Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective To investigate the pathological damage to and inflammation of different intestinal segments in a rat model of severe hemorrhage,and to explore the effect of polarization of intestinal macrophage on the pathophysiology of intestinal inflammation.Methods Male Wistar rats were randomly divided into two groups:the sham operation group and hemorrhage group.In the hemorrhage group,40％of the total blood volume was lost in 25-30 minutes,while in the sham operation group,only the femoral artery and vein were intubated without bleeding.The rats were killed at 0,3,6,12 and 24 hours.The entire intestine was isolated quickly,and sections of the intestine were cut at the duodenum,jejunum,ileocecal junction,colon and rectum for histopathological evaluation.ELISA was adopted to determine related inflammation factors while multi-color immunohistochemistry was used to calculate macrophage surface markers.The data was statistically analyzed.Results(1)Compared with the sham group,there was no significant difference in colon histology at 3 h and 6 h,but significant difference was detected in rectum scores only at 24 h.The scores of other intestinal segments were significantly different at each time point.The severity of ileocecal and colonic lesions after bleeding increased with time.The duodenum,jejunum and ileocecum were more critically injured at 3 h than the rectum at 6 h.The injury to the duodenum,jejunum,ileum and colon was much more pronounced than to the rectum at 12 h.(2)The expressions of TNF-α and IL-1β in the rectum were increased significantly at 12 h post operation.The expressions of IL-1β,TNF-α in the jejunum increased obviously at 3 h and 6 h,respectively.(3)Three hours after severe bleeding,the level of macrophages in the jejunum and ileocececal area increased significantly,and the percentage of M1 macrophages was higher.After 6 hours,the proportion of M2 macrophages in the jejunum and M1 macrophages decreased significantly.After 3 hours,the percentage of M1 macrophages in the colon decreased,but that of M2 macrophages increased.The proportion of M2 polarized macrophages in the duodenum and rectum increased at 3 h after severe bleeding but decreased at 6 h.Conclusion Pathological damage to intestinal sections after bleeding varies depending on the time,and is correlated with the inflammatory level of macrophages.

ObjectiveTo explore the drug resistance of Morganella morganii （Mm） and the risk factors for extended-spectrum β-lactamase （ESBL） positive infection in type 2 diabetes foot （DF） patients with Mm， and to provide a reference for clinical treatment. Methods310 samples of DF patients with Mm infection were collected from Shanghai Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2020 to March 2023. The patients were selected for the first time to detect Mm bacteria through cultivation， and were divided into ESBL producing group （n=45） and non ESBL producing group （n=265）. Bacterial identification and drug sensitivity experiments on Mm were conducted. Multivariate logistic regression analysis was used to analyze the risk factors. The stepwise regression method （SRM） was used to screen the most important correlation factors for constructing risk prediction model and its evaluation. ResultsBoth ESBL producing and non ESBL producing Mm were sensitive to imipenem （IPM） and meropenem （MEM）. Compared with the non ESBL producing group， the resistance of Mm in the ESBL producing group to other tested antibiotics ［excluding ampicillin （AM）/sulbactam （SU）］ was higher （P<0.05）. Aged ≥60 years old， concomitant hypoproteinemia （HP）， combined use of antibiotics， and history of third-generation cephalosporin use were all independent risk factors for the occurrence of ESBL producing strain infection （P<0.05）. SRM screening identified age， HP， and use of third-generation cephalosporins as the most associated factors with ESBL producing strain infection， and these three factors were included in the multivariate logistic regression prediction model. After calculation， when P=0.80， the Jordan index was the highest and the prediction effect was the best. The prediction accuracy was 89.35%， the sensitivity was 86.67%， and the specificity was 89.81%. The model evaluation results showed that the predictive model has good discrimination and high accuracy. ConclusionThe Mm strain producing ESBL has strong resistance to commonly used antibiotics， and it is recommended that clinical physicians use antibiotics reasonably. Age， HP， combined use of antibiotics， and use of third-generation cephalosporins are all independent risk factors for the occurrence of ESBL producing bacterial infections. Clinical monitoring should be carried out on susceptible populations based on risk factors， and infection management should be strengthened.

Thyroid cancer is the most common malignant tumor of the head and neck, among which papillary thyroid carcinoma is the most common. Papillary thyroid carcinoma with a diameter of ≤ 1.0 cm is called thyroid micropapillary carcinoma. In recent years, thermal ablation technology for the treatment of thyroid micropapillary carcinoma has developed rapidly at home and abroad. At present, many guidelines, consensus and clinical studies related to thermal ablation treatment of thyroid micropapillary carcinoma have been published at home and abroad. Based on the existing literature, guidelines and clinical studies, this article summarizes, discusses and analyzes the advantages, indications, efficacy, safety, and existing problems of thermal ablation therapy for thyroid cancer.

Ischemic stroke,due to its high prevalence and mortality,has become one of the most important public health concerns globally.Nerve cell damage is the main biological event in its patho-logical process and there is still a lack of effective neuroprotective drugs for clinical use.Numerous studies have shown that inhibitions of histone deacetylases(HDACs)can exert neuroprotective effects in ischemic stroke.Due to the multiple types of HDACs and the relatively poor specificity of HDAC inhib-itors,it has been difficult to identify any HDAC that plays a key role in ischemic stroke.ClassⅠHDACs include four members:HDAC1,HDAC2,HDAC3,and HDAC8,and have been more in-depth in isch-emic stroke.The complex mechanisms of classⅠHDAC inhibitors that have been discovered so far involve neural cell function,neuroinflammation and blood-brain barriers.This article is intended to study the regulatory role of classⅠHDACs in ischemic stroke in the hopes of providing reference for the developments of effective drugs targeting HDACs.

OBJECTIVE To investigate the distribution and regulation of G-quadruplex(G4)in enzymes related to glycolysis.METHODS The sequences of the transcription start site(TSS)region upstream of 1500 bp to the 5'-Untranslated region in 200 enzymes and their subtypes in glycolysis were selected for bioinformatics analysis.Related enzymes in glycolysis containing putative G-quadru-plex-forming sequences(PQSs)were identified.Circular Dichroism and Native polyacrylamide gel elec-trophoresis were used to verify the formation of G4.The ExonucleaseⅠhydrolysis assay was used to validate the stability of the formed G4 under 0,0.5,2,8,16,and 32 min.A reporter gene plasmid was constructed by inserting specific fragments of the related enzymes before the luciferase expression sequence.The dual-luciferase reporter assay system validate the expression level of luciferase to assess the impact of G4 on promoter activity.Real-time quantitative PCR was performed to validate the transcriptional regulatory role of G4 by detecting the mRNA levels of luciferase.RESULTS ①Bioin-formatics analysis showed that out of the 200 glycolysis-related enzymes,12 contained PQSs.Based on the analysis of the length and structure of PQSs,aldolase A(ALDOA)and phosphoglycerate mutase 2(PGAM2)proved to be able to form stable G4.② ALDOA and PGAM2 had the maximum positive absorption peak at 260 nm and maximum negative absorption peak at 240 nm.Both of them could form a G4 at the same time.③After digestion with ExonucleaseⅠ,ALDOA and PGAM2 showed no significant hydrolysis and demonstrated the stability of G4 structures.However,both of them could be gradually hydrolyzed after mutations in their PQSs.④ After PQS mutation of ALDOA and PGAM2,the mRNA levels and expression of downstream luciferase of ALDOA were significantly increased(P<0.05,P<0.01),while PGAM2 was significantly decreased(P<0.05,P<0.01).CONCLUSION The gene sequences of glycolysis-related enzymes and their subtypes contain a large number of PQSs.ALDOA and PGAM2 can form stable G4 and perform transcriptional regulatory functions.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To study the value of postmortem imaging on the diagnosis of intestinal perforation.Method Postmortem imaging(PMCT and PMCTA)data of 2 intestinal perforation deaths(and 4 controlled cases)were reviewed retrospectively.Diagnosing capacities of intestinal perforation by postmortem imaging method were further investigated.Results PMCT is sensitive in detecting the free air and liquid induced by intestinal perforation.PMCT can sometimes detect the gravity-dependent purulent secretions in the abdominopelvic cavity.PMCTA can visualize the extravasation of contrast agent from the perforation,which can be used to locate the accurate perforation region.Conclusion Postmortem imaging method(PMCT and PMCTA)is an important tool for the diagnosis of intestinal perforation,which can not only be used as a forensic diagnosis method,but is also useful to locate the perforation site before an forensic autopsy.

Objective Based on the gene expression omnibus(GEO)database,bioinformatics methods were employed to analyze the expression characteristics of hypoxia-related differentially expressed genes(HRDEGs)in ischemic stroke,and key genes were screened,to provide important support for a deeper understanding of ischemic stroke.Methods The GSE16561 and GSE58294 datasets were downloaded from the GEO database,and Python software was used for data integration.The Combat method was employed to eliminate batch effects while retaining disease grouping characteristics.Principal component analysis was conducted to reduce dimensionality of the data before and after batch effect removal,and intraclass correlation coefficient(ICC)testing was performed on the ischemic stroke and normal control groups.Gene set enrichment analysis(GSEA)and single-sample GSEA were conducted on the merged and batch effects eliminated dataset,with a nominal P-value(NOM P-val)＜0.05 and false discovery rate P-value(FDR P-val)＜0.25 used as criteria to select significantly different gene sets.Differential expression genes between the ischemic stroke samples and normal control samples after merging and eliminating batch effects of the GSE16561 and GSE58294 datasets were identified using R software,with an absolute value of log2 gene expression fold change(FC)≥0.58 and adjusted P-value(Padj)＜0.05 as selection criteria.Intersection with hypoxia-related genes obtained from the National Center for Biotechnology Information(NCBI)in the United States yielded the HRDEGs.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses were performed on the HRDEGs,and the STRING database was used to construct a protein-protein interaction network of differentially expressed genes.The top 10 key genes were filtered using Cytoscape 3.8 software.Results The ICC analysis results showed excellent consistency in the ischemic stroke and normal control samples after batch effect removal,with ICC values of 0.94 and 0.98 for the GSE16561 and GSE58294datasets,respectively.GSEA results demonstrated significant enrichment of 34 gene sets in the stroke samples in the newly merged and batch effects removed dataset from GSE16561 and GSE58294,leading to the identification of 404 differentially expressed genes(all with Padj＜0.05),including 354 upregulated genes and 50 downregulated genes.Intersection with hypoxia-related genes yielded 64 HRDEGs.GO enrichment analysis indicated significant enrichment of HRDEGs in vesicle lumen,cytoplasmic vesicle lumen,secretory granule lumen,with molecular functions such as amide binding,peptide binding,phospholipid binding,and enzyme inhibitor activity.These genes are primarily involved in the positive regulation of cytokine production,regulation of immune response,response to bacterium-derived molecules,and response to lipopolysaccharide,among other biological processes.KEGG enrichment analysis revealed enrichment of HRDEGs in pathways related to lipid and atherosclerosis,Salmonella infection,neutrophil extracellular trap formation,nucleotide-binding oligomerization domain-like receptor signaling pathway,protein glycosylation in cancer,tuberculosis,and necroptosis.Based on the protein-protein interaction network,10 key genes were identified,including arginase1(ARG1),caspase1(CASP1),interleukin1 receptor type 1(IL-1R1),integrin subunit alpha M(ITGAM),matrix metalloproteinase9(MMP9),prostaglandin-endoperoxide synthase 2(PTGS2),signal transducer and activator of transcription 3(STAT3),Toll-like receptor2(TLR2),TLR4,and TLR8.Conclusion This study has identified 10 key genes associated with ischemic stroke and hypoxia through bioinformatics mining,which maybe provid potential targets for subsequent research and diagnostic and therapeutic interventions.

Objective: To understand the genotype distribution and transmission pattern of rubella virus (RuV) circulating in Yunnan Province. Methods: Throat swab samples were collected from rubella outbreaks and sporadic cases in nine prefectures/cities of Yunnan Province from 2011 to 2021. Virus isolation, amplification of target genes and sequence determination were performed on the RuV-positive samples. The genotypes and lineages of Yunnan strains were determined by comparing them with the reference strains, and further phylogenetic analysis was performed with Yunnan strains and strains circulating in other provinces of China during the same period. Results: RuV circulating in Yunnan province during 2011-2021 showed significant genetic diversity, and three lineages, 1E-L1, 2B-L1 and 1E-L2, were detected. Two lineage-switches were also identified, including the conversion of 1E-L1 to 2B-L1 between 2012 and 2013, and the replacement of 2B-L1 to 1E-L2 after 2018. The time of the switches was basically consistent with the outbreak in Yunnan province in 2012 and the time of the rubella reemergence and epidemic between 2018 and 2019. The amino acid sequence of RuV virus strains in Yunnan province was highly conserved, and no important functional regions were changed. Conclusions: The transmission pattern of RuV in Yunnan province is generally consistent with the epidemic trend of RuV in other provinces of China.
Humans ; Rubella virus/genetics* ; Phylogeny ; China/epidemiology* ; Rubella/epidemiology* ; Genotype