BACKGROUND:With the innovation of examination technique,the number of patients with spinal metastases in different stages is increasing year by year.Percutaneous vertebroplasty is an important treatment for spinal metastases;however,there is no report on the biomechanical effect in different stages and different activities after operation. OBJECTIVE:To simulate thoracic T10 bone stress and displacement of the different locations of the tumor metastasis based on the three-dimensional finite element model. METHODS:According to thoracic three-dimensional CT images of a 30-year-old healthy male,Mimics software was used to construct a three-dimensional geometric model of thoracic vertebrae(T9-T11),including ribs,ligaments and intervertebral discs.Three-dimensional models of T9-T11 vertebral bodies and different parts of the posterior thoracic vertebrae invaded by thoracic metastatic tumors were simulated,including the control group with intact vertebral structure,unilateral metastasis involving the vertebral body area(experimental group 1),unilateral metastasis involving the vertebral body and pedicle area(experimental group 2),unilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 3),and bilateral metastasis involving the vertebral body,pedicle and transverse process area(experimental group 4).Abaqus software was used to create a three-dimensional finite element model.The von Mises stress distribution and the displacement of the model were analyzed under the loading condition,buckling condition,extension condition,and rotation condition. RESULTS AND CONCLUSION:(1)In the study of the maximum total displacement of loading points in different experimental groups under loading,flexion,extension,and rotation conditions,with the increase of metastatic tumor invasion site and invasion surface,the total displacement of loading points increased,and the overall stiffness decreased,especially the total displacement of loading points in experimental group 4 was the largest.(2)Under flexion condition,the maximum Von Mises stress value increased significantly after vertebral body and pedicle destruction,while the maximum Von Mises stress value was almost unchanged when the thoracocostal joint destruction was added.(3)On the basis of finite element analysis and simulation of bone tumor model,the elements in the bone cement region were set as a single set,and the bone cement region was set as the corresponding material properties to simulate bone cement filling.The results showed that the maximum total displacement under loading,flexion,extension,and rotation conditions was less than that of each experimental group.(4)The maximum stress values of the simulated percutaneous vertebroplasty patients in the loading,flexion,extension and rotation conditions were significantly lower than those of the femoral model.(5)It is concluded that the three-dimensional finite element model based on thoracic T9-T11 conducive to the biomechanics characteristics of thoracic vertebrae tumor metastasis,and on the basis of the thoracic vertebrae tumor metastasis model can accurately simulate load point after percutaneous vertebral body under different conditions of total displacement and the maximum Von Mises stress situation.

Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To observe the effect of remifentanil-based fast-track anesthesia on the quality of anesthesia recovery in children with congenital heart disease underwent transcatheter closure.Methods Children with congenital heart disease who underwent transcatheter closure were divided into treatment group and control group according to the anesthesia plan.The anesthesia plan of the control group was as follows:anesthesia induction(intramuscular injection of ketamine at 4 mg·kg-1,intravenous injection of propofol at 2.5 mg·kg-1,fentanyl at 10 μg·kg-1and cisatracurium at 0.1 mg·kg-1)and anesthesia maintenance(fentanyl at0.4μg·kg-1·min-1 and propofol at 8 μg·kg-1·min-1).The anesthesia plan of the treatment group was as follows:anesthesia induction(intramuscular injection of ketamine at 5 mg·kg-,intravenous injection of midazolam at 0.1 mg·kg-1,sufentanil at 1.0 μg·kg-1 and cisatracurium at 0.1 mg·kg-1)and anesthesia maintenance(remifentanil at 0.5 μg·kg-1·min-1 and propofol at 8 μg·kg-1·min-1).Anesthesia recovery,facial expression,leg posture,activity,crying and comfortability(FLACC)of 5 pain scores,Ramsay score,hemodynamics,myocardial injury indexes,and adverse drug reactions were compared between the two groups.Results There were 64 cases in treatment group and 56 cases in control group.The spontaneous respiration recovery time,call time and extubation time of the treatment group were(4.87±1.22),(10.16±2.58)and(12.55±3.19)min,shorter than those in control group,which were(5.49±1.35),(13.34±3.27)and(15.67±3.62)min(all P＜0.05).At 1 h and 2 h after operation,Ramsay scores of treatment group were 2.58±0.35 and 3.69±0.42,were lower than 3.02±0.47 and 4.24±0.39 in control group(all P＜0.05).At 1 h and 2 h after operation,the FLACC scores of the treatment group were 3.03±0.81 and 3.75±0.84,lower than 3.78±0.62 and 4.36±0.51 in control group(all P＜0.05).Mean arterial pressure(MAP)of treatment group at the insertion of laryngeal mask,the insertion of occluder and the end of the operation were(102.45±10.26),(94.18±8.37)and(91.46±10.15)mmHg,lower than those in control group,which were(107.84±10.11),(100.57±9.84)and(97.33±8.53)mmHg(all P＜0.05).On day 1 and day 3 after operation,serum creatine kinase isoenzyme(CK-MB)levels in the treatment group were(10.03±2.58)and(8.65±2.16)U·L-1,lower than those in control group,which were(12.44±3.07)and(10.16±2.35)U·L-1(all P＜0.05).On day 1 and day 3 after operation,serum cardiac troponin Ⅰ(cTn Ⅰ)levels in treatment group[(0.07±0.02)and(0.04±0.01)μg·L-1]were lower than those in control group[(0.09±0.03)and(0.06±0.02)μg·L-1](all P＜0.05).The incidence of adverse anesthesia reactions in treatment group was 6.25％(4 cases/64 cases),lower than 17.86％(10 cases/56 cases)in control group(P＜0.05).Conclusion Remifentanil-based fast-track anesthesia can improve the quality of anesthesia recovery in children with congenital heart disease undergoing transcatheter closure,with good sedative and analgesic effects,stable hemodynamics during operation,and low incidence of adverse drug reactions.

The Piezo protein is a non-selective mechanosensitive cation channel that exhibits sensitivity to mechanical stimuli such as pressure and shear stress. It converts mechanical signals into bioelectric activity within cells, thus triggering specific biological responses. In the digestive system, Piezo protein plays a crucial role in maintaining normal physiological activities, including digestion, absorption, metabolic regulation, and immune modulation. However, dysregulation in Piezo protein expression may lead to the occurrence of several pathological conditions, including visceral hypersensitivity, impairment of intestinal mucosal barrier function, and immune inflammation.Therefore, conducting a comprehensive review of the physiological functions and pathological roles of Piezo protein in the digestive system is of paramount importance. In this review, we systematically summarize the structural and dynamic characteristics of Piezo protein, its expression patterns, and physiological functions in the digestive system. We particularly focus on elucidating the mechanisms of action of Piezo protein in digestive system tumor diseases, inflammatory diseases, fibrotic diseases, and functional disorders. Through the integration of the latest research findings, we have observed that Piezo protein plays a crucial role in the pathogenesis of various digestive system diseases. There exist intricate interactions between Piezo protein and multiple phenotypes of digestive system tumors such as proliferation, apoptosis, and metastasis. In inflammatory diseases, Piezo protein promotes intestinal immune responses and pancreatic trypsinogen activation, contributing to the development of ulcerative colitis, Crohn’s disease, and pancreatitis. Additionally, Piezo1, through pathways involving co-action with the TRPV4 ion channel, facilitates neutrophil recruitment and suppresses HIF-1α ubiquitination, thereby mediating organ fibrosis in organs like the liver and pancreas. Moreover, Piezo protein regulation by gut microbiota or factors like age and gender can result in increased or decreased visceral sensitivity, and alterations in intestinal mucosal barrier structure and permeability, which are closely associated with functional disorders like irritable bowel sydrome (IBS) and functional consitipaction (FC). A thorough exploration of Piezo protein as a potential therapeutic target in digestive system diseases can provide a scientific basis and theoretical support for future clinical diagnosis and treatment strategies.

ObjectiveGQDs has become a superstar among zero-dimensional carbon-based materials. As one of the most abundant and important biological elements, its unique optical properties, high dispersion and biocompatibility have attracted extensive attention from scientists. This paper aims to investigate the effect of GQDs on cell viability, apoptosis and inflammatory factor expression in RAW264.7 macrophages and evaluate cell imaging capability of GQDs in vitro, which could provide theoretical basis for the safe application of GQDs in biomedical field. MethodsGraphene oxide was prepared by modified Hummer’s method. H₂O₂ and W₁₈O₄₉ interacted with each other under hydrothermal conditions to produce hydroxyl radicals, which can cut graphene oxide into GQDs using a top-down approach. The microstructure of GQDs was analyzed in detail by X-ray powder diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, atomic force microscopy, scanning electron microscopy and Fourier infrared transform. The biocompatibility of GQDs on macrophage was evaluated by CCK-8 and dead/alive staining. Flow cytometry results showed the apoptosis of RAW264.7 macrophages induced by GQDs. mRNA expression of inflammatory factors was evaluated byRT-qPCR. Cell imaging was exhibited by laser scanning confocal. ResultsHydroxyl radicals are produced by H₂O₂ and W₁₈O₄₉ under hydrothermal conditions, which contribute to cut graphene oxide into 3-5 nm GQDs in one step. The quantum yield of this method is 43%. Fluorescence lifetime of these blue GQDs is 1.67 ns. The Zigzag-type site and defect state of the triplet carbene radical lead to the excitation wavelength dependence of GQDs, and the optimal excitation and emission wavelengths are 330 nm and 400 nm, respectively. The boundary effect and amphiphilicity of quantum dots make GQDs possess abundant functional groups, vacancy defects and high dispersion, which results in GQDs exhibits good water solubility. RAW264.7 macrophages are incubated with different concentration in DEME medium for 24 h, 48 h and 72 h to evaluate cell. The survival rate of RAW264.7 cells is significantly dependent on the concentration and time of GQDs. CCK-8 and dead/alive staining show that GQDs have high biocompatibility. The effect of 200 mg/L GQDs on apoptosis of RAW264.7 cells is revealed by the scatter plot of bivariate flow cytometry. Under the stimulation of LPS+INF‑γ, the expression of TNF-α was increased in RAW264.7 cells, which co-acted with other cytokines to participate in the immune response of RAW264.7 cells in vitro, and mediated the production of IL-1β inflammatory factor in RAW264.7 cells, thereby inducing apoptosis of RAW264.7 cells. The results of RT-qPCR showed that GQDs can inhibit the growth of RAW264.7 cells in vitro, and stimulate them to increase TNF-α expression in RAW264.7 cells, which make cell membrane rupture and produce IL-1β inflammatory factors to induce cell apoptosis. The high biocompatibility of GQDs is attributed to the rich oxygen-containing functional groups (―COOH, ―OH, and CO) on the surface of GQDs, which makes its surface negatively charged and easy to be swallowed into the cell interior when interacting with the cell membrane with low affinity. Transmission electron microscopy (TEM) observed that the GQDs were swallowed into the cells. Furthermore, laser confocal results displayed that blue GQDs has certain ability of cell imaging in vitro. ConclusionThe water solubility, low toxicity, fluorescence properties and the induction effect of inflammatory factors of GQDs provide broad prospects for their application in the field of immunotherapy and cell imaging in the future.

Nutritional therapy is a core component of critically ill patient management,and the enteral route has become the preferred method due to its dual roles of nutrition and non-nutrition. The use of vasoactive medications makes enteral nutrition decisions more challenging for these patients. This review systematically examines the pathophysiological effects of vasoactive medications on gastrointestinal tract of critically ill patients,the current value and safety of enteral nutrition in this patient's population,summarizes the optimal strategies for implementing enteral nutrition in these patients for clinical reference.

Objective To explore the mechanism of'homotherapy for heteropathy'Zhigancao Decoction in the treatment of coronary heart disease arrhythmia and pulmonary fibrosis by network pharmacology and molecular docking technology.Methods All the active components of Zhigancao Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Herbal Compendium(HERB).The SwissTargetPrediction database was used to predict the targets.Cytoscape software was used to construct the drugs-targets network diagram and network topology analysis was performed to obtain the core drug targets.The disease targets of coronary heart disease,arrhythmia and pulmonary fibrosis were obtained in GeneCards and OMIM databases,and the intersection targets of Chinese medicine and disease were obtained by Venny software.The intersection targets were imported into the STRING online database to construct a protein-protein interaction network,and the data were imported into Cytoscape software for visualization and screening of core targets.Gene ontology(GO)function enrichment analysis and kyto encyclo-pedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using the Metascape database.Molecular docking verification and heat map visualization were performed on the core intersection target and the core drug target through the CB-DOCK2 online platform.Results A total of 137 active components of Zhigancao Decoction were screened out,and 848 corresponding drug targets were obtained by removing repeated values.A total of 9 962 targets of coronary heart disease,5 735 targets of arrhythmia and 7 722 targets of pulmonary fibrosis were obtained.A total of 362 drug-disease intersection targets were obtained by Venny platform processing.The potential core targets with higher degree values were GAPDH,IL-6,ALB,STAT3,TNF,MMP-9 and so on by network topology analysis.GO functional enrichment analysis showed that the main biological processes(BP)involved in Zhigancao Decoction'homotherapy for heteropathy'were the response to hormones,the positive regulation of circulatory system process,phosphorus metabolism process,the response to exogenous stimulation,and the response to organic matter,the main cellular components(CC)include lipid rafts,receptor complexes,cytoplasmic perinuclear regions,dendrites,membrane sides,etc.,the main molecular functions(MF)include protein kinase activity,kinase binding,protein homopolymerization activity,nuclear receptor activity,heme binding,etc..KEGG pathway enrichment analysis showed that the main signaling pathways involved in Zhigancao Decoction'homotherapy for heteropathy'were lipid and atherosclerosis,calcium signaling pathway,cAMP signaling pathway,insulin resistance,cGMP-PKG signaling pathway,JAK-STAT signaling pathway,NF-κB signaling pathway,etc..The results of molecular docking suggested that there was a good binding activity between the main active component targets of Zhigancao Decoction and the core targets of'homotherapy for heteropathy'.Conclusion Zhigancao Decoction mainly regulates JAK-STAT,NF-κB,cAMP and other signaling pathways,acts on IL-6,STAT3,TNF,MMP-9 and other gene targets,and exerts the effect of'homotherapy for heteropathy'on coronary heart disease arrhythmia and pulmonary fibrosis.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

Objective To investigate the efficacy and safety of subcutaneous immunotherapy(SCIT)using dust mites in children with allergic asthma.Methods In a prospective randomized controlled study,98 children with dust mite-induced allergic asthma were randomly divided into a control group(n=49)and an SCIT group(n=49).The control group received inhaled corticosteroid treatment,while the SCIT group additionally received a standardized three-year SCIT regimen.The two groups were compared based on peripheral blood eosinophil percentage,visual analogue score(VAS),total medication score,Asthma Control Test/Childhood Asthma Control Test scores,fractional exhaled nitric oxide(FeNO),and lung function before treatment,and at 6 months,1 year,2 years,and 3 years after treatment.Adverse reactions were recorded post-injection to evaluate the safety of SCIT.Results Compared with pre-treatment levels,the SCIT group showed a significant reduction in the percentage of peripheral blood eosinophils,VAS,total medication score,and FeNO,while lung function significantly improved,and asthma control levels were better 3 years after treatment(P<0.05).Compared with the control group,the SCIT group showed more significant improvement in all evaluated indicators 3 years after treatment(P<0.05).A total of 2 744 injections were administered,resulting in 157 cases(5.72%)of local adverse reactions and 4 cases(0.15%)of systemic adverse reactions,with no severe systemic adverse events.Conclusions SCIT is an effective and safe treatment for allergic asthma in children.