OBJECTIVE To evaluate the cost-effectiveness of capecitabine metronomic chemotherapy combined with aromatase inhibitor （AI） versus AI monotherapy as first-line treatment for hormone receptor-positive （HR+）/human epidermal growth factor receptor 2-negative （HER2－） metastatic breast cancer， thereby providing evidence-based support for clinical therapeutic decision- making and healthcare policy formulation. METHODS Based on the MECCA trial， a partitioned survival model was constructed using a 4-week cycle length to simulate outcomes over patients’ lifetime. The model outputs included total costs， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Sensitivity analyses were performed to validate the robustness of base-case results， while scenario analyses examined the cost-effectiveness of both treatment strategies under 10-year， 20-year， and lifetime time horizons. RESULTS With the willingness-to-pay （WTP） threshold set at 1 times China’s 2024 per capita gross domestic product （GDP） （95 749 yuan/QALY）， patients receiving capecitabine metronomic chemotherapy combined with AI regimen gained incremental utility （0.66 QALYs） while incurring higher costs， with ICER of 27 684.85 yuan/QALY. Results of the one-way sensitivity analysis showed that factors with significant impacts on ICER included the cost discount rate， drug costs of the capecitabine metronomic chemotherapy combined with AI group， utility value in the progression-free survival state， follow-up costs， and treatment costs in the subsequent stablephase. Probabilistic sensitivity analysis indicated that when the WTP threshold ≥49 250 yuan/QALY， the capecitabine metronomic chemotherapy combined with AI regimen had a 100% probability of being cost-effective. Scenario analysis results demonstrated that capecitabine metronomic chemotherapy combined with AI regimen was more cost-effective than the AI alone regimen across 10-year， 20-year， and lifetime study horizons. CONCLUSIONS Under the premise that the WTP threshold is set at 1 times China’s per capita GDP in 2024， capecitabine metronomic chemotherapy combined with AI regimen is more cost-effective than the AI alone regimen as the first-line treatment for HR+/HER2－ metastatic breast cancer.

Objective: To analyze the phylogenetic characteristics of VP1 gene of Coxsackievirus A10 (CVA10) isolates from 2004 to 2023, and to understand the genetic evolution and epidemic trends of CVA10, so as to provide references for the prevention and control of hand, foot, and mouth disease. Methods: The full-length sequences of the VP1 region of CVA10 isolates were retrieved from the BV-BRC database before December 15, 2024. Gene typing, sequence analysis, evolutionary analysis, and amino acid mutation site analysis were conducted using bioinformatics software. Results: A total of 1 253 CVA10 isolates VP1 region nucleotide full-length sequences from 2004 to 2023 were included, with 9 strains from 2004 to 2008, 338 strains from 2009 to 2012, and 906 strains from 2013 to 2023. China had the highest number of CVA10 isolates, with 1 143 strains accounting for 91.22%, and the predominant genotype was C3. Compared to the prototype strain, the nucleotide sequence homology of the VP1 region of CVA10 isolates ranged from 74.94% to 77.63%, while the amino acid sequence homology ranged from 88.59% to 93.62%. The third codon position preferred cytosine and thymine. The top three most abundant amino acids were threonine, alanine, and valine. The average relative synonymous codon usage of 30 amino acid codon groups was greater than 1. The average amino acid substitution entropy value was 0.04, with four amino acid mutation-prone sites identified, and the mutation-prone rate was 1.35%. Conclusions From 2004 to 2023, the majority of CVA10 isolates were primarily sourced from China, with genotype C3 being the predominant circulating strain in China. The nucleotide homology between the CVA10 isolates and the prototype strain was relatively low, and mutation-prone sites were identified, indicating that enhanced monitoring of viral variation is necessary.

OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

OBJECTIVE: To analyze the clinical features of acute myeloid leukemia patients with DEK-NUP214 fusion gene positive. METHODS: The DEK-NUP214 fusion gene was amplified by multi-nested PCR in 26 patients admitted to the First Affiliated Hospital of Soochow University from January 2018 to October 2023, and the disease course and post-transplant survival data were obtained by searching outpatient and inpatient medical records and telephone follow-up. RESULTS: The median follow-up time of pateints was 21.25（0.9-60.2） months. Among 26 patients with DEK-NUP214 fusion gene positive AML, 15 patients had FLT3-ITD gene mutation positive. One patient died after abandoning treatment due to non-remission of induction chemotherapy, one died due to infection, and 23 patients received allo-HSCT after achieving CR, of which one patient died within one month after transplantation due to multiple infections and one died due to severe pulmonary infection that did not respond to treatment. One patient received allo-HSCT in non-remission state and later died due to recurrence. CONCLUSION DEK-NUP214 fusion gene positive AML is a type of acute leukemia subtype with high risk and poor prognosis. Allo-HSCT treatment at the early stage of disease remission is the most effective way to improve the prognosis of patients.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Poly-ADP-Ribose Binding Proteins ; Oncogene Proteins, Fusion/genetics* ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins/genetics* ; Chromosomal Proteins, Non-Histone/genetics* ; Male ; Female ; Adult ; Mutation ; Hematopoietic Stem Cell Transplantation ; Middle Aged

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To study the traditional Chinese medicine(TCM)constitution characteristics of overweight/obese patients in Shanghai region and to investigate the correlation of TCM constitution with body composition.Methods Relevant data were collected from the patients with complete information of TCM constitution and human body composition analysis who visited the specialized outpatient clinic of acup-moxibustion catgut embedding therapy in the Department of Endocrinology,Shanghai Tenth People's Hospital from August 2020 to December 2022.The patients were divided into a normal body mass group(BMI＜24 kg/m2),an overweight group(24 kg/m2≤BMI＜28 kg/m2)and obesity group(BMI≥28 kg/m2),and then the distribution of TCM constitution types in the three groups of patients were analyzed.After that,the correlation between TCM constitution and body composition were explored with multiple regression analysis.Results(1)A total of 315 patients were included,of which 43 patients had normal body mass,85 patients were overweight and 187 patients were obese.(2)The TCM constitution types in descending order of the composition ratio in the normal body mass group and in the overweight group were spleen deficiency constitution,liver stagnation constitution,damp-heat constitution,yang deficiency constitution,and yin deficiency constitution,in the obese group were spleen deficiency constitution,yang deficiency constitution,damp-heat constitution,liver stagnation constitution,and yin deficiency constitution,and in the overweight/obese group were spleen deficiency constitution,damp-heat constitution,yang deficiency constitution,liver stagnation constitution,and yin deficiency constitution.No statistically significant differences of the distribution of TCM constitution types were shown between normal body bass population and overweight/obese population(P＞0.05).In both normal body mass population and overweight/obese population,the single body constitution type was common,and biased constitution was rare,and there was no statistically significant difference when comparing between the two groups(P＞0.05).(3)The results of multiple regression analysis showed that the basal metabolism of all patients was positively correlated with yang deficiency constitution and was negatively correlated with damp-heat constitution,and the differences were statistically significant(P＜0.01).It is indicated that if the score of yang deficiency constitution rose by one point,the basal metabolism would increase by 0.54 kcal,and if the score of damp-heat constitution decreased by one point,the basal metabolism would decrease by 1.005 kcal.Conclusion In Shanghai region,obesity may be the main indication of the variation of the body constitution.In addition to spleen deficiency constitution,the proportions of yang deficiency constitution,damp-heat constitution and liver stagnation constitution are also higher in obese patients.In terms of the correlation between TCM constitution and body composition,basal metabolism is positively correlated with yang deficiency constitution and is negatively correlated with damp-heat constitution.Therefore,for the patients with yang deficiency constitution and damp-heat constitution,the influence of the basal metabolism level on the development of the disease should be taken into account.

Surgical operation is the main treatment of oral and maxillofacial tumors.Dysphagia is a common postoperative complication.Swal-lowing disorder can not only lead to mis-aspiration,malnutrition,aspiration pneumonia and other serious consequences,but also may cause psychological problems and social communication barriers,affecting the quality of life of the patients.At present,there is no systematic evalua-tion and rehabilitation management plan for the problem of swallowing disorder after oral and maxillofacial tumor surgery in China.Combining the characteristics of postoperative swallowing disorder in patients with oral and maxillofacial tumors,summarizing the clinical experience of ex-perts in the field of tumor and rehabilitation,reviewing and summarizing relevant literature at home and abroad,and through joint discussion and modification,a group of national experts reached this consensus including the core contents of the screening of swallowing disorders,the phased assessment of prognosis and complications,and the implementation plan of comprehensive management such as nutrition management,respiratory management,swallowing function recovery,psychology and nursing during rehabilitation treatment,in order to improve the evalua-tion and rehabilitation of swallowing disorder after oral and maxillofacial tumor surgery in clinic.

Objectives:To explore the biological characteristics of human nucleus pulposus decellularized extracellular matrix(NP-dECM)scaffolds with different degrees of degeneration(Ⅱ,Ⅲ,Ⅳ),and to select the NP-dECM scaffold with the best biological characteristics.Methods:Nucleus pulposus mesenchymal stem cells(NPMSCs)were isolated by collagenase type n digestion method.Cell adhesion,cell morphology and growth of NPMSCs were observed under microscope.The cell surface markers CD73,CD90,CD105,CD34,CD45,HLA-DR were detected by flow cytometry,and the differentiation ability of NPMSCs was observed by adipogenic,osteogenic and chondrogenic induction,so as to confirm that they were the seed cells needed for this study.Human NP-dECM scaffolds with different degrees of degeneration were prepared by physical,stain remover and nuclease(group Ⅱ-D,Ⅲ-D and Ⅳ-D).The decellular effect of NP-dECM scaffold was evaluat-ed by visual observation,quantitative and qualitative detection of DNA and extracellular matrix components,and SEM.The cytocompatibility of human NP-dECM scaffolds with different degrees of degeneration was e-valuated using CCK-8 method and living/dead cells in vitro.Results:Human NPMSCs isolated and cultured from the nucleus pulposus tissue grew adherent,and the cells were short spindle shaped and spindle-shaped.The third passage of human NPMSCs expressed high levels of surface markers such as CD73,CD90 and CD105,and low levels of surface markers such as CD34,CD45 and HLA-DR.It met the criteria of mes-enchymal stem cells.Human NP-dECM scaffolds with three degrees of degeneration remained intact,and the scaffolds of each group were loose and porous under electron microscope.HE staining,DAPI staining and DNA determination showed that the NP-dECM scaffold effectively removed cell components in the three de-grees of degeneration.The quantitative and qualitative detection results of GAG and HYP showed that ECM was well retained,and the GAG retention was in the order of group Ⅱ-D＞group Ⅲ-D＞group Ⅳ-D from high to low.There was no statistical significance in HYP content between groups Ⅱ-D and Ⅲ-D,which was higher than that in group Ⅳ-D.The results of CCK-8 and live/dead cell staining showed that groups Ⅱ-D,Ⅲ-D and Ⅳ-D showed good cytocompatibility.Conclusions:The Ⅱ degree degeneration of human nucleus pulposus tissue is the best choice for the preparation of human NP-dECM scaffold.

Polycystic ovary syndrome(PCOS)is a common endocrine and metabolic disease in gynecology.The main clinical manifestations are infertility,hirsuty,obesity,menstrual disorders,etc.,which seriously affect women's health.Studies have shown that the mechanism of action of traditional Chinese medicine in the treatment of PCOS involves a variety of signaling pathways,among which advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway is an important pathway regulating inflammation and oxidative stress.More and more Chinese herbal compounds,single herbs and their extracts can reduce inflammation,oxidative stress,insulin resistance and hyperandrogenemia in patients by regulating AGE-RAGE signaling pathway,which provides a new strategy and direction for the treatment of PCOS.However,there is currently no comprehensive summary of Chinese medicine intervention in the treatment of PCOS by AGE-RAGE signaling pathway.Therefore,this paper reviews the current research status of Chinese medicine regulation of AGE-RAGE signaling pathway in the treatment of PCOS in recent years,so as to provide new directions and thoughts for further research on PCOS.

Objective To study the common basis and association between sickness behaviour and occurrence of classical symptoms of kidney yang deficiency of rats with adriamycin nephropathy.Methods The SD rats were given adriamycin by tail-vein injection for 2 times(4.0 and 3.5 mg·kg-1,one week apart)to construct the model of nephrotic syndrome with Chinese medicine symptom of kidney yang deficiency.After successful modeling,the model rats were randomly divided into adriamycin group(ADR group),corticosterone group(CORT group)and hydrocortisone group(HYD group),with 12 rats per group;another 12 normal rats were taken as normal group.In the HYD group,25 mg·kg-1·d-1 HYD was administered for 14 d to establish kidney yang deficiency model with simple hypothalamus-pituitary-adrenal cortex(HPA)axis inhibition.CORT group was adding 25 μg·mL-1 corticosterone to the water for 6 weeks,and the others drinking water supplied.The levels of urinary 17-hydroxy steroid were measured by enzyme linked immunosorbent assay.Glucocorticoid receptor(GR)and nuclear factor-kappa B(NF-κB)protein expression levels in kidney and hypothalamus were detected by Western blotting.Results In the normal,ADR,CORT and HYD groups,the urinary 17-hydroxysteroid levels were(19.14±1.94),(10.07±1.62),(20.30±1.55)and(14.23±2.37)μg·L-1;the relative expression levels of GR protein in hypothalamic were 0.63±0.05,0.11±0.05,0.85±0.08 and 0.35±0.06;the relative expression levels of NF-κB protein in hypothalamic were 0.06±0.03,0.96±0.03,0.59±0.01 and 0.23±0.04;the relative expression levels of GR protein in kidney tissue were 0.94±0.06,0.06±0.02,0.40±0.02 and 0.09±0.08;the relative expression levels of NF-κB protein in kidney tissue were 0.07±0.05,0.81±0.12,0.72±0.07 and 0.49±0.08,respectively.Compared with the ADR and HYD groups,the above indexes in the normal group were statistically significant(P＜0.05,P＜0.01).And compared with the ADR group,the relative expression levels of NF-κB protein in renal tissue with CORT group were not statistically significant(P＞0.05),but the other indexes in CORT group were statistically significant(all P＜0.01).Conclusion HPA axis dysfunction with GR damaged and activated inflammatory levels are the common basis for the combination of typical symptoms of kidney yang deficiency and sickness behaviour which characterised by"deficiency and cold syndrome".