OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

This paper aims to discuss the construction and promotion strategy of medical care capacity framework based on the core literacy of palliative care， combining domestic and foreign research and clinical status. The research results show that it is particularly important to construct a framework of medical care competence based on palliative care. The core competencies required for palliative care include the ability to comprehensively evaluate and formulate personalized programs， effective communication skills， interdisciplinary teamwork skills， and the ability to continuously learn and improve themselves. The quality of care can be further improved if the above abilities are incorporated into the framework of medical care ability based on palliative care. However， there are a series of problems in the process of constructing the framework of palliative medical care capacity， such as difficult implementation of policy support， poor professionalism of talent team， single and irregular service model， low social acceptance， and difficult interdisciplinary cooperation and resource integration. After a detailed analysis of the problems， this paper puts forward the countermeasures to construct the framework of caring ability literacy based on palliative care. Effective countermeasures such as increasing policy support， cultivating comprehensive talents， developing diversified palliative care models， improving social recognition， and strengthening interdisciplinary cooperation and resource integration can effectively improve the core literacy and professional ability of medical care personnel， and then promote the development and improvement of palliative care services. In-depth discussion of the above contents can provide scientific reference for building a care model and literacy framework with palliative care as the core.

Corticotomy is a clinical procedure to accelerate orthodontic tooth movement characterized by the regional acceleratory phenomenon (RAP). Despite its therapeutic effects, the surgical risk and unclear mechanism hamper the clinical application. Numerous evidences support macrophages as the key immune cells during bone remodeling. Our study discovered that the monocyte-derived macrophages primarily exhibited a pro-inflammatory phenotype that dominated bone remodeling in corticotomy by CX3CR1^CreERT2; R26^GFP lineage tracing system. Fluorescence staining, flow cytometry analysis, and western blot determined the significantly enhanced expression of binding immunoglobulin protein (BiP) and emphasized the activation of sensor activating transcription factor 6 (ATF6) in macrophages. Then, we verified that macrophage specific ATF6 deletion (ATF6^f/f; CX3CR1^CreERT2 mice) decreased the proportion of pro-inflammatory macrophages and therefore blocked the acceleration effect of corticotomy. In contrast, macrophage ATF6 overexpression exaggerated the acceleration of orthodontic tooth movement. In vitro experiments also proved that higher proportion of pro-inflammatory macrophages was positively correlated with higher expression of ATF6. At the mechanism level, RNA-seq and CUT&Tag analysis demonstrated that ATF6 modulated the macrophage-orchestrated inflammation through interacting with Tnfα promotor and augmenting its transcription. Additionally, molecular docking simulation and dual-luciferase reporter system indicated the possible binding sites outside of the traditional endoplasmic reticulum-stress response element (ERSE). Taken together, ATF6 may aggravate orthodontic bone remodeling by promoting Tnfα transcription in macrophages, suggesting that ATF6 may represent a promising therapeutic target for non-invasive accelerated orthodontics.
Animals ; Mice ; Macrophages/metabolism* ; Tumor Necrosis Factor-alpha/genetics* ; Tooth Movement Techniques/methods* ; Activating Transcription Factor 6/metabolism* ; Bone Remodeling ; Flow Cytometry ; Blotting, Western

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

Objective To establish a brucellosis monitoring and testing technique applicable for the rapid field screening of natural epidemic diseases.Methods A rapid testing technique for Brucella was developed based on a double-antibody sandwich testing model using gradient-variant quantum dots as fluorescent tracers.The sensitivity,linearity,precision,and specificity of the technique were evaluated using suspensions of standard Brucella strains.Methodological comparisons across different sample types were conducted to assess the consistency of the test results.Results The gradient-variant quantum dots detection method was evaluated with standard Brucella strains,exhibiting a sensitivity of 1×103 CFU/mL and a linear correlation coefficient(r)of 0.994(95%CI,0.933-1.055).The maximum coefficient of variation was 12.94%in repeated tests,showing good specificity.A comparative assessment of 305 clinical samples was conducted using the Brucella gradient-variant quantum dots detection method,the Rose Bengal plate agglutination test(RBT),and the serum agglutination test(SAT),yielding a Kappa value of 0.95,indicating almost perfect agreement.Additionally,a comparative assessment of 110 environmental samples collected on-site was conducted using the Brucella gradient-variant quantum dots detection method and quantitative real-time PCR(qPCR).The Kappa values for aerosol collection fluid,surface wipes,and wool samples were all above 0.83,demonstrating near-perfect agreement.For fecal and soil samples,the Kappa values were above 0.62,indicating substantial agreement.Conclusion The Brucella detection method based on gradient-variant quantum dots technology is simple and can be conducted rapidly.The detection method demonstrates high sensitivity,linearity,precision,and specificity.It shows consistent performance in clinical sample testing.It is well-suited for field rapid screening of natural epidemic diseases in field settings and shows good application prospects in the monitoring,prevention,and rapid detection of zoonotic diseases.

Objective:To develop and validate a liquid chromatography-tandem mass spectrometry method for determining levofloxacin in plasma sample from pediatric patients.Method:This is a prospective, observational study. The clinical residual plasma samples from healthy individuals for physical examination in Children's Hospital Affiliated to Zhengzhou University were collected as blank matrix. Plasma samples from five pediatric patients who did not receive levofloxacin or ciprofloxacin in the department of Respiration were collected for methodological evaluation. In addition, 34 clinical plasma samples from 22 pediatric patients (9 males and 13 females; mean age (8.1±3.7) years) using levofloxacin was collected, and their plasma concentrations were determined. Using ciprofloxacin as the internal standard, levofloxacin in plasma samples was quantified by liquid chromatography-tandem mass spectrometry following protein precipitation using acetonitrile. A C18 column (Shim-pac GIST-HP C18, 2.1 mm×100 mm, 3 μm) and mobile phase composed of water (containing 0.1% formic acid) and acetonitrile (containing 0.1% formic acid) with gradient elution at a flow rate of 0.4 ml/min were used to separate levofloxacin. The column temperature was 40 ℃, injection volume was 1 μl and the total analysis time was 9 min. Levofloxacin and ciprofloxacin were ionized with an ESI source in positive ion mode and detected in multiple reaction monitoring (MRM) mode. The detected ions of levofloxacin and ciprofloxacin were m/z 362.10→318.1 and 332.15→231.05, respectively. The method′s specificity, sensitivity, linearity, precision, accuracy, recovery rate, stability, matrix effect, and carry-over were validated. All statistical analyses were performed with SPSS statistical software (version 17.0). The normality of the data was detected by the K-S test. A P<0.05 was considered statistically significant for two tailed tests. Results:The LC-MS/MS method showed a good linearity within the range of 0.062 5-20 mg/L, with the lower detection limit of levofloxacin of 0.062 5 mg/L. The calibration curve for levofloxacin was Y=0.093X+0.010 ( R2>0.99). Under different quality control levels, the accuracy ranged from 92.57% to 104.39%, and the intra-day and inter-day imprecision ranged from 2.32% to 9.35%. These values were not affected by the normal matrix, 5% hemolysis matrix and 15% hyperlipidemia matrix. Furthermore, the levofloxacin plasma samples were stable in the short term. A total of 34 plasma samples from 22 patients were collected and analyzed. Only 2 plasma samples were below the lower limit of quantification, while the other plasma concentrations of levofloxacin were ranged from 0.091 to 6.755 mg/L. Cmax was (5.52 ± 1.09) mg/L. Conclusion:The LC-MS/MS method meets the requirements of the reference method and requires a small sample size (50 μl), making it suitable for the determination of levofloxacin in plasma from pediatric patients.

Objective:To investigate the effect of S100A10 macrophage-mediated inflammation and migration.Methods:C57BL/6J mouse model of S100A10-KO,and RAW264.7 cell line of S100A10-KO were established.Taking mice's peritoneal macro-phages(PMs)and bone marrow macrophages(BMDMs),resuscitating RAW264.7 cell lines,and collecting cells.qRT-PCR was used to detect the effect of S100A10 knockout on the secretion of inflammatory factors in macrophages;wound healing assay and Transwell assay were used to detect the effect of S100A10 knockout on macrophage migration;CCK8 kit was used to detect the effect of S100A10 knockout on the proliferation of RAW264.7 cells;qRT-PCR and Western blot were used to detect the expressions of matrix metallopro-teinase 9(MMP9)and non-muscle myosin heavy chain 9(MYH9).Results:After S100A10 knockout,the inflammatory factors IL-6,IL-1β and MCP-1 levels(P<0.05)secreted by RAW264.7,PMs and BMDMs were excreted decreased;cell scratches and Transwell showed that S100A10 knockout inhibited macrophage migration;CCK8 experiments showed that the proliferation capacity of macro-phages weakened after S100A10 knockout;qRT-PCR and Western blot experiments showed that the migration-related proteins MMP9 and MYH9 decreased after S100A10 knockout.Conclusion:S100A10 knockout decreases the secretion of inflammatory factors by macrophages and attenuated the migration and proliferation of macrophages.

Objective:To estimate and analyze the levels of occupational exposure of aircrews in China, and to provide scientific basis for strengthening occupational health management.Methods:Through the FlightAware website, the flight data were collected of a total of 104 routes flying between airports with large passenger volume in China. Four kinds of cosmic radiation dose estimation programs CARI, SIEVERT, PCAIRE, and JISCARD-EX were compared and analyzed from the aspects of covering the number of airports in China, program user experience and example calculation of airline effective dose. Based on route logs, CARI-7A was applied to estimate the levels of occupational exposure of Chinese aircrews to cosmic radiation.Results:The difference in the effective doses calculated by use of these four cosmic radiation dose estimation programs for the routes with different solar activity levels was statistically significant ( M=7.52-180.98, P<0.05). The annual effective dose estimated by PCAIRE for 68 routes from 2014 to 2021 was significantly higher than that estimated by CARI-7A ( Z=2.52, P<0.05). Based on CARI-7A, the annual effective doses from cosmic radiation to aircrews in China from 2014 to 2021 were estimated, being 1.26 (0.57-2.35) mSv for flight attendants and 1.03 (0.47-1.92) mSv for pilots. The effective dose from cosmic radiation to aircrews on a single flight on some high-frequency routes in China ranged from 0.57 to 6.88 μSv. Conclusions:The level of occupational exposure of Chinese aircrews to cosmic radiation meets the requirements of national standards, but is higher than that of occupational exposure from medical and industrial applications of radiation, so it is still necessary to further strengthen the mamagememt of occupational exposure and occupational health of aircrews.

Objective:To investigate the effect of low density lipoprotein cholesterol (LDL-C) on the progression of retinal arteriosclerosis by using a deep learning model.Methods:A cohort study was performed.Data of 1 928 individuals who underwent the medical examination at Beijing Yijiandian Clinic between January 2016 and August 2023 were reviewed, including baseline demographics, physical examination, serological test and fundus photography.Retinal arteriosclerosis was identified using a deep learning model.Five groups were divided according to LDL-C levels, including 389 subjects in group 1 (0.64-1.90 mmol/L), 387 subjects in group 2 (1.91-2.26 mmol/L), 384 subjects in group 3 (2.27-2.57 mmol/L), 385 subjects in group 4 (2.58-2.95 mmol/L), and 383 subjects in group 5 (2.96-6.06 mmol/L).The association between LDL-C levels and progression of retinal arteriosclerosis and the dose-response relationship were analyzed by logistic regression analysis and restricted cubic spline (RCS) regression model.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2021PHB058-001).Written informed consent was obtained from each subject.Results:The incidence of retinal arteriosclerosis progression was 22.10% (426/1 928) during the mean follow-up (66.84±6.58) months.The proportions of fundus progression in groups 1, 2, 3, 4, and 5 were 15.68%(61/389), 21.71%(84/387), 21.35%(82/384), 25.71%(99/385), and 26.11%(100/383), respectively, with statistical significant differences among them ( χ2=15.97, P=0.003).Using group 1 as a reference, LDL-C 2.58-2.95 mmol/L was an independent risk factor for progression of retinal arteriosclerosis ( OR=1.52, 95% CI: 1.04-2.22), and RCS analysis showed an " L" shaped association.The effect of LDL-C on retinal arteriosclerosis showed a threshold effect, with the risk of retinal arteriosclerosis progression increasing with increasing LDL-C when LDL-C was <2.34 mmol/L ( OR=1.97, 95% CI: 1.10-3.62), and stabilizing when LDL-C was ≥2.34 mmol/L. Conclusions:LDL-C has a threshold effect on the impact of retinal arteriosclerosis progression, and the threshold is 2.34 mmol/L.