Objective To observe the effects of dagliflozin combined with levosimendan on soluble growth-stimulated expressed gene 2 protein(sST2),angiopoietin Ⅱ(Ang-Ⅱ)and cardiac function in elderly patients with heart failure after percutaneous coronary intervention(PCI).Methods Eighty patients with acute myocardial infarction(AMI)admitted to the Department of Cardiology of the Affiliated Hospital of Jiangnan University from January 2021 to October 2023 were selected and divided into two groups using the lottery method.Both groups were treated with conventional therapy.The conventional group was treated with levosimendan,and the combination group with dagliflozin combined with levosimendan.Cardiac function indexes,sST2,amino-terminal brain natri-uretic peptide precursor(NT-pro BNP),renin-angiotensin-aldosterone system indexes,cardiac myosin-binding protein-C(cMyBP-C),cardiac troponin I(cTnI),myoglobin(MyO),6-minute walking distance,heart failure scoring system(Lee)score,and the Seattle Angina Scale(SAQ)score were compared between the two groups.The cumulative major adverse cardiovascular event(MACE)rate at 6-month follow-up was counted in both groups.Results The comparison of cardiac function indexes,sST2,NT-proBNP,cMyBP-C,cTnI,MyO,and renin-angiotensin-aldosterone system indexes before treatment between the two groups showed no statistical significance(P>0.05).Left ventricular ejection fraction(LVEF)of the two groups was higher than that before treatment,and the indexes of the renin-angiotensin-aldosterone system,end-systolic left intraventricular diameter(LVEDD),sST2,NT-proBNP,end-diastolic left intraventricular diameter(LVESD),cMyBP-C,cTnI,MyO,and left ventricular mass index(LVMI)were lower(P<0.05).LVEF was higher in the combination group than that in the conventional group after treatment,and the indexes of the renin-angiotensin-aldosterone system,sST2,cMyBP-C,LVEDD,NT-proBNP,LVESD,cTnI,MyO,and LVMI were lower than those in the conventional group(P<0.05).There was no statistically significant difference between the two groups in terms of 6-minute walking distance,Lee score,and SAQ score before treatment(P>0.05).The 6-minute walking distance and SAQ score after treatment in both groups were longer and higher than those before treatment,and the Lee score was lower(P<0.05).The 6-minute walking distance and SAQ score after treatment in the combination group were longer and higher,and Lee score was lower than those in the conventional group(P<0.05).The cumulative incidence of MACE at 6-month follow-up in the combination group was lower than that in the conventional group,and the difference was statisti-cally significant(P<0.05).Two cases of gastrointestinal reactions were found in the conventional group,and one case of hypotension and three cases of gastrointestinal reactions in the combination group.Conclusion Dagliflozin combined with levosimendan improves cardiac function,modulates the renin-angiotensin-aldosterone system,and improves exercise tolerance and quality of life in patients with heart failure after PCI.

Objective To observe the effects of dagliflozin combined with levosimendan on soluble growth-stimulated expressed gene 2 protein(sST2),angiopoietin Ⅱ(Ang-Ⅱ)and cardiac function in elderly patients with heart failure after percutaneous coronary intervention(PCI).Methods Eighty patients with acute myocardial infarction(AMI)admitted to the Department of Cardiology of the Affiliated Hospital of Jiangnan University from January 2021 to October 2023 were selected and divided into two groups using the lottery method.Both groups were treated with conventional therapy.The conventional group was treated with levosimendan,and the combination group with dagliflozin combined with levosimendan.Cardiac function indexes,sST2,amino-terminal brain natri-uretic peptide precursor(NT-pro BNP),renin-angiotensin-aldosterone system indexes,cardiac myosin-binding protein-C(cMyBP-C),cardiac troponin I(cTnI),myoglobin(MyO),6-minute walking distance,heart failure scoring system(Lee)score,and the Seattle Angina Scale(SAQ)score were compared between the two groups.The cumulative major adverse cardiovascular event(MACE)rate at 6-month follow-up was counted in both groups.Results The comparison of cardiac function indexes,sST2,NT-proBNP,cMyBP-C,cTnI,MyO,and renin-angiotensin-aldosterone system indexes before treatment between the two groups showed no statistical significance(P>0.05).Left ventricular ejection fraction(LVEF)of the two groups was higher than that before treatment,and the indexes of the renin-angiotensin-aldosterone system,end-systolic left intraventricular diameter(LVEDD),sST2,NT-proBNP,end-diastolic left intraventricular diameter(LVESD),cMyBP-C,cTnI,MyO,and left ventricular mass index(LVMI)were lower(P<0.05).LVEF was higher in the combination group than that in the conventional group after treatment,and the indexes of the renin-angiotensin-aldosterone system,sST2,cMyBP-C,LVEDD,NT-proBNP,LVESD,cTnI,MyO,and LVMI were lower than those in the conventional group(P<0.05).There was no statistically significant difference between the two groups in terms of 6-minute walking distance,Lee score,and SAQ score before treatment(P>0.05).The 6-minute walking distance and SAQ score after treatment in both groups were longer and higher than those before treatment,and the Lee score was lower(P<0.05).The 6-minute walking distance and SAQ score after treatment in the combination group were longer and higher,and Lee score was lower than those in the conventional group(P<0.05).The cumulative incidence of MACE at 6-month follow-up in the combination group was lower than that in the conventional group,and the difference was statisti-cally significant(P<0.05).Two cases of gastrointestinal reactions were found in the conventional group,and one case of hypotension and three cases of gastrointestinal reactions in the combination group.Conclusion Dagliflozin combined with levosimendan improves cardiac function,modulates the renin-angiotensin-aldosterone system,and improves exercise tolerance and quality of life in patients with heart failure after PCI.

Inflammation reaction is a host defense mechanism that protects the host from harmful external antigens and microorganisms, and the intensification of inflammation reaction can lead to tissue damage and development of systemic inflammatory diseases. As a representative derivative of ω-3 fatty acids, Maresin-1 has been widely explored for its role in regulating innate immune cells (neutrophils and mononuclear/macrophages) and promoting the resolution of infectious inflammation in acute inflammatory diseases. There is now increasing evidence that Maresin-1 also has a direct effect on the adaptive immune system and prevents the transition from acute inflammation to chronic inflammation. By analyzing the literature related to the effect of Maresin-1 on the regulation of inflammation, this paper summarized the role of various immune cells in inflammatory response and the regulatory mechanism of Maresin-1 on various immune cells, so as to deeply understand the research progress of the role of Maresin-1 in regulating immune cells in inflammatory diseases. This study provides a theoretical basis for the basic research and clinical application of Maresin-1 in inflammatory diseases.

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.
Cellular Senescence/genetics* ; Humans ; Immunoglobulin G/metabolism* ; Interleukin-13/pharmacology* ; Mitochondria/metabolism* ; Sialadenitis/metabolism*

Netrin-1, an axon guidance factor, and its receptor UNC5B play important roles in axonal development and angiogenesis. This study examined netrin-1 and UNC5B expression in kidneys with diabetic kidney disease (DKD) and investigated their roles in angiogenesis. Netrin-1 and UNC5B were upregulated in streptozotocininduced DKD Wistar rats, and their expression was compared with that in healthy controls. However, exogenous netrin-1 in UNC5B-depleted human renal glomerular endothelial cells (HRGECs) inhibited cell migration and tubulogenesis. This effect was likely associated with SRC pathway deactivation. Netrin-1 treatment also eliminated the pro-angiogenic effects of exogenous VEGF-165 on UNC5B-silenced HRGECs. These results indicate that UNC5B antagonizes netrin-1 and that UNC5B upregulation contributes partly to enhancing angiogenesis in DKD. Therefore, introducing exogenous netrin-1 and depleting endogenous UNC5B are potential strategies for reducing the incidence of early angiogenesis and mitigating kidney injury in DKD.

This study aimed to compare clinical features between membranous nephropathy (MN) and nonmembranous nephropathy (non-MN), to explore the clinically differential diagnosis of these two types, and to establish a diagnostic model of MN. After renal biopsy was obtained, 798 patients were divided into two groups based on their examination results: primary MN group (n = 248) and non-MN group (n = 550). Their data were statistically analyzed. Logistic regression analysis indicated that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN, and these three parameters were then used to establish the MN diagnostic model. A receiver operating characteristic (ROC) curve confirmed that our diagnostic model could distinguish between patients with and without MN, and their corresponding sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The cutoff value for this combination in MN diagnosis was 0.34. The established diagnostic model that combined multiple factors shows a potential for broad clinical applications in differentiating primary MN from other kidney diseases and provides reliable evidence supporting the feasibility of noninvasive diagnosis of kidney diseases.

Objective:To explore the role and mechanism of the B7-H1 expressed by auto-keratinocytes in the intermingled skin grafting model in vitro(MELC). Methods:The intermingled skin grafting model(MELC) was established in vitro. Flow cytometry was performed to detect the expressions of B7-H1 in keratinocytes. The expressions of PD-1 in lymphocytes were measured at the same time. The levels of IL-10,Foxp3 and GATA-3 mRNA in lymphocytes were detected by Real-time quantitative PCR. Results: Through flow eytometry,in the MELC with auto-keratinocytes,the expression of B7-H1 in auto-keratinocytes and the PD-1 in lymphocytes were rising trend and the rising rate was in time-dependent manners(P<0. 01). RT-PCR assay indicated that the relative levels of IL-10, Foxp3,GATA-3mRNA expression were significant raised and the rising rate was in time-dependent manners (P<0. 01). Conclusion:In the intermingled skin grafting model,the auto-keratinocytes could express B7-H1 to enhance the expression of PD-1 in T cells. When B7-H1 combined with PD-1,the Th2 cells and Foxp3+Tregs were induced and suppressed the immune response in the intermingled skin grafting model.

OBJECTIVE:To observe therapeutic efficacy and safety of Milrinone injection in the treatment of hypertensive heart disease complicated with heart failure. METHODS:A total of 120 patients with hypertensive heart disease complicated with chronic heart failure were randomized into control group and observation group according to random number table,with 60 cases in each group. Control group received routine therapy,including blood pressure controlling,anti-heart failure and other symptomatic treatment;observation group was additionally given Milrinone injection 0.3 mg/kg,continuous pump,qd. A treatment course lasted for 5 d. Both groups received one course of treatment each month for consecutive 6 months. Both groups were followed up for one year. 6 min walking distance(6MWD),BNP,LVEF,CI,LVEDD,heart rate,sitting systolic blood pressure(SiSBP)and sitting diastolic blood pressure(SiDBP),re-hospitalization rate and cardiovascular mortality were observed in 2 groups before treatment, after 3,6 months and 1 year of treatment;therapeutic efficacy of heart function and the incidence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in 6MWD,BNP,LVEF,CI,heart rate,SiSBP and SiDBP between 2 groups;after 3 months,6 months and 1 year of treatment,6MWD,LVEF and CI of 2 groups were increased significantly,while BNP,LVEDD,resting heart rate,SiSBP and SiDBP were decreased significantly;the observation group was significantly better than the control group,with statistical significance(P<0.05). Total response rate of heart function was 90.00%in observation group,which was significantly higher than 63.33% in control group,with statistical significance(P<0.05). After 1 year of follow-up,re-hospitalization rate of observation group was significantly lower than that of control group,with statistical sig-nificance (P<0.05);there was no statistical significance in cardiovascular mortality (P>0.05). There were no statistical signifi-cance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Milrinone injection shows good efficacy in the treatment of hypertensive heart disease complicated with heart failure,can significantly reduce BNP and re-hospitalization rate as well as improve prognosis with good safety.

Higher education for the disabled is essential to education equality and social harmony,it represents the depth of society improvement and the level of social civilization.Inclusive education has develop from adopt physical disability into no discrimination at psychological level.This article explored 3 combination education mode (the disabled combined with the healthy,medicine combined with teaching,general stu.dies combined with the specialty) through education environment,education methods and education pathways using resources in medical colleges.This mode through no discrimination education environment for the disabled using medicine and teaching combination education methods to recover physical and psychological of the disabled,and using general studies combined with the specialty education pathways to train the disabled into a fully skilled person.

OBJECTIVETo summarize operation key points, prevention and management of complications in vascularized autotransplantation of submandibular gland for treatment of severe keratoconjunctivitis sicca.

METHODS23 patients with severe keratoconjunctivitis sicca were treated by this procedure. Postoperative (99m)Tc images, follow-up studies, and management of complications were performed.

RESULTSThe transplantations were successful in 19 cases, whose symptoms of xerophthalmia disappeared. The patients could stop applying artificial tears. In 4 patients the transplanted glands did not survive. Epiphora occurred in 5 cases. They were successfully treated by reducing the size of the graft. Obstruction of the Wharton's duct took place in one case and was treated by reconstructing the duct. When the superficial temporal vein was too small, venous bridging was applied. To select a relevant vein for anastomosis, blood oozing from the three veins was carefully inspected prior cutting off the gland when the external maxillary artery was preserved and was infused with heparin after the gland had been freed.

CONCLUSIONSIf every point has been properly managed, the successful rate of operation could be warranted.

Adolescent ; Adult ; Child ; Female ; Humans ; Keratoconjunctivitis Sicca ; surgery ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Submandibular Gland ; blood supply ; transplantation ; Transplantation, Autologous ; Treatment Outcome