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AIM: To investigate the mechanism of elemene synergistic bortezomib against multiple myeloma based on ROS-NF-κB-p38MAPK signaling pathway. METHODS: CCK-8 assay was used to detect cell activity. Nude mice were randomly divided into control group, bortezomib (BTZ) group, elemene (ELE) group and combination group. Each group was treated with BTZ, ELE and BTZ combined with ELE, respectively. Tunel staining was performed to observe the apoptosis of tumor tissues. The expressions of Caspase-3, Bcl-2, NF-κB and p38 MAPK were detected by Western Blot. Cell cycle, apoptosis and reactive oxygen species (ROS) expression were detected by flow cytometry using human myeloma U266 cells. RESULTS: When 4.0 μmol/L ELE combined with 50 nmol/L BTZ treated U266, the cell activity was significantly reduced compared with that of NC, BTZ and ELE groups (P< 0.05). The tumor volume of nude mice in BTZ group, ELE group and combined group was significantly reduced compared with the control group (P <0.05), and the combined group was the smallest. Tunel staining results showed that the apoptosis level in the control group was lower than that in the BTZ group, ELE group and the combined group (P<0.05), and the combined group had the lowest apoptosis level. Compared with the control group, the expressions of Caspase-3 and p38 MAPK in BTZ group, ELE group and combination group were significantly increased, while the expression of Bcl-2 was significantly decreased. The apoptosis level and expression of ROS in BTZ group, ELE group and the combined group was significantly increased compared with the control group (P<0.05). CONCLUSION: ELE can enhance the role of BTZ in promoting apoptosis of myeloma cells, which may be achieved by regulating ROS/NF-κB/p38 MAPK signaling pathway to enhance the level of apoptosis of tumor cells to achieve anti-tumor effect.
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Objective@# To investigate the epidemiological characteristics of hand, foot, and-mouth disease (HFMD) among children under 6 years in Wuxing District, Huzhou City from 2013 to 2021, so as to provide insights into HFMC control among children. @* Methods @#The surveillance on HFMD and enterovirus 71 (EV71) vaccination among children under 6 years in Wuxing District, Huzhou City from 2013 to 2021 were captured from China Disease Prevention and Control Information System, and the temporal, human and spatial distributions of HFMD cases and pathogenic detection results were descriptively analyzed.@*Results @#A total of 14 272 HFMD cases under 6 years were reported in Wuxing District from 2013 to 2021, with an average annual incidence rate of 465.75/104. There were 8 313 male children with HFMD (522.39/104 incidence) and 5 959 female children with HFMD (404.55/104 incidence), and higher incidence of HFMD was seen among male children than among female children (χ2=239.228, P<0.001). Most HFMD cases were found among children at ages of 1 to 3 years (10 006 cases, 70.11%), and the incidence of HFMD peaked during the period between May and July and between October and December each year. High incidence of HFMD was seen in Zhili Township (741.50/104), Yangjiabu Street (546.99/104) and Balidian Township (438.68/104). There were 717 laboratory-confirmed HFMD cases (5.02%), including 106 EV71-positive cases (14.78%) and 177 CoxA16-positive cases (24.69%). A total of 56 288 doses of EV71 vaccines were administered in Wuxing District from 2017 to 2021, with an annual average full-dose vaccination rate of 14.87%. The detection of EV71 infection was significantly lower after EV71 vaccination than before vaccination (4.49% vs. 24.93%; χ2=62.932, P<0.001).@* Conclusions @#The incidence of HFMD peaks in summer and winter among children under 6 years in Wuxing District, which predominantly occurs among children at ages of 1 to 3 years. The incidence of HFMD is high in Zhili Township, Yangjiabu Street and Balidian Township, and the number of EV71-positive cases significantly reduces after EV71 vaccination than before vaccination.
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Objective:To evaluate the association of microsatellite status with clinicopathological features of colorectal cancer patients after surgery.Methods:In total,572 colorectal cancer cases with clear pathological diagnosis and clinicopathological features from the Department of Pathology,Nanjing Drum Tower Hospital from June 2014 to June 2017 were included in the study.Microsatellite status and RAS mutations were detected by polymerase chain reaction.Ki67,EGFR,MGMT,and Lgr5 were detected by immunohistochemis-try.Clinicopathological features were analyzed based on the microsatellite states.Results:In this study,we found MSI-H in 7.0% of all patients,whereas 93.0% cases showed MSS/MSI-L.Compared with MSS and MSI-L colorectal cancer cases,MSI-H colorectal cancer cases showed the following characteristics:1)more likely located in the right colon,2)comparable incidences at different ages,3)ear-ly cancer stage(Ⅰ/Ⅱ)(P=0.003),4)a lower proportion of lymph node metastasis(P=0.023),5)a lower proportion of cancerous nod-ules(P=0.005),6)a lower mutation rate of KRAS(P=0.004),and no mutation of NRAS.There was no significant difference in the posi-tive rates of MGMT,EGFR,Lgr5,and Ki67 between the two groups.Conclusions:Compared with MSS/MSI-L patients,MSI-H patients have specific clinicopathological features.A lower mutation rate of KRAS/NRAS and higher methylation rate of MGMT were also found in MSI-H patients.Our results provide a basis for individual diagnosis and treatment in colorectal cancer.
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Purpose To investigate the expression of mismatch repair proteins MLH1,MSH2,MSH6 and PMS2 and their clinical significance in colorectal cancer.Methods Immunohistochemical analysis was used to detect MLH1,MSH2,MSH6 and PMS2 protein expression in formalin-fixed paraffin-embedded tissues from 102 colorectal cancer patients,and microsatellite instability (MSI) was tested in 20 cases.The relationship between MMR protein expression and clinical pathological features was also analyzed.Results 15 cases (14.7％) had MMR protein loss.The loss rate of MLH1,MSH2,MSH6 and PMS2 protein was 12.7％ (13/102),3.9％ (4/102),4.9％ (5/102) and 10.8％ (11/102),respectively.MLH1,MSH2,MSH6 and PMS2 protein losses were not related with gender,age,tumor size,depth of invasion and lymph node metastasis (P ＞ 0.05).MLH1 and PMS2 protein losses were related to histological differentiation (P ＜0.05).MSI was detected in 10 Lynch syndrome candidates.2 cases (2.0％)of high-frequency microsatellite instability (MSI-H) were identified,and the remaining 8 cases were MSS.However,10 cases without MMR expression abnormality all showed MSI-L/MSS.Conclusion Immunohistochemical detection of MLH1,MSH2,MSH6 and PMS2 can be used as primary screening for Lynch syndrome and its combination with MSI test can effectively increase the diagnostic rate in Lynch syndrome.
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OBJECTIVE:To establish a method for the content determination of Aciclovir cream. METHODS:Centrifugal parti-tion chromatography(CPC)was conducted. The solvent system was hexane-acetonitrile-water(2∶1∶1,V/V/V),the injection vehicle was an aqueous solution of 5%Tween 80 and the volume was 1.0 ml;the flow rate was 5 ml/min;the wavelength was 254 nm. RE-SULTS:There was a good linear relationship between quality concentration and peak area in the range of 0.012 7-0.126 7 mg/ml (r=0.998 7). The RSD of precision,stability and reproducibility tests was all no more than 2.0% and the average recovery was 97.34%(RSD=0.90%,n=9). CONCLUSIONS:The method is with high precision and accuracy,and can be used for the content determination of principal components of Aciclovir cream.
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Objective:To establish an HPLC method for the determination of related substances in enalapril maleate dispersible tablets.Methods:AKromasil100-SC8(250mm×4.6mm,5μm)columnwasused. ThemobilephaseAwas0.01mol·L-1potassi-um dihydrogen phosphate (adjusting pH to 2. 2 with phosphoric acid) and mobile phase B was acetonitrile with gradient elution,and the flow rate was 1. 0 ml· min-1 . The detection wavelength was 215nm,the column temperature was 40℃,and the injection volume was 20 μl. Results:The linear range of enalaprilat,enalapril maleate and eanlapril diketopiperazine was 14.64-43.92 μg·ml-1(r =0. 999 8), 9. 29-27. 87 μg·ml-1(r=0. 999 1)and 10. 80-32. 40 μg·ml-1(r=0. 999 5), respectively. Enalaprilat was not detec-ted out and enalapril diketone was 0. 2% using the method described in Chinese pharmacopeia, and the content of enalaprilat was 0. 1% and that of enalapril diketone was 0. 2% using the gradient elution. The related substances and enalapril maleate could be sepa-rated well. Conclusion:The method is sensitive, accurate and highly specific in the quality evaluation and control.
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A number of medications have been proved to be able to either improve the antitumor effect of chemotherapeutics and molecular targeted drugs or reverse the resistance of tumors to chemotherapeutics and molecular targeted drugs,which are not traditionally used as anticancer drugs.Especially for late-stage tumors after multiple treatments,these agents are good alternatives when used independently or in combination with chemotherapeutics and molecular targeted drugs.These drugs include proton modulators,hypoglycemic agents and cardiovascular agents,etc.
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Objective To evaluate the significance of COLD-PCR in detecting KRAS mutation of pancreatic cancer and colorectal cancer patients. Methods First, set up COLD-PCR and compared the sensitivities of COLD-PCR/Sanger sequencing with PCR/Sanger sequencing using mixed cell lines ( KRAS wild-type cell line SW116 and KRAS mutant cell line SW480).Then, detected KRAS mutation of 20 formalin-fixed paraffin-embedded samples of pancreatic cancer and 39 formalin-fixed paraffin-embedded samples of colorectal cancer using PCR/Sanger sequencing and COLD-PCR/Sanger sequencing, respectively and compared the coincidence rate and consistency. Results The low detection limits of PCR/Sanger respectively. KRAS frequency detected by COLD-PCR/Sanger sequencing [75% (15/20)] in 20 cases of pancreatic cancer was higher than that detected by regular PCR/Sanger sequencing [40% ( 8/20 ) ,x2 =5.013, P < 0.05]. KRAS frequency detected by COLD-PCR/Sanger sequencing [44% (17/39)] in 39 cases of colorectal cancer was higher than that detected by regular PCR/Sanger sequencing [31% (12/39) ,x2 =1. 372, P = 0. 174]. The coincidence rate of these two methods was 0. 730 and the difference had no statistical significance. The coincidence rate of detecting KRAS mutation was 65% in pancreatic cancer and the results showed a good correlation between two methods and the two methods had bad agreement in diagnosis (Kappa = 0. 364, P < 0. 05 ). COLD-PCR/Sanger sequencing could detect more cases of KRAS mutations from pancreatic caner than regular PCR/Sanger sequencing. This was because there were many non-tumor cells in pancreatic tumor tissue and COLD-PCR/Sanger sequencing was more sensitive than regular PCR/Sanger sequencing. The coincidence rate of detecting KRAS mutations was 87% in colorectal cancer and the results were showed a good correlation between two methods and the two methods had substantical agreement in diagonsis ( Kappa = 0. 730, P < 0. 05 ) . Conclusion COLD-PCR/Sanger sequencing is highly sensitive to screen KRAS mutation in pancreatic cancer and colorectal cancer patients.
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Objective:The aim of this study was to investigate the association of mRNA expressions of ERCC1 (excision repair cross-complementing group 1) and BRCA1 (breast cancer 1) with chemosensitivity to cisplatin in malignant pleural and peritoneal effusions.Methods:Malignant pleural and peritoneal effusions were collected from 46 patients diagnosed with stage Ⅳ malignant tumor, prospectively. The tumor cells were isolated and the sensitivity of tumor cells to cisplatin was detected by adenosine triphosphate-bioluminescence assay (ATP-TCA). Real-time quantitative PCR was used to determine the mRNA expressions of ERCC1 and BRCA1. Results:The expression level of ERCC1 mRNA was negatively correlated with sensitivity of non-small cell lung cancer (NSCLC) to cisplatin (P= 0.001, r=0.685). BRCA1 mRNA expression level had negative correlation with sensitivity to cisplatin in both NSCLC (P=0.014, r=0.541) and gastric cancer (P=0.002, r=0.625). A significant interaction was found between the effects of ERCC1 and BRCA1 mRNA expressions on sensitivity to cisplatin (P=0.010 for all patients;P=0.027 for gastric cancer patients).Conclusion:ERCC1 and BRCA1 mRNA expression levels correlated with ex vivo chemosensitivity of tumor cells to cisplatin in malignant pleural and peritoneal effusions. Detection of both ERCC1 and BRCA1 may have a higher reliability in predicting the sensitivity of tumor cells to cisplatin than detection of single ERCC1 or BRCA1 expression.
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Background and purpose: It has been reported that some low dose chemotherapy drugs have antiangiogenetic effects. The purpose of this study was to investigate the effect of inhibiting angiogenesis by low dose hydroxycamptothecin on H22 hepatoma transplantation tumor mouse models. Methods: H22 transplantation tumor mouse models were established, CTX was administrated in abdominal cavities as positive control group. 0.9%NaC1 solution was administrated as negative control group. Intra abdominal cyclophosphamide and hydroxycamptothecin (0.2 and 0.4 mg/kg) were injected for 10 days continuously. The growth of tumor were observed and measured. The tumor inhibitory rates were tested in animal tumor model with experimental treatment. The expression of VEGF and CD34 were measured by means of immunohistochemistry. Results: Hydroxycamptothecin had effect on tumor growth. Tumor weight inhibitory rates of hydroxycamptothecin with 0.2 and 0.4 mg/kg were 23.53% and 43.25% respectively. The difference was significant when compared with the negative control group (P<0.05). The expression of VEGF and MVD can be suppressed significantly than negative control group in vivo (P<0.05). Conclusion:Hydroxycamptothecin have inhibitory effect on tumor growth and the expression of VEGF and MVD with H22 hepatoma transplantation tumor mouse models in low dose. The mechanism possibly involved inhibiting the angiogenesis.
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Objective To investigate the relationship between the levels of intedeukin(IL)-6, IL-15 and endometriosis (EM). Method The levels of IL-6, IL-15 in the peritoneal fluid (PF) and serum of 74 patients with EM (EM group) and 46 patients without EM (control group) were measured by double-an-tibody ELISA. Results Higher levels of IL-6 in PF and serum were observed in EM group [(1017.81±361.98) ng/L,(455.47±161.52) ng/L]than those in control group [(284.63±70.50) ng/L,(149.37± 43.09) ng/L], and there was significant difference (P<0.01). The levels of IL-6 in PF and serum in EM group with stage Ⅲ-Ⅳ [(1253.44±189.63) ng/L, (556.50±93.34) ng/L]were significantly higher than those in patients with stage Ⅰ-Ⅱ [(582.81±107.75) ng/L, (268.96±63.48) ng/L](P < 0.01). There was positive relationship between the levels of IL-6 in PF and serum (r=0.950, P=0.01). The levels of IL-15 in PF in EM group [(333.45±63.94) ng/L]were significantly higher than those in control group[(203.85± 70.52) ng/L](P<0.01). No significant difference was found in the levels of serum IL-15 between EM group and control group (P>0.05). No significant difference was observed either in the levels of IL-15 in PF and serum between patients with stsge Ⅲ-Ⅳ and stage of EM Ⅰ-Ⅱ (P>0.05). Conclusions The increase of IL-6, IL-15 in PF may contribute to the development of EM. Serum IL-6 levels are of clinical diagnostic value in patients with EM.
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OBJECTIVE:To improve the quality of pharmaceutical care and to provide bases for outpatients and medical staff in drug informatin inquiry.METHODS:Information about drug package inserts wre collected and the drug-inquiry system was designed using the database management function of Access.RESULTS & CONCLUSIONS:The drug-inquiry system is easy to operate,clear in interface,humanization in operation,and it faciliats individualized drug information inquiry through daily mantinance and satisfies the requirments for outpatient drug information inquiry.
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As an emerging tumor therapy, high intensity focused ultrasound (HIFU) therapy has difficulty in controlling its dosage due to the complex human tissues. The dosage is related to the tumor such as its depth, size, characteristics and the tissue performances of its growth site. The existing cases are applied to establishing a repository with the above-mentioned parameters of the tumor analyzed. Then reasoning and self-learning are performed. So, the therapeutic dosage can be provided to the clinician when a new case occurs.
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There are many noise disturbances in ultrasound image, and the surgical treatments are in great request for medical image, but the three dimensional image based on traditional surface graphics method cannot satisfy the request. Nevertheless, researches on visualization technology involves the denotation, operation and vision of the volume data the object contains, and the volume data contains ampler and more intact information than does the surface, therefore visualization technology will be widely used in the field of three dimensional medical image.
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Humans , Computer Graphics , Computer Simulation , Diagnostic Imaging , Methods , Image Processing, Computer-Assisted , Methods , Imaging, Three-Dimensional , Software , Systems Integration , UltrasonographyABSTRACT
Objective: To investigate the effect of tumor specific antigen of HCA520 on the proliferation of HEK293 cells and to obtain some functional implications for HCA520. Methods: MTT assay was performed with HEK293 stable cell lines transfected with pcDNA3-HCA520-flag construct. Cytokines probably involved in HCA520 enhanced proliferation were screened by RT-PCR, and effect of these cytokines on the HEK293 cell proliferation was further confirmed by MTT assay. Results: HCA520 significantly promoted the proliferation of HEK293 cells, which was at least partially attributed to the up-regulation of IL-6 in HEK293 cells by HCA520. Conclusion: HCA520 might accelerate tumorigenesis by promoting proliferation of cancerous cells.
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0.05), but they did at 48 h(P
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Erythrocytes, the most abundant cells in human body with excellent physiologic and morphologic characteristics, have been exploited extensively for their potential applications as drug delivering microspheres for several potential applications, including intravenous slow release of therapeutic agents, enzyme replacement therapy and drug targeting therapy. A series of methods has been tested successfully for the improvement of targeting to reticuloendothelial system.
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Objective:To get a rapid and stable method of induction of rapid cultivation and maturation of Dendritic Cells(DC) from human peripheral blood in vitro.Methods:Cultured plastic-adherent monocytes were isolated from tumor patient peripheral blood mononuclear cells and GM-CSF(1 000 u/ml),IL-4(500 u/ml) were added in the cells at 0 h,which were separated into four groups.Poly(I ∶ C)(Polyriboinosinic Polyribocytidylic Acid) were added in the first group cells at 24 h and the DC cells were collected at 48 h;TNF-? in the second group cells were added at 24 h and the cells were collected at 48 h;Poly(I ∶ C) were added in the third group cells at 36 h and the cells were collected at 72 h;TNF-? were added in the last group cells at 36 and the cells were collected at 72 h.Results:The results of flow cytometer showed that the third group got the most mature DC.The dendritic cells from the third group have significant stimulatory activity in allogeneic lymphocyte proliferation.Conclusion:The method of rapid cultivating and maturating of Dendritic Cells from human peripheral blood in vitro induced by Poly(I ∶ C) is rapid,stable,economical and simple.It may facilitate future studies of DC and its clinical application.
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Background and purpose:The growth,metastasis,relapse and the prognosis of tumor are correlated with tumor angiogenesis.Therefore,target to angiogenesis and antiangiogenic therapy has become one of the hot points in cancer research field.Some chemotherapeutic drugs can inhibit the growth of new vascular endothelial cell markedly in the way of low-dose and high time administration.This is metronomic chemotherapy or antiangiogenic chemotherapy.Traditional Chinese medicine has an effect on tumor control.In recent years,we discovered that some traditional Chinese medicine have an antiangiogenic effect.This experiment aimed to study the antiangiogenetic ability of oxaliplatin combined with composite radix sophora flavescentis injection(CRSFI) in vitro and in vivo. Methods :We used MTT method to observe the influence of oxaliplatin and composite radix sophora flavescentis injection on human umbilical vein endothelial cells(HUVEC) or LoVo proliferation.The influence of oxaliplatin and composite radix sophora flavescentis injection on HUVEC migration was evaluated by transwell.Chick embryo chorioallantoic membrane(CAM)model was used to check whether the neovascularization of CAM could be suppressed in vivo by them. Results :The survival rate of LoVo within the same doses of oxaliplatin and composite radix sophora flavescentis injection were higher than HUVEC.Oxaliplatin(2 ?g/ml) and composite radix sophora flavescentis Injection(25 ?l/ml) could inhibit the prolifetation of HUVEC;the rate of inhibition were 31.6%,32.1% respectively;the rate of the two drugs combination was 54.4%.So when combined,they had synergistic effect.There was coordinate repression to migration of HUVEC in vitro when we used oxaliplatin(0.5 ?g/ml) and composite radix sophora flavescentis injection(6.25 ?l/ml).They also suppressed angiogenesis of CAM in vivo. Conclusions :This experiment showed that low dose oxaliplatin combined with composite radix sophora flavescentis injection has anti-angiogenic synergetic ability in vivo and the ability of inhibiting the growth of the cells in vitro.
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Purpose:To study the effects of hydroxycamptothecin with thermotherapy on anti-angiogenesis in vitro and in vivo. Methods:We chose human microvascular endothelial cell (HMVEC) culture and chick embryo choriallantoic membrane (CAM) model and used MTT and number-calculating methods to observe hydroxycamptothecine on HMVEC’s proliferation , sprouts and CAM blood vessels’ formation.Results:The survival rate of endothelial cells was in the range of (68.2%)-44.7% within the dose of 20-40 ng/ml and 5-80 ng/ml and was negatively correlated with the concentration (correlation coefficient was -0.906,-0.469,P=0.00003,0.0051). Hydroxycamptothecine could significantly suppress the endothelial cells’ proliferation and the sprouts. Hydroxycamptothecine could significantly suppress CAM vessels. The survival rate of HepG II cells is in the range 100%-90% within the dose of 5-80 ng/ml. There was no cytotoxicity.There was a synergestic anti-angiogenetic effect when hydroxycamptothecin (20 ng/ml) was combined with thermotherapy in vitro while there was additive effect when hydroxycamptothecin (40 ng/ml) was combined with thermotherapy in vitro.Conclusions:This experiment shows that small doses of hydroxycamptothecine (20-40 ng/ml) with thermotherapy has anti-angiogenetic synergestic or additive effect on proliferation and migration both in vivo and in vitro.