Pancreatic cancer is currently recognized as one of the most malignant solid tumors， with a 5-year survival rate of 13% over a long period of time， and 80% of the patients have lost the opportunity for surgery at the time of confirmed diagnosis. In addition， the efficacy of conventional radiochemotherapy and targeted therapy is limited by high tumor heterogeneity and the complex immunosuppressive microenvironment. In recent years， mRNA vaccines have become a new focus of tumor immunotherapy due to their unique technical advantages. Based on non-integrating mRNA templates， mRNA vaccines enable precise encoding of tumor neoantigens， which are efficiently expressed in the host and can induce multifaceted immune responses. As for pancreatic cancer， current studies mainly focus on the development and optimization of tumor-associated antigen vaccines and tumor-specific antigen vaccines， as well as next-generation sequencing-guided neoantigen epitope optimization， innovative targeted delivery systems， and artificial intelligence-powered predictive models for immune response， thereby promoting the application of mRNA vaccines in the precise treatment of pancreatic cancer. Further studies should make breakthroughs in the targeted blockade of critical immunosuppressive molecules within the tumor microenvironment， the precise identification of tumor-specific antigenic epitopes， and the development of highly efficient vaccines， so as to bring new hopes for patients with pancreatic cancer.

Objective To analyze the research status and trend of scarlet fever literature in China, and to provide reference for subsequent research. Methods Three major Chinese databases, CNKI, Wanfang, and VIP, as well as Web of Science English database, were used to search for literature related to scarlet fever from 2000 to 2023. Citespace6.2.R2 software was used to statistically analyze the number of publications, authors, institutions and journals, co-cited literature, keyword clustering, and other literature characteristics of the literature. Results From 2000 to 2023, a total of 1 011 Chinese literature were included in the three major Chinese databases. Since 2011, the number of publications had gradually increased, but in recent years, the number of publications had decreased. The organization with the most publications was the Shenyang Center for Disease Control and Prevention. The cluster analysis of key words mainly formed 9 cluster tags, and the high-frequency keywords mainly included epidemic characteristics, epidemiology, incidence rate, etc. A total of 84 English literature were included in the WOS database, with an overall upward trend in publication volume. The institution with the most publications was the China Center for Disease Control and Prevention, and the most frequently cited journal was ^“LANCET INFECT DIS^”.《Resurgence of scarlet fever in China: a 13-year population-based surveillance study》 was the most cited journal. After keyword cluster analysis, 9 cluster labels were mainly formed, and the keywords were mainly outbreak，Hong Kong, and Group A streptococcus. Conclusion Compared with the English literature, which mainly focuses on spatiotemporal aggregation, etiology and strain resistance, Chinese literature focuses more on epidemic surveillance, clinical features and quality nursing.

Objective In this study, a strain of colistin and tigecycline-resistant bacteria isolated in 2009 was analyzed, and the structure of drug-resistant plasmid and genetic environment were discussed, so as to provide basis for the prevention and control of multidrug-resistant bacteria. Methods A strain (GZ12244) with positive mcr and tet(M) was obtained by screening colistin and tigecycline resistance genes. Vitek-2 was used for strain identification, and the drug sensitivity test was carried out by broth dilution method. The molecular typing, drug resistance genes, insertion sequences, plasmid structure and genetic background were analyzed by genome-wide sequencing and bioinformatics. Results Strain GZ12244 is Klebsiella pneumoniae, which is resistant to colistin B, tigecycline, cefuroxime and tetracycline, and carries a variety of drug-resistant related genes such as mcr-1 and tet(M), and some of the drug-resistant genes with antibiotic efflux and antibiotic target change have amino acid substitution mutations. Mcr-1 and tet(M) coexist in a plasmid, and mcr-1 flanked by two insertion sequences ISApl1. There are insertion sequences such as IS15, IS1D and ISEc63 in the upstream and downstream of tet(M) gene. Conclusion Klebsiella pneumoniae GZ12244 is a multidrug-resistant strain. The drug-resistant gene exists in plasmid, and the mobile elements in upstream and downstream may spread the drug-resistant gene.

Objective To explore the research progress, research hotspot and development trend of tigecycline resistance based on the quantitative analysis and visualization function of CiteSpace. Methods The data were collected from 4,263 Chinese and English articles on tigecycline resistance in CNKI, Wanfang, VIP and Web of Science (WOS) databases from 2012 to 2022. CiteSpace 5.8.R3 software was used to analyze the cooperative network of authors, the cooperative network of countries and institutions, the total citation times of journals, and keywords included in the literature, to reveal the hotspots and trends of tigecycline resistance research. Results The number of articles published in English literature was higher than that in Chinese literature. China had the largest number of published documents, showing a significant international academic influence in this research field. Countries all over the world were concerned about the resistance of tigecycline, but Chinese literatures focused more on the clinical infection and prevention of tigecycline resistance, while English literatures placed special emphasis on the research about the drug resistance mechanism of tigecycline. Conclusion The research direction at home and abroad is basically the same, but the research focus has gradually shifted from the clinical treatment and monitoring of tigecycline to the molecular level of drug resistance mechanism.

Background Exposure to diisononyl phthalate (DINP), an endocrine disruptor associated with metabolic diseases and widely used in plastic products, has been linked to the development of several adverse health outcomes in the liver, including non-alcoholic fatty liver disease (NAFLD). Objective To investigate the effects and the possible molecular mechanisms of DINP exposure on lipid metabolism in human hepatocellular carcinoma cells (HepG2 cells). Methods First, HepG2 cells were treated with DINP at three time spots (24, 48, and 72 h) and eleven doses (0, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30, and 100 mmol·L⁻¹). Cell viability were detected using cell counting kit 8 (CCK8). Intracellular lipid deposition was determined by oil red O staining and lipid content detection, and triglyceride (TG) and cholesterol (TC) were further detected. Finally, the mRNA expression levels were detected by fluorescence quantitative PCR, including fatty acid synthesis related genes [acetyl-CoA carboxylase alpha (Accα), fatty acid synthase (Fasn), malonyl-CoA decarboxylase (Mlycd), and sterol regulatory element binding protein 1 (Srebp1)] and β-oxidation related genes [peroxisome proliferator activated receptor alpha (Pparα), AMP-activated protein kinase (Ampk), carnitine palmitoyltransferase 1A (Cpt-1a), transcription factor A, mitochondrial (Tfam), nuclear respiratory factor 1 (Nrf1), and peroxisome proliferator-activated receptor gamma and coactivator 1 alpha (Pgc1-α)]. Results Compared with the control group (0 mmol·L⁻¹), the no observed adverse effect levels (NOAEL) of HepG2 cell viability were 0.3, 0.1, and 0.1 mmol·L⁻¹ after 24, 48, and 72 h exposure to DINP, respectively, and the corresponding lowest observed adverse effect levels (LOAEL) were 1, 0.3, and 0.3 mmol·L⁻¹, respectively (P<0.05). After exposure to 30 mmol·L⁻¹ and 100 mmol·L⁻¹ DINP for 24 h, the intracellular lipid content, lipid deposition, TG, and TC levels were increased significantly compared with the control group (P<0.01). Compared with the control group, the mRNA expression levels of genes related to fatty acid synthesis, such as Mlycd, Srebp1, Fasn, and Accα, were down-regulated after the 100 mmol·L⁻¹ DINP exposure for 24 h, while the mRNA expression level of Mlycd was up-regulated in the 30 mmol·L⁻¹ group. The β-oxidation related genes such as Ampk, Pparα, and Tfam were up-regulated significantly after the 100 mmol·L⁻¹ DINP exposure, while Cpt-1a mRNA expression level was down-regulated (P<0.05). Conclusion Exposure to DINP at 30 mmol·L⁻¹ and 100 mmol·L⁻¹ can interfere with fatty acid synthesis and β-oxidation in lipid metabolism of HepG2 cells, resulting in lipid deposition.

Background and Aims:Preventive temporary stoma has been widely used in surgeries for rectal cancer as a simple and effective method to reduce the severity of postoperative anastomotic leakage.However,some patients with preventive temporary stomas cannot undergo reversal due to various factors,resulting in a permanent stoma.Permanent stomas remain a common adverse outcome in clinical practice,and the reasons behind this are not entirely clear.This study analyzes a continuous surgical sample from a single center to explore the risk factors for forming permanent stoma. Methods:The clinical data of patients who underwent anal-preserving rectal cancer surgery with preventive temporary stoma in Gastrointestinal Cancer Center Ⅲ of Peking University Cancer Hospital from January 2020 to March 2023,with over 12 months of follow-up,were retrospectively collected.The occurrence of permanent stoma was analyzed,and the clinical variables of patients with permanent stoma were compared to those who underwent stoma reversal,along with an analysis of the risk factors for permanent stoma formation.Permanent stoma was defined as ostomy reversal failure for more than 12 months. Results:A total of 299 patients were included,among which 268(89.63％)underwent stoma reversal(stoma closure group),and 31(10.37％)did not(permanent stoma group).Compared to the stoma closure group,the permanent stoma group had a higher incidence of distant organ metastasis at diagnosis(7.5％vs.25.85％,P=0.003)and also had higher proportions of T3 and T4 stages,N2 stage,and clinical stage Ⅳ(all P＜0.05)with an elevated overall postoperative complication rate(19.0％vs.41.9％,P=0.003)as well as a higher rate of severe complications(1.1％vs.9.7％,P=0.016)and an increased incidence of anastomotic leakage(4.9％vs.19.4％,P=0.006).Logistic regression analysis revealed that the presence of distant organ metastasis at diagnosis(OR=5.41,95％CI=1.80-16.27,P=0.003),and occurrence of anastomotic leakage(OR=4.44,95％CI=1.15-17.09,P=0.030)were independent risk factors for the formation of permanent stomas. Conclusion:At present,some patients still cannot undergo reversal of their preventive temporary stoma,resulting in permanent stoma.The formation of permanent stomas is closely related to a low tumor location,distant organ metastasis at diagnosis,and the occurrence of anastomotic leakage.

Objective To evaluate the differences in chemical composition and pharmacological effects between Angelica-Astragalus medicine pair decoction(DGD)and traditional decotion,and to provide a reference for the rational clinical application of Danggui Buxue decoction.Methods With the two comparison methods of unified and non-uniform raw material source batches,we set up different sample groups,established characteristic maps by HPLC,and evaluated the chemical components based on the similarity of characteristic maps,component types,index component content,common peak area,and other factors.The efficacy of the drug was evaluated in the hemorrhagic blood deficiency model mice.Results ①The similarity of the feature map between the DGD and TD was high(similarity was greater than 0.87).②The number of chromatographic peaks was inconsistent.Traditional decoction from self-purchased decoction pieces,or traditional decoction-Factory A decoction pieces had a total of 12 chromatographic peaks each.The DGD of Factory A had a total of 15 chromatographic peaks.There were 10 chromatographic peaks in the DGD of Factory B.③The contents of ferulic acid and calycosin 7-O-glucoside(CG)in DGD of Factory A were higher than those in traditional decoction(P<0.05,n=3).There was no significant difference between DGD and TD ferulic acid content in Factory B,but the content of CG was lower than that in traditional decoction(P<0.05).④The total area of common peaks in DGD was different from that in TD.The relative total ratios of the contents of the components in the self-purchased traditional decoction pieces,the traditional decoction pieces of Factory A,the formula granules of Factory A,and the formula granules of Factory B were 1.00,0.96,2.14,0.60,respectively.⑤Both DGD and traditional decoction could significantly promote the recovery of hemoglobin and red blood cells in hemorrhagic anemia model mice(P<0.01);Compared with the model control group,there was a significantly difference(P<0.05)except for the DGD group of Plant B.There was no significant difference between DGD and TD of Plant A,but there was a very significant difference between DGD and TD of Plant B(P<0.01).Conclusion Whether the raw material source batch is consistent or not,DGD and TD have certain differences in chemical composition.In terms of pharmacological effect,DGD,prepared from a unified batch of decoction pieces,has similar efficacy to traditional decoction in alleviating hemorrhagic anemia.There are certain differences in the pharmacological effects between DGD prepared from different batches of decoction pieces and traditional decoctions.The differences caused by the different preparation processes of the same source batch of prepared slices were compared,and the quality differences of the formula granules from different manufacturers were caused by the different source batches of prepared slices and different preparation processes,indicating the necessity and urgency of the country to formulate a unified quality standard for formula granules and related process specifications.

Objective:To investigate the computed tomography (CT)-based integrated deep learning model for qualitative and quantitative classification of hepatic portal vein.Methods:The retrospective study was conducted. The CT imaging data of 291 patients undergoing upper-abdomen enhanced CT examination in the Beijing Tsinghua Changgung Hospital of Tsinghua University from October 2017 to January 2019 were collected. There were 195 males and 96 females, aged (51±12)years. The hepatic portal vein was reconstructed using the three-dimensional reconstruction system. Three-dimensional point cloud was input to the encoder model to obtain the three-dimen-sional reconstructed vectorized representation, which was used for qualitative classification and quantitative representation classification. Measurement data with normal distribution were repre-sented as Mean± SD, and comparison between groups was conducted using the paired t test. Count data were repre-sented as percentages or absolute numbers, and comparison between groups was analyzed using the paired chi-square test. Results:(1) Three-dimensional reconstruction of portal vein and anatomical classification. Three-dimensional structure was reconstructed in the 291 patients. Classification of main hepatic portal vein showed 211 cases of Akgul type A, 29 cases of Akgul type B, 16 cases of Akgul type C, 10 cases of Akgul type D, and 25 cases of unclassifiable. (2) Prediction of qualitative classification of main hepatic portal vein. Of the 291 patient samples, 25 unclassifiable or poor quality samples were excluded, 266 samples were used for automated qualitative classification of the main portal vein by machine model. There were 211 cases of Akgul type A, 29 cases of Akgul type B, 26 cases of Akgul type C&D. The Macro-F1 of 266 patients was 61.93%±40.50% and the accuracy was 84.99%, versus 32.38%±19.81% and 61.65% of Random classifier, showing significant differ-ences between them ( t=7.85, χ2=62.89, P<0.05). (3) Quantitative representation of portal vein classification. The probabilities of quantitative classification for Akgul qualitative classification of similar samples included P@1 as 73%±45%, P@3 as 70%±37%, P@5 as 69%±35%, P@10 as 67%± 32%, mean reciprocal rank(MRR) as 80%±34%, versus 57%±50%, 58%±35%, 58%±32%, 58%± 30%, 70%±37% of the baseline model, showing significant differences between the two analytical methods ( t=5.22, 5.11, 5.00, 4.99, 3.47, P<0.05). Conclusion:The automated classification model for the hepatic portal vein structure was constructed using CT-based three-dimensional reconstruc-tion and deep learning technology, which can achieve automatic qualitative classification and quanti-tatively describe the hepatic portal vein structure.

ObjectiveTo study the effect of Bazi Bushen capsules on delaying the aging process of naturally aging mice and its mechanism. MethodThe mice were randomly divided into four groups according to their body weight， namely， aging group， low-dose Bazi Bushen capsules group （1 g·kg^-1）， high-dose Bazi Bushen capsules group （2 g·kg^-1）， and rapamycin group （0.002 g·kg^-1）. The debilitating signs were detected by behavioral tests and the weakness index was measured. The percentages of spleen T and B lymphocytes， effector T cells （TE）， memory T cells （TM）， naive T cells （TN）， helper T cells （Th）， cytotoxic T cells （Tc） ，Th1 cells， Th2 cells， and regulatory T cells （Treg） were determined by flow cytometry. Cell proliferation and the cell counting kit-8 （CCK-8） assay was used to detect the proliferation of lymphocytes in mice. The hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the mouse spleen. The expression of cyclin-dependent kinase inhibitor 2A （p16） and cyclin-dependent kinase inhibitor 1A （p21） was detected by immunohistochemistry （IHC）. The mRNA expression of senescence-related proteins p16 and p21 was determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the inflammatory cytokines， including tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin （IL）-1β， IL-2， IL-4， IL-10， and IL-12 p70， in peripheral blood of mice were detected by Luminex. ResultAs compared with the aging group， mice in the Bazi Bushen capsules and rapamycin groups showed significantly improved debilitating signs and reduced weakness index scores （P<0.05， P<0.01）， increased proportions of T cells， TN cells， Tc cells， Th2 cells， and Treg cells in the spleen， decreased proportions of TE cells， TM cells， Th cells， Th1 cells （P<0.05， P<0.01）， and increased proliferation of splenic lymphocytes （P<0.05， P<0.01）. In the Bazi Bushen capsules and rapamycin groups， clear structure of the red and white marrow marginal zone was observed in the spleen of mice， the area of the white marrow was increased， and the area of the red marrow was correspondingly decreased. The protein and mRNA expression of aging-related proteins p16 and p21 in the spleen was decreased （P<0.01）， the levels of serum pro-inflammatory cytokines IL-1β， IL-2， IL-12 p70， IFN-γ， and TNF-α levels were decreased， and the levels of IL-4 and IL-10 were increased （P<0.05， P<0.01） in the Bazi Bushen capsules and rapamycin groups as compared with the aging group. ConclusionBazi Bushen capsules have the effect of regulating the debilitating signs of natural aging mice， regulating the immune homeostasis and inflammation level of the body， and reducing cell aging.

In order to standardize the quality control of traditional Chinese medicine（TCM） dispensing granules， the Chinese Pharmacopoeia Commission has promulgated and implemented 200 national drug standards for TCM dispensing granules， but there are still varieties of TCM dispensing granules without unified standards. Many provinces have actively invested in the formulation of provincial standards for TCM dispensing granules to make up for the gaps in standards for varieties of traditional Chinese medicine dispensing granules other than the national standards. By the end of July 2022， 29 provincial-level administrative regions have successively promulgated and implemented a total of 5 602 provincial standards for TCM dispensing granules， involving more than 400 varieties. In order to better understand the formulation and characteristics of provincial standards， this study took 105 provincial standards that have been promulgated and implemented in Henan province as an example， and comprehensively analyzed the formulation and characteristics through quality control indicators such as dry extract rate of raw materials， contents of index components and their transfer rates， specifications and so on. The formulation and characteristics of the same TCM dispensing granules in the provincial standards of different provinces were further analyzed， in order to provide reference for the formulation of provincial standards of TCM dispensing granules and the implementation of national standards.