ObjectiveTo investigate whether macrophage lipolysis-stimulated lipoprotein receptor （LSR） deficiency affects the progression of metabolic dysfunction-associated steatohepatitis （MASH） by activating the Yes-associated protein （YAP） signaling pathway. MethodsMale wild-type （WT） mice and macrophage-specific Lsr knockout （Lsr^MφKO， KO） mice， with an age of 8 weeks and similar body weights， were selected and fed with a normal diet， a high-fat diet （HFD）， or a high-fat high-cholesterol （HFHC） diet for 30 weeks. HE staining and oil red O staining were used to evaluate liver pathological changes； immunofluorescent staining was used to measure the expression levels of F4/80 and α-smooth muscle actin； RT-qPCR and Western blot were used to measure the levels of markers associated with lipid metabolism， inflammation， and fibrosis. Bone marrow transplantation rescue experiments （WT→KO vs KO→KO groups） were conducted to explore the functional role of LSR in macrophages. At the cellular level， hepatic macrophages were isolated from WT and KO mice to measure the expression levels of YAP signaling pathway-related proteins and their downstream target genes， and in addition， these cells were treated in vitro with verteporfin （VP）， a specific inhibitor of YAP， to verify the regulatory effect of this pathway on the expression of inflammatory factors. The independent samples t-test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data. ResultsUnder the condition of normal diet， there were no significant differences in hepatic indicators between WT and KO mice. KO mice fed an HFD or HFHC diet showed a significant increase in hepatic lipid droplet accumulation， accompanied by lipid metabolism disorder and significant increases in the levels of indicators associated with inflammation and fibrosis （P<0.05）. Bone marrow transplantation experiments confirmed that compared with the KO→KO group， the WT→KO group had significant alleviation of liver injury （P<0.05）. Mechanistic studies showed that there were significant reductions in the levels of phosphorylated large tumor suppressor kinase 1 （LATS1） and phosphorylated YAP and significant increases in the expression levels of total YAP protein and its downstream target genes in hepatic macrophages of KO mice （P<0.05）. In vitro VP intervention significantly inhibited the expression levels of inflammatory factors in hepatic macrophages isolated from KO mice （P<0.05）. ConclusionMacrophage LSR deficiency activates the YAP signaling pathway by inhibiting LATS1/2 kinase activity and promotes the expression of inflammatory factors， thereby accelerating the progression of liver injury in a mouse model of MASH.

Malignant tumor is a serious and difficult disease threatening human health， which has a high morbidity and mortality rate worldwide. Traditional Chinese medicine has unique advantages in improving the therapeutic effect of malignant tumors and alleviating adverse reactions. Traditional Chinese medicine believes that Qi deficiency and blood stasis are important pathogeneses in the development of malignant tumors， and the method of supplementing Qi and activating blood is an effective strategy for treating malignant tumors. Astragali Radix， sweet in taste and warm in nature， has effects of tonifying Qi and rising Yang， strengthening the exterior and reducing sweat， promoting fluid and nourishing blood. Curcumae Rhizoma， acrid and bitter in taste and warm in nature， has the effects of promoting Qi and breaking blood stasis， eliminating mass， and relieving pain. Astragali Radix-Curcumae Rhizoma， as the classic herb pair of invigorating Qi and activating blood， has a clear effect on inhibiting tumor growth and metastasis. Studies have shown that Astragali Radix-Curcumae Rhizoma contains astragalus polysaccharide， astragaloside， calycosin， formononetin， curcumin， β-elemene， curcumenol， curcumenone， curcumendione， gemacrone， and other anti-tumor active ingredients. It can significantly inhibit the occurrence and development of liver cancer， colorectal cancer， gastric cancer， lung cancer， ovarian cancer， cervical cancer， breast cancer， and other cancers and has the advantages of superposition effect， synergistic complementarity， and increased dissolution compared with single herb and monomer of Chinese traditional herbs and has been widely valued in the field of TCM anti-cancer. Its anti-tumor mechanism includes inhibition of tumor cell proliferation， promotion of tumor cell apoptosis and autophagy， anti-invasion and metastasis， regulation of immune function， and enhancement of anti-tumor drug sensitivity. By combining Chinese and foreign literature， the compatibility effect and anti-tumor mechanism of Astragali Radix-Curcumae Rhizoma were summarized， and then scientific compatibility of these two herbs was expounded， in order to provide a useful reference for clinical application and future research of Astragali Radix-Curcumae Rhizoma.

Objective To analyze the causes of HIV-2 specific bands in the Western blot (WB) tests and to understand previous HIV-2 infection status in this city. Methods A total of 68 samples with HIV-2 specific bands in WB were analyzed using two confirmatory reagents. The test results were further analyzed in combination with epidemiological data, nucleic acid testing and gene sequencing. Results When tested with MP reagent, 66 samples (97.06%) were found to be positive for HIV-2 antibody, while the other two were negative or undetermined for HIV-2 antibody. When tested with MIKROGEN reagent, 67 samples (98.53%) were found to be positive for HIV-1 antibody, and one sample was negative for HIV-1 antibody. Further HIV-1 nucleic acid testing was conducted on these samples, and all 68 samples tested positive for HIV-1 RNA, with the results all exceeding 5,000 copies/ml. After BLAST comparison, it was found that the homology similarity of 68 samples to the HIV-1 reference strain sequence was >90%, but there was no similarity with the HIV-2 reference strain sequence. Conclusion The results of the serological test, nucleic acid test and gene sequencing of the 68 samples all have indicated HIV-1 infection. Combined with the epidemiological data, it can be concluded that the double reaction of HIV-1 and HIV-2 antibodies in WB tests of these 68 samples is very likely to be a non-specific cross-reaction rather than HIV-2 infection. This study indicates that no HIV-2 infection cases have been found in Chengdu so far.

Objective To investigate the effect of Qingchi Powder(composed of calamina,Halloysitum Rubrum,Phellodendri Chinensis Cortex,Sophorae Flavescentis Radix,Catechu,Indigo Naturalis,Rhizoma Bletillae,and Notoginseng Radix et Rhizoma powder)retention enema on intestinal flora and Toll-like receptor 4(TLR4)/NOD-like receptor thermoprotein domain-related protein 3(NLRP3)signaling pathway in peripheral blood mononuclear cell(PBMC)of children with ulcerative colitis(UC).Methods A total of 100 children with UC were randomly divided into control group and study group,with 50 cases in each group.The control group was treated with oral administration of Mesalazin Enteric-Coated Tablets,and the study group was treated with Qingchi Powder retention enema on the basis of treatment for the control group.The treatment for the two groups lasted for 8 consecutive weeks.Before and after treatment,the distribution of intestinal flora and the relative mRNA expression levels of TLR4 and NLRP3 in PBMC,serum contents of TLR4 and NLRP3 protein,and serum levels of inflammatory factors such as tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)and interleukin 6(IL-6)in the two groups were observed.After treatment,the clinical efficacy of the two groups was evaluated,and Spearman test was used to analyze the correlation of total effective rate with the relative mRNA expression levels of TLR4 and NLRP3 in PBMC and serum contents of TLR4 and NLRP3 protein.Results(1)After 8 weeks of treatment,the total effective rate of the study group was 94.00%(47/50),and that of the control group was 70.00%(35/50).The intergroup comparison(tested by chi-square test)showed that the efficacy of the study group was significantly superior to that of the control group(P＜0.01).(2)After treatment,the number of Enterococcus and Enterobacteriaceae in the two groups was significantly lowered(P＜0.05),and the number of Bifidobacterium and Lactobacillus was significantly increased compared with that before treatment(P＜0.05).After treatment,the number of Enterococcus and Enterobacteriaceae in the study group was significantly lower(P＜0.05)and the number of Bifidobacterium and Lactobacillus was significantly higher than that in the control group(P＜0.05).(3)After treatment,the mRNA relative expression levels of TLR4 and NLRP3 in PBMC of the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(4)After treatment,the serum TLR4 and NLRP3 protein levels in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(5)After treatment,the levels of serum inflammatory factors of TNF-α,IL-1β and IL-6 in the two groups significantly decreased compared with those before treatment(P＜0.05),and the levels in the study group were significantly lower than those in the control group(P＜0.05).(6)Spearman correlation analysis showed that the mRNA relative expression levels of TLR4 and NLRP3 in PBMC and serum TLR4 and NLRP3 protein levels in children with UC were significantly negatively correlated with the total effective rate of curative effect(P＜0.001).Conclusion Qingchi Powder retention enema can down-regulate the expression levles of key signaling molecules of TLR4/NLRP3 pathway in PBMC of children with UC,regulate the intestinal flora of children,and improve the inflammatory response.It has significant curative effect and is worthy of expanding its application in clinic.

Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.

Objective:To investigate ferroptosis-related genes in pterygium tissue by using bioinformatic analysis.Methods:The pterygium gene expression profile dataset GSE2513 was downloaded from the Gene Expression Omnibus Database to identify differentially expressed genes (DEGs) related to ferroptosis.Functional annotation and enrichment analysis of the DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG).Hub genes were identified from the DEGs using LASSO logistic regression analysis and a support vector machine recursive feature elimination (SVM-REF).Single-gene GSEA analysis was performed on hub genes and a competitive endogenous RNA interaction network was constructed to determine the RNA regulatory relationships of the hub genes.Pterygium tissue samples from 9 patients (9 eyes) undergoing pterygium surgery and conjunctival tissue samples from 9 patients (9 eyes) undergoing strabismus surgery who visited the First Affiliated Hospital of Zhengzhou University were collected from 2022 to 2023 during surgery, and the expression of hub genes and ferroptosis-related marker genes was detected by fluorescence quantitative PCR.This study followed the Declaration of Helsinki, and the study protocol was reviewed and approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (No.2022-KY-0006-001).Results:In the dataset, there were 37 ferroptosis-related genes with significant expression differences, including 16 upregulated genes and 21 downregulated genes.GO analysis revealed significant enrichment in responses to external stimuli, responses to nutritional levels, responses to extracellular stimuli, responses to oxidative stress and starvation, transcription regulatory complexes, and RNA polymerase Ⅱ transcription regulatory complexes, RNA polymerase Ⅱ-specific transcription, and DNA-binding transcription.KEGG analysis showed that the DEGs were primarily enriched in ferroptosis and NOD-like receptor signaling pathways.LASSO regression analysis identified DUOX2, ATF3, NDRG1, EGR1, and ALDH3A2 as hub genes, and SVM-REF analysis identified NDRG1, NF2, IDH2, DUOX2, CHP1, ATF3, and SREBF1 as hub genes. DUOX2, ATF3, and NDRG1 were identified as the intersection hub genes.Single-gene GSEA analysis revealed that DUOX2 was enriched in the cell adhesion molecule CAMs pathway, the heparan sulfate glycosaminoglycan biosynthesis pathway, and the glycosaminoglycan biosynthesis ganglioside series pathway. ATF3 and NDRG1 were enriched in the PPAR signaling pathway and other pathways.Compared with normal conjunctival tissue, the relative expression levels of the ferroptosis markers PTGS2 and TFRC mRNA were increased in pterygium tissue, while the relative expression levels of FTH1, GPX4, SLC40A1, HSPB1, and NFE2L2 mRNA were decreased, with statistically significant differences ( t=12.220, 16.580, 5.664, 6.455, 8.691, 9.883, 17.590; all P<0.01). Conclusions:Ferroptosis may play an important role in the pathogenesis of pterygium. DUOX2, ATF3, and NDRG1 may be the hub genes affecting this complicated process.

OBJECTIVES: Increasing detection of low-risk papillary thyroid carcinoma (PTC) is associated with overdiagnosis and overtreatment. N6-methyladenosine (m⁶A)-mediated microRNA (miRNA) dysregulation plays a critical role in tumor metastasis and progression. However, the functional role of m⁶A-miRNAs in PTC remains unclear. This study aims to elucidate the regulatory mechanism of m⁶A-miR-139-5p expression in PTC, determine its association with PTC metastasis, and evaluate its potential as a diagnostic biomarker for PTC metastasis, thereby providing experimental evidence for precision diagnosis and therapy. METHODS: Expression profiles of m⁶A-miRNAs were compared between the The Cancer Genome Atlas (TCGA) and GSE130512 cohorts to identify metastasis-associated candidates. Clinical specimens from 13 metastasis and 18 non-metastasis PTC patients were analyzed to assess m⁶A-miR-139-5p expression and its correlation with metastasis. Functional experiments were conducted to investigate the effect of fat mass and obesity-associated protein (FTO) on pri-miR-139 methylation and processing, clarifying its regulatory role in miR-139-5p expression. In TPC-1 cells, MTT assays were performed to evaluate whether miR-139-5p overexpression could counteract FTO-mediated cell proliferation. Transwell invasion assays were used to determine the impact of miR-139-5p on PTC cell invasion, exploring whether it functions through the ZEB1/E-cadherin axis. RESULTS: By comparing TCGA and GSE130512 cohorts, it was found that circulating m⁶A-miR-139-5p could serve as a biological indicator for detecting PTC metastasis. Detection of 13 metastatic and 18 non-metastatic clinical specimens showed that FTO inhibited the processing of pri-miR-139 by reducing its methylation level, leading to the dysregulation of miR-139-5p in PTC (P<0.05). In TPC-1 cells, MTT assay showed that overexpression of miR-139-5p could partially reverse FTO overexpression-mediated cell proliferation (P<0.05). In addition, miR-139-5p inhibited the invasive ability of PTC cells by targeting the ZEB1/E-cadherin axis, while FTO overexpression could partially weaken this inhibitory effect. CONCLUSIONS Circulating miR-139-5p can be a potential marker for evaluating PTC metastasis. FTO affects the expression and function of miR-139-5p by regulating m⁶A modification of pri-miR-139, but its clinical value needs further verification.
Humans ; MicroRNAs/metabolism* ; Thyroid Cancer, Papillary/metabolism* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/metabolism* ; Thyroid Neoplasms/metabolism* ; Cell Line, Tumor ; Neoplasm Metastasis ; Adenosine/genetics* ; Gene Expression Regulation, Neoplastic ; Female ; Male ; Cadherins/metabolism* ; Cell Proliferation ; Zinc Finger E-box-Binding Homeobox 1/genetics*

Objective:To explore the epidemiological characteristics of human metapneumovirus (hMPV) in children hospitalized for acute respiratory tract infections in Hebei, and provide a theoretical basis for the clinical diagnosis and treatment of acute respiratory tract infections in children in Hebei.Methods:Retrospectively, 41 499 children hospitalized in Hebei Children′s Hospital for acute respiratory tract infections from January 2017 to December 2021 were included to analyze the morbidity of children of different genders and ages, and in different seasons, and to statistically analyze the epidemiological data such as the positive detection rate of hMPV, the detection rates of mixed infections with other pathogens, and the clinical diagnosis.Results:The overall positive detection rate of hMPV in hospitalized children with acute respiratory infections from 2017 to 2021 was 5.94%(2 464/41 499), with the highest positive detection rate of hMPV in the age group of 3 to 4 years (7.66%, 520/6 789) and the lowest in the age group of ≥5 years (2.89%, 180/6 225), with a statistically significant difference ( P<0.001); the positive detection rates in male and female children were respectively 5.97%(1 496/25 056) and 5.94%(968/16 443), and the difference was not statistically significant ( P>0.05). The positive detection rates of hMPV from 2017 to 2021 were 5.10%(408/7 998), 9.64%(915/9 491), 4.27%(426/9 969), 5.91%(368/6 226), and 4.44%(347/7 815), respectively, and the positive detection rate of hMPV in 2018 was significantly higher than that in the other years ( P<0.001). hMPV circulated throughout the year, with obvious seasonality, with the highest positive detection rate in spring and winter.The mixed detection rate of hMPV with other respiratory pathogens was 42.74% (1 053/2 464), of which mixed detection with rhinovirus was the most common, with a mixed detection rate of 48.24%(508/1 053).Clinical diagnosis of hPMV-positive children was mostly bronchopneumonia. Conclusions:hMPV is one of the important pathogens in hospitalized children with acute respiratory infections in Hebei, which is common in children under 5 years of age and can occur throughout the year, with peak epidemics in winter and spring. Mixed infections of hMPV with other respiratory pathogens are common and can increase the risk of worsening clinical symptoms in children.

Objective:To analyze the factors influencing preoperative anxiety and depression in patients undergoing eye plastic surgery.Methods:A retrospective study was conducted, which included 160 patients awaiting for ocular plastic surgery at the Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January to May 2019. Among them, there were 22 males and 138 females, with an average age of (38.6±9.0) years. A one-on-one survey was conducted on enrolled patients using a paper questionnaire. The survey included general patient information, the simplified coping style questionnaire (SCSQ), the Chinese version of the Kessler 10-item questionnaire (Kessler 10), the perceived social support scale (PSSS), and the hospital anxiety and depression scale (HADS). Factors related to anxiety and depression were screened using through univariate analysis and Spearman correlation analysis, and multivariate logistic regression was used to analyze the factors influencing the anxiety and depression.Results:The detection rate for preoperative anxiety in patients undergoing eye plastic surgery was 16.3% (26/160), and that for depression was 25.0% (40/160). A total of 11.3% (18/160) of patients had both anxiety and depression. Multivariate logistic regression analysis showed that positive coping strategies ( OR=0.206, 95% CI: 0.051-0.836), depression ( OR=3.596, 95% CI: 1.068-12.107), and a high Kessler10 scale total score ( OR=1.081, 95% CI: 1.005-1.162) were related to anxiety. A monthly income of 10 000-<20 000 yuan ( OR=0.196, 95% CI: 0.044-0.875), a high total score on the Kessler10 scale ( OR=1.194, 95% CI: 1.085-1.314), and a high total PSSS score ( OR=0.913, 95% CI: 0.870-0.958) were related to depression. Conclusion:Factors affecting anxiety are positive coping strategies, depression, and a high total score on the Kessler 10 scale, while those affecting depression are a monthly income of 10 000-<20 000 yuan, a high total score on the Kessler 10 scale, and a high total score on the PSSS.