Objective To use direct dilution method to pretreat human urine, and to determine 19 elements in human urine using inductively coupled plasma mass spectrometry, and to evaluate the uncertainty of the entire experimental process. Methods The relevant mathematical models were established according to JJF 10591-2012 ^“Evaluation and Expression of Measurement Uncertainty^” and CNAS-GL006 ^“Guidance for Evaluation of Uncertainty in Chemical Analysis^”. Taking molybdenum as an example, the uncertainty sources in the determination of 19 elements in human urine by inductively coupled plasma method were analyzed and evaluated, including sample pretreatment, sample repeated measurement, standard solution preparation and standard curve fitting. Results The extended uncertainty of molybdenum in human urine is 2.12μg/L, and the measurement result of molybdenum is (44.8±2.12)μg/L. The measurement result of 19 elements in human urine ranges from less than the detection limit to 601μg/L, and the extended uncertainty range is 0.38~33.6μg/L.Conclusion It was found from the calculation that the uncertainty of the determination result was mainly affected by the uncertainty of the sample repeated measurement and the standard curve fitting. By adjusting the range of standard curve and increasing the number of parallel sample measurement, the uncertainty was reduced and the quality of detection was improved.

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

OBJECTIVE: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@^R8LM) for cardiovascular therapy. METHODS: EOFAZ@^R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1β (IL-1β) levels. RESULTS: EOFAZ@^R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1β, exerting protective effects on the vascular endothelium. CONCLUSION Our findings highlight the significant therapeutic potential of EOFAZ@^R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

Cholesterol (CH) plays a crucial role in enhancing the membrane stability of drug delivery systems (DDS). However, its association with conditions such as hyperlipidemia often leads to criticism, overshadowing its influence on the biological effects of formulations. In this study, we reevaluated the delivery effect of CH using widely applied lipid microspheres (LM) as a model DDS. We conducted comprehensive investigations into the impact of CH on the distribution, cell uptake, and protein corona (PC) of LM at sites of cardiovascular inflammatory injury. The results demonstrated that moderate CH promoted the accumulation of LM at inflamed cardiac and vascular sites without exacerbating damage while partially mitigating pathological damage. Then, the slow cellular uptake rate observed for CH@LM contributed to a prolonged duration of drug efficacy. Network pharmacology and molecular docking analyses revealed that CH depended on LM and exerted its biological effects by modulating peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in vascular endothelial cells and estrogen receptor alpha (ERα) protein levels in myocardial cells, thereby enhancing LM uptake at cardiovascular inflammation sites. Proteomics analysis unveiled a serum adsorption pattern for CH@LM under inflammatory conditions showing significant adsorption with CH metabolism-related apolipoprotein family members such as apolipoprotein A-V (Apoa5); this may be a major contributing factor to their prolonged circulation in vivo and explains why CH enhances the distribution of LM at cardiovascular inflammatory injury sites. It should be noted that changes in cell types and physiological environments can also influence the biological behavior of formulations. The findings enhance the conceptualization of CH and LM delivery, providing novel strategies for investigating prescription factors' bioactivity.

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective To investigate the clinical value of fat attenuation index (FAI) on coronary CT angiography (CCTA) in evaluating the degree of coronary artery stenosis and the diagnostic value of plaque vulnerability. Methods A total of 80 patients treated for coronary artery diseases from January 2021 to November 2023 were retrospectively included. All patients were diagnosed with non-calcified plaque (NCP) by CCTA examination. Patients were divided according to the severity of luminal stenosis (39 with mild stenosis, 24 with moderate stenosis, and 17 with severe stenosis). According to plaque vulnerability, the patients were divided into a vulnerable plaque group (27 cases) and a non-vulnerable plaque group (53 cases). A Spearman correlation analysis was used to evaluate the correlation between FAI and stenosis severity in patients with NCP, and a multivariate logistic regression analysis was used to explore the factors influencing vulnerable plaques. Results FAI was significantly lower in the severe stenosis group (−76.95 ± 7.91 HU) than in the mild stenosis group (−66.73 ± 7.69 HU) and the moderate stenosis group (−71.58 ± 8.65 HU), and FAI was significantly lower in the moderate stenosis group than in the mild stenosis group (t = 4.534, 2.190, 4.534, P < 0.05). The correlation analysis showed that FAI was negatively correlated with the severity of coronary artery stenosis (r = −0.726, P < 0.05). There were significant differences between vulnerable and non-vulnerable plaque groups in hypertension [23 (85.19%) vs. 30 (56.60%)], smoking history [8 (29.63%) vs. 4 (7.55)], and FAI (−67.64 ± 8.32 HU vs. −75.69 ± 7.88 HU) (t = 6.535, 6.841, 4.164, P < 0.05). The multivariate logistic regression analysis showed that FAI was a risk factor for vulnerable plaque (odds ratio = 1.439, P < 0.05). Conclusion FAI can be used to effectively assess the risk stratification of NCP and is of great significance in guiding the clinical management of patients.

ObjectiveTo investigate the effect of Dendrobium officinale polysaccharides （DOP） in reversing carbon tetrachloride （CCl₄）-induced hepatic fibrosis （HF） in rats via the Notch signaling pathway and evaluate the therapeutic effect of DOP by ultrasound elastography. MethodFifty-six male SD rats were randomized into normal， model， colchicine （1×10^-4 g·kg^-1）， Fuzheng Huayu powder （0.45 g·kg^-1）， and low-， medium-， and high-dose （0.05， 0.1， 0.2 g·kg^-1） DOP groups （n=8）. The rats in the model group and each treatment group were injected subcutaneously with a mixture of CCl₄-olive oil （2∶3） once every 3 days for 10 weeks. After 6 weeks of modelling， the rats were administrated with corresponding drugs once a day for 4 weeks. Hematoxylin-eosin （HE） staining and Masson staining were employed to observe the pathomorphological changes of the liver tissue. An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， and total bile acids （TBA）. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the serum levels of hyaluronic acid （HA）， laminin （LN）， type Ⅲ precollagen （PC-Ⅲ）， and type Ⅳ collagen （Col-Ⅳ）. The mRNA and protein levels of α-smooth muscle actin （α-SMA）， Notch1， Jagged1， and Hes1 in the liver tissue were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The Young's modulus （YM） of the rat liver was measured by acoustic radiation force impulse （ARFI） elastography before and after treatment. Then， the correlations of YM with the serum levels of HA， LN， PC-Ⅲ， and Col-Ⅳ and the protein levels of α-SMA and Notch1 signaling pathway-related factors in the liver tissue were analyzed. ResultCompared with the normal group， the model group showed disordered arrangement of liver cell cords， obvious infiltration of inflammatory cells， appearance of a large number of fat vacuoles， and fibrous proliferation， elevated levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum， and up-regulated mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.01）. Compared with the model group， drug interventions alleviated the pseudolobule formation and the collagen deposition in confluent areas. Except that the serum level of ALT in the low-dose DOP group had no significant changes， drug interventions， especially high-dose DOP， lowered the levels of ALT， AST， TBA， ALP， HA， LN， PC-Ⅲ， and Col-Ⅳ in the serum and down-regulated the mRNA and protein levels of α-SMA， Notch1， Jagged1， and Hes1 in the liver tissue （P<0.05， P<0.01）. The results of ARFI and correlation analysis showed that the YM of the liver tissue was increased in the model group （P<0.01） compared with that in the normal group， Compared with the model group， drug interventions decreased YM （P<0.01）. YM was positively correlated with the expression levels of HA， LN， PC-Ⅲ， α-SMA， Notch1， Jagged1， and Hes1s （r=0.754， 0.734， 0.801， 0.885， 0.896， 0.757， and 0.800， respectively， P<0.01）， and it had a moderate correlation with Col-Ⅳ （r=0.688， P<0.01）. ConclusionDOP can reverse HF by down-regulating the Notch1/Jagged1/Hes1 signaling pathway. YM can be used as an indicator in the assessment of the efficacy of DOP against HF.

AIM: To understand the visual acuity and spectacle usage among primary and secondary school students in Xi'an city, providing scientific evidence for making myopia prevention and control efforts.METHODS:Vision screening and spectacles usage survey was conducted on 38 226 students in 119 primary and secondary schools from 16 counties and districts in Xi'an city, and uncorrected visual acuity, refractive power, glasses wearing rate, full correction rate were statistically analyzed.RESULTS:The myopia rate among primary and secondary school students in Xi'an city is 61.53%, showing an increasing trend as the grade level goes up(χ2trend=5332.203, P<0.01). Among them, the proportion of mild myopia decreases with the increase of grade level, while the proportion of moderate and high myopia shows an upward trend with the increase of grade level(χ2trend=2671.562, P<0.01). The glasses wearing rate among myopic students is 51.69%, showing an upward trend as the grade level goes up(χ2trend=1486.941, P<0.01). The spectacle prescription rate for female students is higher than that for male students(χ2=23.659, P<0.01), and the rate in urban areas is higher than that in suburban counties(χ2=102.241, P<0.01). The full correction rate among students wearing glasses is 67.08%, and the rate for students wearing glasses in urban areas is higher than that in suburban counties(χ2=4.980, P<0.05). Among myopic students, 63.66% had undergone visual acuity checks more than or equal to twice in the past year, with vocational high school students having the lowest frequency of twice vision screenings, accounting for 58.06%. There is a negative correlation between myopic students residing in suburban counties and their glasses wearing rate, while a higher grade level and increased frequency of annual vision checks are positively correlated with the glasses wearing rate among myopic students(all P<0.01).CONCLUSION:The situation of students' myopia prevention and control is severe in Xi'an city, with low rates of spectacles usage, full correction, and frequency of visual checks. Special attention needs to be paid to the vision correction status of students in suburban counties, primary schools, and vocational high schools.

Objective To investigate the clinical value of fat attenuation index (FAI) on coronary CT angiography (CCTA) in evaluating the degree of coronary artery stenosis and the diagnostic value of plaque vulnerability. Methods A total of 80 patients treated for coronary artery diseases from January 2021 to November 2023 were retrospectively included. All patients were diagnosed with non-calcified plaque (NCP) by CCTA examination. Patients were divided according to the severity of luminal stenosis (39 with mild stenosis, 24 with moderate stenosis, and 17 with severe stenosis). According to plaque vulnerability, the patients were divided into a vulnerable plaque group (27 cases) and a non-vulnerable plaque group (53 cases). A Spearman correlation analysis was used to evaluate the correlation between FAI and stenosis severity in patients with NCP, and a multivariate logistic regression analysis was used to explore the factors influencing vulnerable plaques. Results FAI was significantly lower in the severe stenosis group (−76.95 ± 7.91 HU) than in the mild stenosis group (−66.73 ± 7.69 HU) and the moderate stenosis group (−71.58 ± 8.65 HU), and FAI was significantly lower in the moderate stenosis group than in the mild stenosis group (t = 4.534, 2.190, 4.534, P < 0.05). The correlation analysis showed that FAI was negatively correlated with the severity of coronary artery stenosis (r = −0.726, P < 0.05). There were significant differences between vulnerable and non-vulnerable plaque groups in hypertension [23 (85.19%) vs. 30 (56.60%)], smoking history [8 (29.63%) vs. 4 (7.55)], and FAI (−67.64 ± 8.32 HU vs. −75.69 ± 7.88 HU) (t = 6.535, 6.841, 4.164, P < 0.05). The multivariate logistic regression analysis showed that FAI was a risk factor for vulnerable plaque (odds ratio = 1.439, P < 0.05). Conclusion FAI can be used to effectively assess the risk stratification of NCP and is of great significance in guiding the clinical management of patients.

Objective:To train a deep convolutional neural networks (CNN) using a labeled data set to classify the metaphase chromosomes and test its accuracy for chromosomal identification.Methods:Three thousand and three hundred individuals undergoing surveillance for chromosomal disorders at the Laboratory for Comprehensive Prevention and Treatment of Birth Defects, Ningbo Maternal and Child Health Care Hospital from January 2013 to July 2019 were enrolled. A total of 3 300×46 chromosome images were included, of which 70% were used as the training set and 30% were used as the test set for the deep CNN. The accuracy of chromosome counting and "cutting + recognition + arrangement + automatic analysis" of the model were respectively evaluated. Another 80 images were collected to record the time and accuracy of chromosome classification by geneticists and the model, respectively, so as to assess the practical value of the model.Results:The CNN model was used to count the chromosomes with an accuracy of 61.81%, and the "cutting + recognition + arrangement + automatic analysis" accuracy of the model was 96.16%. Compared with manual operation, the classification time of the CNN model has been greatly reduced, and its karyotyping accuracy was only 3.58% lower than that of geneticists.Conclusion:The CNN model has a high performance for chromosome classification and can significantly reduce the work load involved with the segmentation and classification and improve the efficiency of chromosomal karyotyping, thereby has a broad application prospect.