ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque （CP） in patients with lean metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort， with the presence or absence of CP as the outcome， and fibrosis-4 （FIB-4） index and nonalcoholic fatty liver disease fibrosis score （NFS） were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis， the restricted cubic spline analysis， the receiver operating characteristic curve， and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group（n=607）， the CP group （n=350） had a significantly higher proportion of male patients， a significantly higher proportion of patients with smoking/diabetes/hypertension， and significantly higher levels of age， creatinine， blood urea nitrogen， triglycerides， fasting blood glucose， aspartate aminotransferase， aspartate aminotransferase/alanine aminotransferase ratio， NFS， and FIB-4 index， as well as significantly lower levels of platelet count and albumin （all P<0.05）. The multivariate logistic regression analysis showed that after adjustment for confounding factors， FIB-4 index （odds ratio［OR］=2.979， 95% confidence interval［CI］：2.141 — 4.219， P<0.001） and NFS （OR=1.747， 95%CI： 1.499 — 2.046， P<0.001） were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers， and its mediating effect accounted for 39.5% — 40.8% of the total effect （P<0.001）. ConclusionIn patients with lean MAFLD， NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP， and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

OBJECTIVE To evaluate the effectiveness and safety of warfarin anticoagulation therapy guided by gene test in patients undergoing left ventricular assist device （LVAD） implantation， and to analyze the influencing factors of warfarin anticoagulation efficacy. METHODS Patients who underwent LVAD implantation at the Heart and Vascular Center of Northern Jiangsu People’s Hospital from January 2023 to October 2024 and required warfarin anticoagulant therapy were selected as the study subjects. They were divided into genetic testing group （n＝51） and empirical treatment group （n＝17） based on whether they underwent CYP2C9 and VKORC1 gene test. The gene test group was given warfarin based on the predicted dose calculated by gene test， while the empirical treatment group was given warfarin by clinical doctors based on international normalized ratio （INR） experience， all patients were given warfarin once a day. Follow-up observation was conducted for 6 months to compare the effectiveness [time in therapeutic range（TTR）， the time required to reach INR for the first time， the incidence of embolic events， the incidence of INR＜1.5 events] and safety （the incidence of major and minor bleeding events，the incidence of INR＞3.5 events） of warfarin treatment between two groups of patients. According to whether the patient’s TTR was ≥60%， they were divided into TTR≥60% group （n＝20） and TTR＜60% group （n＝48）. Univariate and multivariate binary Logistic regression analysis were used to determine the factors affecting the anticoagulant effect of warfarin in patients. RESULTS The TTR of patients in the gene test group was significantly higher than that in the empirical treatment group （P＜0.05）. The incidence of INR＜1.5 events in the gene test group was significantly lower than in the empirical treatment group （P＜0.05）. The incidence of minor bleeding events and INR＞3.5 events in the gene test group were lower than in the empirical treatment group， but the difference was not statistically significant （P＞0.05）. The results of multivariate binary Logistic regression analysis showed that gene test was an independent protective factor for warfarin anticoagulant therapy [odds ratio （OR）＝10.842， 95% confidence interval （CI）： 1.211-27.037， P＝0.033]， and the combination of statins was an independent risk factor for warfarin anticoagulant therapy [OR＝0.196， 95%CI： 0.045-0.861， P＝0.031]. CONCLUSIONS Under the guidance of gene test， warfarin anticoagulation therapy for LVAD patients after implantation can improve TTR， shorten the anticoagulation target time， and has good safety； meanwhile， it should be noted that the combination of statins may enhance the anticoagulant effect of warfarin， thereby increasing the risk of bleeding in patients.

OBJECTIVES: To investigate the expression of soluble factor-related apoptosis ligand (sFasL) in peripheral blood and microRNA-147b (miR-147b) in monocytes in children with sepsis and their value in assessing prognosis. METHODS: A prospective study was conducted on 124 children with sepsis (sepsis group), 60 children with common infections (infection group), and 60 healthy children undergoing physical examinations (healthy control group). The independent risk factors for poor prognosis in children with sepsis were analyzed, and the value of serum sFasL and monocyte miR-147b in predicting poor prognosis in children with sepsis was assessed. RESULTS: The serum level of sFasL and the relative expression of miR-147b in monocytes were highest in the sepsis group, followed by the infection group and the healthy control group (P<0.05). The multivariate logistic regression analysis showed that the serum level of sFasL and the relative expression of miR-147b in monocytes were closely associated with the poor prognosis of children with sepsis (P<0.05). The receiver operating characteristic curve analysis showed that the combination of serum sFasL level and relative expression of miR-147b in monocytes had a larger area under the curve compared to each indicator alone in predicting the prognosis of children with sepsis (P<0.05). CONCLUSIONS There are significant increases in the level of sFasL in peripheral blood and the relative expression of miR-147b in monocytes in children with sepsis. The combined use of these two indicators has relatively high clinical value in assessing the prognosis of children with sepsis.
Humans ; Sepsis/diagnosis* ; MicroRNAs/blood* ; Male ; Female ; Monocytes/metabolism* ; Prognosis ; Child, Preschool ; Prospective Studies ; Child ; Infant ; TNF-Related Apoptosis-Inducing Ligand/blood* ; Logistic Models

Objective : To observe the effect of Celastrus orbiculatusextract(COE) on gastric precancerous lesions(GPL) and to explore its role in the Notch-1 signaling pathway. Methods : GPL rat models were established using a composite model replication method, and the rats were randomly divided into a control group, a model group, and COE low, medium and high dose groups [COE at 12.5, 25, and 50 mg/(kg·d)]. After 4 weeks of intervention, gastric tissue was collected, and immunohistochemistry(IHC) was performed to detect the expression of mucins(MUC2, MUC5AC, and MUC6), Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5), Proliferating Cell Nuclear Antigen(Ki67), and Notch-1. Polymerase chain reaction(PCR) was used to determine the mRNA levels of the aforementioned mucins. Human gastric epithelial cells(GES-1) were induced with N-Methyl-N′-nitro-N-nitrosoguanidine(MNNG) to establish a GPL cell model. The cells were randomly divided into control, model, and COE low, medium, and high concentration groups(COE at 5, 10, and 20 μg/ml). After 24 hours of corresponding interventions, changes in cell morphology were observed under an inverted microscope. Western blot was used to measure the expression of Notch-1 and Lgr5, and immunofluorescence(IF) was employed to detect Notch-1 expression. Results : Compared to the control group, the expression of MUC2, Lgr5, Notch-1, and Ki67 in the gastric tissue of the model group rats significantly increased(P<0.000 1), while the expression of MUC5AC and MUC6 decreased(P<0.000 1). In comparison to the model group, the expressions of MUC2, Lgr5, Notch-1, and Ki67 were significantly reduced in the COE groups(P<0.01), while the expression of MUC5AC and MUC6 significantly increased(P<0.01). In the GES-1 model group, the cells exhibited irregular morphology, loose intercellular connections, and disorganized arrangement compared to the control group. In contrast, the cells in the COE groups displayed a more regular morphology and a more organized arrangement than those in the model group. Additionally, compared to the control group, the expression of Lgr5 and Notch-1 in the model group were significantly elevated(P<0.000 1), whereas after COE treatment, their expressions were markedly reduced(P<0.001). Conclusion COE can alleviate GPL, and its mechanism may be associated with the downregulation of the Notch-1 signaling pathway, which improves gastric mucosal mucin barrier function and inhibits the abnormal proliferation of gastric mucosal stem cells.

ObjectiveThis study aims to investigate the mechanism in which Celastrus orbiculatus extract （COE） affects the proliferation and differentiation of gastric organoids and the expression of Lgr5 and thus reverses the precancerous lesions of gastric cancer （PLGC） by regulating the leucine-rich repeat containing G protein-coupled receptor 5 （Lgr5）/Wingless （Wnt）/β-catenin signaling pathway based on a gastric organoid injury model. MethodGastric organoids were established based on stem cells of the mouse gastric gland. Gastric organoid injury models were constructed by treating gastric organoids with N-methyl-N'-nitro-N-nitrosoguanidine （MNNG， 0.02 mg·L^-1）. Gastric organoid injury models were randomly divided into normal group， model group （0.02 mg·L^-1 MNNG）， low， medium， and high dose （5， 10， 20 mg·L^-1） groups of COE， and Wnt inhibitor Dickkopf-related protein 1 （DKK1） （0.5 mg·L^-1） group， and they were treated with respective agents for 24 h. The number and volume of gastric organoids under different drug concentrations were observed under a microscope. The viability of the gastric organoid injury models was detected by Methyl thiazolyl tetrazolium （MTT） assay. The morphology and pathology of gastric organoids were observed using Hematoxylin and Eosin （HE） staining. The expression levels of Lgr5， Mucin2 （MUC2）， Mucin5AC （MUC5AC）， Mucin6 （MUC6）， Wnt， and β-catenin in gastric organoids under different drug concentrations were detected by Western blot （WB）. ResultCompared with the normal group， the number， volume， and activity of gastric organoids in the model group were decreased （P<0.01）， while the expressions of Lgr5， MUC2， Wnt， and β-catenin were significantly increased （P<0.01）. The expressions of MUC5AC and MUC6 were significantly decreased （P<0.01）. Compared with the model group， the number and volume of gastric organoids in the low， medium， and high dose groups of COE were all improved （P<0.01）， and the vitality of gastric organoids was significantly enhanced （P<0.01）. The effect was the most significant at a COE concentration of 20 mg·L^-1 （P<0.01）. The expressions of Lgr5 and MUC2 in the medium and high dose groups of COE were significantly reduced （P<0.01）， while the expression of MUC5AC and MUC6 were significantly increased in the low， medium， and high dose groups of COE （P<0.05， P<0.01）. Compared with the model group， Wnt inhibitors could promote the expression of MUC5AC and MUC6 in gastric organoids （P<0.05， P<0.01） and reduce the expression of MUC2， Wnt， and β-catenin. In addition， the combined use of COE at high concentrations and Wnt inhibitors could further promote this trend （P<0.01）. ConclusionCOE inhibits the Wnt/β-catenin pathway by inhibiting the expression of Lgr5， MUC2， Wnt， and β-catenin and promoting the expression of MUC5AC and MUC6， thus promoting the proliferation and differentiation of gastric organoids and reversing the PLGC process.

AIM: To assess the changes of vessel density in the optic disc and macular of the affected eye and the uninvolved contralateral eye in patients with idiopathic optic neuritis(ON)and to provide clinical guidance for the treatment and follow-up of idiopathic ON.METHODS: A total of 16 patients with first-episode monocular idiopathic ON ≤3 mo diagnosed between December 2019 and December 2021 were included in this cross-sectional study. The eye of patients was divided into 16 eyes in the affected eye group and 16 eyes in the uninvolved contralateral eye group, and 20 healthy age-matched eyes(n=20)served as controls. Optical coherence tomography angiography(OCTA)was performed in all eyes at 4.5 mm×4.5 mm region of the optical disc and 6 mm×6 mm region of the macular, and blood flow indicators were collected and compared. RESULTS: Compared with the control group and the uninvolved contralateral eye group, the density of all vessels and capillary were reduced in the whole area of optic disc, and all subdivisions of the peripapillary region in the ON group(all P<0.05). Compared with the uninvolved contralateral eye group, the density of superficial capillary plexus(SCP)was significantly lower in the whole area of macular and perifovea region, and its all subdivisions of the ON eye, as well as in the superior-hemi and superior subdivision of the parafovea region(all P<0.05). Compared with the control group, the density of SCP in the inferior-hemi, nasal, and inferior perifovea region was significantly reduced in the ON affected eye group(all P<0.05). Compared with the control group, the whole area of macular and its subdivisions in the uninvolved contralateral eye group showed an increase in the density of SCP(P<0.05)and an increase in the density of SCP in the parafovea region(P<0.05), but no significant change in the inferior-hemi and nasal subdivisions; the increase in the density of SCP in the perifovea region was only significant in the superior-hemi and superior subdivisions(P<0.05).CONCLUSION: Patients with ON in the duration of ≤3 mo may showed a decreased vessel density in all peripapillary subdivisions, and a decreased density of SCP in some subdivisions of the perifovea region, accompanied by an increased density of SCP in some subdivisions of the macular region of the contralateral eyes.

Objective: To investigate the causal relationship between junior high school students aggressive behavior, physical exercise and academic performance, so as to provide a reference basis for the development of scientific exercise programs. Methods: A longitudinal followup study was conducted on 502 junior high school students over a 12month period from June 2021 to June 2022 using the Buss-Perry Aggressive Questionnaire (BPAQ), Physical Activity Questionnaire for Adolescents (PAQ-A), and test scores as the measurement tools (T1:June 2021, T2:December 2021, T3:June 2022), and a crosslagged model was constructed to measure the relationship between aggression, physical activity and academic performance. Results: At T1, physical exercise had a positive effect on academic performance at T2 (β=0.22) and a negative effect on aggressive behavior at T2 (β=-0.13), aggressive behavior negatively affected academic performance at T2 (β=-0.23), and academic performance had a negative effect on aggressive behavior at T2 (β=-0.09). Physical exercise at T2 had a negative effect on aggressive behavior at T3 (β=-0.05) and a positive effect on academic performance at T3 (β=0.19). Aggressive behavior at T2 negatively influenced academic performance at T3 (β=-0.08). Academic performance at T2 negatively influenced aggressive behavior at T3 (β=-0.06) (P<0.05). The results of crosslagged modeling of junior high school students aggressive behavior, physical exercise and academic performance showed that the model was well fitted (χ2/df=8.80, CFI=0.96, NFI=0.95, RFI=0.87, IFI=0.96, TLI=0.88, RMSEA=0.12). The results of multigroup structural equation modeling showed that the differences between the models and the baseline model (CFI=0.95, TLI=0.86, RMSEA=0.10, 90%CI=0.08-0.11, P<0.01) were not statistically significant in terms of gender (△CFI<0.05, P>0.05). Conclusions Physical exercise negatively predictes aggressive behavior and positively predictes academic performance, and academic performance and aggressive behavior negatively affect each other. A scientific exercise program should be developed to reduce aggression and effectively improve adolescents academic performance.

Objective To investigate the efficacy of red and blue lights combined with Yufa Shengfa solution and 5% minoxidil solution in treating Ludwig type Ⅰ female androgenetic alopecia. Methods A total of 160 patients with Ludwig type Ⅰ female androgenetic alopecia were randomly divided into group A (Yufa Shengfa solution combined with 5% minoxidil solution), group B (red and blue lights therapy combined with Yufa Shengfa solution), group C (red and blue lights therapy combined with 5% minoxidil solution) and group D (red and blue lights therapy combined with Yufa Shengfa solution and 5% minoxidil solution), with 40 cases in each group. All the patients orally took compound glycyrrhizin tablets and Centrum multivitamins, and the therapeutic period was 3 months. Differences in hair diameter, hair density, and the number of hair follicles with multiple hairs were compared before and after treatment. Results The hair density, hair diameter, and the number of hair follicles with multiple hairs improved significantly in 4 groups compared with those before treatment, and group D showed the best improvement in these parameters, with significant between-group differences (P < 0.001). There were no serious adverse events or side effects during treatment in all the patients. Conclusion Red and blue lights therapy combined with Yufa Shengfa solution and 5% minoxidil solution is an effective non-surgical treatment for Ludwig type Ⅰ female androgenetic alopecia.

Objective To compare the clinical effects of roxadustat and recombinant human erythropoietin (rHuEPO) in treatment of maintenance hemodialysis patients with renal anemia. Methods From January 2021 to December 2023, 100 patients with renal anemia undergoing maintenance hemodialysis admitted to Northern Jiangsu People's Hospital Affiliated to Yangzhou University were selected as study subjects. Based on different treatment approaches, they were divided into control group (n=50) and observation group (n=50). Both groups received iron supplementation therapy, with the control group using recombinant human erythropoietin (rHuEPO) and the observation group using roxadustat. Anemia indicators, iron metabolism indicators, and the incidence of adverse reactions were observed and compared between the two groups. Results Before treatment, there was no statistically significant difference in the indicators between the two groups (P>0.05). After treatment, the indicators of both groups improved compared to before treatment, and the indicators of the observation group were superior to those of the control group (P < 0.05). The incidence of adverse reactions in the observation group was 2.00%, which was lower than 16.00% in the control group (P < 0.05). Conclusion Compared with rHuEPO, roxadustat can significantly improve anemia and iron metabolism, with high safety and application value.