Objective To investigate the effect and mechanism of miR-155-5p targeting suppressor of cytokine signaling 1(SOCS1)in regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcrip-tion 3(STAT3)signaling pathway in renal injury associated with lupus nephritis(LN).Methods Thirty female MRL-faslpr lupus model mice were randomly divided into five groups(n=6 per group):the model group,the antagomir NC group,the miR-155-5p antagomir group,the miR-155-5p antagomir+shRNA control group,and the miR-155-5p antagomir+SOCS1 shRNA group.The mice were treated with adeno-associated virus vectors carrying miR-155-5p antagomir,antagomir NC,SOCS1 shRNA,or shRNA control.Additionally,six age-matched C57BL/6 mice served as a control group and received an equivalent volume of saline.Serum blood urea nitrogen(BUN)and creatinine(Scr)levels,renal histopathological changes,and the expression levels of miR-155-5p,SOCS1,phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)in renal tissues were evaluated.Results Compared with the normal group,the model group exhibited significantly elevated levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins in the kidneys(P<0.01),while the expression level of SOCS1 was markedly reduced(P<0.01).Compared with both the model group and the antagomir NC group,the miR-155-5p antagomir group showed decreased levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),along with a significant increase in SOCS1 expression(P<0.01).Similarly,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group demon-strated significantly higher levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),while SOCS1 expression was notably decreased(P<0.01).Renal pathology analysis revealed that,compared to the normal group,the model group exhibited glomerular atrophy,extensive infiltration of inflammatory cells in the renal tubulointerstitial region,and partial renal tubular necrosis.In contrast,the miR-155-5p antagomir group showed marked improvements in glomerular atrophy,tubular necrosis,and inflammatory cell infiltration compared with the model group and antagomir NC group.Furthermore,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group exhibited more severe glomerular atrophy,tubular necrosis,and inflammatory cell infiltration.Conclusion MiR-155-5p exacerbates renal damage in MRL-faslpr lupus model mice by targeting SOCS1,potentially through the activation of the JAK2/STAT3 signaling pathway.

Objective:To investigate the association between dietary diversity and the risk of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD) .Methods:A total of 553 patients diagnosed with CHD and undergoing PCI in the Department of Cardiology at the Second Affiliated Hospital of Harbin Medical University between May and November 2023 were enrolled using a convenience sampling method. A Semi-Quantitative Food Frequency Questionnaire was used to assess patients' dietary intake after PCI, and the Dietary Diversity Score (DDS) was calculated. Patients were followed up for one year to determine the incidence of MACE.Results:History of hypertension, history of hyperlipidemia, body mass index, use of antiplatelet agents, use of diuretics, triglycerides, smoking index and DDS were identified as factors influencing the occurrence of MACE after PCI ( P<0.05) . Among these, higher dietary diversity had a protective effect against MACE. Conclusions:After PCI, patients with lower DDS experienced MACE more frequently than those with higher scores. Increased dietary diversity can effectively help prevent MACE in patients after PCI.

Objective To investigate the effect and mechanism of miR-155-5p targeting suppressor of cytokine signaling 1(SOCS1)in regulating the Janus kinase 2(JAK2)/signal transducer and activator of transcrip-tion 3(STAT3)signaling pathway in renal injury associated with lupus nephritis(LN).Methods Thirty female MRL-faslpr lupus model mice were randomly divided into five groups(n=6 per group):the model group,the antagomir NC group,the miR-155-5p antagomir group,the miR-155-5p antagomir+shRNA control group,and the miR-155-5p antagomir+SOCS1 shRNA group.The mice were treated with adeno-associated virus vectors carrying miR-155-5p antagomir,antagomir NC,SOCS1 shRNA,or shRNA control.Additionally,six age-matched C57BL/6 mice served as a control group and received an equivalent volume of saline.Serum blood urea nitrogen(BUN)and creatinine(Scr)levels,renal histopathological changes,and the expression levels of miR-155-5p,SOCS1,phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)in renal tissues were evaluated.Results Compared with the normal group,the model group exhibited significantly elevated levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins in the kidneys(P<0.01),while the expression level of SOCS1 was markedly reduced(P<0.01).Compared with both the model group and the antagomir NC group,the miR-155-5p antagomir group showed decreased levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),along with a significant increase in SOCS1 expression(P<0.01).Similarly,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group demon-strated significantly higher levels of BUN,Scr,miR-155-5p,p-JAK2,and p-STAT3 proteins(P<0.01),while SOCS1 expression was notably decreased(P<0.01).Renal pathology analysis revealed that,compared to the normal group,the model group exhibited glomerular atrophy,extensive infiltration of inflammatory cells in the renal tubulointerstitial region,and partial renal tubular necrosis.In contrast,the miR-155-5p antagomir group showed marked improvements in glomerular atrophy,tubular necrosis,and inflammatory cell infiltration compared with the model group and antagomir NC group.Furthermore,compared with the miR-155-5p antagomir group and the miR-155-5p antagomir+shRNA control group,the miR-155-5p antagomir+SOCS1 shRNA group exhibited more severe glomerular atrophy,tubular necrosis,and inflammatory cell infiltration.Conclusion MiR-155-5p exacerbates renal damage in MRL-faslpr lupus model mice by targeting SOCS1,potentially through the activation of the JAK2/STAT3 signaling pathway.

Objective:To investigate the association between dietary diversity and the risk of major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) in patients with coronary heart disease (CHD) .Methods:A total of 553 patients diagnosed with CHD and undergoing PCI in the Department of Cardiology at the Second Affiliated Hospital of Harbin Medical University between May and November 2023 were enrolled using a convenience sampling method. A Semi-Quantitative Food Frequency Questionnaire was used to assess patients' dietary intake after PCI, and the Dietary Diversity Score (DDS) was calculated. Patients were followed up for one year to determine the incidence of MACE.Results:History of hypertension, history of hyperlipidemia, body mass index, use of antiplatelet agents, use of diuretics, triglycerides, smoking index and DDS were identified as factors influencing the occurrence of MACE after PCI ( P<0.05) . Among these, higher dietary diversity had a protective effect against MACE. Conclusions:After PCI, patients with lower DDS experienced MACE more frequently than those with higher scores. Increased dietary diversity can effectively help prevent MACE in patients after PCI.

Objective Taking Sortilin as the entry point,this study aims to explore the mechanism of vascular calcification in chronic renal failure(CRF)and explore the influence of Sanqi on Sortilin,TLRs and vascular calcification,and to provide an effective method for clinical reduction of cardiovascular events in CRF.Methods Thirty-six male SD rats were randomly divided into normal group,model group,low-,medium-and high-dose Sanqi group and calcitriol group,with 6 rats in each.The replicative CRF vascular calcification rat model was fed with adenine combined with high phosphorus diet.Aortic calcium salt deposition,serum creatinine(Scr),urea nitrogen(BUN),blood calcium(Ca),blood phosphorus(P),total cholesterol(TC),triglyceride(TG),TLRs and Sortilin protein in aorta and inflammatory factors were detected.Results In the model group,renal fibrosis was obvious and many adenine crystals were found in renal interstitium.Large deposits of calcium salts were found.Renal fibrosis and calcium salt deposition were alleviated in different degrees in all treatment groups.Compared with those in the normal group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of the model group was ascended(P<0.01),while the level of Ca was descended(P<0.01).Compared with those in the model group,the level of BUN,Cr,P,TG,TC,IFN-γ,IL-6,IL-10 and IL-17A in the serum of rats in the Sanqi medium and high dose group and calcitriol group was significantly decreased(P<0.01),and the contents of Ca were significantly increased(P<0.05 or P<0.01).Compared with those in the normal group,the protein expression of BMP2,RUNX2,Sortilin,TLR7 and TLR9 in aortic tissue of rats in the model group was elevated(P<0.01),while the protein expression of SM22α was declined(P<0.01).Compared with those in the model group,the protein expression of BMP2,RUNX2,Sortilin,TLR7,and TLR9 in the low-,medium-,and high-dose Sanqi group and calcitriol group was decreased significantly(P<0.01);the protein expression of SM22α was increased significantly(P<0.05 or P<0.01),and the high-dose Sanqi group and calcitriol group had more significant effects.Conclusion Sanqi can improve renal fibrosis and vascular calcification in CRF model rats,and its mechanism may be related to the regulation of biological functions of Sortilin and TLRs.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

Objective:To evaluate the effect of resveratrol on radiation-induced myocardial injury in mice.Methods:A total of 80 C57BL/6 mice were randomly divided into the control group, resveratrol (Res) group, radiation (RT) group and radiation+resveratrol (RT+Res) group. In the RT group, mice were given with heart radiation and mice in the Res group were given with resveratrol by gavage for 3 months. Cardiac ultrasound was used to evaluate cardiac function at 3 months after cardiac radiation. The hearts of mice were collected for HE staining, immunofluorescence, TUNEL staining, Masson staining and Western blot to evaluate the expression of silent information regulator 1 (SIRT1), the level of oxidative stress, inflammatory response, apoptosis and the degree of fibrosis in myocardial tissues. Experimental data were expressed as Mean ± SD. Continous data were statistically analyzed by t-test. Results:After 3 months of irradiation, compared with the control group, the ejection fraction (EF) and fractional shortening (FS) of cardiac function were decreased, and myocardial degeneration and disorder, reactive oxygen species (ROS) and inflammatory levels (interleukin-1β, interleukin-6, tumor necrosis factor-α), myocardial apoptosis (TUNEL positive cell rate) and fibrosis were increased in the RT group. In the RT+Res group, the cardiac function was improved, the expression of SIRT1 was increased, and the levels of oxidative stress, inflammation, myocardial apoptosis and fibrosis were decreased.Conclusions:Resveratrol can reduce oxidative stress, inflammatory infiltration, apoptosis and fibrosis of myocardium in mice with radiation-induced myocardial injury, thereby improving cardiac structural abnormalities and cardiac dysfunction. This protective effect can be mediated by upregulation of SIRT1 expression.

Objective: To clarify the structural and functional characteristics of the gut microbiota in individuals with qi stagnation constitution (QSC) and identify the potential biomarkers related to QSC.Methods: This cross-sectional study involved individuals with QSC and balanced constitution (BC) confirmed by TCM clinicians. The clinical features were recorded, and fecal samples were collected for 16S rDNA sequencing. The structure of the fecal-associated microbiome (FAM) was described by the alpha-diversity indexes, beta-distances, and relative abundances of dominant taxa. The differences in FAM distribution were analyzed by the Wilcoxon rank-sum test, MetagenomeSeq, and LEfSe analysis. The 16S rDNA gene sequences were assigned to the KEGG dataset to predict the functional information of bacterial metabolic pathways by using PICRUSt. Differences in functional pathways between groups were assessed with the Wilcoxon rank-sum test. The ROC curve based on specific operational taxonomic units (OTUs) was constructed, and the AUC was calculated. Results: Twenty-two individuals with BC and 8 with QSC were recruited. Significant differences between the two groups were found in body mass index, health status, and low-density lipoprotein, etc. There was no significant difference in the alpha-diversity index. PCoA showed no evident clustering of bacterial communities according to constitutions. Bacteroidaceae, Lachnospiraceae, Ruminococcaceae, and Pre-votellaceae were the four common bacteria with high abundances. Notably, MetagenomeSeq, LEfSe analysis, and the Wilcoxon rank-sum test identified significantly different distributions of 66, 42, and 36 OTUs, respectively. Predictive function analysis showed that 13 metabolic pathways were significantly differentially distributed, including those related to fatty acid synthesis. Five specific OTUs were selected as potential biomarkers of a QSC, and the AUC was 0.94. Conclusion: Individuals with QSC have unique FAM structure and related functional characteristics. Five specific OTUs were identified to serve as potentially effective biomarkers related to QSC.

Area Under Curve ; Breast Neoplasms ; Breast ; Diagnosis ; Diagnosis, Differential ; Elasticity Imaging Techniques ; Estrogens ; Female ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Population Characteristics ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; ROC Curve ; Sensitivity and Specificity ; Ultrasonography

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK⁺ and 9 ones (27.3%) ALK^-. Of them, 25 patients (19 ALK⁺ and 6 ALK^-) underwent auto-HSCT and 8 cases (5 ALK⁺ and 3ALK^-) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.