ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

OBJECTIVE To investigate the immunotoxicity and potential mechanism of Carthamus tinctorius extract on RBL-2H3 cells via direct induction and induction by sensitized serum prepared with an overdose of the extract. METHODS For direct induction by C. tinctorius extract， RBL-2H3 cells were divided into normal control group （no treatment） and C. tinctorius extract group （10 mg/mL）. For induction by sensitized serum prepared with an overdose of C. tinctorius extract， rats were divided into normal control group （no treatment）， adjuvant-treated group （1 mL adjuvant）， C. tinctorius extract-induced sensitization group （2.04 g/mL）， and ovalbumin （OVA）-induced sensitization group （50 mg/mL）. Sensitization was performed once every other day for a total of 3 times. Morphological changes of RBL-2H3 cells were observed， the degranulated rate of cells was counted， and histamine content was determined； the release rate of β -hexosaminidase （ β -Hex） was calculated， the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） and intracellular Ca²⁺ concentration were detected. RESULTS Under direct induction by C. tinctorius extract， compared with the normal control group， the volume of cells in the C. tinctorius extract group was significantly reduced and cell density decreased； the degranulation rate of cells， histamine content， β -Hex release rate， IL-6 and TNF-α levels， as well as intracellular Ca²⁺ concentration were all significantly increased （ P ＜0.01）. Under i nduction by sensitized serum prepared with an overdose of C. tinctorius extract， compared with the adjuvant-treated group， the above indicators in the C. tinctorius extract-induced sensitization group and the OVA-induced sensitization group showed consistent changes with those in the C. tinctorius extract group under direct induction， all being significantly elevated （ P ＜0.01）. CONCLUSIONS C. tinctorius extract may affect degranulation of RBL-2H3 cells and promote Ca²⁺ influx accompanied by the release of pro-inflammatory cytokines through two approaches： direct induction and induction by sensitized serum prepared under overdose administration. Its mechanism may be related to the activation of the calcium signaling pathway and the regulation of inflammatory pathways under the synergistic effect of multiple components.

Extracellular vesicles (EVs) are pivotal mediators of intercellular communication within the tumor immune microenvironment (TME). They are broadly categorized into exosomes, microvesicles, and apoptotic bodies based on their distinct biogenesis pathways. Exosomes originate from the endosomal system via multivesicular body fusion, microvesicles bud directly from the plasma membrane, and apoptotic bodies are released during programmed cell death. By shuttling diverse bioactive cargoes—including proteins, lipids, and nucleic acids such as mRNA, miRNA, and DNA—EVs exert dual modulatory effects on tumor initiation, progression, and immune evasion. Importantly, EVs exhibit remarkable compositional heterogeneity that is intrinsically linked to their cellular origin. Tumor-derived EVs (TDEVs) are typically enriched with immunosuppressive molecules like PD-L1, TGF‑β, and miR-21, which promote tumor immune escape and metastasis. In contrast, EVs derived from immune cells, such as dendritic cells or cytotoxic T lymphocytes, often carry immunostimulatory components including antigens, co-stimulatory molecules, and granzymes, thereby potentiating anti-tumor immunity. This review systematically delineates the biogenesis and molecular composition of EVs, with a particular emphasis on their dynamic regulatory functions within the TME. Specifically, we discuss how EVs mediate intricate crosstalk between immune and tumor cells, facilitating signal transfer that reshapes immune surveillance. For instance, TDEVs can induce macrophage polarization toward an M2-like pro-tumor phenotype, while also suppressing natural killer cell cytotoxicity and dendritic cell maturation. The clinical utility of EV-associated biomarkers in liquid biopsy is increasingly recognized. Circulating EVs carry tumor-specific molecular signatures that mirror the genetic and proteomic alterations of primary tumors, enabling non-invasive early diagnosis, molecular subtyping, and real-time monitoring of therapeutic responses. Their natural biocompatibility, low immunogenicity, and intrinsic ability to traverse biological barriers make them ideal candidates for drug delivery systems. This review explores cutting-edge applications, including the use of EVs in immune checkpoint blockade therapy—for instance, engineered EVs displaying anti-PD-1 antibodies or carrying siRNA to silence immunosuppressive genes. Moreover, EV-based tumor vaccines are being developed, leveraging dendritic cell-derived EVs loaded with tumor antigens to elicit potent T cell responses. The feasibility of loading EVs with therapeutic molecules such as chemotherapeutic agents, oncolytic viruses, or CRISPR-Cas9 components is also under active investigation. The advent of engineered EVs has further expanded their therapeutic potential. Through surface modification or cargo encapsulation, EVs can be tailored for targeted delivery and controlled release, enhancing precision immunotherapy. However, several hurdles impede clinical translation. Current isolation and purification methods, such as ultracentrifugation and size-exclusion chromatography, suffer from low yield and purity. Distinguishing EV subpopulations remains technically challenging due to overlapping size and marker expression. Moreover, the lack of standardized protocols for EV production, characterization, and quality control poses significant barriers to regulatory approval and clinical adoption. Looking forward, the convergence of multi-omics technologies with artificial intelligence offers a powerful approach to decipher EV heterogeneity and identify robust diagnostic signatures. Machine learning algorithms can integrate proteomic, transcriptomic, and lipidomic data from large patient cohorts to construct predictive models for cancer diagnosis and prognosis. Concurrently, advances in bioengineering are enabling the design of next-generation EVs with enhanced targeting specificity, on-demand drug release, and reduced off-target effects. Future efforts should also focus on establishing good manufacturing practice (GMP)‑compliant production processes and conducting rigorous preclinical and clinical evaluations. In summary, this review provides a comprehensive overview of EV biology, their multifaceted roles in the TME, and their transformative potential in cancer diagnostics and therapeutics. By addressing current challenges and leveraging emerging technologies, EV-based strategies are poised to revolutionize precision oncology.

ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

ObjectiveTo investigate the association between serum fasting triglyceride glucose-body mass index （TyG-BMI） and new-onset metabolic dysfunction-associated fatty liver disease （MAFLD） within 10 years. MethodsA retrospective analysis was performed for the data of individuals who underwent physical examination in The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University in 2013， 2018， and 2023 and were not diagnosed with MAFLD in 2013， and a total of 1 340 valid subjects were enrolled according to the inclusion and exclusion criteria. The gbmt package in R 4.3.0 was used to construct the dynamic change trajectory model of TyG-BMI， and four different TyG-BMI trajectory groups were determined， i.e.， the low-level group （n=352）， the medium-level group （n=517）， the high-level group （n=314）， and the extremely high-level group （n=157）. The data on general information and blood biochemical parameters were collected from all subjects and were then compared between groups. The chi-square test was used for comparison of categorical data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data with heterogeneity of variance between multiple groups. The Cox regression analysis was used to investigate the association between different TyG-BMI trajectories and the risk of MAFLD， and the receiver operating characteristic （ROC） curve was used to assess the value of TyG-BMI in the diagnosis of MAFLD. ResultsThe cumulative incidence rate of MAFLD increased with the increase in the level of TyG-BMI trajectory， with a cumulative incidence rate of 4.83% in the low-level group， 29.98% in the medium-level group， 61.15% in the high-level group， and 83.44% in the extremely high-level group （P<0.001）， and the cumulative incidence rate of MAFLD in men was significantly higher than that in women （51.34% vs 20.67%， P<0.001）. The multivariate Cox regression analysis showed that increases in the levels of TyG-BMI trajectory， uric acid， diastolic blood pressure， hemoglobin， and alanine aminotransferase were independent risk factors for the onset of MAFLD （all P<0.05）， while the increase in high-density lipoprotein cholesterol was an independent protective factor against MAFLD （P<0.001）. After adjustment for confounding factors， the medium-， high-， and extremely high-level groups had a hazard ratio of 4.430 （95% confidence interval ［CI］： 2.660 — 7.377， P<0.001）， 6.937 （95%CI： 4.110 — 11.708， P<0.001）， and 7.989 （95%CI： 4.616 — 13.827， P<0.001）， respectively. The ROC curve analysis showed that TyG-BMI had the highest diagnostic value， with an area under the ROC curve of 0.859 （95%CI： 0.840 — 0.879）， a sensitivity of 79.8%， and a specificity of 76.3%. ConclusionThe risk of MAFLD increases with the increase in the level of TyG-BMI trajectory， and TyG-BMI can be used as a predictive indicator for MAFLD.

As a new generation of time-of-flight mass spectrometry,multiple-reflection time-of-flight mass spectrometry(MR-TOF-MS)has been increasingly applied in the fields such as nuclear physics,chemistry,and biology due to its ultra-high resolution and rapid analysis capabilities.However,the analytical performance of MR-TOF-MS largely depends on the ion bunch state entering the mass analyzer.In this study,a rectangular ion trap(RIT)was developed,designed and processed using printed circuit board technology,as an ion accumulating and focusing device for MR-TOF mass analyzer.Compared to traditional ion traps composed of two sets of planar electrodes,this RIT had higher voltage utilization efficiency,resulting in more efficient ion collection and focusing.The ions were cooled to a sufficiently small bunch for precise mass measurement with MR-TOF-MS mass spectrometry in only 1 ms of cooling time in the RIT,then orthogonally ejected to the MR-TOF mass spectrometer for mass analysis.Experimental results indicated that the working cycle,ion flux,and ion focusing state of the RIT fully met the requirements of the MR-TOF mass analyzer.When coupled with the MR-TOF mass analyzer,the RIT enabled MR-TOF-MS to achieve a mass resolution of 1.5×105.

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

An effective method for simultaneously detecting four semivolatile earthy-musty odors in freshwater fish by gas chromatography-mass spectrometry(GC-MS)was developed.The concurrent extraction of geosmin(GSM),2-methylisoborneol(MIB),2-isopropyl-3-methoxypyrazine(IPMP),and 2-isobutyl-3-methoxypyrazine(IBMP)in fish tissue was conducted with n-hexane.The optimized QuEChERS material was implemented,and it was found that C18,primary secondary amine(PSA)and MgSO4 could adsorb the target analytes in n-hexane.So only the graphitized carbon black(GCB)could be used to purify the extraction.The adsorption rates of different materials for the four kinds of odors materials were explored in n-hexane and ethyl acetate.The experimental results revealed that the adsorption rates of silica for the four targets were 99.5%-100%in n-hexane and 0.7%-5.0%in ethyl acetate respectively.Then the silica solid phase extraction(SPE)method was utilized to eluent the compounds using 1.0 mL n-hexane/ethyl acetate in different proportions.The results of the comparative analysis demonstrated that n-hexane/ethyl acetate(4∶1,V/V)was the optimized eluent.Based on the obtained results,n-hexane extraction and GCB purification combined with silica SPE were used to isolate GSM,MIB,IPMP and IBMP from fish and the method was validated.It was found that the method showed good linearity in the range of 0.5-200 ng/mL,and with detection limits of 0.6 μg/kg for GSM and MIB,0.2 μg/kg for IPMP and IBMP.The limits of quantitation(LOQ)were 1.0 μg/kg for GSM and MIB,0.6 μg/kg for IPMP and IBMP.Good recoveries(77.5%-112.0%)and relative standard deviations(1.56%-9.42%)were also obtained.The use of silica SPE greatly mitigated the issue that the off-flavor compounds were easily lost in the gas blowing concentration process.There was no cross contamination in this method because the sample pretreatments were conducted separately,which was different with the most commonly used HS-SPME method for detecting semi-volatile substances.The sensitivity of this method was high enough to produce good quantitative results below the odor thresholds of the examined off-flavor compounds.

A method was developed for determination of dilauryl thiodipropionate(DLTDP)in fried foods by coupling solid-phase extraction(SPE)pretreatment with reverse-phase liquid chromatography-tandem mass spectrometry(RPLC-MS/MS)detection.Samples were extracted with n-hexane as the solvent,purified using a neutral alumina SPE cartridge,and finally analyzed by RPLC-MS/MS.Quantitative analysis was performed using matrix-matched calibration curves combined with an external standard method under optimal experimental conditions.The results showed that DLTDP exhibited good linearity in the range of 2.0-50.0 μg/L,with a correlation coefficient(R2)≥0.999.The limit of detection(LOD)and the limit of quantification(LOQ)of the method were 0.15 mg/kg and 0.5 mg/kg,respectively.The mean recoveries at three fortification levels(0.5,1.0,and 200 mg/kg)in different samples ranged from 84.8%to 96.8%,with the relative standard deviations(RSDs)all less than 8.0%.The developed method was highly sensitive,accurate and reliable,and easy to operate,making it well suited for the routine quantitative analysis of DLTDP in fried foods.

Objective To establish a rapid screening and analysis method for etomidate and its ana-logues using a portable mass spectrometer equipped with a thermal desorption-atmospheric pressure chemical ionization source-linear ion trap.Methods A 10 μL aliquot of a standard solution at a con-centration of 1 μg/mL was taken,and after the solvent evaporated,the sample was inserted into the in-let of the portable mass spectrometer for detection.By adjusting the collision-induced dissociation pa-rameters,the molecular ion peak and fragment ion peak information of the standard were obtained and used to establish a reference database.In addition,the method was applied to 29 seized liquid and plant samples.Results A screening system for etomidate and its analogues was established based on the portable mass spectrometer and the corresponding mass spectrometry library.The system enables qualitative screening analysis by identifying primary protonated molecular ions and secondary product ions of etomidate and its analogues.The limits of detection for etomidate and its 12 analogues ranged from 0.1 to 10 μg/mL.Etomidate and its analogues were detected in all 29 liquid and plant samples.However,this method could not distinguish between isomeric imidazole esters,such as isopropoxate and propoxate.Additionally,when testing 2-SH-etomidate,there was a false positive for the detection of etomidate.Conclusion This study established a rapid screening method for etomidate and its ana-logues using a portable mass spectrometer.The method combines the high sensitivity of mass spectrome-try with the on-site applicability of portable devices,significantly improving detection efficiency and meeting the on-site detection needs of etomidate and its analogues.