ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

This study was aimed at investigating the effect of lymphocyte activation gene-3(LAG3)on liver B lymphocyte subsets and their functions in WT and LAG3-KO mice infected with Echinococcus multilocularis(E.multilocularis).In a mouse model of E.multilocularis infection,the expression and localization of CD19 and α-SMA in liver were detected by immu nohistochemistry.CD80,CD86 and MHC-Ⅱ molecules expressed on B cells and their subsets in mice liver were detected by flow cytometry.After 12 weeks of infection,the area and percentage of CD19 in LAG3-KO group was slightly higher than that in WT group,but the difference was not statistically(t=-1.241、-1.237,P＞0.05).The area and percentage of a-SMA in LAG3-KO group was higher than that in WT group(t=-3.224、-3.227,P＜0.05).The proportion of CD80 and MHC-Ⅱ molecules expressed on liver B cells in LAG3-KO group was up-regulated(t=-2.379,-3.321,P＜0.05).The percentage of liver B2 cells in LAG3-KO group was higher than that in WT group(t=-2.695,P＜0.05).The expression of CD80 on Blb cells in LAG3-KO group was significantly up-regulated(t=-5.315,P＜0.001).The proportion of CD80 of B2 cells in LAG3-KO group was lower than that in WT group(t=2.806,P＜0.05).The expression of MHC-Ⅱ molecule in B2 cells in LAG3-KO group was up-regulated(t=-4.227,P＜0.01).It is suggested that LAG3 molecules affected the B cell subsets and func-tion of mouse liver in the middle stage of E.multilocularis infection,especially B2 lymphocytes.LAG3 molecule exerted an in-hibitory effect on the activation of B cells and the expression of MHC-class Ⅱ molecules,suggesting that it may be involved in B cell exhaustion caused by E.multilocularis.

Mitochondrial diabetes mellitus (MDM) is a genetically heterogeneous disorder caused by mitochondrial DNA (mtDNA) or nuclear DNA mutations, characterized by multi-system involvement and diverse clinical phenotypes. We report a pediatric case presenting with growth retardation followed by subsequent development of diabetes mellitus. Systematic evaluation revealed concurrent bilateral sensorineural hearing loss, bilateral basal ganglia calcification, and electroencephalographic abnormalities. A post-exercise lactate test demonstrated significant elevation of serum lactate levels immediately after physical exertion. Genetic analysis identified a large-scale mitochondrial DNA deletion spanning from m.8649 to m.16084. This case report is complemented by a literature review focusing on the pathogenesis, genetic characteristics, and therapeutic approaches of mitochondrial diabetes, with particular emphasis on mitochondrial disorders exhibiting large-scale mtDNA deletions alongside diabetic manifestations. Our comprehensive analysis aims to enhance clinical understanding and inform diagnostic strategies for this complex disease entity.

Objective To investigate the risk factors for recurrence of persistent atrial fibrillation(AF)after radiofrequency ablation with circumferential pulmonary vein isolation+top line+back wall line based on the features of cardiac imaging and serum biomarkers,and then to establish a nomogram risk prediction model.Methods A total of 172 patients with persistent AF admitted to our hospital from June 2022 to September 2023 were enrolled and then according to recurrence or not in 6 months after surgery,they were divided into the recurrence group(51 cases)and the non-ecurrence group(121 cases).Before surgery,routine electrocardiography,and transthoracic and esophageal echocardiography were performed,while blood routine indicators and related biochemi-cal indicators were measured.All patients underwent radiofrequency ablation with circumferential pulmonary vein isolation,top line,and back wall line.They were followed up for 6 months after surgery.Binary logistic analysis was used to analyze the independent risk factors for postoperative recurrence,and then a nomogram risk prediction model was constructed and its diagnostic per-formance was evaluated.Results Lager LAD,higher LAVI,neutrophil count and NLR,and ele-vated BNP and CRP levels,while lower LAAFV,LAAEV and LAAEF were observed in the re-current group than those in the non-recurrent group(P＜0.01).Binary logistic regression analysis showed that elevated LAVI(OR=1.160,95％CI:1.006-1.337),decreased LAAEV(OR=0.740,95％CI:0.583-0.940),decreased LAAEF(OR=0.608,95％CI:0.422-0.877),elevated BNP(OR=1.017,95％CI:1.004-1.030),and higher NLR(OR=10.116,95％CI:1.316-77.755)were independent risk factors for recurrence after radiofrequency ablation of pulmonary vein isolation+top line+posterior wall line in persistent AF patients(P＜0.05,P＜0.01).The AUC value of the nomogram model constructed with LAVI,LAAEV,LAAEF,BNP and NLR in predicting postop-erative recurrence was 0.889(95％CI:0.833-0.932).Conclusion The cardiac imaging parame-ters LAVI,LAAEV and LAAEF,and serum biomarkers BNP and NLR are closely associated with postoperative recurrence of persistent AF in patients after radiofrequency ablation with cir-cumferential pulmonary vein isolation+top line+back wall line,and the relevant nomogram mod-el has better diagnostic value for postoperative recurrence.

Objective:To investigate the predictive value of myocardial perfusion-related parameters measured by echocardiography on the prognosis of patients with coronary artery disease at 90 d after percutaneous coronary intervention (PCI).Methods:Eighty-five patients with coronary artery disease who underwent PCI in Linping Branch of the Second Affiliated Hospital of Zhejiang University from October 2020 to October 2022 were selected retrospectively. Patients were divided into the occurrence myocardial perfusion injury group (40 cases) and the non-occurrence myocardial perfusion injury group (45 cases). The quantitative echocardiographic parameters of left ventricular end-diastolic internal diameter (LVEDD) and left ventricular end-systolic internal diameter (LVESD) were compared between the two groups, and the effects of LVEDD and LVESD on the risk of myocardial perfusion injury after PCI in patients with coronary artery disease were analyzed. Logistic regression was used to analyze the factors influencing the major adverse cardiovascular events (MACE) of patients with coronary artery disease at 90 d after PCI. A line graph model was constructed, the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were constructed to verify the predictive efficiency of the line graph model.Results:Compared with the day of admission, the levels of LVEDD and LVESD were increased at 2 and 6 h after PCI, and showed an increasing trend at each time point ( P<0.05). The levels of LVEDD and LVESD at 2 and 6 h after PCI in the occurrence myocardial perfusion injury group were higher than those in the non-occurrence myocardial perfusion injury group: (45.56 ± 2.35) mm vs. (43.27 ± 2.12 ) mm, (47.87 ± 3.56) mm vs. (45.73 ± 2.98) mm; (33.49 ± 2.32) mm vs. (31.29 ± 2.29) mm, (35.62 ± 3.03) mm vs. (33.74 ± 2.12) mm, there were statistical differences ( P<0.05). The risk of myocardial perfusion injury was 4.469 and 6.081 times higher in patients with high levels of LVEDD and LVESD than in patients with low levels. The results of Logistic regression analysis showed that coronary multiple lesions, time from onset to balloon dilation, coronary Gensini score and LVEDD, LVESD were independent influencing factors of MACE at 90 d after PCI in patients with coronary artery disease ( P<0.05). Based on the above five independent influencing factors, a column line graph model was established to predict the risk of poor prognosis at 90 d after PCI. According to the column line graph model, the coronary multiple lesions were scored as 5; the corresponding prognostic adverse risk increased with the increase of time from onset to balloon dilation, coronary Gensini score and quantitative echocardiographic parameters LVEDD and LVESD; the internal validation of the column line graph prediction model was performed, and the C-index of the model was 0.978; the calibration curve showed that the model had good differentiation and accuracy in predicting the risk of MACE at 90 d after PCI. The results of ROC curve showed, the area under the curve (AUC) was 0.955 (95% CI 0.952 - 1.000). The DCA showed that when the line graph model was in the high risk threshold range (0 - 0.9), the prediction of the model had clinical practical value and the net benefit of patients was high. Conclusions:The abnormal increase of LVEDD and LVESD determined by echocardiography is associated with myocardial perfusion injury in patients with coronary heart disease after PCI, and a line graph model based on LVEDD and LVESD can predict the occurrence of MACE at 90 d after PCI, so as to guide early risk assessment and prevention.

Objective To construct a prediction model for postoperative healthcare-associated infection(HAI)in elderly patients with hip fracture,analyze the economic burden,provide a reference and basis for the development of clinical prevention and control programs.Methods 627 elderly patients who underwent hip fracture surgery in a hospital from January 1,2017 to May 31,2023 were selected as the study subjects.Patients were randomly divided into a modeling group and a validation group at a 7:3 ratio.A logistic regression prediction model was constructed based on data from the modeling group,the discriminant and consistency of the model were evaluated by receiver ope-rating characteristic(ROC)curve and Hosmer-Lemeshow test,and the direct economic burden of postoperative HAI in patients was analyzed with 1∶1 propensity score matching(PSM).Results The incidence of postoperative HAI in elderly patients with hip fracture surgery was 12.1％,with pulmonary infection being the most common(52.6％).Logistic regression analysis showed that male,old age,perioperative disturbance of consciousness,gradeⅣ of American Society of Anesthesiologists(ASA)classification,low albumin level,and intensive care unit(ICU)admission were all independent risk factors for postoperative HAI in patients(all P＜0.05).There was good model discrimination and consistency between the training and validation groups in predicting the risk of postoperative HAI.The direct economic burden of postoperative HAI in patients was 7 927.4 Yuan,of which the burden of wes-tern medicine was the largest(3 139.7 Yuan).HAI prolonged patients hospitalization time by 3.6 days.Conclusion Postoperative HAI increases the economic burden of patients,the nomogram model constructed in this study can effectively predict the risk of postoperative HAI in patients,which can provide a basis for the early identification,as well as the implementation of targeted preventive and diagnostic measures for high-risk patients in the clinic.