ObjectiveTo investigate the mechanism by which Jianpi Xiao'ai prescription （JPXAP） inhibits colorectal cancer progression by regulating the inducible nitric oxide synthase-arginase 1 （iNOS-ARG1） metabolic axis and inducing mitochondrial reactive oxygen species （mito-ROS）-mediated mitochondrial structural and functional impairment. MethodsAn arginine metabolism disorder model of human colorectal cancer HCT116 cells was established by combined treatment with recombinant human interferon-γ （IFN-γ， 10 μg·L^-1） and N（ω）-hydroxy-L-arginine （Nor-NOHA， 200 μmol·L^-1） for 24 h， followed by intervention with 5%， 10%， or 20% JPXAP-containing serum. Cell proliferation was assessed using cell counting kit-8 （CCK-8）， 5-ethynyl-2′-deoxyuridine （EdU） staining， and colony formation assays. Cell invasion and migration were evaluated using Transwell chamber and wound healing assays. Mitochondrial membrane potential （MMP） and ROS levels were assessed by JC-1 and MitoSOX staining， respectively. Mitochondrial ultrastructure was observed by transmission electron microscopy （TEM）. The expression of iNOS， ARG1， and mitochondrial dynamics-related proteins， including mitofusin 2 （MFN2） and dynamin-related protein 1 （DRP1）， was analyzed by Western blot and immunofluorescence. The levels of L-arginine， citrulline， and urea were determined by colorimetric methods and enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the blank group， the model group exhibited significantly upregulated iNOS expression， downregulated ARG1 expression， a decreased ARG1/iNOS ratio， reduced L-arginine and urea levels， and increased citrulline levels （P<0.05）. Meanwhile， mito-ROS accumulation was significantly increased， the JC-1 red/green fluorescence ratio was decreased， and mitochondria showed swelling and cristae disruption， indicating that metabolic disorder induced mitochondrial injury. Compared with the model group， all JPXAP-treated groups further decreased the ARG1/iNOS ratio， enhanced nitric oxide （NO） and reactive nitrogen species accumulation， further reduced L-arginine and urea levels， and increased citrulline levels （P<0.01）. EdU-positive rate， colony formation rate， wound healing rate， and Transwell invasion number all decreased significantly with increasing serum concentration （P<0.01）. Mito-ROS levels were further elevated， and the JC-1 red/green ratio further decreased. TEM revealed aggravated mitochondrial swelling and vacuolization. MFN2 expression was downregulated and DRP1 expression was upregulated （P<0.01），in a dose-dependent manner. ConclusionJPXAP further activates NO-mediated oxidative/nitrosative stress under arginine metabolism imbalance， inducing mito-ROS accumulation， MMP collapse， and mitochondrial dynamics imbalance， thereby inhibiting colorectal cancer cell proliferation and migration. These findings reveal an antitumor mechanism of JPXAP based on coordinated targeting of the "metabolism-mitochondria" axis.

Objective To understand the utilization of immunization program vaccines in Liaoning Province and evaluate the vaccine management mode, and to provide a scientific basis for optimizing immunization strategies. Methods The vaccine collection data and vaccine administration data of vaccination units (including obstetric clinics) in the province from 2021 to 2024 were collected, and the vaccine utilization rate of immunization program was calculated. SPSS 13.0 software was used for data analysis, and χ² test was used for comparison. A two-sided P value of <0.05 was considered statistically significant. Results (1) From 2021 to 2024, vaccination units and obstetric clinics received a total of 15 993 884 doses of immunization program vaccines, with a total utilization rate of 79.34%. The highest utilization rate was the single-dose vaccine MPSV-AC (94.02%), followed by JE-L (91.92%). The lowest rate of use was the 5-dose strength vaccine MPSV-A (48.12%), followed by the 4-dose strength vaccine DT (63.13%). (2) Comparing MPSV-A and DT in different years, the utilization rate of MPSV-A and DT was the highest in 2021, 59.53% and 67.71%, respectively. From 2021 to 2024, the utilization rate of MPSV-A had a decreasing trend year by year, with the lowest being 38.65% (2024), and the loss coefficient of MPSV-A in each year was higher than that of DT. (3) Comparison of vaccine utilization rates in immunization programs around 2020, the utilization rate of single-dose vaccines increased significantly compared with before, while the utilization rate of multi-dose vaccines decreased compared with before 2020. Conclusion After 2020, the vaccine utilization rate of the immunization program in Liaoning Province has increased significantly, and the optimized vaccine management strategies has achieved remarkable results. Multi-dose vaccines remain highly susceptible to formulation-related factors and vaccination density. It is recommended to formulate precise vaccination strategies to reduce the loss of multi-dose vaccines.

Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

ObjectiveTo investigate the intervention effect of Tengli Kangliu prescription （TKP） on the carcinogenesis of colorectal adenoma （CRA） induced by azoxymethane （AOM）/dextran sulphate sodium salt （DSS） in C57BL/6 mice and decipher the potential mechanism through regulating the signal transducer and activator of transcription 3 （STAT3） pathway to target M2-type macrophages. MethodsA total of 55 male C57BL/6 mice were randomized into a blank group （n=10）， a model group （n=15）， a celecoxib （0.02 g·kg^-1·d^-1） group （n=15）， a TKP （42.43 g·kg^-1·d^-1） group （n=15）. The mice in the model， TKP， and celecoxib groups were modeled for CRA lesions through the AOM/DSS three-cycle protocol. The intervention in each group began one week after free access to DSS and lasted for 12 weeks， and the blank group received 20 mL·kg^-1·d^-1 normal saline through gavage. Throughout the study period， changes in body mass and survival rate were recorded， alongside measurements of colorectal length and spleen mass. Histological changes of the colonic tissue were observed by HE staining. Immunohistochemical （IHC） staining was performed to detect the positive expression of CD68 and CD11c in the colorectal tissue. Western blot was employed to assess the protein levels of STAT3， phosphorylated （p）-STAT3， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the intestinal tissue. Real-time quantitative PCR was employed to analyze the mRNA levels of arginase 1 （Arg1）， CD206， and vascular endothelial growth factor （VEGF）. Enzyme-linked Immunosorbent assay（ELISA） was employed to measure the serum concentrations of Th2-type cytokines interleukin （IL）-4， IL-6， and IL-13 in mice. ResultsCompared with the blank group， the model group exhibited symptoms including diarrhea， hematochezia， and body mass loss， accompanied by shortened colon length， mucosal damage， and multiple tumors. In addition， the model group showcased up-regulated protein levels of STAT3， p-STAT3， and Bcl-2， down-regulated protein level of Bax， increased positive expression of CD68 and CD11c， and up-regulated mRNA levels of Arg1， CD206， and VEGF in the colon tissue， together with elevated serum levels of IL-4， IL-13， and IL-6 （P<0.05）. Compared with the model group， the above-mentioned indicators were partially reversed in both TKP group and celecoxib group， with superior effects observed in the TKP group （P<0.05）. ConclusionTKP significantly improves the survival quality of the mouse model of AOM/DSS-induced CRA by reducing intestinal inflammation and decreasing colorectal tumor number and size. It may delay the progression of AOM/DSS-induced colorectal tumor-like lesions by inhibiting activation of the STAT3/p-STAT3 signaling pathway in the intestinal tissue， targeting regulation of M2-type macrophages， and improving the tumor microenvironment， thereby suppressing CRA carcinogenesis.

Objective:To investigate the the differential expression of EIF5A2 in intrahepatic cholangiocarcinoma cell lines RBE,HCCC9810,and HUCCT1,and its effects on HCCC9810 cell migration and invasion,epithelial mesenchymal transition,and PI3K/AKT signaling pathway.Methods:The differential expression of EIF5A2 in RBE,HCCC9810,and HUCCT1 cell lines was detected using WB method.The HCCC9810 cell line,with the highest expression of EIF5A2,was selected for this experiment.The expression of EIF5A2 in HCCC9810 cell line was silenced by transient transfection of small interfering RNA.The best silencing effect of small interfering RNA was screened by WB.Scratch assay and Tran-swell migration invasion assay were used to detect the effect of silencing EIF5A2 on the migration and invasion ability of HCCC9810 cells.WB was used to detect the effect of silencing EIF5A2 on PI3K/AKT signaling pathway and epithelial mesenchymal transition in HCCC9810 cells.Results:The WB results showed that EIF5A2 had the highest expression in the HCCC9810 cell line,and siRNA1 had the best silencing effect on EIF5A2 in the HCCC9810 cell line.Scratch assay and Transwell migration invasion assay results showed that silencing EIF5A2 in the HCCC9810 cell line resulted in a decrease in cell invasion and metastasis ability(P＜0.05).At the same time,the expression of p-PI3K and p-AKT in the PI3K/AKT signaling pathway was significantly decreased(P＜0.05),while the epithelial cell marker E-cadherin expression increased(P＜0.05)and the stromal cell marker N-cadherin expression decreased(P＜0.05).Conclusion:EIF5A2 may promote epi-thelial mesenchymal transition and enhance the migration and invasion ability of intrahepatic cholangiocarcinoma cells through the PI3K/AKT signaling pathway.

Objectives:This study aims to evaluate the causal relationship between plasma proteins and myocardial infarction(MI)using two-sample bidirectional Mendelian randomization(MR)analysis,identify key biomarkers,and validate their expression.Methods:The study utilized publicly available genome-wide association study(GWAS)data of 4 907 plasma proteins as the exposure factor,with single nucleotide polymorphisms(SNPs)as instrumental variables,and four MI datasets as outcomes.Two-sample MR analysis was performed using the inverse variance weighted(IVW)method,complemented by simple model,weighted model,weighted median estimator(WME),and MR-Egger regression methods to assess the causal relationship between exposure factors and outcomes.Venn diagrams and word clouds were used to screen proteins associated with MI as candidate biomarkers.Reverse MR analysis was conducted to evaluate reverse causality.Sensitivity analysis was performed to assess the robustness of the results.Immunohistochemistry(IHC)was used to validate the expression of proteasome activator subunit 1(PSME1)and vacuolar protein sorting 29(VPS29)in the aorta of mice,and enzyme-linked immunosorbent assay(ELISA)was used to verify the expression of PSME1 and VPS29 in plasma from patients with acute myocardial infarction(AMI).Results:The two-sample MR analysis indicated that PSME1 was significantly negatively associated with myocardial infarction in all four datasets,with OR(95%CI)of 0.684(0.557-0.839),0.990(0.987-0.993),0.579(0.448-0.748),and 0.993(0.990-0.996),respectively,with all P<0.001.Similarly,VPS29 also showed a significant negative association with MI in all four datasets,with OR(95%CI)of 0.902(0.862-0.945),0.998(0.997-0.999),0.866(0.808-0.929),and 0.998(0.997-0.999),respectively,with all P<0.001.Reverse MR analysis did not detect reverse causality,and sensitivity analysis confirmed the robustness of the results.IHC results showed significantly reduced expression of PSME1 and VPS29 in the aortas of AMI mice with an atherosclerotic background compared to control mice(both P<0.05).ELISA results indicated significantly lower plasma levels of PSME1 and VPS29 in AMI patients compared to healthy controls(both P<0.05).Conclusions:Higher levels of PSME1 and VPS29 are negatively associated with the risk of MI,suggesting that PSME1 and VPS29 may serve as protective biomarkers for cardiovascular diseases.

A sandglass ladder residual network(SLRN)is proposed for multi-label chest X-ray classification,thereby improving the accuracy of clinical diagnosis.SLRN consists of 3 key modules:(1)a sandglass convolutional module to simultaneously extract inter-channel and spatial information;(2)a ladder self attention block to achieve different window divisions through shift operations,expand the receptive field,and realize multi-scale feature extraction and fusion;(3)class specific residual attention in the multi-label classification stage to capture the correlation between different labels and the importance of features for accomplishing more accurate classification by adjusting the weights of different features.The proposed model is validated using the IU X-Ray dataset collected by Indiana University and the publicly available Chest X-Ray14 dataset collected by the National Institutes of Health in the United States;and the results demonstrate that SLRN which combines the advantages of convolutional neural network and vision transformer enables the capture of local features and global correlations in images,better handles long-distance dependencies,and assists doctors in clinical diagnosis.

Objective:To compare the types and contents of trace elements in compound trace element preparations used in parenteral nutrition in Beijing against the doses recommended by the guidelines, so as to facilitate optimal choice of preparations for different populations in clinical practice.Methods:The available compound trace element preparations were determined according to the drug list from the Medical Insurance Recruitment and Procurement System of Beijing and the recommended doses of trace elements in the guidelines released by Chinese domestic and foreign nutrition societies were collected and compared.Results:The compound trace element preparations used in Beijing comprised 4 varieties and 6 specifications, with the daily cost ranging from 11.32 to 471 Chinese Yuan. There were 3 varieties of trace element preparations for adults, including multi-trace elements injection (Ⅱ), multi-trace elements injection (Ⅲ), and multi-trace elements injection. Among those, multi-trace elements injection (Ⅲ) met the guideline recommendations best and the price was moderate. For pediatric populations, multi-trace elements injections (Ⅰ) satisfied better the trace element requirements for preterm infants and infants from term to 3 months, while multi-trace elements injections (Ⅲ) outperformed in meeting the trace element requirements for 3-to-12-month infants and children. However, there were still some differences in the trace element contents between the two preparations and the guideline recommendations.Conclusion:The currently available varieties and specifications of trace element preparations basically meet the recommendations of evidence-based guidelines, but there is still the need to improve the instructions for and evidence on the pediatric application of certain preparations.

Aim To explore the effect of the classical famous prescription Dahuang Zhechong pill(DHZCP)on relieving liver cirrhosis by regulating the stress fiber remodeling mediated by mechanistic signaling pathway and to explore the underlying mechanism.Methods Mice were randomly divided into the control group,model group,DHZCP low-dose group,DHZCP high-dose group,and Colchicine-positive control group.The liver cirrhosis mouse model was constructed by intrap-eritoneal injection of olive oil-solubilized CCl4.HE staining and serologic markers were used to reflect liver injury.Masson staining was used to evaluate collagen deposition in liver tissue.ELISA was applied to detect vasoactive molecules and cancer indicators.Atomic force microscopy was employed to detect liver tissue stiffness.Color Doppler diagnostic instrument was used to assess portal blood flow velocity.Western blot was utilized to detect ROCK2 expression and phosphoryla-tion of YAP,Cofilin,and MLC.Results The liver tis-sues in the model group had obvious inflammatory cell infiltration and collagen deposition,accompanied by significant elevation of serum transaminases and fibrosis indexes.Similarly,vasoactive molecules and cancer in-dicators were elevated,and the mechanoregulatory pro-tein ROCK2 expression and phosphorylation of Cofilin and MLC were elevated,with YAP being strongly de-phosphorylated.Both low and high doses of DHZCP re-versed the pathological changes,serological indices,and inhibited the activation of the stress fiber(SF)re-modeling mechanistic signaling pathway.Conclusion DHZCP effectively ameliorates liver tissue lesions in mice with liver cirrhosis,and its mechanism may be re-lated to the inhibition of SF remodeling mechanistic signaling pathway.

Objective:Exploring the changes in the expression of transient receptor potential vanilloid 1 (TRPV1) in the peripheral and central nervous system in rats temporomandibular joint osteoarthritis (TMJOA) and its relationship with TMJOA pain .Methods:From February 2024 to April 2025, 48 healthy male Sprague Dawley rats were randomly divided into a control group and an experimental group, with 24 rats in each group. The modeling periods for both groups were 2, 4, and 6 weeks, with 8 rats per group at each time point. After bilateral injection of monosodium iodoacetate (MIA) into the temporomandibular joint (TMJ) cavity to establish a TMJOA model, the TMJ condyle, trigeminal ganglion (TG), trigeminal nucleus caudate (TNC), and hippocampal tissue were collected. Pain threshold detector von Frey silk was used to evaluate the head withdrawal threshold (HWT) of rats, and HE staining and micro-CT scanning were used to observe the histological changes of TMJ. Immunohistochemical staining was used to detect the expression of TRPV1 in TG and hippocampal tissues, as well as the expression of glial fibrillar acidic protein (GFAP) in TNC.Results:On the first day after modeling, the HWT of rats significantly decreased and then gradually increased. From day 7 to day 14, HWT decreased again, and after day 14, HWT gradually increased. Statistically significant differences were observed between the experimental group and the control group at each time point ( P<0.001). HE staining and micro-CT revealed that in the second week after modeling, the arrangement of condylar bone trabeculae was disordered, the trabeculae became thinner, the bone marrow cavity became larger, and then the trabeculae became thicker and the bone marrow cavity became smaller. The number of TRPV1 positive cells in TG of TMJOA rats reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001), with no statistically significant difference in the control group ( P=0.941). The number of GFAP positive cells in TNCs of TMJOA rats significantly increased, reaching its peak in the second week of modeling and gradually decreasing in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.720). The number of TRPV1 positive cells in the hippocampus of TMJOA rats significantly increased. The number of TRPV1 positive cells reached its peak in the second week of modeling, and then gradually decreased in the fourth and sixth weeks ( P<0.001). There was no statistically significant difference between the control group ( P=0.776). Conclusions:In the MIA induced rat TMJOA model, the expression of TRPV1 in TG and hippocampal tissue, as well as the expression of GFAP in TNC, were upregulated, which may be involved in the occurrence and development of TMJOA pain and related to the development of TMJOA lesions.