OBJECTIVES: To verify whether hesperetin (Hes) alleviates doxorubicin (DOX)-induced cardiotoxicity by reducing inflammation via regulating the AMPK/NLRP3 pathway. METHODS: C57/bl6 mice and H9c2 cells treated with DOX to mimic cardiotoxicity were randomly divided into Sham (or control) group, DOX group, DOX+Hes group, DOX+Hes+compound C (CC, an AMPK inhibitor) group. Cardiac function and myocardial pathologies of the mice were evaluated, and the changes in H9c2 cell morphology and viability were assessed. Lactate dehydrogenase (LDH) activity in mouse myocardial tissues and H9c2 cells was measured using ELISA, and H9c2 cell apoptosis was detected with TUNEL staining. In both H9c2 cells and the myocardial tissues of the mice, cellular expression levels of TNF-α, IL-6 and IL-1β mRNAs and cleaved caspase-3, Bcl2, Bax, IL-1β, IL-18, p-AMPK, AMPK, p-mTOR, mTOR, NLRP3, ASC and caspase-1 proteins were detected using RT-PCR and Western blotting. RESULTS: DOX treatment caused cell swelling, decreased cell viability and increased LDH activity in H9c2 cells, resulting also in significantly increased cell apoptosis and cleaved caspase-3 expression and decreased Bcl2/Bax ratio. The DOX-treated mice showed obvious myocardial fiber swelling and inflammatory infiltration, decreased cardiac function and significantly increased myocardial LDH activity. In H9c2 cells, DOX treatment significantly increased the mRNA expressions of TNF-α, IL-6 and IL-1β and protein expressions of IL-1β and IL-18, lowered the expressions of p-AMPK and p-mTOR, and increased the expressions of NLRP3, ASC and caspase-1. Hes treatment obviously reduced these toxic effects of DOX in H9c2 cells, but its protective effects were blocked by application of compound C. CONCLUSIONS Hes reduces DOX-induced cardiotoxicity by inhibiting inflammation via regulating the AMPK/NLRP3 pathway.
Animals ; Doxorubicin/toxicity* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Mice ; Signal Transduction/drug effects* ; Cardiotoxicity ; AMP-Activated Protein Kinases/metabolism* ; Apoptosis/drug effects* ; Cell Line ; Myocytes, Cardiac/drug effects* ; Rats

Objective To explore the feasibility of direct low-dose CT thyroid protection scanning technology for detecting lower respiratory tract infectious diseases in children.Methods A total of 1 128 children who underwent CT chest examination due to suspected lower respiratory tract infectious diseases were enrolled and divided into 2 groups according to scanning scheme,which in group A(n=1 088)covered the whole lung apex and used conventional or direct low-dose scanning techniques,while in group B(n=40)did not include lung apex(the starting line located horizontally at the upper edge of manubrium sterni)and adopted direct low-dose scanning technique.Forty children in group A with age and gender matched with those in group B who received direct low-dose CT scanning were taken as group A1.The property of lung apex lesions and whether the lesions impacted the diagnostic outcomes in group A,as well as the display of thyroid gland in both group A and B were analyzed.Radiation dosage was compared between group A1 and group B.Results The radiation dose in group B was 22.1-35.6 mGy,with an average of(28.34±2.86)mGy,significantly lower than that in group A1(29.1-44.3 mGy,with an average of[34.71±3.07]mGy,P＜0.001).Among 1 088 cases in group A,CT showed lung apex lesions in 54 cases(54/1 088,4.96%),including 49 cases(49/1 088,4.50%)of inflammatory,4 cases(4/1 088,0.37%)of linear atelectasis and 1 case(1/1 088,0.09%)of space-occupying,all were expended from other lung lobe and did not impact final imaging diagnosis.Thyroid gland was displayed in 1 046 cases(1 046/1 088,96.14%)in group A(including 40 cases in group A1),which was not displayed in all 40 cases(40/40,100%)in group B.The display rate of thyroid gland in group A1 was significantly higher than that in group B(χ2=80.000,P＜0.001).Conclusion Direct low-dose CT thyroid protection scanning technology was feasible for detecting lower respiratory tract infectious diseases in children,which could reduce radiation dose and protect thyroid from ionizing radiation damage.

Objective To explore the feasibility of direct low-dose CT thyroid protection scanning technology for detecting lower respiratory tract infectious diseases in children.Methods A total of 1 128 children who underwent CT chest examination due to suspected lower respiratory tract infectious diseases were enrolled and divided into 2 groups according to scanning scheme,which in group A(n=1 088)covered the whole lung apex and used conventional or direct low-dose scanning techniques,while in group B(n=40)did not include lung apex(the starting line located horizontally at the upper edge of manubrium sterni)and adopted direct low-dose scanning technique.Forty children in group A with age and gender matched with those in group B who received direct low-dose CT scanning were taken as group A1.The property of lung apex lesions and whether the lesions impacted the diagnostic outcomes in group A,as well as the display of thyroid gland in both group A and B were analyzed.Radiation dosage was compared between group A1 and group B.Results The radiation dose in group B was 22.1-35.6 mGy,with an average of(28.34±2.86)mGy,significantly lower than that in group A1(29.1-44.3 mGy,with an average of[34.71±3.07]mGy,P＜0.001).Among 1 088 cases in group A,CT showed lung apex lesions in 54 cases(54/1 088,4.96%),including 49 cases(49/1 088,4.50%)of inflammatory,4 cases(4/1 088,0.37%)of linear atelectasis and 1 case(1/1 088,0.09%)of space-occupying,all were expended from other lung lobe and did not impact final imaging diagnosis.Thyroid gland was displayed in 1 046 cases(1 046/1 088,96.14%)in group A(including 40 cases in group A1),which was not displayed in all 40 cases(40/40,100%)in group B.The display rate of thyroid gland in group A1 was significantly higher than that in group B(χ2=80.000,P＜0.001).Conclusion Direct low-dose CT thyroid protection scanning technology was feasible for detecting lower respiratory tract infectious diseases in children,which could reduce radiation dose and protect thyroid from ionizing radiation damage.

Objective To investigate the impact of overweight on the prognosis of patients with acute mild ischemic stroke or moderate-high risk transient ischemic attack (TIA). Methods A total of 366 patients with acute mild ischemic stroke or moderate-high risk TIA who carried CYP2C19 loss-of-function alleles were included in the study. Baseline data were collected at admission, and clinical outcomes were collected within 3 months post-onset (primary outcomes: stroke recurrences within 3 months post-onset; secondary outcomes: composite outcome of stroke recurrence or death within 3 months post-onset, vascular events, and quality of life within 3 months). Kaplan-Meier method was used to plot the cumulative incidence curve of outcomes. Multivariate Cox proportional hazards model and multivariate Logistic regression model were used to evaluate the relationship between overweight and clinical outcomes within 3 months post-onset in patientswith ischemic stroke or TIA. The integrated discrimination improvement index (IDI) and net reclassification improvement index (NRI) were calculated to assess the predictive value of adding body mass index (BMI, whether overweight or not) based on traditional models for predicting the prognosis of acute ischemic stroke or TIA. Results After 3 months of follow-up, 28 patients had stroke recurrence, 1 patient died, and 31 patients had vascular events. The Kaplan-Meier cumulative incidence curve showed that the cumulative incidences of stroke recurrence, stroke recurrence or death, and vascular events after 3 months of onset were lower in overweight patients compared with non-overweight patients (Log-rank P < 0.05). Multivariate analysis showed that compared with non-overweight patients, overweight patients had significantly reduced risks of stroke recurrence within 3 months (HR=0.24; 95%CI, 0.08 to 0.71), composite outcome of stroke recurrence or death (HR=0.24; 95%CI, 0.08 to 0.69), and vascular events (HR=0.22; 95%CI, 0.07 to 0.63), and significantly improved quality of life within 3 months (OR=0.39; 95%CI, 0.20 to 0.76). The IDI and NRI calculations showed that compared with traditional models, the new model adding BMI (whether overweight) had significantly improved predictive ability for the prognosis of acute ischemic stroke or TIA. Conclusion Overweight may be a protective factor for the prognosis of TIA patients with acute mild ischemic stroke or moderate-high risk who carry CYP2C19 loss-of-function alleles. Compared with non-overweight patients, overweight patients have reduced risks of stroke recurrence, composite outcome of stroke recurrence or death, and vascular events within 3 months post-onset, and improved quality of life within 3 months post-onset.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

BACKGROUND:The embryonic epicardium can differentiate into myocardial cells and the cardiac stem cells with the potential of vascular smooth muscle cells, and it can differentiate into cardiac three-line cells which provide a new cellsource for the regeneration of cardiac injury. But the directed differentiation mechanisms and regulatory factors are stil unclear. OBJECTIVE:To establish the in vitro culture model of epicardial cells of mouse embryonic heart. METHODS:Embryonic hearts were dissected from the mice at pregnant 10.5-11.5 days, and the pulmonary veins, atrial tissue and left ventricle were cut off, then the embryonic hearts were transplanted into the 6-wel plates (or 35 mm dish) for culture. After cultured for 24 hours, the embryonic heart tissues were removed and cultured continuously. Phase contrast microscope was used to observe the growth characteristics of embryonic epicardial cells;the immunofluorescence technique was used to stain the specific antibody Wt-1 and Tbx18 of embryonic epicardial cells. RESULTS AND CONCLUSION:The embryonic epicardial cellmonolayers grew from tissue block edge with cobblestone-like and extended outwardly around the tissue blocks. After removed the embryonic heart, the cells grew continuously with rapid proliferation, and got fusion at 34 days. Al the embryonic epicardial cells could positively express the specific antibody Wt-1 and Tbx18 of embryonic epicardial cells. The results indicate that embryonic epicardial cells have the characteristics of rapidly growth and uniform morphology, and can express the embryonic epicardial cellspecific antibody with high purity. The successful y constructed in vitro culture models of embryonic epicardial cells provide new idea for the molecular mechanisms of directed differentiation.