OBJECTIVE To evaluate the cost-effectiveness of amivantamab combined with lazertinib （hereinafter referred to as “AL”） regimen as first-line treatment for EGFR -mutated advanced non-small cell lung cancer （NSCLC） from the perspective of China’s healthcare system. METHODS A partitioned survival model was established based on updated data from the MARIPOSA study， with a 10-year time horizon and 28-day cycles. The primary outcome index was quality adjusted life year （QALY）， and the willingness-to-pay （WTP） threshold was set at three times China’s per capita GDP in 2024 （287 247 yuan/QALY）. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of AL regimen versus osimertinib monotherapy regimen as first-line treatment for EGFR -mutated advanced NSCLC. One-way and probabilistic sensitivity analyses were performed to test model robustness. Scena rio analyses were conducted to explore the impact of utility values for different health states on the outcomes and determine the required price reductions of amivantamab and lazertinib to achieve cost-effectiveness. RESULTS Compared with the osimertinib monotherapy regimen， the ICER for the AL regimen as first-line treatment for advanced EGFR -mutated NSCLC was 2 062 096.15 yuan/QALY， significantly exceeding the WTP threshold established in this study. One-way sensitivity analysis revealed that the utility value of progression-free survival state and the price of amivantamab were the primary factors influencing the ICER. Probabilistic sensitivity analysis revealed that the AL regimen only became cost-effective when the WTP threshold was set at 2 050 000 yuan/QALY. Scenario analysis indicated that altering the utility value still rendered the AL regimen non-cost-effective. When amivantamab （350 mg） prices decreased by 80%， 85%， and 90% respectively， lazertinib （80 mg） prices would need to decrease by 95.97%， 40.63%， 5.29%， respectively. This would enable the AL regimen’s ICER to consistently fall within the WTP threshold established in this study. CONCLUSIONS At the WTP threshold established in this study， the AL regimen does not demonstrate cost-effectiveness for first-line treatment of advanced EGFR -mutated NSCLC compared to the osimertinib monotherapy regimen. Significant price reductions for both drugs would be required to alleviate the financial burden on patients.

OBJECTIVE To evaluate the cost-effectiveness of culmerciclib combined with fulvestrant as second-line treatment for patients with hormone receptor-positive（HR+）/human epidermal growth factor receptor 2-negative （HER2–） locally advanced or metastatic breast cancer， within the context of the Chinese healthcare system. METHODS A partitioned survival model was established based on the CULMATE-1 study， with a simulation time horizon set at 15 years and a cycle length of 28 days. The incremental cost-effectiveness ratio （ICER） of culmerciclib combined with fulvestrant versus fulvestrant monotherapy as second-line treatment for HR+/HER2– breast cancer was calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the model. Meanwhile， scenario analysis of culmerciclib price reduction was conducted； the required price reduction and price to reach the willingness-to-pay （WTP） threshold in this study were calculated. RESULTS The results of the base-case analysis indicated that， compared with the fulvestrant monotherapy regimen， culmerciclib combined with fulvestrant yielded an additional 0.823 quality-adjusted life year （QALY）， with a corresponding ICER of 371 696.26 yuan/QALY， which exceeded the WTP threshold （199 330 yuan/QALY）. The results of the univariate sensitivity analysis indicated that the cost of culmerciclib， the discount rate， the utility values for progression disease and progression free survival status were significant factors influencing the ICER； both the univariate sensitivity analysis and the probabilistic sensitivity analysis validated the robustness of the model results. Scenario analysis indicated that when the price of culmerciclib was reduced by 30%， 55% and 85% respectively， the corresponding ICER values fell below 3， 2， and 1 times China’s per capita GDP in 2025， with the probability of cost-effectiveness being 3.00%， 94.90%， 100%. When the cost of culmerciclib （60 mg） was reduced by 52.6% to 50.96 yuan， the ICER value met the WTP threshold established in this study. CONCLUSIONS When the WTP threshold is set at twice China’s per capita GDP in 2025， second-line treatment with culmerciclib combined with fulvestrant for HR+/HER2– locally advanced or metastatic breast cancer does not exhibit cost-effectiveness advantage over fulvestrant monotherapy. Therefore， a reasonable price reduction is required to alleviate the financial burden on patients.

OBJECTIVE To establish the UPLC fingerprint and the method for multi-component content determination in Jingangteng capsules， and to evaluate its quality by combining chemical pattern recognition analysis. METHODS An UPLC method was established. Separation was performed on a Zorbax SB-C 18 Rapid Resolution HD column， with acetonitrile-0.1% formic acid as the mobile phase for gradient elution.Using the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicines （2012 edition）， UPLC fi ngerprints were established for 10 batches of Jingangteng capsules， and similarity was evaluated. SPSS 22.0 and SIMCA 14.1 software were used to perform hierarchial-cluster analysis and orthogonal partial least squares discriminant analysis （OPLS-DA）， respectively. The same UPLC method was employed to determine the contents of chlorogenic acid， 3，5-dihydroxy-2-methylbenzoic acid-3- O -glucoside （M1）， caffeic acid， astilbin， oxyresveratrol， quercitrin and resveratrol in the 10 batches of samples. RESULTS A total of 17 common peaks were identified in UPLC fingerprints of the 10 batches of samples， of which 7 were identified as chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol. The similarities of 10 batches of samples ranged from 0.820 to 0.985. The results of hierarchial-cluster analysis showed that 10 batches of samples were grouped into four categories： S1-S4 formed one group， S5 and S6 formed another， S7， S8 and S10 formed a third， and S9 formed a fourth， consistent with the OPLS-DA results； the variable importance projection values for peaks 7， 10， 2， 16 （resveratrol）， 13 （oxyresveratrol）， 11， 6 （caffeic acid）， 5 （M1） and 15 （quercitrin） were ＞1. Quantitative analysis results showed that the contents of chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol were 1.650 8-4.213 7， 0.636 2-2.161 7， 0.031 0-0.086 5， 0.239 1-1.069 3， 0.211 9-1.104 0， 0.488 8-2.399 2， and 0.164 0-0.699 8 mg/g， respectively. CONCLUSIONS UPLC fingerprint and content determination methods established in this study are simple to operate， accurate， reliable and reproducible； when combined with chemical pattern recognition analysis， they can be used to evaluate the quality of Jingangteng capsules. Nine components， such as resveratrol， oxyresveratrol， caffeic acid， M1 and quercitrin， may serve as markers of quality variation.

The Split-Cre system consists of two inactive polypeptides: NCre and CCre, which can be recombined into an active full-length Cre under certain conditions. This system is typically used with LoxP. To develop an efficient Split-Cre system, this study used Rma intein from Rhodothermus marinus to split Cre and screened out the split site S102 which could efficiently mediate the recombination of Cre in the "Traffic Light" reporter cell line. Moreover, the S102 Split-Cre system was delivered to mice by dual-adeno-associated virus (AAV), and it was demonstrated that the efficiency of the Rma intein-mediated S102 Split-Cre system was comparable to the full-length Cre in mice. This system lays a foundation for both basic and applied research on Split-Cre.
Inteins/genetics* ; Animals ; Integrases/biosynthesis* ; Mice ; Dependovirus/metabolism* ; Bacterial Proteins/genetics* ; Recombination, Genetic ; Humans

Allergic conjunctivitis has a high incidence rate, which is difficult to cure after repeated attacks, and seriously affects people's quality of life.Animal models are the main tools and means for the study of allergic conjunctivitis diseases, and animal modeling is an important step in the study of allergic conjunctivitis diseases.Because the study of allergic conjunctivitis is relatively late than that of other allergic diseases, the animal model of allergic conjunctivitis mainly refers to the animal model building methods of allergic asthma, rhinitis and other allergic diseases, or makes improvements on them, resulting in a variety of animal model building methods, poor reference of animal model building methods, and low survival rate and success rate of animal model building.This paper analyzes the pathogenic mechanism of allergic conjunctivitis and the purpose of animal modeling, searches and analyzes the modeling process of allergic conjunctivitis in Pubmed in the past 10 years, sorted and analyzed the modeling methods according to the sensitization mechanism, and summarized four modeling process models, which provided a reference for the selection of animal strains, sensitization dose and sensitization process in the modeling of allergic conjunctivitis.

Objective:To explore the mediating effect of self-rated health status between living space and social frailty of the elderly in community, and to provide reference for intervention strategies.Methods:From December 2023 to March 2024, 550 community elderly in Yandun Community, Yicheng Community and Binhu Community in Baohe District of Hefei City were selected as the research objects by convenient sampling method. The general information questionnaire, self-rated health questionnaire, social frailty index and living space assessment scale were used to investigate a cross-sectional survey. Spearman correlation analysis was used to explore the correlation between self-rated health, living space and social frailty of community elderly. Bootstrap method was used to test the mediating effect.Results:A total of 542 valid questionnaires were collected. Among the 542 elderly residents in the community, aged 65-94 (71.69 ± 6.54) years, there were 267 males and 275 females. Among the 542 community elderly, the self-rated health score, living space score and social frailty index were (2.52 ± 0.95), (73.39 ± 16.77) and 0.0 (0.0, 3.0), respectively. Spearman analysis showed that the total score of living space was negatively correlated with the scores of self-rated health and social frailty ( r=-0.477, -0.538, both P<0.01), and the score of self-rated health was positively correlated with the score of social frailty ( r=0.711, P<0.01).The mediating effect results showed that the living space could play a partial mediating effect on social frailty through the mediating variable of self-rated health (-0.028), accounting for 49.12% of the total effect. Conclusions:The self-rated health status of the elderly in the community has an indirect mediating effect between living space and social frailty. Medical workers should take the improvement of the living space mobility of the elderly as the starting point, and improve their self-rated health level through diversified intervention means, so as to reduce the occurrence of social frailty and promote active aging.

Objective:To explore the correlation between phase angle, determined by bioelectrical impedance analysis, and common chronic metabolic diseases in centrally obese individuals, aiming to assess the role of phase angle as a potential biomarker in screening for and preventing common chronic metabolic diseases associated with central obesity.Methods:In this retrospectivel study, body composition measurement was conducted among centrally obese patients attending the outpatient clinic of the Department of Clinical Nutrition of the First Affiliated Hospital of Xinjiang Medical University from July 2022 to May 2024, along with the collection of current medical histories. The subjects were divided into three groups from Q1 to Q3 according to the tertiles of phase angle (Q1 group: phase angle<5.1°; Q2 group: phase angle≥5.1° but <5.6°; and Q3 group: phase angle>5.6°), and the prevalence of metabolic diseases and the differences in body compositions were compared among these three groups. Pearson's correlation was used to analyse the potential associations of phase angle and each body composition with common chronic metabolic diseases.Results:A total of 3 476 centrally obese individuals (1 141 males and 2 335 females) were included in the study. The Q1 group had significantly older age [(45.0±15.1) years vs. (36.1±10.0) years], higher prevalence of type 2 diabetes mellitus (T2DM) (23.9% vs. 17.3%), higher body fat percentage [(41.80%±6.36%) vs. (36.81%±7.21%)], and larger visceral fat area [(171.43±43.46) cm2 vs. (157.57±47.05) cm2] but significantly lower body mass index [(29.98±4.93) kg/m2 vs. (32.57±4.94) kg/m2], basal metabolic rate [(5 692.12±653.33) kJ/d vs. (6 809.04±923.49) kJ/d], skeletal muscle index [(7.16±0.86) kg/m2 vs. (8.60±0.94) kg/m2], body cell mass [(29.47±4.63)(38.18±6.70) kg], and waist-to-hip ratio [(0.972±0.069) vs. (0.977±0.063)] than the Q3 group (all P<0.001). However, there were no significant differences in the prevalence rates of hypertension and dyslipidemia among the three groups (all P>0.05). Among female centrally obese patients, those with all three metabolic diseases had significantly smaller phase angle (4.85°±0.54°) than those with 1-2 metabolic diseases (5.10°±0.62°) and those without metabolic diseases (5.17°±0.55°) (both P<0.001). Among T2DM patients receiving different treatment regimens, phase angle was significantly smaller in the insulin treatment group and the combined treatment group than in the lifestyle intervention group and oral hypoglycemic medication group (all P<0.05). Conclusions:Phase angle is an effective indicator of T2DM in centrally obese individuals and has potential clinical value in the screening and evaluation of metabolic diseases in centrally obese individuals.

Background and purpose:Immune checkpoint blockade(ICB)has become a promising strategy for treating cervical cancer(CC),but terminal T cell depletion still limits the therapeutic efficacy of ICB.The deletion of sorting nexin-9(SNX9)can inhibit thymocyte selection-associated high mobility group box protein(TOX),alleviate T cell exhaustion,and provide new ideas for preventing T cell exhaustion and enhancing the efficacy of cancer immunotherapy.Therefore,this study aimed to explore the immune escape mechanism mediated by the depletion of CD8+T cells induced by the SNX9/TOX signaling pathway in the CC microenvironment.Methods:Fifty-four peripheral blood samples were collected,including 18 from CC patients,18 from patients with high-grade squamous intraepithelial lesions(HSIL)and 18 from subjects with normal cervix.In addition,the study collected 153 pairs of CC and adjacent tissues from patients who received operation in our hospital for the first time.Clinicopathological features,tumor stages,follow-up records and other relevant clinicopathological data of CC patients were obtained from hospital records.The research was approved by the ethics committee of Changsha Fourth Hospital(approval number:20220206).A total of 24 mice were randomly assigned to the following four groups:immunoglobulin G(IgG)group,Anti-SNX9 group,Anti-programmed death-1(PD-1)group and Anti-SNX9+Anti-PD-1 group,with 6 mice in each group.Each group received intraperitoneal injection of blocking antibody and isotype control treatment respectively.ELISpot was used to detect the ability of CD8+T cells to secrete tumor necrosis factor-α(TNF-α)and interferon-γ(IFN-γ).The expressions of TOX and SNX9 in cervical cancer tissues were detected by western blot and immunohistochemistry.Results:The expressions of SNX9 and TOX mRNA in peripheral blood mononuclear cell(PBMC)of CC patients were higher compared with HSIL and normal controls(P＜0.05).The positive cell level of SNX9 and TOX immunohistochemical score were higher in CC tissue than in adjacent tissues(t=18.63,21.10,P＜0.001).The high expression of SNX9 in CC was related to low differentiation/undifferentiation,tumor size,parauterine infiltration,vaginal infiltration,late FIGO stage and pelvic lymph node metastasis(P＜0.05).Compared with the low expression group of SNX9,the overall survival time of CC patients in the high expression group of SNX9 was shorter(P＜0.05).The percentage of CD8+SNX9+T cells was significantly higher in CC patients than in normal controls and HSIL patients(P＜0.05).The ability of CD8+SNX9+T cells to secrete cytokines(TNF-α and IFN-γ)was significantly lower compared with CD8+SNX9-T cells(P＜0.05).Compared with the Anti-SNX9 group,the growth and proliferation of cervical tumor,the expression of SNX9 and TOX protein in tumor tissue in the Anti-SNX9+Anti-PD-1 group further decreased(P＜0.05),and the level of infiltrating CD8+T lymphocytes in tumor tissue and the ability of CD8+T lymphocytes to secrete functional factors TNF-α and IFN-γ further increased(P＜0.05).Conclusion:SNX9/TOX signaling pathway exhibits enhanced activity in patients with cervical cancer and mouse models,and is related to immunosuppression.Targeting SNX9/TOX signaling pathway may be a potential therapeutic strategy for CC.

Objective:To explore drug detoxification motivation in methamphetamine-dependent female youth and its relationship with time perspective,perceived social support and emotion regulation strategies.Methods:To-tally 200 methamphetamine-dependent female youths under compulsory isolation were assessed with the Drug De-toxification Motivation Scale,Zimbardo Time Perspective Inventory-Chinese(ZTPI-C),Emotion Regulation Scale(ERS),and Perceived Social Support Scale(PSSS).Results:Multiple linear regression analysis showed that drug detoxification motivation scores were positively correlated with the scores of ERS reevaluation and expression inhi-bition,PSSS family support scores and level of education(β=0.24,0.16,0.20,0.16).Conclusion:Time perspec-tive,perceived social support and emotion regulation strategies are closely related to drug detoxification motivation in methamphetamine-dependent female youth.

To address the problem of data silos in dental specialties caused by equipment heterogeneity, this study developed an Intelligent Internet of Things (IoT)-enabled dental chair platform (hereinafter referred to as the intelligent platform) based on the concept of medical-engineering integration. The platform adopts a three-tier chair-domain interconnection architecture: the bottom tier integrates multi-source sensors and standardized interfaces for automated data acquisition and linkage with hospital information systems; the middle tier provides clinic-level management and remote teaching collaboration; and the top tier employs a blockchain-based secure cloud database for resource allocation and data management. Clinical validation at The Affiliated Stomatological Hospital of Nanjing Medical University demonstrated that, compared with a control group from the same period in 2023, the trial group achieved a 38.0% increase in average daily patient visits (80.6±6.8 vs. 58.4±5.2, t=15.16, P<0.001), a 24.6% reduction in average treatment time [(36.1±6.3) min vs. (47.9±8.5) min, t=7.72, P<0.001], a 39.2% reduction in waiting time [23.3 (16.5, 30.1) min vs. 38.3 (28.3, 48.3) min, U=32.00, P<0.001], a 30.4% reduction in equipment idle rate [8.7% (5.1%, 12.3%) vs. 12.5% (7.4%, 17.6%), U=251.00, P=0.003], and an increase in patient satisfaction from 88.2% (1 519/1 723) to 94.3% (2 186/2 318) ( t=7.26, P<0.001). User research confirmed that the functions most favored by clinicians and patients were "dental chair parameter updating and clinical data integration" [74.7% (80/107)] and "chairside display of diagnostic images" [76.8% (119/155)], respectively. Looking forward, the intelligent platform has the potential to integrate artificial intelligence-assisted diagnosis and 5G-enabled multicenter collaboration to further expand its clinical applications and accelerate the digital transformation of dental healthcare.