ObjectiveTo investigate the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Baoshan District of Shanghai from 2008 to 2023, and to provide scientific evidence for surveillance and standardized management of HFMD. MethodsCase data for HFMD reported in the China Disease Control and Prevention Information System from 2008 to 2023 were collected. Descriptive epidemiological methods were used to analyze the population characteristics, and the Joinpoint regression models were applied to assess the temporal trends of HFMD in Baoshan District. ResultsA total of 43 853 HFMD cases were reported from 2008 to 2023 in Baoshan District, with a male-to-female ratio of 1.50∶1. The majority of cases were children, among which scattered children and preschool children accounted for 54.67% and 36.58%, respectively, with 88.00% occurring in children under 5 years old. The average annual incidence rate was147.22/100 000 individuals. The pathogen detection rate in 2018 was 58.60% (109/186). Prior to 2020, CoxA16 was the predominant strain, while EV71 was not detected after 2019. ConclusionThe incidence of HFMD in Baoshan District of Shanghai was influenced by multiple factors including the inclusion in the notifiable infectious disease surveillance system, the introduction of EV71 vaccination, and the COVID-19 pandemic timeline. Populations characterized by highly mobility and frequent external contacts were at high risk for HFMD in Baoshan District. The predominant circulating strains had shifted sequentially from EV71 and CoxA16 to CoxA6.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.

Objective:To investigate the control status of out-of-hospital blood glucose and blood lipids in patients with acute myocardial infarction (AMI) complicated with diabetes mellitus and its correlation with prognosis.Methods:The clinical data of 406 patients with AMI complicated with diabetes mellitus from January 2017 to December 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The demographic and out-of-hospital clinical information of patients were recorded, and the control level of out-of-hospital risk factors and the occurrence of major adverse cardiovascular event (MACCE) were also recorded. The patients were grouped according to the levels of glycosylated hemoglobin (HbA 1c) and low-density lipoprotein cholesterol (LDL-C). HbA 1c<6.0% was the low HbA 1c group, HbA 1c 6.0% to 7.0% was the medium HbA 1c group, and HbA 1c>7.0% was the high HbA 1c group; LDL-C<1.4 mmol/L was low LDL-C group, LDL-C 1.4 to 1.8 mmol/L was medium LDL-C group, and LDL-C>1.8 mmol/L was high LDL-C group. Multivariate Cox regression analysis was used to analyze the independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus. Results:The HbA 1c data of 249 patients were recorded in detail, and only 51.0% (127/249) of patients with HbA 1c≤7%. There were statistical differences in the history of cerebral infarction, out-of-hospital fasting blood glucose, out-of-hospital total cholesterol (TC) and out-of-hospital LDL-C among the low HbA 1c group (24 cases), medium HbA 1c group (103 cases) and high HbA 1c group (122 cases) ( P<0.05). The incidences of out-of-hospital MACCE in low HbA 1c group, medium HbA 1c group and high HbA 1c group were 20.8%(5/24), 12.6%(13/103) and 32.0%(39/122), respectively. The incidence of out-of-hospital MACCE in high HbA 1c group was significantly higher than that in medium HbA 1c group, and there was statistical difference ( P<0.05); there was no statistical difference between low HbA 1c group and high HbA 1c group ( P>0.05). Among the 406 patients, 53.4%(217/406) had LDL-C≤1.8 mmol/L, and only 20.0%(81/406) had LDL-C<1.4 mmol/L. There were statistical differences in hyperlipidemia, out-of-hospital HbA 1c, out-of-hospital fasting blood glucose, out-of-hospital alanine aminotransferase (ALT), out-of-hospital TC and out-of-hospital triglyceride (TG) among low LDL-C group (81 cases), medium LDL-C group (136 cases) and high LDL-C group (189 cases) ( P<0.05). The incidences of MACCE in low LDL-C group, medium LDL-C group and high LDL-C group were 18.5% (15/81), 25.7% (35/136) and 36.5% (69/189), respectively. The incidence of MACCE in high LDL-C group was significantly higher than that in low LDL-C group, and there was statistical difference ( P<0.05); there was no statistical difference between low LDL-C group and medium LDL-C group ( P>0.05). In the different HbA 1c groups, multivariate Cox regression analysis result showed that HbA 1c>7% and high out-of-hospital fasting blood glucose were independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 2.575 and 1.064, 95% CI 1.345 to 4.927 and 1.005 to 1.128, P<0.01 and <0.05). In different LDL-C groups, multivariate Cox regression analysis result showed that high out-of-hospital HbA 1c was an independent risk factor for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 1.303, 95% CI 1.144 to 1.485, P<0.01). Conclusions:The control rates of out-of-hospital blood glucose and blood lipids are low in patients with AMI complicated with diabetes mellitus, and HbA 1c level can independently predict the risk of out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus.

Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.

Objective:To investigate the control status of out-of-hospital blood glucose and blood lipids in patients with acute myocardial infarction (AMI) complicated with diabetes mellitus and its correlation with prognosis.Methods:The clinical data of 406 patients with AMI complicated with diabetes mellitus from January 2017 to December 2022 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The demographic and out-of-hospital clinical information of patients were recorded, and the control level of out-of-hospital risk factors and the occurrence of major adverse cardiovascular event (MACCE) were also recorded. The patients were grouped according to the levels of glycosylated hemoglobin (HbA 1c) and low-density lipoprotein cholesterol (LDL-C). HbA 1c<6.0% was the low HbA 1c group, HbA 1c 6.0% to 7.0% was the medium HbA 1c group, and HbA 1c>7.0% was the high HbA 1c group; LDL-C<1.4 mmol/L was low LDL-C group, LDL-C 1.4 to 1.8 mmol/L was medium LDL-C group, and LDL-C>1.8 mmol/L was high LDL-C group. Multivariate Cox regression analysis was used to analyze the independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus. Results:The HbA 1c data of 249 patients were recorded in detail, and only 51.0% (127/249) of patients with HbA 1c≤7%. There were statistical differences in the history of cerebral infarction, out-of-hospital fasting blood glucose, out-of-hospital total cholesterol (TC) and out-of-hospital LDL-C among the low HbA 1c group (24 cases), medium HbA 1c group (103 cases) and high HbA 1c group (122 cases) ( P<0.05). The incidences of out-of-hospital MACCE in low HbA 1c group, medium HbA 1c group and high HbA 1c group were 20.8%(5/24), 12.6%(13/103) and 32.0%(39/122), respectively. The incidence of out-of-hospital MACCE in high HbA 1c group was significantly higher than that in medium HbA 1c group, and there was statistical difference ( P<0.05); there was no statistical difference between low HbA 1c group and high HbA 1c group ( P>0.05). Among the 406 patients, 53.4%(217/406) had LDL-C≤1.8 mmol/L, and only 20.0%(81/406) had LDL-C<1.4 mmol/L. There were statistical differences in hyperlipidemia, out-of-hospital HbA 1c, out-of-hospital fasting blood glucose, out-of-hospital alanine aminotransferase (ALT), out-of-hospital TC and out-of-hospital triglyceride (TG) among low LDL-C group (81 cases), medium LDL-C group (136 cases) and high LDL-C group (189 cases) ( P<0.05). The incidences of MACCE in low LDL-C group, medium LDL-C group and high LDL-C group were 18.5% (15/81), 25.7% (35/136) and 36.5% (69/189), respectively. The incidence of MACCE in high LDL-C group was significantly higher than that in low LDL-C group, and there was statistical difference ( P<0.05); there was no statistical difference between low LDL-C group and medium LDL-C group ( P>0.05). In the different HbA 1c groups, multivariate Cox regression analysis result showed that HbA 1c>7% and high out-of-hospital fasting blood glucose were independent risk factors for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 2.575 and 1.064, 95% CI 1.345 to 4.927 and 1.005 to 1.128, P<0.01 and <0.05). In different LDL-C groups, multivariate Cox regression analysis result showed that high out-of-hospital HbA 1c was an independent risk factor for out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus ( OR = 1.303, 95% CI 1.144 to 1.485, P<0.01). Conclusions:The control rates of out-of-hospital blood glucose and blood lipids are low in patients with AMI complicated with diabetes mellitus, and HbA 1c level can independently predict the risk of out-of-hospital MACCE in patients with AMI complicated with diabetes mellitus.

Objective:To investigate the staging of cardiovascular-kidney-metabolic (CKM) syndrome before onset, and to analyze its impact on short-term prognosis in patients with acute myocardial infarction (AMI).Methods:The clinical data of 2 993 patients with AMI from January 2017 to December 2023 in Xuanwu Hospital, Capital Medical University were retrospectively analyzed. The basic information, baseline data, in-hospital data, cardiac-related examination results, CKM syndrome staging and in-hospital outcomes were recorded.Results:Among the 2 993 patients with AMI, the CKM syndrome stage 0 was in 23 cases (0.77%), stage 1 in 35 cases (1.17%), stage 2 in 2 015 cases (67.32%), stage 3 to 4 in 920 cases (30.74%). The male proportion, high density lipoprotein-cholesterol (HDL-C) and neutrophil-to-lymphocyte ratio in patients with CKM syndrome stage 0 and 1 were significantly higher than those in patients with CKM syndrome stage 2 and 3 to 4, the hypertension proportion, diabetes proportion, chronic kidney disease proportion, triglyceride (TG), glycated hemoglobin (HbA 1c) and creatinine were significantly lower than those in patients with CKM syndrome 2 stage 3 to 4, and there were statistical differences ( P<0.05); the body mass index (BMI) and non-ST-elevation myocardial infarction (NSTEMI) proportion in patients with CKM syndrome stage 0 were significantly lower than those in patients with CKM syndrome stage 1, 2 and 3 to 4, and there were statistical differences ( P<0.05); the cerebrovascular diseases proportion, Killip stage ≥3 proportion, N-terminal pro-brain natriuretic peptide (NT-proBNP) and left main coronary artery lesions proportion in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4, and there were statistical differences ( P<0.05); the global registry of acute coronary events score (GRACE score) in patients with CKM syndrome stage 0 was significantly lower than that in patients with CKM syndrome stage 3 to 4, and there was statistical difference ( P<0.05). Although there were statistical differences in low density lipoprotein-cholesterol (LDL-C) and number of blood vessels involved among the four groups ( P<0.05), but pairwise comparisons showed no statistically significant differences ( P>0.05). There were no statistical differences in age, smoking history, hyperlipidemia, high-sensitivity C-reactive protein, uric acid, cardiac troponin I (cTnI) peak, left ventricular ejection fraction and left ventricular end-diastolic diameter among the four groups ( P>0.05). The incidence of in-hospital major adverse coronary events (MACE) was 10.76% (322/2 993). Among them, the incidence of MACE, all-cause mortality and longer length of stay in patients with CKM syndrome stage 0, 1 and 2 were significantly lower than those in patients with CKM syndrome stage 3 to 4: 4.35% (1/23), 8.57% (3/35) and 8.59% (173/2 015) vs. 15.76% (145/920), 0, 2.86% (1/35) and 2.38% (48/2 015) vs. 4.78% (44/920), (8.17 ± 3.87), (8.15 ± 5.32) and (8.89 ± 6.42) d vs. (9.81 ± 9.29) d, and there were statistical differences ( P<0.05); the incidences of acute kidney injury and atrial fibrillation in patients with CKM syndrome stage 0 and 1 were significantly lower than those in patients with CKM syndrome stage 2 and 3 to 4: 8.70% (2/23) and 8.57% (3/35) vs. 24.17% (487/2 015) and 34.35% (316/920), 0 and 0 vs. 3.52% (71/2 015) and 10.00% (92/920), and there were statistical differences ( P<0.05); there were no statistical differences in the incidences of ventricular tachycardia/ventricular fibrillation, cardiac arrest, mechanical complications and mechanical circulatory support among the four groups ( P>0.05). Conclusions:The severity of CKM syndrome is closely related to the occurrence of AMI. CKM patients with higher CKM stages have more severe AMI and poorer in-hospital prognosis. CKM syndrome staging can serve as a potential prognostic indicator for AMI patients.

Objective:To investigate the molecular markers involved in death related to acute myocardial infarction (AMI) and provide new targets for early intervention.Methods:Consecutive patients who hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from January 2017 to December 2021 and diagnosed with AMI were enrolled. The clinical factors and markers associated with in-hospital death after AMI were analyzed. In addition, patients diagnosed with AMI hospitalized in department of cardiology, Xuanwu Hospital, Capital Medical University from September 2022 to April 2023 were enrolled. We prospectively analyzed the plasma protein of death related to AMI via Olink Precision Proteomics based on proximity extension assay (PEA) technology.Results:In the retrospective study, 2 325 patients with AMI were analyzed, including 75 patients in the in-hospital death group and 2 250 subjects in the survival group. The overall mortality rate during hospitalization was 3.23% (75/2325). The patients in the death group were older: 72 (64, 80) years vs. 63 (55, 71) years. And Interleukin-6 (IL-6), hypersensitive C-reactive protein (Hs-CRP), leukocyte counts and neutrophil counts were markedly higher in the death group than those in the survival group: 69.0 (26.7, 136.6) ng/L vs. 18.2 (9.4, 36.5) ng/L, 45.7 (28.7, 50.5) mg/L vs. 5.5 (2.0, 17.2) mg/L, 12.0 (9.8, 14.1) ×10 9/L vs. 8.9 (7.2, 11.2) × 10 9/L, 9.8 (7.8, 12.1) ×10 9/L vs. 6.5(4.7, 8.8) ×10 9/L ( P<0.01). In this prospective study, 86 patients with AMI were analyzed. 61 proteins including Insulin-like growth factor-binding protein 1, 2 (IGFBP-1, IGFBP-2), Chitotriosidase-1 (CHIT1), Complement component C1q receptor (CD93) were independently associated with in-hospital death related to AMI ( P<0.05). The differential proteins were mainly enriched in inflammatory response, cell adhesion, cytokine signaling pathway and apoptosis. Moreover, 22 proteins including Urokinase plasminogen activator surface receptor (U-PAR), Trefoil factor 3 (TFF3), Perlecan (PLC), Growth differentiation factor 15 (GDF-15), Junctional adhesion molecule A (JAM-A) were plotted according to a logistic regression model, and the area under the curve (AUC) was more than 0.9, showing the high accuracy in predicting in-hospital death after AMI. Conclusions:Molecular markers of the inflammatory response, cell adhesion, cell growth and apoptosis might be involved in death related to AMI, which provides new targets for early intervention.

Objective:To evaluate the role of ubiquitin-specific peptidase 22 (USP22) in myocardial ischemia-reperfusion (I/R) injury in diabetic mice.Methods:Seventy-eight SPF male C57BL/6 mice, aged 6-8 weeks, were divided into 6 groups using a random number table method: sham operation group (Sham group, n=12), type 1 diabetes mellitus + sham operation group (T1D+ Sham group, n=12), myocardial I/R injury group (I/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury group (DI/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury + empty vector group (DI/R+ V group, n=15), and type 1 diabetes mellitus + myocardial I/R injury + USP22 overexpression group (DI/R+ U group, n=15). Type 1 diabetes mellitus was induced by intraperitoneal injection of streptozotocin-citrate buffer. Myocardial I/R was induced by ligation of the left coronary artery. At 1 day before developing the myocardial I/R injury model, DI/R+ U group and DI/R+ V group received an intramyocardial injection of USP22 overexpression plasmid or empty vector plasmid, respectively. At 24 h of reperfusion, cardiac function was assessed using the echocardiography to measure the left ventricular ejection fraction and left ventricular fractional shortening. The mice were then sacrificed, and their hearts were harvested for measurement of the myocardial infarct size, for microscopic examination of pathological changes (using HE staining) and for determination of the apoptosis rate (TUNEL staining), reactive oxygen species(ROS) activity (DHE staining), and USP22 expression (by Western blot, immunofluorescence, and immunohistochemistry). Proteomic analysis was performed to identify downstream proteins regulated by USP22, and protein-protein interactions were investigated using co-immunoprecipitation. Results:Compared with Sham group, the cardiac function indices were significantly decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct size was significantly increased, the cardiac function indices were decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was aggravated in DI/R group. Compared with DI/R+ V group, the percentage of myocardial infarct size was significantly decreased, the cardiac function indices were increased, the apoptosis rate of myocardial cells and ROS activity were decreased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was alleviated in DI/R+ U group. The results of proteomics combined with co-immunoprecipitation experiments showed an interaction between calponin 1 and USP22. Conclusions:During myocardial I/R injury in diabetic mice, USP22 may act as an endogenous protective mechanism, and calponin 1 might be a downstream mechanism through which USP22 exerts its protective effects.

Objective:To evaluate the effect of esketamine on learning and memory function after chronic stress and the signaling pathway of N-methyl-D-aspartate receptor (NMDAR)-calmodulin-dependent protein kinase type 2 (CaMKⅡ)-cAMP-responsive element-binding protein (CREB) in the hippocampus of developing rats.Methods:Sixty clean-grade healthy Sprague-Dawley rats of either sex, aged 7 days, weighing 10-15 g, were divided into 3 groups ( n=20 each) using a random number table method: control+ normal saline group (CN group), chronic stress+ normal saline group (NS group), and chronic stress+ esketamine group (ES group). A chronic stress model was established using a chronic unpredictable stress method. After the end of stress stimulation, esketamine 10 mg/kg was intraperitoneally injected once a day for 7 consecutive days in ES group, and the equal volume of normal saline was given instead in NS group. Y maze test and Morris water maze test were used to assess the learning and memory function after intraperitoneal administration. Venous blood samples were obtained to measure the serum cortisol and reactive oxygen species (ROS) concentrations by enzyme-linked immunosorbent assay. The animals were then sacrificed under anesthesia, the brain was removed and the hippocampal tissue was isolated for examination of the pathological changes in the hippocampal CA1 region and for determination of the ratios of phosphorylated NMDAR (p-NMDAR)/NMDAR, phosphorylated CaMKII (p-CaMKⅡ)/CaMKⅡ, and phosphorylated CREB (p-CREB)/CREB (by Western blot). Results:Compared with CN group, the time spent in the novel arm was significantly shortened, the number of entries into the novel arm was reduced, the escape latency was prolonged, the number of crossing the original platform was reduced, the serum cortisol and ROS concentrations were increased, the p-NMDAR/NMDAR ratio, p-CaMKⅡ/CaMKⅡ ratio and p-CREB/CREB ratio were decreased ( P<0.05), and the pathological changes of neurons were marked in NS group. Compared with NS group, the time spent in the novel arm was significantly prolonged, the number of entries into the novel arm was increased, the escape latency was shortened, the number of crossing the original platform was increased, the serum cortisol and ROS concentrations were decreased, the p-NMDAR/NMDAR ratio, p-CaMKⅡ/CaMKⅡ ratio and p-CREB/CREB ratio were increased ( P<0.05), and the pathological changes of neurons were significantly attenuated in ES group. Conclusions:Esketamine can improve the learning and memory function after chronic stress in developing rats, and the mechanism may be related to reduction of oxidative stress and enhancement of the activity of hippocampal NMDAR-CaMKII-CREB signaling pathway.