Circular RNAs (circRNAs) are a type of endogenous noncoding RNAs with covalently looped structures. Compared with other noncoding RNAs, circRNAs have the characteristics of stable structures, high abundance and tissue-specific expression. Recent studies have demonstrated that circRNAs can act as sponges, decoys and scaffolds for microRNAs and proteins, and play an important role in skin tumors. This review summarizes recent advances in the functions and mechanisms of action of circRNAs in common skin tumors, in order to understand the way in which they affect skin tumors, and to assess the value of further research on them.

To understand the infection status of main intestinal protozoa in BALB/c mice and pro-vide a basis for further control of intestinal protozoa infection.Five hundred and forty BALB/c mice provided by four domestic suppliers of BALB/c mice were detected for intestinal protozoa,in which 140 from supplier A,130 from supplier B,135 from supplier C,and 135 from supplier D,re-spectively.Fresh faecal samples were collected from each mouse separately to extract the genome and amplified by nested PCR based on primers for the 18S rRNA gene sequences of Pent-atrichomonas hominis(P.hominis)and Cryptosporidium tyzzeri(C.tyzzeri),and the 16S-like rRNA gene sequence of Tritrichomonas muris(T.muris)and sequenced.The results showed that the total intestinal protozoan infection rate was 7.1％(10/140)in 140 mice faecal samples provided by supplier A.Among them,the positivity rate of T.muris was 7.1％(10/140),C.tyzzeri was 2.1％(3/140),and P.hominis was 7.1％(10/140),the co-infection rate of two intestinal protozoa was 7.1％(10 mice:T.muris+P.hominis),and three intestinal protozoa was 2.1％(3 mice:T.muris+P.hominis+C.tyzzeri).The total intestinal protozoan infection rate in 135 mice faecal samples provided by supplier C was 7.4％,in which,7.4％(10/135)was positive for T.muris.There are no intestinal protozoa to be detected in 130 mice faecal samples from supplier B and 135 mice faecal samples from supplier D.The homology analysis showed that the homology of ampli-fied sequence of T.muris,P.hominis and C.tyzzeri was 98.52％,98.27％and 99.87％compared with published sequence of GenBank No:AY886846.1,GenBank No:AF156964.1 and GenBank No:KJ000486.1,which was clustered as an independent branch by phylogenetic analysis respec-tively.In conclusion,there are intestinal protozoan infection in BALB/c mice in some animal sup-pliers.The co-infections of more than 3 parasites such as T.muris,P.hominis and C.tyzzeri has been found.It will provide a basis for control of intestinal protozoa infection in BALB/c mice in the future.

In the era of precision medicine,integrating radionuclide-based molecular imaging with targeted internal radiotherapy,integrated theranostics of nuclear medicine emerged as a promising and rapidly advancing field to achieve both visualization and precise treatment of tumors.The advances of commonly used and emerging radiotheranostic agents in oncology were systematically reviewed in this article.

Objective:To investigate the relationship between serum soluble interleukin-2 receptor(sCD25)and insulin-like growth factor-Ⅰ(IGF-Ⅰ)and the immunophenotype and therapeutic efficacy of newly diagnosed multiple myeloma(MM)patients.Methods:125 newly diagnosed MM patients(MM group)who received treatment at Tianmen First People's Hospital from January 2023 to June 2024 were selected,and another 70 healthy individuals who underwent physical examinations at our hospital during the same period were selected(control group).The serum sCD25 and IGF-Ⅰ levels in newly diagnosed MM patients of different stages were compared,and newly diagnosed MM patients were divide into remission group(76 cases)and non remission group(49 cases)based on treatment efficacy,the serum sCD25 and IGF-Ⅰ levels between the remission group and non remission group were compared.The patients were divided into high sCD25 group and low sCD25 group,high IGF-Ⅰ group and low IGF-Ⅰgroup according to the median levels of serum sCD25 and IGF-Ⅰ,the immunophenotypic differences between high sCD25 group and low sCD25 group,as well as high IGF-Ⅰ group and low IGF-Ⅰ group were analyzed.Serum sCD25 and IGF-Ⅰ for evaluating the efficacy of newly diagnosed MM patients were analyzed by receiver operating characteristic(ROC)curve.Factors affecting the therapeutic effect of newly diagnosed MM patients were analyzed by multivariate logistic regression analysis.Results:Serum sCD25 and IGF-Ⅰ levels in the control group were significantly lower than those in the MM group(P＜0.05).There was a statistically significant difference in serum sCD25 and IGF-Ⅰ levels among newly diagnosed MM patients at different stages(P＜0.05).Serum sCD25 and IGF-Ⅰ levels in stage Ⅲ newly diagnosed MM patients were significantly higher than those in stage Ⅰ and Ⅱ(P＜0.05),And stage Ⅱ was higher than that in stage Ⅰ(P＜0.05).The positive expression rate of CD56 in the high sCD25 group was higher than that in the low sCD25 group,there was no significant difference in the positive expression rates of CD117 and CD200 between the two groups(P＞0.05).The positive expression rates of CD56 and CD117 in the high IGF-Ⅰ group were higher than those in the low IGF-Ⅰ group(P＜0.05),and there was no significant difference in the positive expression rate of CD200 between the two groups(P＞0.05).Serum sCD25 and IGF-Ⅰ levels in the remission group were significantly lower than those in the non remission group(P＜0.05).ROC curve analysis showed that,the area under the curve(AUC)for evaluating the efficacy of newly diagnosed MM patients using serum sCD25 and IGF-Ⅰ detection alone and in combination were 0.748,0.775 and 0.832,respectively,and the AUC for combined detection was greater than that for each indicator detected separately.The results of multivariate Logistic regression model showed that elevated serum sCD25 level,elevated serum IGF-Ⅰ level and MM stage Ⅲ were independent risk factors affecting the efficacy of newly diagnosed MM patients(P＜0.05).Conclusion:Serum sCD25 and IGF-Ⅰ levels are closely related to the disease stage and therapeutic efficacy of newly diagnosed MM patients.Combined detection has a high evaluation value for efficacy and can be used as an important evaluation index affecting efficacy.

[Objective] To investigate the factors associated with alanine aminotransferase (ALT) abnormalities in multi-ethnic blood donors across five Zang autonomous prefectures in the plateau regions of Qinghai Province, and to provide evidence for ensuring blood safety and formulating screening strategies. [Methods] A retrospective analysis was performed on the ALT abnormal test results of blood donors in the Zang autonomous prefectures of Qinghai from 2022 to 2024. The correlations between ALT levels and factors including gender, age, altitude, and infectious markers were investigated. [Results] The overall ALT unqualified rate among blood donors in this region was 9.01%. Significant differences in ALT levels were observed across genders and age groups (P<0.05). Variations in ALT abnormality rates were also noted among different plateau regions (P<0.05). Overall, ALT values exhibited an increasing trend with rising altitude. The average ALT unqualified rates were 11.19% in Zang donors, 7.96% in Han donors, and 4.79% in donors from other ethnic groups (P<0.05). No statistically significant association was observed between ALT abnormality and the presence of HBV/HCV infectious markers (P>0.05). [Conclusion] In the plateau areas of Qinghai, multi-ethnic blood donors have a relatively high ALT levels and ALT unqualified rates, showing distinct regional characteristics. ALT elevation in voluntary blood donors is related to non-pathological factors such as gender, age, and dietary habits, but not to infectious indicators.

Colorectal cancer(CRC) is a common malignant tumor worldwide. Due to the treatment intolerance and side effects, CRC rank the top among various cancers regarding the incidence and mortality rates. Therefore, exploring new therapies is of great significance for the treatment of CRC. Aerobic glycolysis(AEG) plays an important role in the microenvironment formation, proliferation, metastasis, and recurrence of CRC and other tumor cells. It has been confirmed that intervening in the AEG pathway can effectively curb CRC. The active ingredients and compound prescriptions of traditional Chinese medicine(TCM) can effectively inhibit the proliferation, metastasis, and drug resistance and regulate the apoptosis of tumor cells by modulating AEG-associated transport proteins [eg, glucose transporters(GLUT)], key enzymes [hexokinase(HK) and phosphofructokinase(PFK)], key genes [hypoxia-inducible factor 1(HIF-1) and oncogene(c-Myc)], and signaling pathways(MET/PI3K/Akt/mTOR). Accordingly, they can treat CRC, reduce the recurrence, and improve the prognosis of CRC. Although AEG plays a key role in the development and progression of CRC, the specific mechanisms are not yet fully understood. Therefore, this article delves into the intrinsic connection of the targets and mechanisms of the AEG pathway with CRC from the perspective of tumor cell glycolysis and explores how active ingredients(oxymatrine, kaempferol, and dioscin) and compound prescriptions(Quxie Capsules, Jiedu Sangen Decoction, and Xianlian Jiedu Prescription) of TCM treat CRC by intervening in the AEG pathway. Additionally, this article explores the shortcomings in the current research, aiming to provide reliable targets and a theoretical basis for treating CRC with TCM.
Humans ; Colorectal Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; Glycolysis/drug effects* ; Animals ; Medicine, Chinese Traditional ; Signal Transduction/drug effects*

This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified＿f＿Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Lung/metabolism* ; Mice, Inbred C57BL ; Capsules ; Orthomyxoviridae Infections/virology* ; Gastrointestinal Microbiome/drug effects* ; Male ; Humans ; Female ; Influenza A virus/physiology* ; Influenza, Human/virology*

Heart failure(HF) is the terminal stage of various cardiovascular diseases, characterized by high morbidity and mortality, and it represents one of the major disease burdens for families and society. In recent years, as research on the molecular mechanisms of HF has deepened, a competing endogenous RNA(ceRNA) network mediated by long non-coding RNAs(lncRNAs) and circular RNAs(circRNAs) has been gradually constructed. Extensive research results have confirmed that the ceRNA network is widely involved in pathological processes such as inflammation, oxidative stress, myocardial hypertrophy, apoptosis, remodeling of extracellular matrix components and structure, and ferroptosis in HF. It reveals the complex pathological mechanisms of HF at the epigenetic level. Traditional Chinese medicine(TCM) plays a unique role in improving symptoms and prognosis of HF and intervenes in the ceRNA network in HF through multi-level and multi-target mechanisms. It improves key pathological processes such as myocardial fibrosis and inflammation, making progress in treating HF at the molecular level. This article summarized recent Chinese and international research on the regulatory mechanisms of ceRNA networks in HF, elaborated on the mechanisms of action of ceRNA networks in different pathological stages of HF, and summarized how effective components and compounds of TCM intervene in the ceRNA network to improve HF, so as to refine the molecular mechanisms of HF and provide directions for more precise molecular targeted therapeutic strategies.
Humans ; Heart Failure/metabolism* ; Medicine, Chinese Traditional ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Circular/genetics* ; RNA, Long Noncoding/metabolism* ; Gene Regulatory Networks/drug effects* ; RNA/metabolism* ; RNA, Competitive Endogenous

Objective To specifically extract and analyze nascent proteins synthesized by bone marrow mesenchymal stem cells(BMSCs)after transplantation into ischemic hearts using a technique employing mutant methionyl-tRNA synthetase(MetRSL247G)for nascent protein labeling,in order to explore the potential mechanisms of action in BMSCs post-transplantation.Methods Point mutation at position 274 of the MetRS gene in BMSCs was induced via lentiviral infection to enable azidonorleucine(ANL)-mediated labeling of nascent proteins in BMSCs.The labeling efficiency was verified by means of fluorescent non-canonical amino-acid tagging(FUNCAT).Thirty healthy female C57BL/6J mice(8-10 weeks old)were divided into control and experimental groups,with 15 mice in each group.The acute myocardial infarction model was constructed by ligating the left anterior descending coronary artery in experimental group,while control mice underwent only thoracotomy without coronary ligation.After modeling,both groups received intramyocardial injections of MetRSL247G-modified BMSCs(MetRSL247G-BMSCs)at 3 different sites in the peri-infarct ischemic region.Mice were intraperitoneally injected with ANL every 6 hours for 4 times on postoperative days 0,2,and 6(n=5 for each time point)respectively,euthanized 24 h after the last injection,and cardiac tissues were isolated.The newly synthesized and labeled proteins produced by BMSCs after transplantation into the myocardium of experimental and control groups were collected,using an enrichment technique for ANL-tagged proteins and liquid chromatography-tandem mass spectrometry(LC-MS)analysis.Gene ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis,protein-protein interaction(PPI)analysis,and heatmap visualization analysis were performed to identify differentially expressed proteins at the 3 time points and screen key pathways and genes.Results Under fluorescence microscopy,the MetRSL247G lentivirus-infected BMSCs were observed to be labelled with mCherry signals,confirming the successful construction of the MetRSL247G-BMSCs cell line.Green fluorescent signals were detected only in nascent proteins in culture medium containing both MetRSL247G-BMSCs and ANL,validating the sensitivity and specificity of the labeling method.GO analysis revealed that differentially expressed proteins were primarily involved in basic cellular biological processes such as extracellular exosome formation,extracellular matrix organization,and focal adhesion.KEGG and PPI analyses indicated that the differential proteins were mainly involved in complement and coagulation cascade pathway,actin cytoskeleton regulation pathway,and apoptosis pathway.Heatmap analysis showed significantly upregulated expression of anti-apoptosis and cell adhesion-related factors in experimental group on day 1(P＜0.05),upregulated anti-apoptotic factors,pro-apoptotic factors,and cell adhesion-related factors on day 3(P＜0.05),and upregulated anti-apoptotic factors,cell differentiation-related factors,and cell adhesion-related factors on day 7(P＜0.05)compared with control group.Expression of apoptosis-inducing factor 1 was significantly downregulated on days 1 and 7(P＜0.05).On day 3,most differentially expressed proteins,including anti-apoptosis factors(Protein S100-A11,Clusterin,Gelsolin),pro-apoptosis factor(Cathepsin B),cell differentiation-related factor(Transgelin-2),and cell adhesion-related factors(Cofilin-1,Periostin,Fibronectin)were significantly upregulated(P＜0.05).Conclusions The MetRSL247G mutation enables BMSCs to incorporate ANL and synthesize labeled proteins,confirming the feasibility of this nascent protein labeling technique.Nascent proteins of BMSCs in ischemic myocardium primarily contribute to extracellular exosome secretion and extracellular matrix organization.BMSCs may adapt to and respond to ischemic and hypoxic environments by influencing complement and coagulation cascades,activating inflammatory factors,regulating actin cytoskeleton structure,and modulating apoptosis,thereby maintaining the survival of BMSCs.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.