OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

OBJECTIVE To evaluate the cost-effectiveness of lecanemab for early Alzheimer disease （AD） from a whole-society perspective. METHODS Based on data from the Clarity AD study， a global multicenter， randomized， double-blind， placebo-controlled study of lecanemab for early AD， a Markov model was developed according to the disease progression of AD， with a monthly cycle and a time horizon extending to 99% patient mortality. Quality-adjusted life year （QALY） and incremental cost-effectiveness ratio （ICER） were used as outcome indicators， with a willingness-to-pay （WTP） threshold set at twice China’s per capita gross domestic product （GDP） for 2025 （199 330.00 yuan/QALY）. The model simulated the cost-effectiveness of lecanemab plus standard of care （SoC） versus placebo plus SoC for early AD. One-way sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis were employed to test the robustness of the results. RESULTS Compared with placebo plus SoC， the ICER for lecanemab plus SoC was 4 364 711.54 yuan/QALY. One-way sensitivity analysis showed that the hazard ratio for disease progression， the price of lecanemab， body weight， the monthly progression probability of mild cognitive impairment， and the discount rate were key parameters affecting model robustness. Results of the probabilistic sensitivity analysis showed that the probability of lecanemab being cost-effective was 0 at the current WTP threshold. Scenario analysis indicated that a price reduction of at least 94.88% would be required for lecanemab to fall below the WTP threshold. CONCLUSIONS At the current WTP threshold， lecanemab plus SoC is not cost-effective compared with placebo plus SoC for early AD.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Objective:To explore gait symmetry of unilateral functional ankle instability(FAI).Method:Fifteen male subjects with right functional ankle instability were recruited,Qualisys was used to col-lect and intercept gait cycle data on both sides.Coupling angle and standard deviation of the coupling angle were calculated using Matlab and the effect size was evaluated using Cohen's d.Result:①The coupling angles of the healthy side and the affected side were different in the sagittal plane.The average coupling angles of the hip-knee joint and the hip-ankle joint were higher on the healthy side than on the affected side in the pre-swing period(P<0.05,d=1.02;d=1.11);The average coupling angle of the knee to ankle was higher in 50%of the healthy side than the affected side after the end of support(P<0.05,d=1.21),higher in the pre-swing stage than in the affected side(P<0.05,d=1.07),and lower in 25%—50%of the healthy side during the swing stage than in the affected side(P<0.01,d=1.51).②The coupling angle between the healthy side and the affected side was different in the coronal plane only between the hip and an-kle joint,that is,the healthy side was higher than the affected side in the pre-swing stage(P<0.05,d=1.07)and the healthy side was higher than the affected side in the last part of the gait swing stage(P<0.05,d=1.06).③The standard deviation of coupling angle of sagittal plane of healthy side was lower than that of af-fected side(P<0.01),and the standard deviation of coupling angle of coronal plane of healthy side was high-er than that of affected side(P<0.01).Conclusion:①In patients with functional ankle instability,the coordination pattern of the affected side was mainly in the same pattern of proximal sagittal domination and the reverse pattern of distal coronal domina-tion,that is,the dominance of the ankle joint increased,while the dominance of the hip and knee joint de-creased.②The lower or higher variability of knee-ankle joint in sagittal plane or hip-ankle joint in coronal plane respectively than that of healthy side suggest that ankle joint on the affected side has lower gait adapt-ability,resulting in gait asymmetry and increasing the risk of ankle joint injury.③Based on the above re-sults,it is suggested that future rehabilitation therapy should focus on strengthening the strength of the knee extensor and abductor muscles of the affected hip,improving the symmetry of the left and right gait of unilat-eral FAI,and reducing the risk of recurrent injury in patients with ankle instability.

Aim To investigate the effects of acteoside(ACT)on ulcerative colitis(UC)mice from the per-spective of inflammation and intestinal flora.Methods The UC model was prepared by dextran sulfate sodi-um(DSS)drinking method and treated with ACT for 14 d,during which the activity of the mice was ob-served and the disease activity index(DAI)was scored.ELISA was used to detect the expression of in-flammatory factors.HE staining was used to observe the injury of colon tissue.16S rRNA high-throughput sequencing method was used to detect the structure and abundance of fecal intestinal flora in mice,and the correlation between the flora and inflammatory indica-tors was analyzed.Results After ACT administra-tion,the fear of cold and lazy movement of mice were improved,and the DAI of mice was reduced.The in-tegrity of colon mucosal epithelial cells was restored and mucosal damage was alleviated.The expressions of pro-inflammatory factors MPO,IL-1 β,IL-6,TNF-α,TF and PAF decreased,while the expression of anti-in-flammatory factor IL-10 increased.The abundance of harmful bacteria such as Firmicutes and Bacteroides de-creased,while the abundance of beneficial bacteria such as Bacteroidetes and Alistipes increased.Protective bacteria such as Bacteroidetes and Lachnospira were negatively correlated with IL-1β,IL-6 and other pro-inflammatory factors,while harmful bacteria such as Proteobacteria and Streptococcus were positively correla-ted with the above pro-inflammatory factors.Conclu-sions The therapeutic mechanism of ACT on chronic UC mice is related to its alleviation of inflammation and regulation of intestinal flora,and there is a correlation between inflammatory factors and intestinal flora.

Objective To explore the effects of cerium-doped mesoporous bioactive glass nanoparticles(Ce-MBGNs)as reactive oxy-gen species(ROS)-responsive nanocarriers on inflammation in pulp and their potential to promote odontogenic differentiation of dental pulp stem cells(DPSCs).Methods The cytotoxicity of Ce-MBGNs was assessed by CCK-8.The expression of mRNA of osteogenic/odontogenic differentiation in DPSCs and that of inflammatory factor in RAW264.7 cells were detected by RT-qPCR.Alkaline phospha-tase and Alizarin Red S staining were utilized to investigate their ability to promote dentin mineralization.The ability of Ce-MBGNs to scavenge ROS was evaluated by immunofluorescence and JC-1 staining was used to assess the membrane potential(MMP)of mitochon-drial.Results Ce-MBGNs exhibited good biocompatibility and significantly increased the expression of osteogenic/odontogenic-related genes in DPSCs,promoting mineralization.Additionally,Ce-MBGNs effectively scavenged intracellular ROS,maintained MMP,inhib-ited the expression of pro-inflammatory factors,and promoted the expression of anti-inflammatory factors.Conclusion Ce-MBGNs can protect DPSCs from oxidative damage by maintaining the MMP of mitochondrial and controlling inflammation,and promote their odonto-blastic differentiation,providing a theoretical basis for the development of novel therapeutic agents for oral treatment.

Stereotactic radiotherapy is widely favored because of its high treatment precision and less fractionations.ZND-A is a new domestic gamma-ray cone-beam focused stereotactic radiotherapy system.Herein the technical characteristics of ZND-A system are described in detail from the aspects of the treatment frame,gamma-ray module,collimator module,six-dimensional treatment couch module and image-guided system module,and the main parameters are compared with the mainstream gamma knife equipments at home and abroad.With reference to Response Evaluation Criteria in Solid Tumors(RECIST 1.1),the initial efficacy of the patients treated by the ZND-A system is analyzed to evaluate the advantages and disadvantages of the ZND-A system for providing a reference for the hospital clinical use of this type of gamma knife.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

This study explored whether Astragalus polysaccharide(APS)can regulate the VEGF/VEGFR signaling pathway to affect the proliferative activity of rat intestinal mucosal microvascu-lar endothelial cells(RIMMVECs).RIMMVECs were isolated from newborn rats,then purified and treated with APS at concentrations of 0.1,1.0,10.0,100.0,1 000.0,and 10 000.0 mg/L.MTT was used to determine the effect of APS on RIMMVECs proliferation and screen for the optimal concentration of APS.Subsequently,flow cytometry was used to detect the changes in cell cycle to evaluate the stage of action of APS on the cell cycle in RIMMVECs.Then,the ELISA was used to detect the changes of VEGFA in cell supernatant to evaluate the potential of cell proliferation and angiogenesis.The changes in fluorescence intensity of Fluo-8AM was observed using fluorescence microscopy to evaluate intracellular Ca2+levels.Finally,Western blot was used to detect the ex-pression of PERK in RIMMVECs to analyze the possible mechanism of APS.The results showed that 100 mg/L APS significantly enhanced the proliferative activity of RIMMVECs,increased the content of VEGFA in the cell supernatant,the intracellular Ca2+levels,and the expression of PERK protein,indicating that APS promotes the proliferation of RIMMVECs,which may be a-chieved by promoting the expression of VEGFA and activating the ERK pathway.