (27.55%), all of which showed a decreasing trend ( P<0.001). About 69.80% of cases were slight, and 79.38% were discharged after treatment, which showed an increasing trend ( P<0.001). Conclusions:The injury data for individuals aged 60 and older in Jiangsu Province exhibited varying trends from 2006 to 2022. There was a noticeable increase in the proportion of elderly injury cases within the overall injury population, as well as an upward trend in falls, animal injuries, and knife/sharp injuries as leading causes of injury. It is imperative to actively develop prevention measures based on the epidemiological characteristics and evolving trends of elderly injuries in Jiangsu Province.

ObjectiveTo assess the quality of randomized controlled trials （RCTs） of compound traditional Chinese medicine （TCM） prescriptions in the treatment of nonalcoholic steatohepatitis （NASH）， and to provide recommendations for standardizing the design and reporting of RCTs in this field. MethodsDatabases such as PubMed， Web of Science， Embase， the Cochrane Library， CNKI， VIP， and Wanfang Data were searched for RCTs of compound TCM prescriptions in the treatment of NASH published from January 1， 2018 to December 31， 2023， and the articles were screened and assessed based on the Cochrane risk-of-bias assessment tool （RoB 2）， the unified standard for clinical trial reporting （CONSORT 2010）， and CONSORT-CHM Formulas 2017 for compound TCM prescriptions. ResultsA total of 45 articles were finally included， and most of these studies were rated as high-risk bias by RoB 2.0. The analysis based on the CONSORT control checklist showed a relatively low reporting rate for most of the key items regarding the quality of RCT studies. ConclusionA relatively large risk of bias is observed in the clinical studies on compound TCM prescriptions in the treatment of NASH published in the past six years， which may lead to the poor quality of reporting and evidence. It is suggested that the top-level design of clinical studies should be taken seriously in addition to investigating the advantages of TCM， so as to improve the quality of clinical studies.

ObjectiveTo investigate the effect of Gualou Xiebai Banxiatang on cardiac function and myocardial histopathological changes in rats with ischemic myocardial injury， and to observe the effect of myocardial microvascular density （MVD）， phosphatidylinositol 3-kinase （PI3K）， mammalian target of rapamycin （mTOR）， hypoxia-inducible factor-1 alpha （HIF-1α）， and vascular endothelial growth factor （VEGF） signaling pathways on myocardial microangiogenesis. MethodSeventy male SD rats were randomly selected， with six rats in the normal group. The remaining rats were fed a high-fat diet and injected with isoproterenol hydrochloride （ISO，80 mg·kg^-1·d^-1， 2 d） to induce a hyperlipidemia-based ischemic heart disease model. After successful modeling， the rats were randomly divided into the model group， high， medium， and low dose groups of Gualou Xiebai Banxiatang， and the metoprolol group. The high， medium， and low dose groups of Gualou Xiebai Banxiatang were given Gualou Xiebai Banxiatang at 10.42， 5.21， 2.61 g·kg^-1·d^-1， respectively， while the metoprolol group was given metoprolol at 2.6 mg·kg^-1·d^-1. Both the normal and model groups were given an equivalent volume of physiological saline for 28 days. After the intervention， relevant tests were conducted， and serum was collected to measure heart function-related indicators. Hematoxylin-eosin （HE） and Masson staining were performed on ventricular tissue to observe pathological changes under a light microscope. Immunohistochemistry （IHC） was used to detect the positive expression of platelet endothelial cell adhesion molecule （CD31）. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of N-terminal pro-brain natriuretic peptide （NT-proBNP） and VEGF. Western blot was used to detect the protein expression levels of PI3K/mTOR/HIF-1α/VEGF. ResultCompared with the normal group， the model group showed significantly increased serum levels of LDH， CK， CK-MB， NT-proBNP， and VEGF （P<0.01）， significantly increased collagen volume fraction （CVF） （P<0.01）， significantly decreased MVD （P<0.01）， and elevated protein expression levels of PI3K， mTOR， HIF-1α， and VEGF （P<0.05， P<0.01）. Compared with the model group， the metoprolol group had significantly lower serum levels of LDH， CK， CK-MB， and NT-proBNP （P<0.01）， significantly higher VEGF levels （P<0.01）， significantly decreased CVF （P<0.01）， significantly increased MVD （P<0.01）， and significantly increased protein expression levels of PI3K， mTOR， and VEGF （P<0.01）， with no statistically significant change in HIF-1α protein expression. Compared with the model group， the high and medium dose groups of Gualou Xiebai Banxiatang had decreased serum levels of LDH， CK， CK-MB， and NT-proBNP （P<0.05， P<0.01）， increased VEGF levels （P<0.05， P<0.01）， significantly reduced CVF （P<0.01）， increased MVD （P<0.05， P<0.01）， and significantly increased protein levels of PI3K， mTOR， HIF-1α， and VEGF （P<0.01）. In the low dose group of Gualou Xiebai Banxiatang， compared with the model group， serum levels of LDH and NT-proBNP were decreased （P<0.05）， VEGF was increased （P<0.05）. Moreover， CVF was decreased （P<0.05）， and the protein expression levels of PI3K， mTOR， HIF-1α， and VEGF were significantly increased （P<0.01）. ConclusionGualou Xiebai Banxiatang can improve cardiac function， reduce myocardial pathological damage， enhance endothelial cell function， promote myocardial microvascular formation， and upregulate the expression of PI3K， mTOR， HIF-1α， and VEGF proteins in myocardial tissue in rats with ischemic myocardial injury.

Objective To quantitatively analyze the effects of population aging and other risk factors on the burden of colorectal cancer in China from 1990 to 2019. Methods The Global Burden of Disease Study 2019 was used to describe the temporal trend of the burden of colorectal cancer. A decomposition method established by Gupta was applied to quantify the burden related to population growth, aging, age-specific prevalence, and disease severity. Results The age-standardized disability adjusted life years (DALY) rates of colorectal cancer in China showed an overall upward trend from 1990 to 2019. The DALY in 2019 increased by 191.12% compared with that in 1990, with 34.54% of the increase attributed to population growth, 111.36% to population aging, and 77.56% to the rise of age-specific prevalence. Meanwhile, -32.54% benefited from the changes in disease severity. Diet low in milk was the primary risk factor for the disease burden of colorectal cancer in China in 2019, followed by diet low in whole grains and calcium. In the last 30 years, the corresponding risk factor of the most rapid increase in China was high BMI with an average annual percentage of change of 4.14%, and the corresponding risk factor of the most rapid decrease in China was diet low in fiber with an average annual percentage of change of -2.00%. Conclusion Aging population is mainly responsible for the considerable increase in the burden of colorectal cancer in China from 1990 to 2019. The health administrative authorities should take corresponding measures to address the adverse impacts associated with aging.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Chinese materia medica and its compound formulas have the characteristics of multi-component,multi-target,and multi pathway effects,and have unique advantages in preventing and treating complex diseases.Network pharmacology explains disease patterns and drug mechanisms from the perspective of complex biological networks,and explores the pharmacological substance basis and target of Chinese medicine.This article summarized the application of network pharmacology from the aspects of biological basis of TCM syndrome,the substance basis and pharmacological mechanism of TCM,compatibility theory of TCM compound formulas,etc.,with the purpose to provide a reference for the research and application of network pharmacology in TCM.

Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

OBJECTIVE To screen the potential drug targets and signaling pathways of Acanthopanax senticosus for the treatment of Alzheimer’s disease(AD) by bioinformatics and network pharmacology-based approach, and to preliminarily validate its efficacy. METHODS The ingredients of Acanthopanax senticosus were obtained through literature, the ingredients were screened by Swiss ADME, and potential targets were predicted by Swiss Target Prediction. AD’s differentially expressed genes were screened from the GSE28146 dataset. The target of Acanthopanax senticosus and AD target were mapped to construct a “drug-ingredients-potential target-disease” network and protein-protein interaction network. The DAVID database was used for GO and KEGG enrichment analysis. Autodock software was used to verify the molecular docking between key active ingredients and core targets. AD mice model was induced by D-galactose combined with aluminum chloride. Morris water maze test was performed to examine the learning memory ability of each group of mice and to observe the pathological changes in the hippocampus of mice. RESULTS Screened to obtain 24 active components and 74 potential targets of Acanthopanax senticosus for the treatment of AD. “Drug-ingredients-potential target-disease” network indicated that quercetin and kaempferol were the main components of Acanthopanax senticosus for the treatment of AD, and the protein-protein interaction network indicated that STAT3, MAPK1 and PIK3CA were the key targets. Obtained 366 GO enrichment entries(P<0.01) and 109 KEGG enrichment pathways(P<0.01). It mainly involved PI3K-AKT, AGE-RAGE, TNF and other pathways. The molecular docking results showed that the main active ingredients of Acanthopanax senticosus were able to bind well to the main targets. The in vivo pharmacological results showed that Acanthopanax senticosus could significantly improve the learning and memory ability of mice, reduce hippocampal tissue damage, and decrease the content of TNF-α, IL-6, and IL-1β in hippocampal tissue. CONCLUSION Acanthopanax senticosus may exert anti-AD effects by inhibiting the expression of inflammatory factors and reducing inflammatory damage.

【Objective】 To evaluate the application of monoclonal typing reagents and human anti-A/B antibodies for absorption-elution test in ABO grouping. 【Methods】 The specificity of monoclonal typing reagents and human anti-A/B antibodies with standard A, B, O and AB phenotypes at 4 ℃, room temperature, and 37 ℃ were compared. Affinity was evaluated by the titer, agglutination time and agglutination intensity of the reaction with A1/B cells. 29 samples with ABO discrepancy were tested to evaluate the ability of monoclonal typing reagents and human anti-A/B antibodies to detect weak antigens in absorption-elution test. 【Results】 The specificity and affinity of human anti-A/B antibodies are low, and monoclonal typing reagents have cross reactivity. Human anti-A/B antibodies can detect most weak antigens in absorption-elution test with no cross reactivity. 【Conclusion】 In ABO grouping, the human anti A/B antibody binding absorption-elution test can serve as a supplement method for identifying ABO weak antigens. Accurate results can be obtained with reasonable reagents and corresponding methodology in serological tests,thus ensuring the safety of blood transfusion.