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Platycodon grandiflorum (Jacq.) A. DC. is a famous medicinal plant commonly used in East Asia. Triterpene saponins isolated from P. grandiflorum are the main biologically active compounds, among which polygalacin D (PGD) has been reported to be an anti-tumor agent. However, its anti-tumor mechanism against hepatocellular carcinoma is unknown. This study aimed to explore the inhibitory effect of PGD in hepatocellular carcinoma cells and related mechanisms of action. We found that PGD exerted significant inhibitory effect on hepatocellular carcinoma cells through apoptosis and autophagy. Analysis of the expression of apoptosis-related proteins and autophagy-related proteins revealed that this phenomenon was attributed to the mitochondrial apoptosis and mitophagy pathways. Subsequently, using specific inhibitors, we found that apoptosis and autophagy had mutually reinforcing effects. In addition, further analysis of autophagy showed that PGD induced mitophagy by increasing BCL2 interacting protein 3 like (BNIP3L) levels.In vivo experiments demonstrated that PGD significantly inhibited tumor growth and increased the levels of apoptosis and autophagy in tumors. Overall, our findings showed that PGD induced cell death of hepatocellular carcinoma cells primarily through mitochondrial apoptosis and mitophagy pathways. Therefore, PGD can be used as an apoptosis and autophagy agonist in the research and development of antitumor agents.
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Humans , Mitophagy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Cell Line , Autophagy , Apoptosis , Membrane Proteins , Proto-Oncogene Proteins/genetics , Tumor Suppressor Proteins/pharmacologyABSTRACT
OBJECTIVE To compare the short-term therapeutic effect and safety of bevacizumab versus anlotinib respectively combined with chemotherapy drug in the treatment of epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKI） acquired resistant advanced lung adenocarcinoma. METHODS The information of 84 patients with EGFR-TKI acquired resistant advanced lung adenocarcinoma in the Third People’s Hospital of Chengdu was analyzed retrospectively during Jun. 2019-Oct. 2021. The patients were divided into chemotherapy group （32 cases）， anlotinib combined chemotherapy group （24 cases） and bevacizumab combined chemotherapy group （28 cases）. Patients in the chemotherapy group were given Pemetrexed disodium for injection and Carboplatin injection， and symptomatic treatment was given for adverse reactions. On the first day of chemotherapy， patients in the anlotinib combined chemotherapy group received Anlotinib hydrochloride capsules 10 mg orally， once a day， for 14 consecutive days and 7 days of discontinuation， based on the treatment of the chemotherapy group. Patients in the bevacizumab combined chemotherapy group were given Bevacizumab injection of 15 mg/kg intravenously 1 day before chemotherapy， based on the treatment of the chemotherapy group. Three groups of patients were treated for a total of four cycles， with one cycle every three weeks. The overall response rate （ORR）， disease control rate （DCR）， median progression-free survival （mPFS）， and the changes of serum tumor markers were compared among three groups before and after treatment； meanwhile， the occurrence of adverse drug reactions was recorded， and the 1-year survival rate was followed up. RESULTS After 4 treatment cycles， ORR and DCR of bevacizumab combined chemotherapy group and anlotinib combined chemotherapy group were higher than chemotherapy group （P＜0.05）； mPFS of the two groups were significantly longer than chemotherapy group， and DCR of anlotinib combined chemotherapy group was significantly higher than bevacizumab combined chemotherapy group （P＜0.05）. After 4 treatment cycles， the serum levels of tumor markers in three groups were significantly lower than before treatment， and both combined chemotherapy groups were significantly lower than chemotherapy group （P＜0.05）. There was no statistically significant difference in the incidence of adverse reactions such as nausea， vomiting， bone marrow suppression， and 1-year survival rate among the three groups of patients （P＞0.05）. CONCLUSIONS Bevacizumab and anlotinib combined with chemotherapy drug are effective and safe in the treatment of advanced lung adenocarcinoma with acquired EGFR-TKI resistance.
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OBJECTIVE:To explore the clinical efficacy and safety of nedaplatin combined with docetaxel in the treatment of advanced cervical cancer. METHODS:A total of 53 patients with advanced cervical cancer selected from our hospital during Apr. 2014-Apr. 2016 were divided into observation group(31 cases)and control group(22 cases)according to chemotherapy plan. Con-trol group was given Docetaxel injection 60 mg/m2,ivgtt,qw. Observation group was additionally given Nedaplatin for injection 35 mg/m2+0.9% Sodium chloride injection diluted into 500 mL,ivgtt (≥60 min),qw. A chemotherapy cycle lased for 21 d,and both groups received 2 cycles of chemotherapy. Clinical efficacies of 2 groups were evaluated 2 weeks after treatment,and the level of PCNA integal was detected before and 2 weeks after treatment. The occurrence of ADR was recorded. RESULTS:The total re-sponse rate of observation group (77.42%) was significantly higher than that of control group (63.64%),with statistical signifi-cance(P0.05). After treat-ment,PCNA integval of 2 groups were decreased significantly,and the observation group was significantly lower than the control group,with statistical significance(P0.05). CONCLUSIONS:Docetaxel combined with nedaplatin can significantly improve the clinical efficacy of patients with advanced cervical cancer,and does not increase the adverse reactions compared to docetaxel alone.
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Objective:To explore the correlation of nurses ’ organizational commitment and their professional identity status.Methods:Using Chinese employee organizational commitment scale and nurses professional identity evaluation scale questionnaire survey was conducted in 400 cases of clinical nurses , nurse compare different characteristics of organi-zational commitment and professional identity level , and USES the Pearson correlation analysis to investigate the correla-tion of both.ResultsNurses organizational commitment and professional identity total score , respectively (2.16-0.45) and (3.49 +0.84);Different cultural degree , job title, working years and the way of hiring nurses ’ professional identi-ty score comparison, the difference was statistically significant (P <0.05);Different ways of title, working years, and hire nurses’ organizational commitment score comparison , the difference was statistically significant (P <0.05);Pear-son correlation analysis showed that organizational commitment and the scores of each dimension career cognitive apprais -al, professional social skills , professional setback coping , social support and total scores of professional identity were sig -nificantly positive correlation (P <0.05).Conclusions:The nurse was significantly positively related to organizational commitment and their professional identity , and both have big room to improve .
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Objective: To explore the predictive value of the brachial-ankle artery pulse wave velocity [baPWV] for heart failure with preserved ejection fraction [HFpEF]. Methods: Echocardiographic data, B-type natriuretic peptide [BNP] level, and baPWV were assessed in 111 consecutive patients admitted for acute dyspnea. The patients were divided into the HFpEF group [n=71] and the control group [n=40]. Results: Multivariate logistic regression analyses revealed that the ratio of the early mitral inflow velocity to the tissue Doppler velocity [E/e'] at the lateral mitral annulus, BNP, and baPWV were independently predictive of HFpEF. Adding the baPWV to E/e' at the lateral annulus and to the BNP resulted in an increase in the area under the curve [AUC] to 0.855 [vs. lateral E/e' alone, P=0.02] or 0.880 [vs. BNP alone, P=0.02], respectively. The AUC of the three combining indicators including the lateral E/e', BNP, and baPWV was 0.910 [vs. E/e' lateral alone, P<0.001; vs. BNP alone, P=0.001]. The diagnostic accuracy was improved significantly after adding the baPWV to the diagnostic criteria of the 2007 ESC consensus statement [net reclassification improvement 0.127, P=0.02]. Conclusions: Adding the baPWV to the current diagnostic indicators of the 2007 ESC consensus statement could increase the accuracy of predicting HFpEF
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Objective: To explore the diagnostic value of brachial-ankle artery pulse wave velocity (baPWv) in patients of heart failure with preserved ejection fraction (HFpEF). Methods: A total of 86 consecutive dyspnoea patients without coronary artery diseases (CAD) were studied and they were divided into 2 groups: HFpEF group,n=46 and Control group, the patients had no organic heart disease,n=40. The incremental diagnostic value of HFpEF by baPWv improving the echocardiographic index and plasma BNP level was assessed by logistic regression model, receiver operation curve (ROC) of multi-parameter combination and net reclassiifcation index analysis. Results: Multiple stepwise logistic regression analysis presented that the ratio of early mitral inlfow velocity to tissue Doppler velocity at the lateral mitral annulus, BNP level and baPWv had the independent predictive value for HFpEF diagnosis, P<0.05. The ROC for baPWv with the combination of 2 or 3 parameters was better than the ROC for a single parameter, P<0.05. The baPWv added with 2007 ESC consensus statement signiifcantly improved HFpEF diagnosis, NRI = 0.127,P<0.05. Conclusion: The baPWv combining with current diagnostic criteria could increase the diagnostic value in patients of HFpEF.
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Objective To study the epidemiology,pathologies and clinical manifestations of renal diseases in elderly patients of different genders in China northwest region.Methods Retrospective analysis was used to evaluate the clinical and pathological informations of patients above 60 years old who underwent renal biopsy and had the integrated data in the past 20 years.Results (1)Among the 559 patients,there were 347 men accounting for 62.1％,and there were 212 women accounting for 37.9％ ； the average age was (66.7±5.3)years,the median course of disease was 5.0months when receiving renal biopsy,and 50％ cases was (1.3 ～ 12.0)months.(2) Primary glomerulopathy accounted for 69.59％(389/559),secondary glomerulopathy,tubulointerstitial disease and the others accounted for 25.4％ (142/559),3.8％ (21/559) and 1.3％ (7/559),respectively.(3)According to clinical manifestation,nephrotic syndrome was the most common disease(accounting for 60.7％),and then chronic glomerulonephritis accounted for 31.6％.In pathology,membranous nephropathy was the most frequently category accounting for 34.5％,then mesangial proliferative glomerulonephritis accounted for 32.4％.(4) Among secondary glomerulopathy,the frequent diseases were primary polyangitis,diabetic nephropathy,amyloidosis of kidney and lupus nephritis,accounting for 24.7％,19.7 ％,13.4 ％ and 10.6 ％,respectively,and the number of women was more than men in lupus nephritis(P＜0.05).(5) The common diseases of primary glomerulopathy that would result in renal insufficiency were nephrotic syndrome and chronic glomerulonephritis,accounting for 76.5 ％ (26/34)and 76.2 ％ (48/63),respectively,and the common pathological type was both mesangial proliferative glomerulonephritis.The common diseases of secondary glomerulopathy that would result in renal insufficiency were primary small vessel vasculitis and diabetic nephropathy,accounting for 46.3％(19/41)and 34.4％(11/32),respectively.Conclusions (1)the number of men was more than women in this group,and was opposite in lupus nephritis.(2) The most common disease was primary glomerulopathy,as for clinical manifestation,nephrotic syndrome and chronic glomerulonephritis were most common； the most common pathological type were membranous nephropathy and mesangial proliferative glomerulonephritis.(3) The common disease resulting in secondary kidney damage were primary small-vessel vasculitis and diabetic nephropathy.(4)The pathological type of disease resulting in renal insufficiency was mesangial proliferative glomerulonephritis,the common diseases resulting in acute renal insufficiency were nephrotic syndrome,primary small vessel vasculitis,and those resulting in chronic renal insufficiency were chronic glomerulonephritis and diabetic nephropathy.
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Objective To understand the differences between sexes in the clinical and pathological features of patients with mesangial proliferative glomerulonephritis(MPGS).MethodsOne hundred and five patients with MPGS admitted to our hospital were retrospectively studied in clinical and pathological aspects.Results( 1 ) The proportion of male patients were 75 of 105 ( 71.43 ％ ) and that of females were 30 of 105 ( 28.57％ ) ; ( 2 ) The average age of the male patients was ( 40.25 ± 15.50 ) and that of the females was (36.23 ± 15.26) in year.There was no significant difference between the two groups( t =1.206,P =0.231 ) ;(3) There was no significant difference in duration of disease,hematuria,edema,hypertension prevalence and mean blood pressure( P ＞ 0.05 ).The proportion of patients with hematuria was 56.19％ (59/105).The males accounted for 69.33％ ( 52/75 ) and the females were 63.33％ ( 19/30 ) in the main clinical manifestations of nephrotic syndrome.There was no significant difference( x2 =0.352,P ＞ 0.05 ) between the proportion of males and females; (4)Males and females groups had no significant difference( P ＞ 0.05 )on levels of urinary protein,serum albumin,immunoglobulin,complement,urea nitrogen and serum creatinine.Complement decreased in 53 cases,accounting for 53％ of all the participants.The proportion of male patients with renal insufficiency was 24.00％ (18/75),and the proportion of females with renal insufficiency was 13.33％ (4/30).There was no significant difference ( x2 =1.472,P ＞ 0.05 )on the percentage of males and females with renal insufficiency.The mean value of urea nitrogen was higher than the normal levels ; (5) The proportion of male cases with different deposition of immune complexes was 93.06％ (67/72),and the proportion in females were 92.86％ (26/28) in the exception of 5 cases ( male 3 and female 2 ) with no glomeruli in immunofluorescence examination.No significant difference was found between the two groups( x2 =0.001,P ＞ 0.05 ) ; ( 6 ) There was no significant gender differences( x2 =1.696,P ＞ 0.05 ) found in risk assessment.ConclusionThe prevalence of MPGS is higher in male patients than in females,the main clinical manifestations of which were nephrotic syndrome.Patients were found to have a higher rate of hematuria,decreased complement C3,and renal dysfunction than the normal levels.There was no significant difference in gender on the clinical and pathological aspects of MPGS.
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A mouse-anti-human monoclonal antibody was produced by using the membrane proteins of human lung carcinoma cell line A549 as the immunogen to generate monoclonal antibodies against lung carcinoma with the use of hybridoma techniques. McAb4E7 was prepared successfully. To identify its antigen, proteomic technologies such as two-dimenstional electrophoresis, western blotting and mass spectrometry were employed. The targeting antigen of McAb4E7 expressed positive in human lung cancer cell lines A549 and human hepatocarcinoma cell line HepG2, moreover, the expression of the antigen was stronger in A549 cells. Finally, we obtained one positive protein in A549 cell line that has strong affinity and specificity for McAb4E7, which was identified to be ATP synthase beta subunit. We identified ATP synthase beta subunit as the targeting antigen of lung carcinoma special monoclonal antibody McAb4E7.
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Animals , Humans , Mice , Antibodies, Monoclonal , Chemistry , Allergy and Immunology , Antibodies, Neoplasm , Allergy and Immunology , Antibody Specificity , Antigens, Neoplasm , Genetics , Allergy and Immunology , Cell Line, Tumor , Lung Neoplasms , Allergy and Immunology , Membrane Proteins , Allergy and Immunology , Mice, Inbred BALB C , Mitochondrial Proton-Translocating ATPases , Allergy and ImmunologyABSTRACT
The co-culture system of early embryos and cancer cells is an important means to observe the biological behavior changes of embryos and cancer cells in vitro. In this study, we co-cultured the 3.5 dpc mouse embryo with malignant tumor cells, investigated the development of blastocyst by observing the hatchment, attachment and outgrowth, observed the biological behavior changes of cancer cells in the embryonic circumstances, and detected the proliferation and apoptosis of cancer cells. Compared with the control, the embryos developed normally in the tumor environments, and the rate of hatchment, attachment and outgrowth increased significantly (P<0.05). However, there was no significant change of cancer cells in morphology, proliferation and apoptosis in the co-culture system (P>0.05). Under the co-culture system, the early embryo developed normally, and the cancer cells also grew well. There may be similarities between the embryos and cancer cell's choice for living. Moreover, the growth of embryos could be promoted by cancer cells in the co-culture system. This might be related to the similarities of gene expression, growth factors and signal transduction mechanisms between embryos and cancer cells.