Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 &mu;m/year in women and 5.8 &mu;m/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Humans ; Retrospective Studies ; Bronchiectasis ; Mycobacterium avium Complex ; Syndrome ; Nocardia Infections/drug therapy* ; Nocardia ; Mycobacterium avium-intracellulare Infection

【Objective】 To investigate the role of microRNA-218 (miR-218) in regulating prostate cancer (PCa) cell stemness and epithelial-mesenchymal transition (EMT). 【Methods】 PCa cell line stably overexpressing miR-218 was constructed with lentivirus transfection. The expression of miR-218 was detected with real-time fluorescence quantitative polymerase chain reaction (q-PCR). The migration ability was detected with Transwell assay. The expression of EMT related proteins were detected with Western blot. The properties of cells were determined with colony formation and tumor sphere formation assays. 【Results】 The results of q-PCR showed that the mRNA level of miR-218 was significantly lower in PCa cell lines LNCaP and C4-2 than in BPH-1. Transwell assay showed that miR-218 inhibited the migration of PCa cells. Western blot showed that the expression of EMT related proteins were inhibited by miR-218. Colony formation and tumor sphere formation assays showed that overexpression of miR-218 significantly inhibited the properties of cells. 【Conclusion】 The expression of miR-218 is downregulated in PCa cell lines. miR-28 can inhibit cell migration, EMT and cancer stem cell properties.

Objective To explore the effectiveness of virtual autopsy-based postmortem computed tomography(PMCT)liver three dimensional slicer(3D slicer)artificial intelligence(AI)volume reconstruction to assist forensic practice.Methods Twenty cases of the deceased who underwent both virtual autopsy and traditional autopsy in our center were selected and subjected to liver volume segmentation by 3D slicer method,Tada's formula method and literature method,and the data obtained from the traditional autopsy were compared and analyzed to obtain the accuracy rate.Results The 3D slicer method yielded higher consistency(95%confidence interval),lower volumetric variability(standard deviation),and a smaller region(variance)of uncertainty than the Tada formula method and the methods mentioned in the literature.Conclusion 3D slicer AI reconstruction based on virtual autopsy can visualize virtual anatomy,help increase the diagnostic accuracy of traditional autopsy,assist in pathological diagnosis,and provide new directions and tools for the development of imaging histology of virtual autopsy.

One hundred and nine consecutive coronary heart disease (CHD) patients with obstructive sleep apnea (OSA) undergoing percutaneous coronary intervention (PCI) during February 2016 to August 2018 were enrolled in the study. After treatment the quality of sleep was improved in 35 cases (observation group) and was not improved in 74 patients (control group). The basic characteristics, coronary lesions of patients were compared between two groups. Compared with the control group, patients in observation group had significant higher proportion of males [80.0%(28/35) vs. 59.5%(44/74), χ²=4.471, P=0.035], smoking history [85.7% (30/35) vs. 63.5% (47/74), χ²=5.647, P=0.018], lower body mass index [(25.8±3.1) kg/m² vs. (27.4±3.2) kg/m², t=2.461, P=0.033]. Compared with control group, the observation group had lower coronary Gensini score[(35.4±5.7) vs. (38.7±6.5), t=2.571, P=0.011], less number of stent[ (1.4±0.4) vs. (1.6±0.4), t=2.427, P=0.016]. And the lesions were mostly distributed in the right coronary artery in observation group (61.9%, 26/35) (χ²=11.759, P=0.003).Conclusion The improvement of sleep quality by PCI depends on the clinical features and coronary artery lesions of CHD patients with OSA.

Objective To investigate the early predictors of Mycoplasma pneumoniae pneumonia (MPP) in children with blockage of airway mucous plug.Methods Retrospective analysis was executed on the clinical data of 130 children,who were diagnosed as MPP and treated with fiberoptic bronchoscopy at the Department of Pediatrics,the First Hospital of Jilin University,from September 2016 to January 2017.The patients were divided into the mucus plug group (60 cases)and the control group(70 cases) according to the performance of flexible bronchoscopy.The general information,clinical manifestations,laboratory examination,radiological features,bronchofibroscopic findings and treatment were compared between 2 groups.The multiple Logistic regression analysis and receiver operating characteristic (ROC) curve were used for the single factor with clinical and statistical significance to identify the early predictors of the MPP with blockage of airway mucus plug.Results Compared with the control group,the fever peak [39.8 ℃ (39.5 ℃,40.0 ℃) vs.39.5 ℃ (39.0 ℃,39.8 ℃)],the fever duration [(11.3 ± 3.1) d vs.(7.8 ± 2.4) d],hospitalization time [(13.5 ± 3.8) d vs.(8.5 ± 3.2) d],white blood cells (WBC) [(9.4 ± 3.7) × 109/L vs.(8.2 ± 2.9) × 109/L],the percentage of neutrophils (NE) (0.698 ± 0.112 vs.0.623 ± 0.119),C-reactive protein (CRP) [48.2 (19.8,91.0) mg/L vs.12.4 (7.1,25.4) mg/L],lactic dehydrogenase(LDH) [466.5(371.5,639.0) U/L vs.323.0 (273.2,376.8) U/L],the proportion of combined with pleural effusion (56.7％ vs.17.1％),atelectasis(23.3％ vs.7.1％),necrosis (16.7％ vs.0) and involved lobes more than 2 (40.0％ vs.21.4％) were higher in the mucus plug group,and these indicators had significantly statistical differences (Z =-3.394,t =-6.957,-8.021,-2.046,-3.672,Z =-6.402,-6.433,x2 =22.074,6.786,12.639,5.306,all P ＜ 0.05).The multiple Logistic regression analysis showed that the febrile time,CRP and LDH were independent predictors for the MPP with blockage of airway mucus plug.The ROC curve analysis showed that the cut-off values of the 3 predictors were febrile time ≥ 9.5 d [area under curve (AUC) =0.810,95 ％ confidence interval (CI):0.738-0.883],CRP ≥ 30.4 mg/L (AUC =0.826,95％ CI:0.757-0.895),and LDH ≥ 343.5 U/L (AUC =0.828,95％ CI:0.756-0.900).Conclusion The fever duration ≥9.5 d,increased CRP (≥30.4 mg/L),and increased serum LDH (≥343.5 U/L)can be applied as one of the early predictors for MPP in children with mucus plug.

Objective To evaluate the efficacy and safety of combined use of ticagrelor and cilostazol for patients with acute coronary syndrome (ACS) complicated with upper digestive tract diseases following percutaneous coronary intervention ( PCI).Methods A total of 262 consecutive ACS patients complicated with upper digestive tract diseases followed-up for one-year after PCI were included in this study.The patients were allocated into control group (combined use of ticagrelor and aspirin , n＝184) and cilostazol group ( combined use of ticagrelor and cilostazol , n ＝78) for antiplatelet treatment.The basic characteristics of the patients , change of the treatment regimens , cardiovascular events and hemorrhagic events were compared between two groups .Results After one year of follow-up, 16.8%(31/184)patients in control group and 3.8%(3/78)in cilostazol group changed antiplatelet regimens (χ2＝8.200,P＝0.004).There was no statistical difference in use of statins and ACEI/ARB between two groups(P＞0.05).The rate of proton pump inhibitor use in control group was significantly higher than that in cilostazol group [82.1%(151/184) vs.52.6%(41/78), χ2＝24.35, P＝0.000].However, the dosage of β-blockers in cilostazol group was significantly higher than that in control group [(39.1 ±12.4) mg vs.(28.6 ±10.1) mg, t ＝7.174,P＝0.000].No statistical difference was found in total cardiovascular events between two groups [21.7%(40/184) vs.12.8%(10/78),χ2＝2.822,P＝0.121].The incidence of gastrointestinal hemorrhage in control group was significantly increased compared with cilostazol group [12.0%(22/184) vs.2.6%(2/78),χ2＝5.807,P ＝0.018], however, there was no significant difference in hemorrhagic events concerning the thrombolysis for myocardial infarction between two groups [17.4%(32/184) vs.9.0%(7/78), χ2＝3.063,P＝0.089].Conclusion Combined use of cilostazol and ticagrelor is effective and safe for ACS patients with gastrointestinal hemorrhage or a higher risk of hemorrhage .

Objective nvestigate the propofol combined with fentanyl anesthesia in orthopedic manual reduction applications.MethodsAugust 2015 to December 2016 in our hospital treated 120 cases of acute long bone closed fracture and ankle, shoulder dislocation and other patients, efficient analysis anesthesia, surgery time, patient recovery time, propofol is added volume and total volume, and detection 3min, 1min, 3min, 5min and waking SpO2, HR, MAP, RR values.Two groups of patients after treatment, were given nursing intervention, such as routine diet guidance, nutrition support, health education.after administration before it is administered.Resultsanesthetic effect experimental group total efficiency is higher, the difference was statistically significant (P<0.05);after simultaneous administration of all patients 1min, 3min, 5min signs were lower than prodrug 3min signs, the difference statistically significant (P<0.05), after clear signs of its former administration 3min with no significant difference;experimental group recovery time, propofol bolus of propofol than with total control were lower, the difference was statistically significant (P<0.05);and the two groups were similar to the operation time, the difference was not statistically significant.ConclusionIn summary, propofol combined with fentanyl anesthesia for patients to take the treatment of orthopedic manual reduction obviously worthy of clinical use.

Objective To investigate the status on children of 3-14 years old who suffered from cerebral palsy in Liaoning province. Methods One thousand three hundred and twenty-three cases of children with cerebral palsy of 3-14 years old who received rehabilitation in city hospital, county hospital and community hospital were investigated from January 2013 to October 2016 in 14 cities in Liaoning Province. The proportion of cerebral palsy children in 3-4 years old, 4-5 years old, 8-9 years old, 5-6 years old , 6-7 years old and 7-8 years old was about 10%, and in the other age the proportion was about 7%. The proportion of men and women generally was 4:1;neonatal convulsion (252 cases, 19%), premature delivery (230 cases , 17.3%) and low birth weight infant (187 cases, 14.1%) were main risk factors and accounted for more than 10%. Spastic type cerebral palsy accounted for the highest proportion (54.35%, 719 cases)and ataxia cerebral palsy accounted for the lowest proportion (2.95%). In complications , lower intelligence accounted for the highest proportion (50.34%, 666 cases), followed by the language barrier (43.99% , 582 cases), and the other complications accounted for less than 10%.;gross motor function classification in most studied children was stageⅡ(35%) and stageⅢ(32.50%); 6.95% patients could go to school, and 84.96% patients had health insurance. Patients coming from city accounted for 69.01%, and patients coming from rural area accounted for 30.99%. Mothers′ education below primary school was 4.16% . 36.05% children received rehabilitation in comprehensive hospital, 60.09%in children′s hospital and 3.85%in maternal and child health hospital. Conclusions Spastic cerebral palsy is the main type of children with cerebral palsy in Liaoning.High risk factors include neonatal convulsions, premature birth and low birth weight infants. Most patients complicate with low intelligence and language barriers.This paper can be used as the basis of further research on prevention and treatment