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.

This paper aimed to explore the intestinal toxicity of Euphoriae Ebracteolata Radix(EER) before and after being processed with Mongolian medicine Hezi Decoction(HZD) and the toxicity-reducing mechanism of this processing method. The intestinal toxicity in rats treated with unprocessed EER and HZD-processed EER extracts via 95% ethanol was compared. The comparison was based on several indicators, including fecal volume, serum diamine oxidase(DAO) and D-lactate(D-LA) levels, the water content of various intestinal segments and their contents, and inflammatory factor levels in intestinal segments. Tandem mass tag(TMT) quantitative proteomics technology was employed to analyze the key proteins associated with changes in intestinal toxicity between unprocessed EER and HZD-processed EER. The results indicated that compared with the blank group, unprocessed EER significantly increased the fecal volume, serum DAO and D-LA levels, water content of the ileal segment and its contents, as well as the release levels of inflammatory factors, including tumor necrosis factor(TNF-α) and interleukin-1 beta(IL-1β) in the ileal segment of rats(P<0.05), indicating that EER can cause diarrhea, increase intestinal permeability, and induce intestinal inflammation. Compared with those in the unprocessed EER group, all indicators in the HZD-processed EER group were significantly reduced(P<0.05). The TMT quantitative proteomics analysis revealed that a total of 6 487 proteins were identified in the rat ileum tissue. Compared to the blank group, 182 proteins exhibited significant changes in the unprocessed EER group, while 907 proteins in the HZD-processed EER group showed significant changes. The intersection of the differential proteins between the two groups identified 38 common proteins. Among them, the protein levels of intestinal barrier tight junction protein claudin3, squalene monooxidase(Sqle), clusterin, Na~+/H~+ exchange regulatory cofactor NHE-RF3(Pdzk1), and Y+L amino acid transporter 1(Slc7a7) exhibited significant changes before and after processing, and these changes were closely related to intestinal barrier function. Compared with the blank group, the expression of claudin3, Pdzk1, and Slc7a7 in the raw product group was significantly down-regulated(P<0.05),while the expression of Sqle and clusterin was significantly up-regulated(P<0.05).Compared with the raw product group, the expression of claudin3, Pdzk1, and Slc7a7 in the processed product group of HZD was significantly up-regulated(P<0.05), while the expression of Sqle and clusterin was significantly down-regulated(P<0.05). Western blot was used to detect the expression level of claudin 3 in the ileum of rats in each group. The results show that compared to that in the blank group, the expression level of claudin 3 in the unprocessed EER group was significantly reduced(P<0.01); compared to that in the unprocessed EER group, the expression level of claudin 3 in the HZD-processed EER group was significantly increased(P<0.01). This finding aligned with the proteomic outcomes, indicating that claudin 3 protein levels could serve as a crucial indicator for intestinal damage caused by EER. In summary, HZD-processed EER can reduce EER's intestinal toxicity, and the primary mechanism for its alleviation of intestinal barrier damage is the regulation of the intestinal barrier tight junction protein claudin 3 and other intestinal-related proteins.
Animals ; Drugs, Chinese Herbal/adverse effects* ; Proteomics ; Rats ; Male ; Rats, Sprague-Dawley ; Intestines/drug effects* ; Intestinal Mucosa/drug effects* ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: To investigate the effects of wheat-grain moxibustion at the Guanyuan point on testosterone (T) synthesis and the hypothalamic-pituitary-gonadal (HPG) axis in naturally aged mice. METHODS: We fed 40 twelve-month-old SPF male C57BL/6J mice with a normal diet for 3 months, randomized them into a moxibustion and an aged group of an equal number, and selected 7 four-month-old ones as young controls. We treated the animals of the moxibustion group by wheat-grain moxibustion at the Guanyuan point, once 5 moxibustion sticks, qd, 5 times a week, and fed those of the aged group normally, all for 12 weeks. After treatment, we obtained the testicular index of the mice, observed the histomorphology of the testis tissue by HE staining, measured the contents of T in the testis, gonadotropin-releasing hormone (GnRH) in the hypothalamus and total T (tT), free T (fT), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the serum by ELISA, and determined the expressions of silence information regulator-1 (SIRT1), P53, glutathione peroxidase (GPX4) and cholesterol side-chain?cleavage enzyme (CYP11A1) in the testis by Western blot. RESULTS: Compared with the young controls, the mice in the aged group showed obviously losing and dull hair, energy declination, loose structure of the spermatogenic tubule with different degrees of cell loss and rupture, reduced testicular index, and evident aging phenotype. In comparison with the aged mice, the animals of the moxibustion group were fairly energetic and exhibited distinct structure of the spermatogenic tubules, orderly arranged and highly differentiated cells at all levels, significantly increased T level, up-regulated expressions of SIRT1, GPX4 and CYP11A1, and down-regulated expression of P53 in testis tissue, and elevated levels of GnRH, FSH, LH, tT and fT in the HPG axis. CONCLUSION Wheat-grain moxibustion at the Guanyuan point protects testosterone synthesis in the testis tissue of naturally aged mice, promotes negative feedback regulation of the HPG axis, and improves low testosterone.
Animals ; Male ; Moxibustion ; Mice ; Testosterone/metabolism* ; Mice, Inbred C57BL ; Testis/metabolism* ; Hypothalamo-Hypophyseal System/metabolism* ; Triticum ; Gonadotropin-Releasing Hormone/metabolism* ; Luteinizing Hormone/blood* ; Follicle Stimulating Hormone/blood* ; Aging ; Hypothalamus/metabolism* ; Acupuncture Points ; Sirtuin 1/metabolism* ; Hypothalamic-Pituitary-Gonadal Axis

Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.

Cardiac troponin I (cTnI), a widely used biomarker for assessing cardiovascular risk, can provide a window for the evaluation of drug-induced myocardial injury. Label-free biosensors are promising candidates for detecting cell secretomes, since they do not require labor-intensive processes. In this work, a label-free electrochemical aptasensor is developed for in situ monitoring of cardiac cell secretomes in cell culture media based on target-induced strand displacement. The aptasensing system contains an aptamer-functionalized signal nanoprobe facing trimetallic metal-organic framework nanosheets and a gold nanoparticle-based detection working electrode modified with DNA nanotetrahedron-based complementary DNA for indirect target detection. The signal nanoprobes (termed CAHA) consisted of copper-based metal-organic frameworks, AuPt nanoparticles, horseradish peroxidase, and an aptamer. When the aptasensor is exposed to cardiac cell secretomes, cTnI competitively binds to the aptamer, resulting in the release of signal nanoprobes from the biorecognition interface and electrochemical signal changes. The aptasensor exhibited rapid response times, a low detection limit of 0.31 pg/mL, and a wide linear range of 0.001-100 ng/mL. We successfully used this aptasensor to measure cTnI concentrations among secreted cardiac markers during antitumor drug treatment. In general, aptasensors can be used to monitor a variety of cardiac biomarkers in the evaluation of cardiotoxicity.

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People

OBJECTIVES: This study aims to investigate factors influencing dental arch development in patients aged 0-6 years with cleft palate after Sommerlad-Furlow (SF) palatoplasty. METHODS: A total of 183 patients who underwent primary SF repair for cleft lip and palate before 18 months of age were included. Follow-ups were conducted at different ages, and digital dental casts of the maxillary dental arch were obtained using 3-matic Research 12.0 software. The length and width of the dental arch and palate were measured to explore developmental changes in the maxillary dental arch of the patients after the procedure. The study also investigated the influence of gender, age, cleft palate type, and relaxation incision on maxillary dental arch development. RESULTS: After SF, maxillary dental arch measurements showed statistically significant differences between children aged 0-2 years and those aged 3-6 years (P<0.05). However, no statistically significant differences were observed among different age groups within the 3-6 years range. Statistically significant differences were detected between males and females, with males having greater width of the posterior dental arch and palate (P=0.001) and shorter length of the anterior dental arch and entire dental arch (P<0.05). The unilateral cleft lip and palate group had shorter dental arch length (P<0.01) and wider posterior palate (P<0.01) than the cleft palate only group. Maxillary dental arch measurements had no statistically significant differences between groups with or without a relaxing incision. CONCLUSIONS Gender and age influence the width of the maxillary dental arch in children aged 0-6 years after SF, while age and cleft palate type affect dental arch length.
Humans ; Child, Preschool ; Male ; Cleft Palate/surgery* ; Female ; Child ; Infant ; Dental Arch/growth & development* ; Maxilla/growth & development* ; Cleft Lip/surgery* ; Age Factors ; Sex Factors ; Palate/surgery* ; Infant, Newborn

With reference to the Information and Documentation-Resource Description (GB/T 3792-2021) and Bibliographical Description for Ancient Chinese Books (GB/T 3792.7-2008) and other cataloging standards and rules, drawing on the practical experience of cataloging ancient TCM books, Bibliographical Cataloging for Ancient TCM Books was formulated. This standard specifies the entry items and their order of ancient TCM books, cataloging identifier, cataloging text, cataloging information source, and cataloging item details. The standard can provide standardized and unified guiding principles and methods for the work of ancient TCM books, and promote the sharing and utilization of ancient TCM books.

Objective To find out whether photobiomodulation(PBM)can mitigate cognitive dysfunction caused by chronic stress by affecting levels of adenosine triphosphate(ATP)and adenosine receptors.Methods Twenty-four C57BL/6J mice were randomly divided into a control group,a stress group,and a treatment group.Chronic unpredictable mild stress was used to establish a mouse model of stress.Six weeks into modeling,the treatment group was subjected to one week of PBM interventions.Behavioral tests were conducted to observe behavioral changes in the mice.Western blotting(WB)was used to detect the expressions of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex of mice in the three groups.Twelve C57BL/6J mice were randomly divided into a control group and an intervention group.The intervention group received a week of PBM interventions and underwent behavioral testing.WB was used to detect the expression changes of A1,A2B,and A3 adenosine receptors in the hippocampus and prefrontal cortex in both groups.Immunofluorescence assay was adopted to detect the expression of c-Fos in the hippocampus of mice in the two groups.The ATP assay kit made by Beyotime Biotechnology Co.,Ltd.was used to measure changes in ATP contents in the hippocampus and prefrontal cortex tissues of mice.Cell experiments were conducted to verify the effect of PBM on intracellular ATP contents.Results Mice in the stress group covered a similar distance to the control group,but finished far fewer platform crossings.There was no significant difference between the treatment group and the control group in the number of times of platform crossings,but compared favorably with the stress group where the levels of adenosine receptors in the hippocampus and prefrontal cortex were lower,but were increased by PBM.After PBM interventions in normal mice,platform crossings were increased significantly compared to the control group.PBM also raised adenosine receptor levels and ATP contents in the hippocampus and prefrontal cortex,and increased hippocampal c-Fos expressions.In vitro,PBM elevated intracellular ATP levels.Conclusion PBM may improve chronic stress-induced cognitive dysfunction by regulating ATP levels and adenosine receptor expressions,thereby modulating neuronal responsiveness in the hippocampus.

Objective To observe the effects of indobufen tablets combined with clopidogrel tablets on levels of serum myocardial injury indexes and incidence of major adverse cardiovascular events(MACE)in elderly patients with coronary heart disease after percutaneous coronary intervention(PCI).Methods The elderly patients with coronary heart disease after PCI were divided into treatment group[clopidogrel 75 mg(qd)combined with indobufen 200 mg(qd)]and control group[clopidogrel 75 mg(qd)combined with aspirin 100 mg(qd)]according to cohort method.All patients were treated for 3 months.The total effective rate,serum myocardial injury indexes[N terminal pro B type natriuretic peptide(NT-proBNP),cardiac troponin Ⅰ(cTn Ⅰ)],coagulation-fibrinolysis indexes[fibrinogen(FIB),prothrombin time(PT),antithrombin Ⅲ(AT-Ⅲ)]and platelet function indexes[platelet distribution width(PDW)]were compared between two groups.Occurrence of bleeding events and MACE within 6 months were compared between the two groups.The safety was evaluated.Results There were 32 cases in control group and 32 cases in treatment group.After treatment,the total effective rates in treatment group and control group were 93.75％(30 cases/32 cases)and 78.13％(25 cases/32 cases),without significant difference(P＞0.05).After treatment,NT-proBNP levels in treatment group and control group were(202.65±30.77)and(283.52±31.42)pg·mL-1,cTn Ⅰ levels were(0.06±0.01)and(0.12±0.03)ng·mL-1,FIB levels were(3.17±0.51)and(3.84±0.59)g·L-1,PT were(15.87±1.23)and(14.92±1.35)s,AT-Ⅲ levels were(138.95±14.18)％and(125.17±14.96)％,PDW were(17.04±2.04)％and(19.13±2.32)％,the differences were statistically significant(all P＜0.05).The incidences of bleeding events in treatment group and control group were 6.25％and 15.63％,adverse drug reactions were 9.38％and 15.63％,respectively,the differences of above indexes were statistically significant between two groups(all P＞0.05).The total incidences of MACE in treatment group and control group were 6.25％and 25.00％,respectively(P＜0.05).Conclusion Indobufen tablets combined with clopidogrel tablets can reduce levels of serum myocardial injury indexes in elderly patients with coronary heart disease after PCI,improve coagulation-fibrinolysis function and reduce the incidence of MACE.