Objective To investigate the risk factors for lymph node metastasis in resectable lung adenocarcinoma by combining spatial location, clinical, and imaging features, and to construct a lymph node metastasis prediction model. Methods A retrospective study on patients who underwent chest CT at the First Affiliated Hospital of Nanjing Medical University from June 2016 to June 2020 and were surgically confirmed to have invasive lung adenocarcinoma with or without lymph node metastasis was conducted. Patients were divided into a positive group and a negative group based on the presence or absence of lymph node metastasis. Clinical and imaging data of the patients were collected, and the independent risk factors for lymph node metastasis in resectable lung adenocarcinoma were analyzed using univariate and multivariate logistic regression. A combined spatial location-clinical-imaging feature prediction model for lymph node metastasis was established and compared with the traditional lymph node metastasis prediction model that does not include spatial location features. Results A total of 611 patients were included, with 333 in the positive group, including 172 males and 161 females, with an average age of (58.9±9.7) years; and 278 in the negative group, including 127 males and 151 females, with an average age of (60.1±11.4) years. Univariate and multivariate logistic regression analyses showed that the spatial relationship of the lesion to the lung hilum, nodule type, pleural changes, and serum carcinoembryonic antigen (CEA) levels were independent risk factors for lymph node metastasis. Based on this, the combined spatial location-clinical-imaging feature prediction model had a sensitivity of 91.67%, specificity of 74.05%, accuracy of 87.88%, and area under the curve (AUC) of 0.885. The traditional lymph node metastasis prediction model, which did not include spatial location features, had a sensitivity of 76.40%, specificity of 72.10%, accuracy of 53.86%, and AUC of 0.827. The difference in AUC between the two prediction methods was statistically significant (P=0.026). Compared with the traditional prediction model, the predictive performance of the combined spatial location-clinical-imaging feature prediction model was significantly improved. Conclusion In patients with resectable lung adenocarcinoma, those with central/inner spatial location, solid density, pleural changes with wide base depression, and elevated serum CEA levels have a higher risk of lymph node metastasis.

The relationship between hyperuricemia (HUA) and erectile dysfunction (ED) remains inadequately understood. Given that HUA is often associated with various metabolic disorders, this study aims to explore the multivariate linear impacts of metabolic parameters on erectile function in ED patients with HUA. A cross-sectional analysis was conducted involving 514 ED patients with HUA in the Department of Andrology, Jiangsu Province Hospital of Chinese Medicine (Nanjing, China), aged 18 to 60 years. General demographic information, medical history, and laboratory results were collected to assess metabolic disturbances. Sexual function was evaluated using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Based on univariate analysis, variables associated with IIEF-5 scores were identified, and the correlations between them were evaluated. The effects of these variables on IIEF-5 scores were further explored by multiple linear regression models. Fasting plasma glucose ( β = -0.628, P < 0.001), uric acid ( β = -0.552, P < 0.001), triglycerides ( β = -0.088, P = 0.047), low-density lipoprotein cholesterol ( β = -0.164, P = 0.027), glycated hemoglobin (HbA1c; β = -0.562, P = 0.012), and smoking history ( β = -0.074, P = 0.037) exhibited significant negative impacts on erectile function. The coefficient of determination ( R ²) for the model was 0.239, and the adjusted R ² was 0.230, indicating overall statistical significance ( F -statistic = 26.52, P < 0.001). Metabolic parameters play a crucial role in the development of ED. Maintaining normal metabolic indices may aid in the prevention and improvement of erectile function in ED patients with HUA.
Humans ; Male ; Erectile Dysfunction/metabolism* ; Hyperuricemia/metabolism* ; Adult ; Middle Aged ; Cross-Sectional Studies ; Glycated Hemoglobin/metabolism* ; Blood Glucose/metabolism* ; Uric Acid/blood* ; Young Adult ; Triglycerides/blood* ; Adolescent ; Cholesterol, LDL/blood* ; Penile Erection/physiology* ; Surveys and Questionnaires

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.

Objective To describe and analyze the epidemiological characteristics of scrub typhus in Huai'an, Jiangsu Province from 2006 to 2024 and explore the long-term incidence trend and distribution of high-risk areas, and to formulate targeted prevention and control strategies. Methods The scrub typhus case report data of Huai'an from 2006 to 2024 in the Chinese Disease Prevention and Control Information System were extracted for descriptive analysis. Results A total of 898 cases of scrub typhus were reported in Huai'an, with an average annual incidence rate of 0.96 per 100 000 from 2006 to 2024. There was a turning point in the incidence trend of scrub typhus in 2011. From 2006 to 2011, the annual percentage change (APC) was 47.09% (95% CI: 7.53 - 859.39), and the upward trend was statistically significant (P < 0.05). From 2012 to 2024, the APC was -2.12% (95% CI: -29.09 - 3.75), and the downward trend was not statistically significant. October and November were the high-incidence months, and the total concentration from 2006 to 2024 was 0.93, indicating that scrub typhus had strict seasonality. The circular distribution method estimated that the peak period of the epidemic was from October 11th to November 25th, and the peak day of incidence was November 3rd. Jinhu County was a high-incidence area. The ratio of male to female cases was 1.03. The age group with the highest reported incidence was 40 to < 80 years old. The occupation with the highest proportion was farmers, accounting for 78.03%. Conclusion From 2006 to 2024, scrub typhus in Huai'an shows a peak every 3 - 4 years. Middle-aged and elderly farmers are the key population at risk, and Jinhu County is a key area. In the future, targeted health education should be carried out to effectively control the prevalence of scrub typhus.

OBJECTIVE: To investigate the distribution of traditional Chinese medicine (TCM) syndrome types of and influencing factors on ED with hyperuricemia. METHODS: Based on the clinical data on 271 cases of ED with hyperuricemia admitted to our Department of Andrology, we studied the characteristics of syndrome elements, summarized the TCM syndrome types, and investigated the influencing factors on the distribution of the syndrome types by factor analysis and cluster analysis. RESULTS: By factor analysis of the data collected on TCM symptoms, 12 common factors and 15 syndrome type elements were identified, including disease type syndrome elements dampness, phlegm, heat, qi stagnation, blood stasis, qi deficiency, blood deficiency, yin deficiency, yang deficiency and essence deficiency, and disease-location syndrome elements kidney, liver, spleen, limbs and joints. Common factor cluster analysis revealed the main TCM syndrome types kidney deficiency damp-heat syndrome, spleen and kidney deficiency syndrome, liver depression and kidney deficiency syndrome, kidney deficiency and blood stasis syndrome, and the main influencing factors on the distribution of syndrome types including uric acid, systolic blood pressure, urea, obesity and so on. CONCLUSION The main TCM syndrome types of ED with hyperuricemia include kidney deficiency damp-heat syndrome, spleen and kidney deficiency syndrome, liver depression and kidney deficiency syndrome, kidney deficiency and blood stasis syndrome, and the related influencing factors can be used as an objective basis for the differentiation of TCM syndromes.
Humans ; Medicine, Chinese Traditional ; Hyperuricemia/complications* ; Male ; Cluster Analysis

AIM To explore the clinical effects of Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes on patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment.METHODS One hundred and sixty patients were randomly assigned into control group(80 cases)for 4-week intervention of both warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules,and observation group(80 cases)for 4-week intervention of Heiguteng Zhuifeng Huoluo Capsules,warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules.The changes in clinical effects,TCM syndrome scores,WOMAC scores,Lequesne indices,pain mediators(PGE2,β-EP),growth factors(TGF-β1,IGF-1),bone metabolism indices(OPG,RANKL),TLR4/NF-κB signaling pathway and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,WOMAC scores,Lequesne indices,PGE2,RANKLE,TLR4,NF-κB(P＜0.05),and increased β-EP,growth factors,OPG(P＜0.05),especially for the observation group(P＜0.05).No serious adverse events or reactions were observable in the two groups.CONCLUSION For the patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment,Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes can safely and effectively alleviate clinical symptoms,improve knee joint pain,and enhance joint functions,whose action mechanisms may contribute to the inhibition of TLR4/NF-κB signaling pathway expression and regulations of serum TGF-β1,IGF-1,OPG,RANKL levels.

AIM To explore the clinical effects of Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes on patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment.METHODS One hundred and sixty patients were randomly assigned into control group(80 cases)for 4-week intervention of both warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules,and observation group(80 cases)for 4-week intervention of Heiguteng Zhuifeng Huoluo Capsules,warm acupuncture at musculotendinous pathological nodes and Celecoxib Capsules.The changes in clinical effects,TCM syndrome scores,WOMAC scores,Lequesne indices,pain mediators(PGE2,β-EP),growth factors(TGF-β1,IGF-1),bone metabolism indices(OPG,RANKL),TLR4/NF-κB signaling pathway and safety indices were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P＜0.05).After the treatment,the two groups displayed decreased TCM syndrome scores,WOMAC scores,Lequesne indices,PGE2,RANKLE,TLR4,NF-κB(P＜0.05),and increased β-EP,growth factors,OPG(P＜0.05),especially for the observation group(P＜0.05).No serious adverse events or reactions were observable in the two groups.CONCLUSION For the patients with knee osteoarthritis due to Cold-Dampness Obstruction and Fixed Impediment,Heiguteng Zhuifeng Huoluo Capsules combined with warm acupuncture at musculotendinous pathological nodes can safely and effectively alleviate clinical symptoms,improve knee joint pain,and enhance joint functions,whose action mechanisms may contribute to the inhibition of TLR4/NF-κB signaling pathway expression and regulations of serum TGF-β1,IGF-1,OPG,RANKL levels.

A liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was developed for determination of three kinds of β-agonists(Clenbuterol(CL),Ractopamine(RAC)and Salbutamol(SAL))residues in animal liver samples.The liver sample homogenates were extracted with organic solvent,followed by clean-up using the automatic magnetic solid-phase extraction(MSPE),and then analyzed using LC-MS/MS.The results showed that the magnetic mixed-mode cation exchange adsorbent(M-MCX)exhibited 34%higher adsorption capacity than the conventional mixed-mode cation exchange(MCX)column.Furthermore,the clean-up was conducted by using an automatic MSPE device,and 8 samples could be simultaneously treated within 30 min.The limits of detection(LOD)were 0.01-0.1 μg/kg,the average recoveries ranged from 88.2%to 110.5%,and the relative standard deviations(RSDs)were in range of 2.9%-10.3%at three spiked levels for the three kinds of β-agonists.Compared with the traditional SPE technique,the present method had many advantages such as simple operation,rapidity and high efficiency,which was suitable for high-throughput and automatic detection of residues in routine analysis.

Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived car-diomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a po-tential reagent for repairing damaged hearts.

Objective To investigate the effect of cinobufacini on immune escape of acute myeloid leukemia(AML)by regulating myosin heavy chain 9(MYH9)/ubiquitin-specific protease 7(USP7)/cellular-myelocytomatosis viral oncogene(c-MYC)pathway.Methods(1)In vivo experiment:a nude mouse xenograft tumor model was established to evaluate the effect of cinobufotalin on the growth and immune escape of AML cells in vivo.(2)In vitro experiments:human AML cell line HL-60 was treated with different concentrations of cinobufacini,cell viability was detected by cell counting kit 8(CCK-8),and HL-60 cell invasion was detected by Transwell assay.HL-60 cells were co-cultured with activated CD8+ T cells,the expression of CD25,the surface marker of CD8+ T cells,was detected by flow cytometry,the levels of cytokines[interleukin-2(IL-2)and interferon(IFN-γ)]in the co-culture supernatant were detected by enzyme-linked immunosorbent assay(ELISA).CytoTox96 non-radioactive cytotoxicity assay was used to evaluate the cytotoxicity of CD8+ T cells to HL-60 cells.The protein expressions of MYH9,USP7 and c-MYC in HL-60 cells were detected by Western Blot.The interaction between MYH9,USP7 and ubiquitination was detected by co-immunoprecipitation(Co-IP)assay.The MYH9 overexpression plasmid was tranfected to verify the mechanism of cinobufacini in AML.Results Cinobufacini treatment inhibited xerograft tumor growth in nude mice and enhanced the anti-tumor ability of CD8+ T cells.Cinobufacini treatment inhibited HL-60 cell viability and invasion in a concentration-dependent manner.Cinobufacini treatment up-regulated the expression of CD25,a surface marker of CD8+ T cells,and also up-regulated the levels of IL-2 and IFN-γ.Cinobufotalin enhanced the toxicity of CD8+ T cells to HL-60 cells.Cinobufacini inhibits the protein expressions of MYH9,USP7 and c-MYC in HL-60 cells.MYH9 promotes c-MYC deubiquitination by recruiting USP7,but cinobufacini inhibits MYH9-mediated c-MYC deubiquitination.Conclusion Cinobufacini can reduce the recruitment of c-MYC by deubiquitinating enzyme USP7 by inhibiting the expression of MYH9,and promote the ubiquitination and degradation of c-MYC,thereby inhibiting the immune escape of AML cells.