OBJECTIVES: To investigate the synergistic inhibitory effects of AKBA and doxorubicin on malignant phenotype of triple-negative breast cancer (TNBC) MDA-MB-231 cells. METHODS: CCK-8 assay was used to determine the 48-h IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells, and SynergyFinder was employed to calculate the synergistic index and the optimal concentrations of the two agents. MDA-MB-231 cells treated with AKBA (22.5 μmol/L), doxorubicin (0.84 μmol/L) or their combination were examined for changes in cell proliferation, migration, invasion and apoptosis using Transwell migration, scratch assay, clone generation, RT-qPCR and Western blotting. Network pharmacology analysis was conducted to identify the downstream targets of AKBA in TNBC. In nude mouse models bearing subcutaneous MDA-MB-231 cell xenografts, the effects of normal saline, AKBA (50 mg/kg), doxorubicin (2.5 mg/kg), and AKBA combined with doxorubicin on xenograft growth and histopathology were observed. RESULTS: The IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells at 48 h was 45.15±0.97 μmol/L and 0.42±0.99 μmol/L, respectively. SynergyFinder confirmed the synergistic effect of AKBA and ADR with a ZIP>10. The combined treatment with AKBA and doxorubicin significantly inhibited the proliferation, migration and invasion, promoted apoptosis of MDA-MB-231 cells, and effectively suppressed xenograft growth in nude mice. Network pharmacology analysis predicted that AKBA affects the progression of TNBC through its downstream target AKBA. CONCLUSIONS AKBA combined with doxorubicin inhibits proliferation, migration and invasion, promotes apoptosis of MDA-MB-231 cells and suppresses MDA-MB-231 cell xenograft growth in nude mice. The combined use of AKBA can attenuate the toxic effects of doxorubicin in nude mice.
Animals ; Doxorubicin/pharmacology* ; Triple Negative Breast Neoplasms/pathology* ; Mice, Nude ; Mice ; Cell Proliferation/drug effects* ; Cell Line, Tumor ; Humans ; Female ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Xenograft Model Antitumor Assays ; Drug Synergism ; MDA-MB-231 Cells

Objective : To investigate the knowledge, attitude and practice on e-cigarette use among college students in Guiyang City, so as to provide insights into tobacco control health education among colleges and universities. Methods College students were sampled from full-time colleges and universities in Guiyang City using a multi-stage stratified cluster sampling method from March to May in 2022. Students' knowledge, attitude and practice on e-cigarette use were collected using a questionnaire designed based on the 2019 China National Youth Tobacco Survey Questionnaire, and factors affecting the attempt to use e-cigarette were identified using a multivariable logistic regression model. Methods: College students were sampled from full-time colleges and universities in Guiyang City using a multi-stage stratified cluster sampling method from March to May in 2022. Students' knowledge, attitude and practice on e-cigarette use were collected using a questionnaire designed based on the 2019 China National Youth Tobacco Survey Questionnaire, and factors affecting the attempt to use e-cigarette were identified using a multivariable logistic regression model. Results : Totally 2 800 questionnaires were recovered, including 2 694 valid questionnaires, with an effective recovery rate of 96.21%. The respondents included 687 males (25.50%) and 2 007 females (74.50%). The total score of knowledge on e-cigarette use was (2.95±1.02) points, and there were low proportions of knowing that e-cigarettes contained hazardous substances, including nicotine and tar (59.06%) and knowing that e-cigarette use may cause diseases (53.27%). The total score of attitudes towards e-cigarette use was (5.09±2.36) points, and 93.50% of respondents did not use e-cigarettes given by companions. There were 132 students with attempts to use e-cigarettes (4.90%), and there were 29 current e-cigarette users (1.08%). Multivariable logistic regression analysis identified age of 20 years and lower (OR=0.438, 95%CI: 0.267-0.719), living in rural areas (OR=0.458, 95%CI: 0.264-0.794), thinking that e-cigarettes are addictive (OR=0.449, 95%CI: 0.217-0.928), and thinking that e-cigarette smoking is harmful (OR=0.263, 95%CI: 0.131-0.527) as factors protecting from e-cigarette use, and monthly living expenses of more than 2 000 Yuan (OR=2.995, 95%CI: 1.135-7.902), cigarette smoking (OR=19.826, 95%CI: 11.385-34.527), and using companions' e-cigarettes (OR=9.141, 95%CI: 5.534-15.101) and thinking that people around me support my use of e-cigarettes (OR=2.673, 95%CI: 1.426-5.013) were risk factors for e-cigarette use among college students. Conclusions There is a low awareness rate of e-cigarette use among college students in Guiyang City, and the majority oppose e-cigarette use, with a low proportion of attempt to use e-cigarettes. Age, source of students, monthly living expenses, e-cigarette smoking, knowledge on e-cigarette use and use of companions' e-cigarettes may affect the attempt to use e-cigarettes.

Objective To explore the molecular mechanism of prolonged atrial repolarization in rats with reperfusion atrial arrhythmia.Methods Sixteen Langendorff isolated heart perfusion models made by male SD rats were randomly divided into control group(group C,n = 8)and hypothermic ischemia-reperfusion group(group IR,n = 8).According to the occurrence of atrial arrhythmia after reperfusion,group IR was further subdivided into reperfusion non-atrial arrhythmia subgroup(group N-RAA)and reperfusion atrial arrhythmia subgroup(group R-AA).Group C was perfused with 37℃K-H solution for 120 min.In group IR,the isolated heart was perfused with 37℃K-H solution for 30 min and stopped,and the isolated heart was perfused with 4℃Thomas solution(20 mL/kg)for 60 mins.When the heart stopped for 30 mins,the isolated heart was perfused with a half dose of 4℃Thomas solution(10℃).During cardioplegia,the isolated heart was protected by low temperature Thomas solution(4℃),and then reperfused for 30 mins with 37℃K-H solution.The monophasic action potential(MAP)of the right atrium was recorded at balanced perfusion for 30 mins(T0),balanced perfusion for 105 mins in group C/reperfusion for 15 mins in group IR(T1)and balanced perfusion for 120 mins in group C/reperfusion for 30 min in group IR(T2);The duration of 50%and 90%repolarization of monophasic action potential(MAPD50 and MAPD90)was measured.After electrophysiological monitoring,the expression of Kir2.1 and CaMKⅡ in right atrium was detected by Western blot.Results Compared with T0,MAPD50 and MAPD90 at T1 and T2 were significantly prolonged in group R-AA(P<0.05),and MAPD90 at T1 and T2 in group R-NAA and group R-AA were significantly longer than those in group C(P<0.05).Compared with group R-NAA,MAPD50 and MAPD90 in group R-AA were significantly prolonged at T1 and T2(P<0.05).The results of Western blot showed that the expression of Kir2.1 in group R-NAA and group R-AA was significantly lower than that in group C(P<0.05),and that in group R-AA was significantly lower than that in group R-NAA(P<0.05).The expression of CaMKⅡ in group R-NAA and group R-AA was significantly higher than that in group C(P<0.05),and the expression of CaMKⅡ in group R-AA was significantly higher than that in group R-NAA.Conclusion The prolonged duration of atrial repolarization in rats with hypothermic ischemia-reperfusion atrial arrhythmia may be related to the down-regulation of Kir2.1 expression and the up-regulation of CaMKⅡ expression.

Objective:To explore the effect of weight loss on endothelial function and cerebrovascular risk factors in obese and overweight people.Methods:A total of 127 obese or overweight subjects received 6-month body weight management. Subjects who lost 3 kg or more than 5% of their body weight prior to the 6-month intervention were defined as achievement group. Endothelial function (FMD) and other cerebrovascular risk factors were measured before and after intensified lifestyle management.Results:The achievement group comprised 57 (44.9%) cases and the non-achievement group 70 (55.1%) cases. After 6-month intervention, FMD (6.98±2.88% vs 7.90±2.96%, P<0.05) and HDL-C increased in the achievement group. Significant decreases were observed in the achievement group in BMI, SBP, DBP, FPG, TC, LDL-C, TG and uric acid. However, only DBP and FPG decreased in the non-achievement group. Conclusion:Weight loss can reverse endothelial dysfunction and metabolic dysfunction. Decrease of body fat ratio contributes to the improvement of endothelial function.

Objective:To investigate the effect of diabetes mellitus on pulmonary uptake of sevoflurane.Methods:Twenty patients with type 2 diabetes mellitus, aged 40-64 yr, with body mass index of 18.5-22.9 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective surgery with general anesthesia, served as diabetes group (group D). Twenty non-diabetic patients matched by age, gender and surgery were selected as control group (group C). After anesthesia induction and tracheal intubation, sevoflurane was inhaled at a concentration of 2% (oxygen flow 2 L/min). The inhaled concentration (Fi) and exhaled concentration (Fa) at 1, 3, 5, 10, 15, 20 and 30 min of inhalation of sevoflurane were recorded, and the Fa/Fi ratio was calculated.The time required for the Fa/Fi ratio to reach 0.7 was recorded. Results:Compared with group C, the Fa/Fi ratio was significantly increased at each time point, and the time required for the Fa/Fi ratio to reach 0.7 was shortened in group D ( P<0.05). Conclusion:Diabetes mellitus can reduce pulmonary uptake of sevoflurane in the patients.

Objective:To observe the changes in the expression of microRNAs in ventricular myocardium in a rat model of hypothermic ischemia-reperfusion (I/R).Methods:Healthy clean-grade male Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were anesthetized with intraperitoneal chloral hydrate.Their hearts were excised and perfused in a Langendorff apparatus with K-H solution saturated with 95%O 2-5%CO 2.Sixteen Langendorff-perfused hearts were prepared and divided into 2 groups ( n=8 each) by a random number table method: control group (group C) and hypothermic I/R group (group I/R). The hearts were made globally ischemic for 60 min followed by 30-min hypothermic (4 ℃) reperfusion to establish the model of hypothermic I/R injury.The type and duration of arrhythmia and time of recovery of spontaneous heartbeats were recorded during reperfusion.The rats in group I/R were further divided into low-risk group (I/R-L group) and high-risk group (I/R-H group). The left ventricular myocardium was collected after the end of perfusion for high throughput sequencing to screen the differentially expressed microRNAs, and the reliability of the sequencing results was verified by quantitative real-time polymerase chain reaction.Gene Ontology and KEGG databases were used to analyze the biological regulatory pathways of differentially expressed target genes. Results:Compared with group C, there were 437 up-regulated microRNAs and 242 down-regulated microRNAs in group I/R-L and 419 up-regulated microRNAs and 260 down-regulated microRNAs in group I/R-H.Compared with group I/R-L, 392 microRNAs were up-regulated, and 287 microRNAs were down-regulated in group I/R-H.There were 84 microRNAs with absolute value of fold change ≥2 and significantly differential expression ( P<0.01) among the three groups.Subsequently, 4 microRNAs were randomly selected for validation using quantitative real-time polymerase chain reaction, confirming that the sequencing results were reliable.These differentially expressed target genes were involved in 11 biological processes and 6 KEGG pathways which were related to reperfusion arrhythmia.Potassium ion transmembrane transport and the adrenergic receptor signaling pathway in cardiomyocytes were enriched by the largest number of target genes. Conclusion:The expression of microRNAs in ventricular myocardium changes significantly after heart hypothermic I/R.These differentially expressed microRNAs regulate potassium ion transmembrane transport probably and mainly through the adrenergic receptor signaling pathway in the cardiomyocytes and thus are involved in the occurrence and development of hypothermic I/R arrhythmias.

Objective:To evaluate the relationship between decreased atrial myoelectric conduction and gap junction protein 40 (Cx40) and Cx43 in rats with reperfusion atrial arrhythmia.Methods:Sixteen Langendorff-isolated heart perfusion models were randomly divided into control group (group C) and ischemia-reperfusion group (group IR), with 8 rats in each group.According to whether the atrial arrhythmia occurred after reperfusion, group IR was further divided into reperfusion non-atrial arrhythmia subgroup (group R-NAA) and reperfusion atrial arrhythmia subgroup (group R-AA). Group C was balanced perfusion with K-H solution (37 ℃) for 120 min.In group IR, hearts were perfused with K-H solution (37 ℃) for 30 min, perfusion was then stopped, Thomas solution (4 ℃, 20 ml/kg) was injected to induce cardiac arrest for 60 min, the surrounding of the heart was protected with 4 ℃Thomas solution, and hearts were perfused with Thomas solution (4 ℃, 10 ml/kg) again after 30 min of cardiac arrest and then with K-H solution 37 ℃ for 30 min.At 120 min of equilibration or 30 min of reperfusion, the effective refractory period (ERP) and conduction velocity (CV) of the right atrium were measured, the expression of Cx40 and Cx43 in the right atrial myocardium was detected by Western blot, and ratio of Cx40 to Cx40+ Cx43 and the ratio of Cx43 to Cx40+ Cx43 were calculated.Results:The incidence of reperfusion atrial arrhythmia was 38% in group IR.Compared with group C, ERP was significantly prolonged, CV was decreased, the expression of Cx40 and Cx43 was down-regulated, the ratio of Cx40 to Cx40+ Cx43 was increased, and the ratio of Cx43 to Cx40+ Cx43 was decreased in R-NAA and R-AA groups ( P<0.05). Compared with group R-NAA, ERP was significantly prolonged, CV was decreased, the expression of Cx40 and Cx43 was down-regulated, the ratio of Cx40 to Cx40+ Cx43 was increased, and the ratio of Cx43 to Cx40+ Cx43 was decreased in group R-AA ( P<0.05). Conclusion:The decreased atrial myoelectric conduction may be related to the down-regulation of Cx40 and Cx43 expression in rats with reperfusion atrial arrhythmia.

Objective:To evaluate the effect of electroacupuncture (EA) on electrophysiological characteristics of ventricular myocardium during myocardial ischemia-reperfusion (I/R) in rats.Methods:Twenty-four clean-grade healthy adult male Sprague-Dawley rats, weighing 280-320 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group SH), I/R group and group EA.The model of myocardial I/R injury was established by ligating the left anterior descending branch of coronary artery for 30 min followed by 30-min reperfusion in anesthetized rats.Bilateral Neiguan acupoints in forelimbs were stimulated for 30 min during the period of reperfusion in group EA.Heart rate (HR), monophasic action potential amplitude (MAPA), maximum depolarization rate (V max), and monophasic action potential duration at 90% repolarization (MAPD 90) were recorded.The development of arrhythmias and arrhythmias score were recorded during reperfusion. Results:Compared with group SH, HR was significantly decreased, MAPA and V max were decreased, MAPD 90 was prolonged, and the incidence of ventricular premature beat, ventricular tachycardia and ventricular fibrillation and arrhythmias score were increased at T 1, 2 in I/R and EA groups ( P<0.05). Compared with group I/R, HR was significantly increased, MAPA and V max were increased, MAPD 90 was shortened, and the incidence of ventricular tachycardia and ventricular fibrillation and arrhythmias score were decreased at T 2 in EA group ( P<0.05). Conclusion:EA can accelerate myocardial depolarization and shorten repolarization, thus decreasing the occurrence of reperfusion arrhythmia in rats.

Objective:To determine the changes in the expression of myocardial miRNA and the target genes in the rats with hypothermic ischemia-reperfusion (I/R) arrhythmia.Methods:Clean-grade healthy male Sprague-Dawley rats, aged 2-3 months, weighing 300-400 g, were anesthetized, the chest was opened, and the heart was taken to establish an isolated heart perfusion model.Six successfully perfused isolated hearts were divided into 2 groups ( n=3 each) using a random number table method: control group (group C) and heart I/R group (IR group). The model of hypothermic global I/R injury was established by interrupting perfusion for 60-min followed by 30-min reperfusion in chloral hydrate-anesthetized rats.The arrhythmia score was recorded during reperfusion.High-throughput sequencing was used to identify the differentially expressed miRNAs in two groups.The RNAhybrid and miRanda databases were used to predict the target genes of mRNA regulated by the differentially expressed miRNAs, and the enrichment for target genes was performed by Gene Ontology and KEGG databases, and the miRNAs closely related to arrhythmia and with higher expression were selected to carry out the real-time polymerase chain reaction detection. Results:The results of high-throughput sequencing showed that there were 7 differentially expressed miRNAs (novel-miR-17, novel-miR-19, novel-miR-30, novel-miR-43, rno-miR-122-5p, novel-miR-16 and rno-miR-429) in group IR as compared with group C. There were 4 miRNAs that were closely related to arrhythmia and had higher expression: the expression of novel-miR-17, novel-miR-30 and rno-miR-122-5p was significantly up-regulated, and the expression of rno-miR-429 was down-regulated in group IR when compared with group C ( P<0.05). The miRNA-mRNA correlation analysis revealed that GJA1 gene was the target of novel-miR-17. Conclusion:Myocardial novel-miR-17 is involved in the occurrence of hypothermic I/R arrhythmia probably by acting on GJA1 gene in rats.

Objective To evaluate the effect of family doctor contracted service system in Shenzhen and explore the influencing factors for families to contract their family doctors. Methods A total of 480 residents were selected from 12 first-class community medical rehabilitation centers in Luohu, Futian and Nanshan districts of Shenzhen. The contents of the survey included the contracting status between the contracted and non-contracted residents, the utilization of four basic public health services, and the difference of satisfaction with community medical rehabilitation centers.Meanwhile, logistic regression was used to explore the important influencing factors of the contracted family doctors. Results The overall contracting rate of residents was 51.9% (248/478), and the lowest contracting rate was 23.1% (27/117) (P<0.05), found among patients under 40 years old.The utilization rate of contracted residents for growth and development examination, maternal health care as well as guidance of chronic disease prevention and treatment was higher than that of non-contracted residents ( P <0.05 ). fees and medical environment, service attitude,medical fees was higher than that of non-contracted residents(P<0.05).The satisfaction for convenience in medical environment, service attitude,medical fees and access to medical service was higher than that of non-contracted residents(P<0.05).The results of binary logistic regression analysis showed that age, education level, occupation ( retirement ) and chronic diseases were important factors affecting the signing of contracts.Conclusions The family doctors tend to be embraced by residents better than before. Family doctors contracted service system is conducive to improving the utilization rate of basic health services, acceptance rate of health services and satisfaction of residents. At the same time, the young population at large requires greater efforts before they can embrace the family doctor system.