ObjectiveTo observe the inhibitory effect of the Weiliuan mixture （WLAHJ） on the subcutaneous xenograft tumor of MKN-74 gastric cancer cells， and explore the potential anti-gastric cancer mechanism of WLAHJ by using transcriptomic sequencing technology to reveal related genes and pathways. Methods30 Balb/c nude mice were randomly divided into model， low-， medium-， and high-dose（15，30，45 g·kg^-1） WLAHJ and 5-FU （0.025 g·kg^-1） groups to build a subcutaneous xenograft tumor model with MKN-74 human gastric cancer cells. After modeling，each group was continuously treated with the corresponding drugs for 28 days. During the treatment period， the body weight and tumor size of the mice were observed and recorded every 2 days. At the end of the treatment， the mice were sacrificed， and required samples were collected to calculate the tumor inhibition rate of WLAHJ on the subcutaneous xenograft tumor. High-throughput transcriptomic sequencing （RNA-seq） technology was used to analyze the differentially expressed genes in the subcutaneous tumor tissues of the model group and the medium-dose WLAHJ group， thus exploring the potential mechanism of WLAHJ in gastric cancer intervention. Immunofluorescence experiments were conducted to detect the protein expression levels of glutathione peroxidase 4 （GPX4）， solute carrier family 7 member 11 （SLC7A11）， transferrin receptor protein-1 （TFR-1）， and acyl-CoA synthetase long-chain family member 4 （ACSL4） in subcutaneous xenograft tumors of each group. Cell counting kit-8（CCK-8） and colony formation assays were used to detect the viability and anti-proliferative ability of human gastric cancer AGS and MKN-74 cells at different concentrations of WLAHJ. Kits were used to detect the levels of Fe²⁺， reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） activity in cells. Western blot was used to detect the expression levels of GPX4， SLC7A11， TRF-1， ACSL4， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonic acid 15-lipoxygenase （ALOX15）， and key proteins in the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. ResultsThe mechanism of WLAHJ in gastric cancer intervention may be related to ferroptosis and the PI3K/Akt /mTOR signaling pathway. The growth of subcutaneous xenograft tumors in nude mice of the WLAHJ and 5-FU groups（P<0.05，P<0.01）， GPX4， and SLC7A11 dropped significantly（P<0.01）， while TFR-1， ACSL4， SAT1， and ALOX15（P<0.05，P<0.01）increased significantly compared with those in the model group. The levels of ROS， Fe²⁺， and MDA increased in the WLAHJ and 5-FU groups and the proliferation of gastric cancer cells， SOD activity， the ratios of phosphorybation （p）-mTOR/mTOR， p-PI3K/PI3K， and p-Akt/Akt protein expressions（P<0.05，P<0.01）decreased compared with those in the blank group. ConclusionThe mechanism of WLAHJ in treating gastric cancer may be related to the regulation of the PI3K/ Akt /mTOR signaling pathway to intervene in ferroptosis.

Objective To construct programmed cell death protein-ligand 1(PD-LI)^hi tolerogenic dendritic cell (tol-DC) derived from bone marrow of DA rats and identify its immunological function. Methods DA rat bone marrow cells were extracted, combined with recombinant mouse granulocyte macrophage colony-stimulating factor and recombinant mouse interleukin (IL)-4, and cultured for 6 days in vitro to induce the differentiation of bone marrow cells into immature dendritic cells (imDC). Lipopolysaccharide was used to stimulate cell maturation and cultured for 2 days to collect mature dendritic cells (mDC). PD-L1 lentiviral vector virus stock solution or equivalent dose lentiviral stock solution was added, and PD-L1^hitol-DC and Lv-imDC were collected after culture for 2 days. The morphology of PD-L1^hitol-DC was observed by inverted phase contrast microscope and transmission electron microscope. Real-time fluorescence quantitative reverse transcription polymerase chain reaction, Western blotting and flow cytometry were used to detect the expression level of specific markers on cell surface. CD8⁺T cells derived from Lewis rat spleen were co-cultured with imDC, mDC, Lv-imDC and PD-L1^hitol-DC, respectively. The levels of inflammatory factors in the supernatant of each group were detected by enzyme-linked immunosorbent assay. The apoptosis of T cells and the differentiation of regulatory T cells (Treg) in each group were analyzed by flow cytometry. Results The morphology of PD-L1^hitol-DC modified by PD-L1 gene was consistent with tol-DC characteristics, and the expression levels of CD80, CD86 and major histocompatibility complex (MHC) on the surface were low. After mixed culture with CD8⁺ T cells, the levels of IL-10 and transforming growth factor (TGF) -β1 in the supernatant of PD-L1^hitol-DC group were higher, the levels of tumor necrosis factor (TNF) -α and IL-17A were lower, and the apoptosis of T cells and Treg differentiation were increased. Conclusions Overexpression of PD-L1 through lentiviral vectors may successfully induce the construction of bone-marrow derived PD-L1^hitol-DC in DA rats, promote the secretion of anti-inflammatory factors and T cell apoptosis, induce the differentiation of Treg, and inhibit the immune response of allogeneic CD8⁺T cells, which provides experimental basis for the next organ transplantation immune tolerance study.

ObjectiveTo investigate the association between serum creatinine/cystatin C ratio （CCR） and nonalcoholic fatty liver disease （NAFLD） based on the NHANES database， and to evaluate the potential significance of CCR as an indicator reflecting the metabolic status of the body. MethodsBased on the data from the NHANES database in 1999‍ ‍—‍ ‍2004， a total of 4 217 participants were enrolled and divided into NAFLD group with 1 726 participants and non-NAFLD group with 2 491 participants. CCR was compared between the two groups， and the association between CCR and NAFLD was analyzed. The Wilcoxon rank-sum test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression model was used to investigate the association between CCR and NAFLD； CCR was divided into 4 groups based on quartiles， and odds ratio （OR） and 95% confidence interval （CI） in the regression model was calculated with the first quartile as reference. In addition， the restricted cubic spline analysis was used to investigate whether there was a non-linear relationship between CCR and NAFLD， and interaction items were introduced into the Logistic regression model to perform an interaction analysis. Subgroup analyses were performed based on the stratification of variables to investigate the difference in the association between CCR and NAFLD in different populations. ResultsThe non-NAFLD group had a significantly higher CCR than the NAFLD group （Z=-4.76，P<0.01）. The Logistic regression analysis showed that in model 1 without adjustment of variables， CCR was negatively associated with NAFLD （OR=0.993，95%CI：0.989‍ ‍—‍ ‍0.996，P<0.01）， and in model 3 with adjustment of all variables， CCR was still negatively associated with NAFLD （OR=0.986，95%CI：0.981‍ ‍—‍ ‍0.991，P<0.01）. The analysis of CCR based on quartiles showed a significant association between the increase in CCR and the reduction in the risk of NAFLD. In model 3， compared with the individuals with the lowest quartile of CCR， the individuals with the highest quartile of CCR had a significantly lower risk of NAFLD （OR=0.426，95%CI：0.316‍ ‍—‍ ‍0.574，P<0.01）. Further interaction and subgroup analyses showed that the interaction between CCR and age/sex had a statistical significance （P_interaction<0.01 and P_interaction=0.04）. The subgroup analysis based on age showed a more significant association between CCR and NAFLD in the middle-aged population （≤60 years） （OR=0.982，95%CI：0.976‍ ‍—‍ ‍0.987）， and the subgroup analysis based on sex showed a stronger association between CCR and NAFLD in women （OR=0.979，95%CI：0.972‍ ‍—‍ ‍0.986）. ConclusionThis study shows a significant negative association between CCR and NAFLD， and such association is more significant in middle-aged individuals and women.

Epigenetic mechanisms play a crucial role in the development and progression of nonalcoholic fatty liver disease （NAFLD）， especially among lean individuals. The research on related epigenetic mechanisms has provided new clues and directions for revealing the underlying causes and treatment strategies of NAFLD. This article introduces the role of epigenetics in the development and progression of NAFLD among lean individuals in recent years， analyzes the latest research advances in the epigenetics of NAFLD in this population， and briefly describes the basic concepts of epigenetics， including DNA methylation， histone modifications， and non-coding RNA regulation. This article also discusses how epigenetic alterations impact the pathogenesis， disease progression， and treatment strategies of NAFLD in lean individuals.

Based on current national policies, regulations, standards, relevant literature, and departmental experience regarding the protection against radionuclides in China, this study provides a brief overview of key issues in the management of hospital wards for patients with internal radionuclide contamination. The discussion covers the detection of internal contamination, general requirements for internal radionuclide contamination wards, and inpatient management. In addition, the study explores in depth the daily responsibilities, protective measures, and management protocols for both healthcare staff and patients within such wards. This article summarizes a framework for the construction of internal radionuclide contamination wards, along with specific plans and detailed role-based guidelines. These results provide a reference for the management of hospital wards for patients with internal radionuclide contamination.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Objective:To propose a method for obtaining noise from thoracic CT images based on the Canny edge detection algorithm.Methods:A total of 250 pieces of thoracic CT images of male volunteers collected in 2021 were selected. The contours of thoracic CT images were extracted by the Canny adaptive threshold method. The similarity of the Sobel algorithm, the Canny double threshold method, and the Canny adaptive threshold method was compared. The Hoff transform was used to determine the regions of interest. The effects of the selection size of the regions of interest, the reconstructed convolution kernel, and tube current on the noise of thoracic CT images were investigated.Results:The Canny adaptive threshold method preserved more detail, and the continuity and integrity of the edges were improved, indicating that it was more flexible and robust for edge detection and image segmentation. The Canny adaptive threshold method had the highest structural similarity index (0.644) and the lowest root mean square error (0.371). It had the highest similarity in edge contour detection, and the effect was more significant. As the size of the square area of interest increased, the average noise decreased. The noise standard deviation increased in some intervals, especially in larger square regions. In the case of the same reconstructed convolution kernel, the mean noise of the ascending aorta in thoracic CT images was higher than that of the thoracic aorta. The noise standard deviation of the ascending aorta was lower than that of the thoracic aorta. For ascending aorta, the mean ascending aorta noise (41.97 dB) of reconstructed convolutional nucleus E was the lowest, with the highest noise standard deviation (20.64 dB). For the thoracic aorta, the mean noise (30.78 dB) of the reconstructed convolutional nucleus E was the lowest. The mean noise and standard deviation of the thoracic aorta decreased with the increase in tube current.Conclusions:A method based on the Canny edge detection algorithm to obtain noise from thoracic CT images is proposed, which is suitable for detecting thoracic CT images.

Objective:To investigate the effects of extracts of Rhizoma Sparganii and Rhizoma Curcumae on cartilage damage in osteoarthritis rats and NADPH oxidase 2 (NOX2)/reactive oxygen species (ROS)/nuclear factor-κB (NF-κB) signaling pathways. Methods:Rats (50 cases) were divided into the sham group, and model group, as well as the low, medium, and high dose groups of extracts of Rhizoma Sparganii and Rhizoma Curcumae, with 10 rats in each group. Except for sham group, the rat model of cartilage damage in knee osteoarthritis was established. On the second day after modeling, the rats in the low, medium, and high dose groups received intragastric extracts perfusion of Rhizoma Sparganii and Rhizoma Curcumae at the doses of 5, 10, and 20 g/kg respectively. The rats in the sham and model groups received intragastric equivalent 0.9% sodium chloride solution perfusion, once daily, for 20 days by continuous administration. The knee joint behavior, bone metabolism indicators, serum superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH) levels, inflammatory factors, NOX2, and NF-κB levels of each group were observed. Results:Compared with the model group, the behavioral abnormality scores, cartilage oligomeric matrix protein (COMP), MDA, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), NOX2, and NF-κB levels in the low, medium, and high dose groups were all gradually decreased (all P < 0.05), while proteoglycan, SOD, GSH, and interleukin-10 (IL-10) levels in the low, medium, and high dose groups were all gradually increased (all P < 0.05), and it was dose-dependent. Conclusions:Rhizoma Sparganii and Rhizoma Curcumae extracts can effectively improve cartilage damage in osteoarthritis rats, and it may be related to the inhibition of the NOX2/ROS/NF-κB signaling pathway.

Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.