BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95％confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95％Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95％Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95％Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95％Cl,0.969-0.980;P＜0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25％and 32.11％,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Background: Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear. Objective: The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenolinduced MI in rats. Methods: A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats. Results: Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels. Conclusions: Our findings indicate that ICS II exerts anti-MI effects, and its preliminary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.

Objective To investigate the compatible stability of esketamine hydrochloride,sufentanil citrate,butorphanol tartrate,and metoclopramide in 0.9%sodium chloride injection,and to provide a reference for the rational use of medication for postoperative analgesia.Methods The four drugs were compounded by simulating the clinical concentrations of the drugs,and the samples were taken at 0,4,8,12,24 and 48 h under light-shielded and light-exposed conditions at room temperature.The appearance,pH value,relative drug content,and insoluble particles were determined.Results The appearance of esketamine hydrochloride,sufentanil citrate,butorphanol tartrate,and metoclopramide concoction was clear at 48 h.The pH values were in the range of 4.69 to 4.79,and the relative drug content of the four drugs were in the range of 95%to 105%.The number of insoluble particles exceeded the specified range in the Chinese Pharmacopoeia(2020 edition)at 4 h and 8 h.Conclusions Under light-shielded and light-exposed conditions at room temperature,the appearance,pH value and relative drug content of the compounded solution remained stable for 48 h.However,the number of insoluble particles exceeded the specified standard.Therefore,it is not recommended to mix the above 4 drugs with 0.9%sodium chloride injection for use in analgesic pumps.

Objective To explore the effect and molecular mechanism of cabozantinib combined with programmed cell death-ligand 1(PD-L1)monoclonal antibody in the treatment of hepatocellular carcinoma(HCC).Methods Subcutaneous tumor-bearing model was constructed using mouse hepatoma cells Hepa1-6.Model mice were divided into the control group,cabozantinib treatment group,PD-L1 monoclonal antibody treatment group,and cabozantinib+PD-L1 monoclonal antibody treatment group according to the intervention methods.The tumor growth rate of mice in each group was analyzed;the proportion of T cell infiltration in tumor tissues of mice in each group was detected by flow cytometry.Multicolor immunofluorescence was used to analyze the infiltration of T cells in tumor tissues of mice in each group.The expression levels of cytokines in the serum of mice in each group were detected by enzyme-linked immunosorbent assay(ELISA).Results The inhibitory effect of the cabozantinib+PD-L1 monoclonal antibody on the tumorigenic ability of hepatoma cells in vivo was significantly stronger than that of the cabozantinib or PD-L1 monoclonal antibody.The results of flow cytometry and multicolor immunofluorescence detection showed that the proportion of CD8+T cells in the tumor tissues of the cabozantinib+PD-L1 monoclonal antibody treatment group was significantly higher than that of the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of TNF-α,IFN-γ and IL-6 in the serum of mice in the cabozantinib+PD-L1 monoclonal antibody treatment group were significantly higher than those in the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of the in vivo tumorigenesis experiment showed that the CD8 antibody could antagonize the inhibitory effect of cabozantinib combined with PD-L1 on the tumorigenic ability of mouse hepatoma cells.Conclusion Cabozantinib may enhance the anti-hepatocellular carcinoma effect of PD-L1 by recruiting CD8+T cells,and is expected to become a new strategy to enhance the effect of anti-tumor immunotherapy.

Objective To explore the effect and molecular mechanism of cabozantinib combined with programmed cell death-ligand 1(PD-L1)monoclonal antibody in the treatment of hepatocellular carcinoma(HCC).Methods Subcutaneous tumor-bearing model was constructed using mouse hepatoma cells Hepa1-6.Model mice were divided into the control group,cabozantinib treatment group,PD-L1 monoclonal antibody treatment group,and cabozantinib+PD-L1 monoclonal antibody treatment group according to the intervention methods.The tumor growth rate of mice in each group was analyzed;the proportion of T cell infiltration in tumor tissues of mice in each group was detected by flow cytometry.Multicolor immunofluorescence was used to analyze the infiltration of T cells in tumor tissues of mice in each group.The expression levels of cytokines in the serum of mice in each group were detected by enzyme-linked immunosorbent assay(ELISA).Results The inhibitory effect of the cabozantinib+PD-L1 monoclonal antibody on the tumorigenic ability of hepatoma cells in vivo was significantly stronger than that of the cabozantinib or PD-L1 monoclonal antibody.The results of flow cytometry and multicolor immunofluorescence detection showed that the proportion of CD8+T cells in the tumor tissues of the cabozantinib+PD-L1 monoclonal antibody treatment group was significantly higher than that of the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of enzyme-linked immunosorbent assay(ELISA)showed that the expression levels of TNF-α,IFN-γ and IL-6 in the serum of mice in the cabozantinib+PD-L1 monoclonal antibody treatment group were significantly higher than those in the cabozantinib or PD-L1 monoclonal antibody treatment group.The results of the in vivo tumorigenesis experiment showed that the CD8 antibody could antagonize the inhibitory effect of cabozantinib combined with PD-L1 on the tumorigenic ability of mouse hepatoma cells.Conclusion Cabozantinib may enhance the anti-hepatocellular carcinoma effect of PD-L1 by recruiting CD8+T cells,and is expected to become a new strategy to enhance the effect of anti-tumor immunotherapy.

OBJECTIVE To establish a total quality management system for pharmacy intravenous admixture services （PIVAS）， in order to promote the standardization， accuracy and rationalization of clinical intravenous infusion. METHODS Based on information system in PIVAS， the management system and quality monitoring items of the whole process before， during and after PIVAS infusion preparation were formulated. The quality control and quality improvement were carried out regularly with quality management tools and methods such as PDCA （plan， do， check， process） cycle， quality control circle， and root cause analysis. The main quality control indexes of PIVAS were retrospectively analyzed before （in 2019） and after PDCA cycle management （in 2020 and 2021）. RESULTS The indexes of quality monitoring in the whole process of PIVAS infusion preparation， such as the score of drug quality management， the drug residue qualification rate and the qualified rate of drug content in infusion， were increased from 92 points， 79%， 86.4% in 2019 to 99 points， 92%， 99.8% in 2021， respectively. The indexes of safe and rational drug use， such as the ratio of intravenous irrational medical orders， the rate of drug repercussion， the rate of antibiotics use， and the rate of TCM injection use decreased from 0.98%， 6.1%， 40.55%， 39.70% to 0.23%， 3.2%， 37.18%， 26.00%， respectively. CONCLUSIONS The established total quality management system for PIVAS can improve the quality management level in the infusion preparation process， improve the quality of infusion preparation and promote clinical safe and rational drug use.

Objective To investigate biomechanical differences of two posterior occipitocervical internal fixation techniques for treating basilar invagination with atlantoaxial dislocation (BI-AAD). Methods Intra-articular cage + posterior occipital plate+C2 pedicle screw (Cage+C2PS+OP), and intra-articular cage+C1 lateral mass screw+C2PS (Cage+C1LMS+C2PS) models were established based on occipitocervical CT data of the BI-AAD and clinical operation scheme, and the stability of atlantoaxial joint and stress distribution characteristics of C2 endplate and implanted instruments under different motion states were analyzed. Results Compared with the Cage+C1LMS+C2PS model, the atlantoaxial range of motion ( ROM) under flexion, extension, lateral bending and axial rotation in the Cage+C2PS+OP model were reduced by 5. 26% , 33. 33% , 43. 75% , -5. 56% , and stress peak of screw-rod fixation system were reduced by 47. 81% , 60. 90% , 48. 45% , 39. 14% , respectively. Under two internal fixation modes, stresses of C2 endplate and cage were mainly distributed on the compressive side during the motion, and both the screw-bone interface and the caudal side of screw subjected to large loading. Conclusions Two internal fixation methods could provide similar stability. However, the stress concentration of screw-rod system was more obvious and the possibility of screw loosening and fracture was greater under Cage+ C1LMS+C2PS fixation.