Objective To evaluate the clinical effect of levocarnitine in the treatment of continuous blood purification and its effect on matrix metalloproteinase-2(MMP-2),interleukin-18(IL-18)and heart function.Methods 118 patients with continuous blood purification were randomly divided into the control group(n=59)and treatment group group(n=59).Two groups were treated with hemodialysis treatment.Control group was given folic acid,vitamin B and alpha keto acid,treatment group intravenous given levocarnitine injection 20mg/kg+0.9％NaCl 20mL on the basis of control group.A cycle of treatment was 28 days,and treated for 3 cycles.Serum levels of MMP-2 and IL-18,heart function,clinical effect and adverse drug reaction were compared between the two groups.Results After treatment,the total effective rate in control group was 84.74％,lower than 94.92％in treatment group(P<0.05).After treatment,serum MMP-2,IL-18,left atrial diameter(LAD),left ventricular end diastolic diameter(LVDd),left ventricular posterior wall thickness(LVPWT),ventricular septal thickness(IVST),left ventricular volume index(LVMI)in two groups were lower than pre-treatment(P<0.05),and the indexes in treatment group were more lower than control group(P<0.05).The E/A and left ventricular ejection fraction(LVEF)in two groups were all increased after treatment,and those in treatment group were higher than control group,the differences were significant(P<0.05).There was no significant in the incidence rate of adverse drug reactions between two groups.Conclusion Levocarnitine in the treatment of continuous blood purification was effective,and significantly reduce the serum MMP-2,IL-18 level and improve the heart function.

Objective To screen the 12 mers-phage random peptide library using the serum from the new model rabbit and to identify the immuno-protection of the positive phages. The new model infected with Schistosoma japonicum was proved that has a high protection against the challenge infection. Methods After being absorbed by E.coli antibody, the serum of the new model rabbit was used to screen the peptide library. Through three rounds of biopaning and enriching, lots of positive phages were obtained and their antigenic ability was tested. Every mouse was immunized by subcutaneously injecting 1?10 14 pfu positive phages from the new model rabbit serum respectively at 0-2-4 th week. After 4 weeks of the last immunization, the challenge infection was performed. At the same time, several control groups including the group immunized with the phages from the rabbit serum of the normal model infected with Schistosoma japonicum, the group immunized with the original 12 mers-phage random peptide library and the control group of challenge infection were arranged. Results ①The positive clones of phage(1?10 14) from the new model rabbit serum were strongly recognized by the rabbit serum of the new model, weakly recognized by the rabbit serum of the normal model infected with Schistosoma japonicum,but not recognized by the serum of healthy rabbit. ②The reduction rate of adult worms and liver eggs induced by phages screened with the rabbit serum of the new model group and the nomal model group and that induced by the original peptide library were respectively 27 2% and 38 8 %, 17 8% and 35 0%, 4 5% and 6 0% Conclusion The new model group obtained a higher reduction rate of adult worms than the nomal model group (P

Objective To study the immuno-protective effect against Schistosoma japonicum challenge of the positive monoclonal phages which were screened from the 12 mers-phage random peptide library by the new model rabbit serum. Methods The new model was established by injecting the Schistosoma japonicum infection rabbits with inhibitor of phenol oxidose. Positive clones immunoscreened with the new model rabbit sera were absorbed by SEA immune rabbit sera, and 14 clones selected randomly from them were compared and their antigenic ability was identified by ELISA. The two best positive monoclonal phages (No.8, No.13) recognized by the new model rabbit sera were selected to immunize Kunming mice by subcutaneously injecting 1?10~15 pfu positive phages at 0, 2nd, 4th week respectively. After 4 weeks of the last immunity,each mouse was challenged with 40?1 S.japonicum cercariae. All mice were sacrificed after 42 days and the reduction rates of adult worms and the liver eggs were investigated. Results The positive phage clones after immune absorption were weakly recognized by the SEA immune rabbit sera. The 14 monoclonal phages were recognized by the rabbit sera of the new model and the normal model. Especially No.8, No.13 were strongly recognized by the rabbit sera of the new model,while weakly recognized by the SEA immune rabbit sera. The reduction rates of adult worms and liver eggs induced by the monoclonal phage No.13, the monoclonal phage No.8 and the original peptide library were 35.81% and 63.32%, 32.09% and 52.02%, 14.90% and 30.64%, respectively. Conclusion Most clones of simulated epitopes of SEA can be removed by absorbing positive clones with SEA immune rabbit serum .The 14 monoclonal phages from the new model contain the simulated S.japonicum epitope. The two monoclonal phages have higher reduction rates of adult worms and eggs than original 12 mers-phage random peptide library and the positive polyclonal phages.[

Objective To observe the influencing of Yiqi Huayu Jiedu Prescription on the growth of HepG2 nude mice transplantation tumor and the expression of related factors of vascular mimicry. Methods Models of transplanted tumors, which were made by HepG2 cells in nude mice, were randomly divided into 7 groups, Yiqi Huayu Jiedu Prescription group, Astragali Radix group, Curcumae Rhizoma group, Paridis Rhizoma group, Gecko group, cis-platinum group, and model group. Except for the model group, the rest groups were given relevant medicine for intervention. 21 days later. HIF-1α, MMP-2, MMP-9, and E-cad were detected by immunohistochemistry, and Twist1 and Bcl-2 were detected by fluorescence quantitative PCR. Results Compared with the model group, tumor volume in the rest groups decreased (P<0.05), and the effect in the Yiqi Huayu Jiedu Prescription group was more obvious than the Astragali Radix group, Paridis Rhizoma group and Gecko group (P<0.05);The expression of vasculogenic mimicry structure was rare in each group, and the model group and cis-platinum group were the most obvious;Except for the Astragali Radix group, the expressions of HIF-1α, MMP-2, and MMP-9 showed statistical significance compared with model group (P<0.05);The expression of E-cad in the Yiqi Huayu Jiedu Prescription group and Astragali Radix group showed statistical significance (P<0.05);The expression of Bcl-2 in the Yiqi Huayu Jiedu prescription group, Paridis Rhizoma group, and Gecko group decreased significantly compared with the model group (P<0.05);The expression of Bcl-2 in the Yiqi Huayu Jiedu prescription group was much better than the other groups (P<0.05);The expression of Twist1 showed statistical significance in the Yiqi Huayu Jiedu Prescription group, Curcumae Rhizoma group, Paridis Rhizoma group, and cis-platinum group (P<0.05). Conclusion Yiqi Huayu Jiedu Prescription can reduce expression of HIF-1α, Twist1, Bcl-2, MMP-2, and MMP-9, and increase expression of E-cad, thereby inhibiting the formation of vascular mimicry.

Objective:Meta analysis was used to evaluate the diagnostic value of miRNA-25 in different malignant tumors in Chinese population.Methods:The research on the diagnostic value of miRNA-25 in China national knowledge internet (CKNI), VIP, Wanfang, PubMed and EMBase was searched. The publication time was from the establishment of database to October 2019. After the data was extracted, the Meta.DiSc1.4 software was used for preliminary statistical analysis. The Review Manager 5.3's QUADAS-2 tool was used for quality control of the incoming literature. The STATA 15.0 software was used to analyze whether there was publication bias.Results:A total of 10 articles were included in the study, including 792 cases in the case group and 715 cases in the control group. The combined sensitivity, combined specificity, combined specificity, combined positive likehood ratio(PLR), negative likehood ratio (NLR) were 0.71(95% CI: 0.69-0.74), 0.84(95% CI: 0.81-0.86), 4.29(95% CI: 3.39-5.42), 0.35(95% CI: 0.31-0.40), respectively. Diagnostic odds rate (DOR) was 13.09(95% CI: 9.64-17.78), and the area under curve (AUC) was 0.80(95% CI: 0.77-0.84). Subgroup analysis showed that the diagnostic value of miRNA-25 for different malignant tumors suggested that the lung cancer group had the highest diagnostic value and specificity (DOR=16.418, SPE=0.863). Funnel plot indicated that no significant publication bias was found ( P=0.21). Conclusions:miRNA-25 is highly sensitive and specific to different malignancies, especially lung cancer, and can be used as a potential screening biomarker to assist diagnosis.

Cancer is a prevalent and challenging disease that is difficult to treat.Western medicine recognizes the disruption of the immune and inflammatory microenvironment as a crucial factor in the development and progression of cancer.According to traditional Chinese medicine,cancer falls into the categories of"accumulation"and"abnormal masses".Based on the attributes of cold and heat in the overall and local conditions as well as the characteristic of the struggle between the vital qi and pathogenic factors at different stages of this disease,this article proposes the concept of"body coldness and tumor heat"to describe the pathogenesis of cancer formation and progression.This pathogenesis aligns with the disruption of the immune and inflammatory microenvironment in modern medical oncology.The article suggests a treatment approach that focuses on balancing cold and heat,nourishing and protecting yang qi,warming the kidneys,and strengthening the spleen to address the"coldness of the entire body".This approach also involves promoting qi circulation,eliminating dampness,phlegm,and stasis,and detoxifying and dispersing nodules to address the"heat in the tumor locally".By addressing deficiencies,eliminating pathogenic factors,and promoting circulation to alleviate stagnation,the aim is to restore the balance of yin and yang and improve the complex state of"coldness of the entire body"and"heat in the tumor locally".These interventions can ameliorate the disorder in the microenvironment and enhance clinical efficacy.

Objective:To study the biological behavior of nasopharyngeal carcinoma stem cells and to explore the activation of Ras signaling pathway regulated by CD44.Methods:CNE2-SC and 5-8F-SC were nasopharyngeal carcinoma stem cells and obtained by serum-free suspension culture. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, cell adhesion array were used to investigate the growth, proliferation, migration and adhesion of nasopharyngeal carcinoma stem cells. Western blot test was used to detect the expressions of Ras signaling pathway related proteins and siRNA-mediated interference was used to determine the activation of Ras signaling pathway regulated by CD44.Results:The growth rates of CNE2-SC and 5-8F-SC cells were significantly lower than those of nasopharyngeal carcinoma cells at 24, 48 and 72 hours after inoculation ( P<0.05). After 14 days of implantation, the colony formation rates of CNE2-SC (44.5±1.9)% and 5-8F-SC (47.4±1.8)% were higher than those of CNE2 (34.9±1.5)% and 5-8F (37.2±1.7)%, respectively( P<0.01). The migration cell number of CNE2-SC was (87.6±7.8), 3.97 times higher than that of CNE2 ( P<0.01). The migration cell number of 5-8F-SC was (67.2±5.7), 3.07 times higher than 5-8F ( P<0.01). The adhesion rates of CNE2-SC and CNE2 cells were (42.1±7.6)% and (8.9±2.0)%, respectively at 3 hours after inoculation and were (82.4±5.0)% and (12.1±2.2)% at 6 hours after inoculation, respectively. The adhesion rate of CNE2-SC cells was higher than that of CNE2 cells (all P<0.01). The adhesion rates of 5-8F-SC and 5-8F cells were (53.6±6.1)% and (7.3±1.5)% at 3 hours after inoculation, and (90.7±3.6)% and (11.0±1.2)% at 6 hours after inoculation, respectively. The adhesion rate of 5-8F-SC cells was higher than that of 5-8F cells ( P<0.01). The expression levels of CD44, Ras and N-cadherin were significantly higher, while phosphatase and tensin homolog deleted on chromosome 10 (PTEN), E-cadherin in nasopharyngeal carcinoma stem cells were lower than those of the nasopharyngeal carcinoma cells. Furthermore, the levels of phosphorylated mitogen extracellular kinase1/2 (p-MEK1/2) and phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2)were significantly increased in nasopharyngeal carcinoma stem cells ( P<0.01). Correlation analysis showed that the protein expression levels of CD44 was highly positively correlated with RAS in nasopharyngeal carcinoma stem cells( r=0.985, P=0.002; r=0.962, P=0.038). Deletion of CD44 in CNE2-SC decreased the expression levels of HER-2, Ras and p-ERK1/2, p-Akt and phosphorylated protein kinase C-δ(p-PKCδ) ( P<0.01). Conclusions:Despite compare to the nasopharyngeal carcinoma cell, nasopharyngeal carcinoma stem cells grows at a relatively slow rate, the capacities of clone formation, migration, adhesion are promoted. This may be related to the CD44-regulated abnormal activation of Ras signaling pathway.

Objective:To study the biological behavior of nasopharyngeal carcinoma stem cells and to explore the activation of Ras signaling pathway regulated by CD44.Methods:CNE2-SC and 5-8F-SC were nasopharyngeal carcinoma stem cells and obtained by serum-free suspension culture. Cell counting kit-8 (CCK-8) assay, colony formation assay, Transwell migration assay, cell adhesion array were used to investigate the growth, proliferation, migration and adhesion of nasopharyngeal carcinoma stem cells. Western blot test was used to detect the expressions of Ras signaling pathway related proteins and siRNA-mediated interference was used to determine the activation of Ras signaling pathway regulated by CD44.Results:The growth rates of CNE2-SC and 5-8F-SC cells were significantly lower than those of nasopharyngeal carcinoma cells at 24, 48 and 72 hours after inoculation ( P<0.05). After 14 days of implantation, the colony formation rates of CNE2-SC (44.5±1.9)% and 5-8F-SC (47.4±1.8)% were higher than those of CNE2 (34.9±1.5)% and 5-8F (37.2±1.7)%, respectively( P<0.01). The migration cell number of CNE2-SC was (87.6±7.8), 3.97 times higher than that of CNE2 ( P<0.01). The migration cell number of 5-8F-SC was (67.2±5.7), 3.07 times higher than 5-8F ( P<0.01). The adhesion rates of CNE2-SC and CNE2 cells were (42.1±7.6)% and (8.9±2.0)%, respectively at 3 hours after inoculation and were (82.4±5.0)% and (12.1±2.2)% at 6 hours after inoculation, respectively. The adhesion rate of CNE2-SC cells was higher than that of CNE2 cells (all P<0.01). The adhesion rates of 5-8F-SC and 5-8F cells were (53.6±6.1)% and (7.3±1.5)% at 3 hours after inoculation, and (90.7±3.6)% and (11.0±1.2)% at 6 hours after inoculation, respectively. The adhesion rate of 5-8F-SC cells was higher than that of 5-8F cells ( P<0.01). The expression levels of CD44, Ras and N-cadherin were significantly higher, while phosphatase and tensin homolog deleted on chromosome 10 (PTEN), E-cadherin in nasopharyngeal carcinoma stem cells were lower than those of the nasopharyngeal carcinoma cells. Furthermore, the levels of phosphorylated mitogen extracellular kinase1/2 (p-MEK1/2) and phosphorylated extracellular signal-regulated protein kinase1/2 (p-ERK1/2)were significantly increased in nasopharyngeal carcinoma stem cells ( P<0.01). Correlation analysis showed that the protein expression levels of CD44 was highly positively correlated with RAS in nasopharyngeal carcinoma stem cells( r=0.985, P=0.002; r=0.962, P=0.038). Deletion of CD44 in CNE2-SC decreased the expression levels of HER-2, Ras and p-ERK1/2, p-Akt and phosphorylated protein kinase C-δ(p-PKCδ) ( P<0.01). Conclusions:Despite compare to the nasopharyngeal carcinoma cell, nasopharyngeal carcinoma stem cells grows at a relatively slow rate, the capacities of clone formation, migration, adhesion are promoted. This may be related to the CD44-regulated abnormal activation of Ras signaling pathway.

Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide (As2O3) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As (iAsIII) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by As2O3 exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, Na+-K+ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of As2O3 exposure. AST showed a significant protective effect against As2O3-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to iAsIII from natural sources or cancer therapy.
Adenosine Triphosphatases ; Administration, Oral ; Animals ; Arsenic ; Humans ; Kidney ; Leukemia, Promyelocytic, Acute ; Oxidative Stress ; Rats ; Rats, Wistar*

ObjectiveTo study the effect of Jianpi Xiaoai prescription on the protein expression of metastasis-related factors in tumor microenvironment such as chemokine receptor 4 （CXCR4）， transformation growth factor-β （TGF-β）， integrin a_v β₅ （ITGα_v β₅）， serum calcium-binding protein A4 （S100A4）， serum calcium-binding protein A8 （S100A8）， and serum calcium-binding protein A9 （S100A9） in the liver tissue of the nude mouse model of liver metastasis of colon cancer， and to explore the possible mechanism of its anti-liver metastasis of colon cancer. MethodBALB/c nude mice were randomly divided into blank group， model group， and Jianpi Xiaoai prescription low， medium， and high-dose groups. A nude mouse model of liver metastasis of human colon cancer was established. Jianpi Xiaoai prescription low， medium， and high-dose groups were given 5.4， 10.8， 21.6 g·kg^-1 liquid medicine， respectively， and the model group and the blank group were given the same volume of distilled water by gavage， once a day for 3 consecutive weeks. 24 h after the last administration， the nude mice were sacrificed by neck removal， and the liver metastasis of each group was observed. Western blot was used to determine the protein expression of metastasis-related factors in the tumor microenvironment， such as CXCR4， TGF-β， ITGα_v β₅， S100A4， S100A8， and S100A9. ResultThe proportion of metastatic tumor area was 73% in the model group， 72% in the low-dose group， 55% in the medium-dose group， and 42% in the high-dose group. The high-dose group was significantly lower than the model group （P<0.05）. As compared with the model group， the expression of CXCR4， TFG-β， ITGα_v β₅， S100A8， and S100A9 in the Jianpi Xiaoai prescription high and medium-dose groups were significantly decreased （P<0.05）. As compared with the model group， the expression of S100A4 in the Jianpi Xiaoai prescription high， medium， and low-dose groups was significantly decreased （P<0.05）. The expression of CXCR4， TFG-β， ITGα_v β₅， S100A8， and S100A9 in the Jianpi Xiaoai prescription low-dose group was not significantly different from that in the model group. ConclusionJianpi Xiaoai prescription can inhibit liver metastasis of colon cancer， and its mechanism may be related to the reduction of the expression of metastasis-related factors such as CXCR4， TGF-β， ITGα_v β₅， S100A4， S100A8， and S100A9 in tumor microenvironment.