BACKGROUND: Gallbladder cancer (GBC) is the most common malignant tumor of biliary tract. Isoliquiritigenin (ISL) is a natural compound with chalcone structure extracted from the roots of licorice and other plants. Relevant studies have shown that ISL has a strong anti-tumor ability in various types of tumors. However, the research of ISL against GBC has not been reported, which needs to be further investigated. METHODS: The effects of ISL against GBC cells in vitro and in vivo were characterized by cytotoxicity test, RNA-sequencing, quantitative real-time polymerase chain reaction, reactive oxygen species (ROS) detection, lipid peroxidation detection, ferrous ion detection, glutathione disulphide/glutathione (GSSG/GSH) detection, lentivirus transfection, nude mice tumorigenesis experiment and immunohistochemistry. RESULTS: ISL significantly inhibited the proliferation of GBC cells in vitro . The results of transcriptome sequencing and bioinformatics analysis showed that ferroptosis was the main pathway of ISL inhibiting the proliferation of GBC, and HMOX1 and GPX4 were the key molecules of ISL-induced ferroptosis. Knockdown of HMOX1 or overexpression of GPX4 can reduce the sensitivity of GBC cells to ISL-induced ferroptosis and significantly restore the viability of GBC cells. Moreover, ISL significantly reversed the iron content, ROS level, lipid peroxidation level and GSSG/GSH ratio of GBC cells. Finally, ISL significantly inhibited the growth of GBC in vivo and regulated the ferroptosis of GBC by mediating HMOX1 and GPX4 . CONCLUSION ISL induced ferroptosis in GBC mainly by activating p62-Keap1-Nrf2-HMOX1 signaling pathway and down-regulating GPX4 in vitro and in vivo . This evidence may provide a new direction for the treatment of GBC.
Animals ; Mice ; Carcinoma in Situ ; Chalcones/pharmacology* ; Ferroptosis ; Gallbladder Neoplasms/genetics* ; Glutathione Disulfide ; Kelch-Like ECH-Associated Protein 1 ; Mice, Nude ; NF-E2-Related Factor 2/genetics* ; Reactive Oxygen Species ; Humans

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm³ and (105.18±31.16)cm³, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.
Male ; Humans ; Middle Aged ; Aged ; Female ; Coronary Artery Disease/diagnostic imaging* ; Cross-Sectional Studies ; Retrospective Studies ; Myocardial Ischemia/diagnostic imaging* ; Coronary Stenosis ; Calcium

Humans ; Neoplasms ; Rhabdomyosarcoma

Objective     To investigate the influence of prior percutaneous coronary intervention (PCI) on the outcome of coronary artery bypass grafting (CABG). Methods     Clinical data of 5 216 patients from Jiangsu Province CABG registry who underwent primary isolated CABG from 2016 to 2019 were retrospectively analyzed. Patients were divided into a PCI group (n=673) and a non-PCI group (n=4 543) according to whether they had received PCI treatment. The PCI group included 491 males and 182 females, aged 62.6±8.2 years, and the non-PCI group included 3 335 males and 1 208 females, aged 63.7±8.7 years. Multivariable logistic regression and propensity score matching (PSM) were used to compare 30-day mortality, incidence of major complications and 1-year follow-up outcomes between the two groups. Results     Both in original cohort and matched cohort, there was no statistical difference in the 30-day mortality [14 (2.1%) vs. 77 (1.7%), P=0.579; 14 (2.1%) vs. 11 (1.6%), P=0.686], or the incidence of major complications (myocardial infarction, stroke, mechanical ventilation≥24 h, dialysis for new-onset renal failure, deep sternal wound infection and atrial fibrillation) (all P>0.05). The rate of reoperation for bleeding in the PCI group was higher than that in the non-PCI group [19 (2.8%) vs. 67 (1.5%), P=0.016; 19 (2.8%) vs. 7 (1.0%), P=0.029]. Both in original cohort and matched cohort, there was no statistical difference in 1-year survival rate between the two groups [613 (93.1%) vs. 4 225 (94.6%), P=0.119; 613 (93.1%) vs. 630 (95.2%), P=0.124], while the re-admission rate in the PCI group was significantly higher than that in the non-PCI group [32 (4.9%) vs. 113 (2.5%), P=0.001; 32 (4.9%) vs. 17 (2.6%), P=0.040]. Conclusion     This study shows that a history of PCI treatment does not significantly increase the perioperative mortality and major complications of CABG, but increases the rate of cardiogenic re-admission 1 year postoperatively.

OBJECTIVE To evaluate the bioequivalence and safety of two k inds of Nadroparin calcium injection in healthy Chinese volunteers by subcutaneous injection. METHODS According to the block randomization method ，24 Chinese healthy adult volunteers were included and divided into TR （test preparation-reference preparation ）group and RT （reference preparation-test preparation）group at a ratio of 1∶1. A randomized ，open-labelled，single-dose and two-cycle crossover study was designed ，the fasting subjects of two groups were given test or reference preparation 6 150 AⅩaIU subcutaneously on the first day of each cycle and exchanged in the second cycle ，and the wash-out period was 7 days. The blood samples were collected at different time points before and after administration. The activity of anti-coagulant factor Ⅹa（Anti-Ⅹa）and Anti- Ⅱa in human plasma were determined by chromogenic substrate method ，and the pharmacodynamic parameters were calculated according to the non-atrioventricular model and the bioequivalence was evaluated. The occurrence of adverse events （AEs）was recorded. RESULTS After administration ，the main pharmacodynamic parameters for Anti- Ⅹa activity of test preparation and reference preparation were as follows ：t1/2 were（4.87±1.06） and（4.03±1.00）h，tmax were 4.50（2.00，8.00）and 5.50（2.50，8.00）h，Anti-Ⅹamax were（0.66±0.12）and（0.56±0.11）IU/mL；main pharmacodynamic parameters of Anti- Ⅱa activity of two preparations were as follows ：t1/2 were（3.64±1.60）and（5.74±7.23）h，tmax were 4.00（2.50，8.00）and 4.00（2.00，8.00）h，Anti-Ⅱamax were both （0.10±0.03）IU/mL. The values of 90％confidence interval of geometric mean ratio of Anti- Ⅹamax，AUEC0－t and AUEC 0－∞ were 110.98％-123.50％，112.11％-121.24％and 111.57％-120.00％， respectively. During experiment ，14 subjects reported 19 cases of mild AEs ，among which hematoma ，purpura and maculopapular rash may be related to drugs ；no serious AEs were observed. CONCLUSIONS The domestic Nadroparin calcium injection is bioequivalent to the reference preparation ，and both of them show good safety.

Objective: To explore the association between inflammation activity of left atrial epicardial adipose tissue (LA-EAT) measured by ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) and atrial fibrillation (AF). Methods: A total of 78 patients with AF, who underwent ¹⁸F-FDG PET/CT in the Nuclear Medicine Department of the Third Affiliated Hospital of Soochow University due to abnormally elevated levels of tumor indicators or malignant tumors from March 2018 to December 2019, were enrolled in this retrospective study. According to the examination date of PET/CT and basic characteristics of AF patients (gender, age), a 1∶1 propensity score matching was used to enroll a non-AF control group (78 patients). The maximum standard uptake value of left atrial epicardial tissue (LA-EAT FDG SUV_max) and total EAT volume (V-EAT) were measured by ¹⁸F-FDG PET/CT. Left ventricular ejection fraction (LVEF) and left atrial diameter (LAD) were obtained by echocardiography. Blood lipids and biomarkers of inflammation were measured. The differences of clinical data and EAT-related indicators were compared between the AF group and control group. Logistic multivariate regression analysis was used to determine the related factors of AF. Then the receiver operating characteristic (ROC) curve was used to determine the cutoff value of LA-EAT FDG SUV_max on the diagnosis of AF. Univariate and multivariate logistic regression analysis were used to analyze the relationship between the increase of LA-EAT FDG SUV_max and AF. Results: The age was (66.9±10.2) years and there were 55 males (70.5%) in the AF group. The age was (66.9±8.0) years, and there were 52 males (66.7%) in the control group (both P>0.05). The LAD ((44.2±5.8) mm vs. (35.4±4.4) mm), V-EAT ((122.1±42.0) cm³ vs. (91.6±34.5) cm³), and LA-EAT FDG SUV_max ((1.6±0.3) vs. (1.4±0.2)) values were significantly higher, while LVEF ((60.1±4.7)% vs. (63.9±2.9)%) was lower in the AF group than in the control group (P all<0.001). Multivariate logistic regression analysis showed that LAD (OR=1.340, 95%CI 1.195-1.502), V-EAT (OR=1.016, 95%CI 1.001-1.031), and LA-EAT FDG SUV_max (OR=1.375, 95%CI 1.095-1.723) were positively correlated with AF, LVEF (OR=0.781, 95%CI 0.659-0.926) was negatively correlated with AF(P all<0.05). The area under the ROC curve of LA-EAT FDG SUV_max for diagnosis of AF was 0.680 (95%CI 0.597-0.764, P<0.001), and the best cut-off value was 1.415 with a sensitivity of 65.4% and specificity of 61.5%. After adjusting for high-density lipoprotein cholesterol, LVEF, LAD and V-EAT, LA-EAT FDG SUV_max≥1.415 was independently associated with AF (OR=2.982, 95%CI 1.122-7.926, P=0.010). Conclusions: The inflammatory activity of LA-EAT measured by ¹⁸F-FDG PET/CT is an independent risk factor of AF, and the increased inflammatory activity of LA-EAT is positively correlated with AF.
Adipose Tissue/diagnostic imaging* ; Aged ; Atrial Fibrillation/diagnostic imaging* ; Fluorodeoxyglucose F18 ; Humans ; Inflammation/diagnostic imaging* ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left

Objective: To explore and analyze the effect of comprehensive nursing care in endoscopic treatment of esophageal and gastric varicose bleeding. Methods: A retrospective analysis of 60 cases of patients with esophageal and gastric varicose hemorrhage admitted to the hospital was conducted. The patients were randomly divided into 30 cases of control group and 30 cases of observation group. Routine nursing and comprehensive nursing were adopted respectively to evaluate different nursing effects. Results: Intraoperative and postoperative heart rate of the observation group (91.0 ± 4.0) times/min, (89.2 ± 4.2) times/min, which were lower than (98.0 ± 4.2) times/min, (94.7 ± 4.5) times/min of the control group. There was statistically significant difference (t values were 6.610, 4.894, P < 0.05). The bleeding prevention effectiveness rate of the observation group (93.33%, 28/30) was higher than the control group (73.33%, 22/30), The difference was statistically significant (χ² value was 4.32, P < 0.05). The total nursing satisfaction rate (100.00%, 30/30) in the observation group was higher than that in the control group (86.70%, 26/30), the difference was statistically significant (χ² value was 4.29, P< 0.05). Quality of life, disease cognition, compliance behavior, proper rest, self-protection, General Quality of life Inventory (GQOLI) score in the observation group were (33.5 ± 3.5), (21.5 ± 3.7), (32.5 ± 2.8), (21.5 ± 3.3), (22.0±4.2), (130.2 ± 17.4) points, which were higher than those in the control group (28.2 ± 3.2), (17.5 ± 2.5), (28.5 ± 3.0), (17.2 ± 3.0), (18.0 ± 3.0), and (110.2 ± 15.2) points. The differences were statistically significant (t values were 4.245-6.121, P<0.05). Conclusions Endoscopic treatment of esophageal and gastric varicose bleeding patients combined with comprehensive nursing intervention, can effectively prevent the occurrence of rebleeding, improve the quality of life of patients. The application effect is significant.

Diabetes, obesity, and metabolic diseases are globally prevalent, and induction and increase of endogenous energy consumption, especially activation of brown adipose tissue (BAT), is a new therapeutic target. Non-invasive imaging techniques, including radionuclide imaging, MRI, ultrasound imaging, and optical imaging, have attracted wide attention in BAT monitoring and have good application prospects. This article reviews the progress and application of these imaging techniques in BAT monitoring.

Worldwide increasing prevalence of obesity and lifestyle changes has put nonalcoholic fatty liver disease (NAFLD) as the most prevalent liver disease of the coming decade. NAFLD not only causes cirrhosis and hepatocellular carcinoma, but also acts as a component of metabolic syndrome together with obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and dyslipidemia. Consequently, its mutual cause-and-effect interactions have brought a huge clinical and financial burden to patients and society.

Objective: To evaluate the left ventricular systolic synchrony and investigate the early diagnostic value of left ventricular systolic dyssynchrony on cardiotoxicity caused by anthracyclines in patients with diffuse large B-cell lymphoma (DLBCL). Methods: Thirty-two patients (22 males, 10 females, age: 22-73(54.4±14.2) years) from June 2016 to January 2019 with confirmed DLBCL and normal gated myocardial perfusion imaging (GMPI) before anthracyclines chemotherapy were enrolled prospectively. GMPI was performed after 6 cycles or more of chemotherapy. Changes of myocardial markers, electrocardiogram (ECG) indicators, left ventricular function indicators including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), peak filling rate (PFR), summed motion score (SMS) and summed thickening score (STS) as well as left ventricular systolic synchrony indicators including phase bandwidth (BW), phase standard deviation (SD) and entropy before and after anthracyclines chemotherapy were analyzed. Paired t test, Wilcoxon signed rank test and χ² test were used for data analysis. Results: Compared with pre-chemotherapy, the left ventricular systolic synchrony indicators were significantly higher than those before chemotherapy (BW: (42.81±11.37)° vs (29.28±8.68)°; SD: (11.65±4.64)° vs (8.79±3.14)°; entropy: (39.84±5.51)% vs (36.19±5.94)%; t values: -9.132 to -3.173, all P<0.05). There were no significant differences in other indicators (t values: -1.161 to 1.750, z values: -1.633 to -0.096, all P>0.05). Of 32 patients, 13 patients (40.62%) had left ventricular systolic dyssynchrony, and the rate of chemotherapy-induced left ventricular systolic dyssynchrony was significantly higher than that of left ventricular dysfunction (15.62%, 5/32; χ²=4.947, P=0.025). All 5 patients with left ventricular dysfunction caused by chemotherapy had left ventricular systolic dyssynchrony. The LVEF of the chemotherapy-induced left ventricular systolic dyssynchrony group was significantly lower than that of the left ventricular systolic synchronization group ((54.54±9.25)% vs (66.79±7.65)%; t=4.087, P<0.01). Conclusion Left ventricular systolic dyssynchrony can be appeared in DLBCL patients after chemotherapy and is significantly earlier than left ventricular dysfunction, which can be an early indicator of cardiotoxicity caused by anthracycline chemotherapy.