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BACKGROUND:Clinical treatment for colon cancer mainly includes fluorouracil,irinotecan and oxaliplatin-based therapy.Studies have shown that membrane transport proteins such as ATP-binding cassette transport protein of G2(ABCG2)mediate the transport of these drugs.However,when patients develop resistance to these chemotherapeutic drugs,the high expression of ABCG2 leads to a significant decrease in the therapeutic effect and raises the problem of drug resistance in colon cancer.New drugs and treatments are urgently needed to improve the efficacy.Lycium barbarum polysaccharide has a wide range of biological activities.It can be used as anti-tumor drug to overcome the damage to normal cells in the process of chemotherapy and radiotherapy in tumor patients. OBJECTIVE:To explore the reversal effect of Lycium barbarum polysaccharide in combination with oxaliplatin on colon cancer drug-resistant cells through in vitro experiments to investigate the possible molecular mechanism of Lycium barbarum polysaccharide reversal on colon cancer drug-resistant cells. METHODS:Colon cancer cell line HCT116 and oxaliplatin-resistant cell line HCT116-OXR were selected for in vitro experiments.The optimal intervention concentration and intervention time of Lycium barbarum polysaccharide and oxaliplatin were determined by CCK8 assay of cell proliferation.Samples were further divided into the HCT116 control group,HCT116-OXR blank treatment group,Lycium barbarum polysaccharide group(2.5 mg/mL Lycium barbarum polysaccharide),and oxaliplatin group(10 μmol/L oxaliplatin),and Lycium barbarum polysaccharide + oxaliplatin group(2.5 mg/mL Lycium barbarum polysaccharide +10 μmol/L oxaliplatin).Cell apoptosis was detected by flow cytometry.The protein expression levels of phosphomannose isomerase(PMI)and ABCG2 were detected by immunofluorescence and western blot assay.Phosphatidylinositol3-kinase(PI3K),protein kinase B(AKT),B-cell lymphoma 2(Bcl-2)and BCL2-Associated X(Bax)were detected by western blot assay. RESULTS AND CONCLUSION:(1)HCT116-OXR was more sensitive to Lycium barbarum polysaccharide compared to HCT116(P<0.05).(2)Compared with the HCT116-OXR blank group,Lycium barbarum polysaccharide + oxaliplatin could promote apoptosis of HCT116-OXR cells(P<0.05).The protein expression of Bcl-2 was significantly down-regulated(P<0.05);the protein expression of Bax was significantly up-regulated(P<0.05);the protein expression of ABCG2,PMI,PI3K and AKT was significantly down-regulated(P<0.05).(3)These results indicate that Lycium barbarum polysaccharide reverses drug resistance in colon cancer by inhibiting PMI/PI3K/AKT signaling pathway,which lays the foundation for studying the molecular mechanism of Lycium barbarum polysaccharide's sensitizing chemotherapeutic effects.
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Objective:To study the population distribution of Pomacea spp. in Shandong Province and the risk of angiostrongyliasis cantonensis in the local population, and to provide a basis for scientific prevention and control of related diseases. Methods:From July to December 2021, Yanzhou District of Jining City, Ningyang County of Taian City, and Dongying District of Dongying City were selected as surveillance sites to investigate the population and distribution range of Pomacea spp., live snail samples were collected for morphological and genetic identification, and Pomacea spp. infected with the larva of Angiostrongylus cantonensis was detected by lung test. At the same time, sentinel hospital case surveillance was carried out in Yanzhou District, Jining City, and questionnaire was used to study the local residents' awareness of angiostrongyliasis cantonensis and their personal health behaviors. Results:A total of 312 live snail samples were collected. After morphological identification, they were all Pomacea spp.. After gene sequencing, two populations of Pomacea canaliculata and Pomacea maculata were found. No positive snails infected with Angiostrongylus cantonensis were found. A total of 126 patients with headache as the main neurological symptom were admitted to the sentinel hospital, but there were no monitoring cases that met the inclusion criteria. Among the survey population, 48.38% (134/277) of the respondents had heard of angiostrongyliasis cantonensis, 44.77% (124/277) knew that eating Margarya melanioides might cause angiostrongyliasis cantonensis, and 83.39% (231/277) had no related unhealthy eating behavior. Conclusion:Pomacea spp. is found and reported for the first time in Shandong Province, and there is a risk of population infection with angiostrongyliasis cantonensis.
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Objective:To investigate the clinical significance of grip strength, three simple lung functions[functional volume capacity(FVC), forced expiratory volume in the first second(FEV1)and peak expiratory flow(PEF)], 6-minute walking distance test(6MWD)and left ventricular ejection fraction(LVEF)for assessing overall integrative function in elderly versus non-elderly patients with coronary artery disease(CAD).Methods:A total of 35 hospitalized CAD patients aged 70.4±10.6 years from January 2017 to December 2018 were retrospectively enrolled.Patients were divided into the non-elderly group(<65 years, n=8)and the elderly group(≥65 years, n=27). FVC, FEV1 and PEF were tested by a portable lung function machine.The grip strength, 6MWD, three simple lung functions(FVC, FEV1, PEF), LVEF and echocardiography were detected after admission.The above indexes were re-examined in outpatient clinic at 3 months after discharge.The results of above indexes were compared at admission versus at three months after discharge.The consistency and correlation between FVC, FEV1, PEF, 6MWD, grip strength and LVEF were analyzed.Results:The detected results of FVC, FEV1, PEF, 6MWD, left-hand grip strength, right-hand grip strength and LVEF showed no significant difference at admission versus at 3 months after discharge( P>0.05)in a total of 35 hospitalized CAD patients.Pearson bivariate correlation analysis showed that FVC, FEV1, PEF, left-hand and right-hand grip strength had pairwise correlation between them( P<0.01).6MWD had no correlation with LVEF.And LVEF was related with FVC and FEV( P<0.01), but not related with PEF, 6MWD and grip strength( P>0.05). The detective values of FVC, FEV1, PEF, 6MWD, left-hand and right-hand grip strength were lower in the elderly group than in the non-elderly group[(2.11±0.66 )L vs.(2.88±0.55) L, (1.74±0.46 )L vs.(2.62±0.49 )L, (5.50±1.79 )m/s vs.(8.22±1.59) m/s, (332.07±115.58)m vs.(446.14±99.81 )m, (25.14±7.87) vs.(35.15±8.30), (27.37±8.39 )kg vs.(38.37±10.20)kg, P<0.01]. LVEF had no significant difference between the two age groups. Conclusions:FVC, FEV1, PEF, 6MWD and grip strength are lower in elderly group than in non-elderly group.A comprehensive set of tests of grip strength, three simple lung function and 6MWT is helpful to evaluate the overall integrative function in elderly CHD patients.
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Objective:To evaluate the application value of electrical impedance tomography(EIT)imaging combining bedside bronchoscopy sputum suction by observing the changes of pulmonary ventilation, tidal volume and dynamic pulmonary compliance after bedside bronchoscopy sputum suction in elderly stroke-associated pneumonia(SAP).Methods:A randomized controlled study was conducted.Patients with SAP admitted to the respiratory intensive care unit of Henan Provincial People's Hospital from January 2017 to December 2018 were enrolled as research objects.They were divided into the control group versus observation group with the only difference in receiving bedside bronchoscope sputum suction replacing control's receiving conventional sputum suction.Impedance imaging region of interest 4(ROI4)values collected by using EIT at admission and 1, 3, 5 days after fiberoptic bronchoscope sputum suction were compared between the two groups.Meanwhile, the tidal volume, dynamic lung compliance, the duration of mechanical ventilation and hospitalization time in intensive care unit were recorded in the two groups.Results:A total of 78 patients meeting an inclusion and exclusion criterion were enrolled, with 37 cases in the control group and 41 cases in the observation group.Compared with control group, the bronchoscope sputum suction group showed the significantly increased regional gas distribution values(2.24±0.77% vs.0.49±0.65%, 7.05±0.77% vs.2.49±0.87%, 12.34±1.47% vs.5.57±0.50%, t=10.85, 24.56 and 26.54, respectively, all P<0.001)at 1, 3, 5 days after fiberoptic bronchoscope sputum suction.The tidal volume and dynamic lung compliance were significantly higher in the observation group than in the control group at 1, 3, 5 days after fiberoptic bronchoscope sputum suction.The duration of mechanical ventilation and hospitalization time in the intensive care unit were shorter in the observation group than in the control group(12.22±0.88 d vs.14.65±0.92 d, 18.41±1.12 d vs.21.14±1.06 d, t=11.91 and 11.01, both P< 0.001). Conclusions:For patients with SAP, an intermittent bedside fiberoptic bronchoscope sputum suction can effectively improve the pulmonary ventilation in the dorsal area, optimize pulmonary respiratory dynamics, facilitate the early withdrawal of the mechanic ventilation, and shorten the hospitalization time in the intensive care unit.
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Objective:To evaluate the efficacy and safety of statin combined with ezetimibe for elderly patients with coronary heart disease (CHD) and dyslipiclemia.Methods:Clinical data of 293 patients with CHD and dyslipidemia treated with statins and ezetimibe in the outpatient clinic of Beijing Hospital from November 2009 to June 2019 were retrospectively analyzed. There were 153 patients aged ≥65 years (elderly group) and 140 patients aged<60 year (control group). The low density lipid cholesterol reduction (ΔLDL-C), LDL-C compliance rate and safety were compared between the two groups.Results:The longest follow-up time was 9 months, the average follow-up time was 5.3 months in the elderly group, and 5.2 months in the control group. After treatment the TC, LDL-C, and TG levels were lower than those before treatment in both groups ( P<0.05), and there was no significant changed in HDL-C levels. After treatment there were no significant differences in TC [3.50(3.15,4.01) vs.3.49(3.14,4.00) mmol/L], LDL-C [1.85(1.56,2.23) vs.1.85(1.56,2.40) mmol/L], and TG [1.23(0.94,1.57) vs.1.32(0.84,1.70)mmol/L] between two groups (all P>0.05). There were also no significant differences in ΔLDL-C [-0.85(1.14,-0.55) vs.-0.81 (-1.34, -0.50) mmol/L], LDL-C decline rate (29.3% vs. 28.5%), and LDL-C compliance rate [44.4%(68/153) vs.45.0%(63/140)] between two group (all P>0.05). After combined treatment, AST and ALT increased in both groups, but they were still in the normal range. The difference of AST and ALT before and after treatment in the two groups was not statistically significant. There were no significant changes in CK in both groups ( P>0.05). Conclusion:The combined administration of ezetimibe and statin can significantly reduce LDL-C level and increase LDL-C compliance rate in treatment of elderly patients with coronary heart disease and dyslipidemia safety.
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Atherosclerotic cardiovascular disease is one of the leading causes of death and disability worldwide.Dyslipidemia mainly with elevated LDL-C is closely related to atherosclerotic cardiovascular disease.Statins are the most effective drugs for lowering LDL-C and play an important role in the prevention and treatment of atherosclerotic cardiovascular disease.However,a considerable number of patients receiving statin therapy can not tolerate its adverse reactions or their low-density lipoprotein can not meet the standard,and the cardiovascular risk remains high.The clinical application of new lipid-lowering drugs such as ezetimibe,PCSK9 inhibitors and cholesterol ester transfer protein(CETP) inhibitors has marked the post-statin era of lipid-lowering therapy.
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PARP inhibitors are a kind of anticancer drugs approved for the clinical treatment of ovarian cancer and primary peritoneal cancer on the basis of the strategy of synthetic lethality. With the publication of two phase Ⅲ clinical trials results, the indications for PARP inhibitors have been expanded to advanced breast cancer with germline BRCA-1/2 mutations. However, the current exploration of PARP inhibitors in breast cancer is still at early stage. This article summarizes the anticancer mechanism of PARP inhibitors and new advances in treatment of breast cancer.
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Objective To evaluate the predicting value of circulating miRNAs for sepsis secondary to pneumonia in elderly patients.Methods From April 2016 to January 2017,44 cases with sepsis secondary to pneumonia,52 elderly patients with pneumonia and 21 healthy older adults as control were involved in this study.The expression levels of MiRNA-150 5p,miRNA-25-3p,miRNA-122 5p and miRNA-223-3p in plasma were evaluated by fluorescence quantitative PCR.The demographic characteristics,sequential organ failure assessment (SOFA)scores,prognosis and days stayed in ICU were recorded.The area under the receiver operating charaeteristic(ROC)curve was used to calculated the specificity and sensitivity of miRNA in identifying sepsis-associated pneumonia.Results There were significantly differences among levels of circulating miRNA-223-3p in pneumonia,sepsis and healthy control groups(F =36.441,P =0.000),△CT values were 2.39 ± 1.36,1.44± 1.43,and 4.58 ± 0.91,respectively.The relative expression levels of miRNA-223-3p in the three groups were significantly different (P =0.000),which were 0.189 (0.107,0.367),0.361 (0.221,0.735),and 0.044 (0.022,0.061),respectively.The AUC of miRNA-223-3p for predicting sepsis from pneumonia was 0.964(95 ％CI =0.925 1.000).At a cutoff value of 2.759,miRNA-223-3p yielded a sensitivity of 82.9％ and a specificity of 100.0％.Conclusions MiRNA-223-3p expression is up-regulated in patients with sepsis secondary to pneumonia compared to that of patients with pneumonia,and it could be used to predict sepsis associated pneumonia.
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Objective:To study the silencing gene expression level of RhoGDI2 small interfering RNA(siRNA)and the colorectal cancer cell malignant behaviors such as cell proliferation,migration,invasion.Methods:Testing RhoGDI2 expression using Westen blot analysis and Real-time reverse transcription polymerase chain reaction(RT-qPCR)in the colorectal cancer cell lines of RKO,HT29,SW620,SW480,HCT116.The siRNA of RhoGDI2 with Lipofecta mineTM2000 was transfected into target cells,as well as negative control and normal control groups.Cell counting kits(CCK-8)to detect proliferation,Wound healing assay and the Transwell plate migration and invasion was detected.The epithelial-mesenchymal transition(EMT)relevant protein E-cadherin/Vimentin expression was detected.Results:Human colon cancer cell lines RhoGDI2 expression levels decreased in the order of RKO,HT29,SW620,SW480,HCT116:siRNA inhibited RhoGDI2 expression rate of RKO cell by 70%;in silence group,negative control group and blank contro1 group,the proliferation rates were(0.683±0.013),(0.866±0.088),(0.905±0.008),P<0.05;Wound healing assay and Transwell assay suggested RhoGDI2 silencing could inhibit migration;siRNA interference of colon cancer cells downregulated Vimentin,but upregulated E-Cadherin protein.Conclusion:RhoGDI2 down-regulation could significantly inhibit the cell proliferation,migration,invasion of colon cancer cell.
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Objective To evaluate the efficacies of upfront simultaneous integrated boost-intensity-modulated radiation therapy (SIB-IMRT) and epidermal growth factor receptor (EGFR) etyrosine kinase inhibitor (TKI) in patients with epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancers who developed brain metastasis (BM).Methods Sixty-eight patients diagnosed as having EGFR-mutant non-small-cell lung cancer developed BM were recruited in our hospital from July 2012 to January 2016.Of these patients,45 received upffont EGFR-TKI gefitinib and 23 accepted SIB-IMRT.The clinical data of these patients were recorded;the viability curve and encephalic progressive cumulative incidence curve were compared between the two groups.Cox multiple-factor analysis was performed to analyze the influencing factors of prognoses.Results The median survival time in the SIB-IMRT group was shorter than that in upfront EGFR-TKI group (18.9 months [95％ CI:16.5-21.4 months] vs.27.5 months [95％CI:21.6-33.5 months]).Log-rank test indicated that the survival rate of patients from SIB-IMRT group was significantly higher than that of patients from EGFR-TKI group (P＜0.05);in the patients from SIB-IMRT group,61％ patients had encephalic progressive changes,with the median survival time of 20.7 months (95％CI:9.6-14.2 months);in the patients from EGFR-TKI group,89％ patients had encephalic progressive changes,with the median survival time of 11.9 months (95％CI:19.7-49.2 months).The encephalic progressive cumulative incidence in patients from EGFR-TKI group was significantly higher than that in patients from SIB-IMRT group (P＜0.05).Multiple-factor analysis indicated that initial therapeutic schedule,prognosis evaluation and extra-cerebral metastasis were the key influencing factors of prognoses.Conclusion The patients accepted upfront EGFR-TKI treatment has longer overall survival and progression free survival than those accepted upfront SIB-IMRT in patients with EGFR-mutant non-small-cell lung cancer who develop BM.