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Idiosyncratic drug-induced liver injury (IDILI) has long posed a challenging and pivotal concern in pharmaceutical research. The complex composition of traditional Chinese medicine (TCM) has introduced a bottleneck in current research, hindering the elucidation of the component basis associated with IDILI in TCM. Using Epimedii Folium (EF) and Psoraleae Fructus (PF) as illustrative examples, this study endeavors to establish an in vitro evaluation model, providing a high-throughput and preliminary assessment method for screening components related to TCM-induced IDILI. A TNF-α-mediated HepG2 susceptible model was first established in this study, with the focus on the index components present in EF and PF. The release of lactate dehydrogenase (LDH) in the cell supernatant served as the detection index. A concentration-toxicity response curve was constructed, and the hepatotoxic components of EF and PF were identified utilizing the synergistic toxicity index. The LDH results unveiled the hepatotoxic effects of bavachin, backuchiol, isobavachin, neobavaisoflavone, psoralidin, isobavachalcone, icarisid I, and icarisid II on both normal and susceptible cells, categorizing these 8 components as both direct hepatotoxicity components and idiosyncratic hepatotoxicity components. Bavachin and neobavaisoflavone exhibited no hepatotoxicity on normal cells but demonstrated significant effects on susceptible cells, designating them as potential idiosyncratic susceptible hepatotoxicity components. The study further delineated that 10 EF components and 3 PF components were direct immune-promoting hepatotoxicity components. Additionally, 14 idiosyncratic immune-promoting hepatotoxicity components were identified, encompassing 10 EF components and 4 PF components, with neobavaisoflavone, bavachinin, and isobavachin being potential idiosyncratic susceptible immune-promoting hepatotoxicity components. Synergistic toxicity index results indicated that 13 idiosyncratic immune-promoting hepatotoxicity components (except anhydroicaritin) combined with bavachin demonstrated synergistic hepatotoxicity on susceptible cells. Notably, 3 idiosyncratic susceptible immune-promoting hepatotoxicity components combined with bavachin exhibited synergistic hepatotoxicity, with neobavaisoflavone displaying the highest synergistic toxicity index and bavachinin the lowest. In summary, this methodology successfully screens hepatotoxic and immune-promoting hepatotoxic components in EF and PF, distinguishing the types of components inducing hepatotoxicity, evaluating the hepatotoxicity degree of each component, and elucidating the synergistic relationships among them. Importantly, these findings align with the characteristics of IDILI. The method provides an effective model tool for the fundamental research of TCM-related IDILI components.
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Objective: To investigate the effect and underlying mechanism of paeoniflorin on hippocampal neuron apoptosis induced by lead acetate. Methods: In September 2020, primary hippocampal neuronal cells were isolated and cultured from fetal rats, and identified using cellular immunofluorescent. MTT assay was used to measure the cell viability to determine the concentration and time of lead acetate-induced hippocampal neuron apoptosis. MTT was also used to evaluate the effect of paeoniflorin concentration on the apoptosis of hippocampal neurons induced by lead acetate. According to the results, different concentrations of paeoniflorin were selected to intervene hippocampal neuron cells, after 24 h, lead acetate was added to the cells, meanwhile, blank and model groups were set up, the content of reactive oxygen species (ROS) , superoxide dismutase (SOD) , lactate dehydrogenase (LDH) , malondialdehyde (MDA) and Caspase-3 were measured. Extracellular signal regulated kinase (ERK) , phosphorylated ERK (p-ERK) , p38 mitogen -activated protein kinases (p38MAPK) , phosphorylated p38MAPK (p-p38MAPK) , c-Jun N-terminal kinase (JNK) and phosphorylated JNK (p-JNK) protein expression in hippocampal neuronal cells were determined by Western blotting. Results: The isolated and cultured hippocampal neurons were identified by immunofluorescence chemical staining and then treated with lead acetate, MTT results showed that lead acetate had the best toxicity effect when treated for 24 h at a concentration of 25 μmol/L. Paeoniflorin showed no cytotoxic effect on hippocampal neuronal cells when the concentrations below 80 μmol/L. Compared with the model group, the activity of hippocampal neuronal cells was significantly increased after treating with 20, 40 or 80 μmol/L paeoniflorin (P<0.05) . Compared with the blank group, the ROS activity, LDH release level, MDA content and caspase-3 content were significantly increased (P<0.01) , and the SOD activity was significantly decreased (P< 0.01) in the hippocampal neuronal cells of the model group. Compared with the model group, the ROS activity, LDH release level, MDA content and caspase-3 content were obviously decreased (P<0.05) , SOD activity was significantly increased (P <0.01) after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin. Relative to the model group, the ratio of p-ERK/ERK were significantly up-regulated (P<0.01) , while the ratios of p-p38MAPK/p38MAPK and p-JNK/JNK were significantly down-regulated after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin (P<0.05) . Conclusion: Paeoniflorin may down-regulate the expression of p-p38MAPK and p-JNK protein, up-regulate the expression of p-ERK protein, and inhibit the apoptosis of hippocampal neurons induced by lead acetate through the MAPK signaling pathway.
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Animaux , Rats , Acétates/pharmacologie , Apoptose , Caspase-3/métabolisme , Extracellular Signal-Regulated MAP Kinases/métabolisme , Glucosides , Hippocampe/métabolisme , JNK Mitogen-Activated Protein Kinases/pharmacologie , Plomb , Monoterpènes , Neurones/métabolisme , Espèces réactives de l'oxygène/métabolisme , Superoxide dismutase/métabolisme , p38 Mitogen-Activated Protein Kinases/métabolismeRésumé
OBJECTIVE@#To investigate the characteristics of gene mutation in elderly patients with acute myeloid leukemia (AML) and its effect on prognosis.@*METHODS@#The clinical and laboratorial characteristics of 54 AML patients (≥60 years old) in Department of Hematology, Tangdu Hospital were analyzed retrospectively during April 2016 to October 2019. Thirty-four AML/myelodysplastic syndrome/myeloproliferative neoplasm related mutant genes were detected by second-generation sequencing technology, and their clinical characteristics, treatment effect, and influence on prognosis were analyzed.@*RESULTS@#All the patients received DAC+CAG induction treatment, after 1-2 couses of treatment, 36 cases (66.7%) achieved complete response, with a total effective rate of 75.9%, and the median survival time was 17 months. The most frequent mutant genes were TET2 (33.3%), CEBPA (31.5%), DNMT3A (18.5%), ASXL1 (16.7%), NRAS (14.8%), RUNX1 (14.8%), FLT3-ITD (12.9%), TP53 (12.9%), NPM1 (12.9%), and IDH2 (12.9%). Among 7 patients with TP53 mutation, 6 cases obtained complete response after 1-2 courses of induction treatment, but there was no statistically significant difference in the effect on prognosis. Patients with FLT3-ITD and NRAS mutations had shorter overall survival time compared with who had no mutation (P=0.47, P=0.48). Multivariate analysis showed that FLT3-ITD and NRAS mutations were poor prognostic factors.@*CONCLUSION@#The incidence of TET2 gene mutation is high in elderly AML patients. AML patients with TET2 and TP53 mutations may benefit from Decitabine-based chemotherapy. However, patients with FLT3-ITD and NRAS mutations have a short survival time, and may have a poor prognosis.
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Sujet âgé , Humains , Adulte d'âge moyen , Leucémie aigüe myéloïde/génétique , Mutation , Nucléophosmine , Pronostic , Études rétrospectives , Tyrosine kinase-3 de type fmsRésumé
OBJECTIVE@#To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML) patients with ASXL1 mutation.@*METHODS@#The clinical data of 229 newly diagnosed AML patients treated in our hospital from April 2016 to October 2019 were analyzed retrospectively. The next-generation sequencing technology was used to detect gene mutations in all the patients, the clinical characteristics of the patients with ASXL1 mutation were analyzed.@*RESULTS@#ASXL1 gene mutation was detected out in 45 patients(19.6%). Among these patients, the frameshift mutation (n=22,48.9%) was most common, followed by missense mutation (n=15, 33.3%) and nonsense mutation (n=8,17.8%), respectively, all of them were located at exon 12. The median mutation rate was 32.47%(range, 2.74%-53.50%). The median age of the patients with ASXL1 mutation was 54(range, 14-74) years old, and most of the patients were male, and most of them with the history of MDS or MPN, and low white blood cell count at the initial diagnosed (P<0.05). Patients with ASXL1 mutation showed a lower CR rate than that of without ASXL1 mutation. Patients with or without ASXL1 mutation showed a statistically significant difference in survival at 20 months (P=0.042), while there was no significant difference between the patients in the two groups over 20 months (P=0.505). All the 6 patients with ASXL1 mutation in low-risk group were survived, while the median OS time was 16 months in the high-risk group(P=0.034). Multivariate analysis showed that the history of MDS or MPN and CR rate from induction therapy were the independent risk factors affecting survival of the patients.@*CONCLUSION@#Frameshift mutation is commonly in AML patients with ASXL1 gene mutation, and ASXL1 mutation were more often in men, the history of MDS or MPN, and low white blood cell count. The CR rate of the patients with ASXL1 mutation was lower than that of the AML patients without ASXL1 mutations, AML patients with ASXL1 mutation showed poor short-term efficacy, but there was no significant difference between the two groups in long-term survival over 20 months.
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Adolescent , Adulte , Sujet âgé , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Leucémie aigüe myéloïde/génétique , Mutation , Pronostic , Protéines de répression/génétique , Études rétrospectivesRésumé
In recent years, the focus of anti-cancer agents has gradually shifted from cytotoxic chemotherapy to molecular-targeted agents that interfere with frequently overexpressed or mutated molecules in cancer cells. Compared with cytotoxic chemotherapy, molecular-targeted therapy is a new biological therapy with higher specificity and lower toxicity, however, the adverse reactions caused by molecular-targeted agents cannot be ignored. Diarrhea is one of the most common adverse drug reactions, which could seriously affect the quality of life and even lead to treatment discontinuation and consequently decreased cancer control. To provide a reference for relevant research and clinical medication, we review the current reports on the incidence, pathogenic mechanism, and management of diarrhea induced by the molecular-targeted agents.
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OBJECTIVE:s To investigate the prevalence, clinical features, risk factors and treatment of anemia in patients with stage3 a-5 D CKD at high altitude. METHODS: A total of 525 patients with stage3 a-5 D CKD admitted to Diqing Tibetan Autonomous Prefecture People's Hospital between Nov.2017 and Nov.2018 were enrolled in this cross-sectional study, and then categorized into 5 groups according to eGFR and whether depending on dialysis. Clinical and laboratory data were collected and analyzed to study the prevalence, clinical features, risk factors as well as the treatment of anemia in these CKD patients.RESULTS: Among 525 patients with stage3 a-5 D CKD(average age:59.2 ± 15.4 ys,CKD staging:stage3 a:n = 269;stage3 b:n=113;stage4:n=56;stage5:n=36;stage5 D:n=51),anemia was established in 233(44.4%)patients, 68.2% of which had mild anemia. The prevalence of anemie was 29%,33.6%64.3%,88.9% and 96.1,respectively from stage 3 a to stage 5 D, and the prevalence increased and the severity of anemia deteriorated with CKD progression, along with other clinical parameters including serum creatinine, albumin, uric acid,MDRD-eGFR, and calcium and phosphorus metabolism. Logistic regression analysis showed that advanced CKD stage(OR=2.206,P<0.001), hypoalbuminemia(OR=0.919,P=0.034), lower BMI(OR=0.868,P=0.012)and low serum calcium(OR=0.062,P=0.019)were independent risk factors for anemia in CKD patients at high altitude. Among 233 patients with anemia, only 37.7% had ever received treatment for anemia and the average hemoglobin concentration when initiating the treatment was(79.9±19.3)g/L. Erythropoietin was not widely used and the target-achieving rate was only 37.5%(33/88).CONCLUSION:s The prevalence of anemia increases with CKD progression in CKD patients at high altitude. Advanced CKD stage, hypoalbuminemia, lower BMI and low serum calcium are independent risk factors for anemia. The general situation of treatment for anemia is not good,with late starting time of treatment and low treatment rate,low rate in EPO use and low target-achieving rate,which should be paid affention to.
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The Lewis lung carcinoma (LLC) metastatic mouse model was used to investigate the effects of gefitinib and Sijunzi Tang (SJZ) on pre-metastatic niche. The experimental protocol was approved by the Ethics Committee which belongs to Cancer Hospital, Chinese Academy of Medical Sciences. To generate spontaneous lung metastatic models, 1×106 luciferase-labeled LLC cells were injected subcutaneously in the shaved right flank of mice. One day after LLC inoculation, the mice were randomly divided into model (saline), gefitinib (50 mg·kg-1) treatment, SJZ treatment (25.74 g·kg-1), and co-treatment gefitinib with SJZ groups, with intragastrical administration. After 14 days of continuous administration, tumor size was detected by IVIS® Spectrum system. The number of monocytes and neutrophils and the expression levels of chemokine receptors (CXCR1, CCR2) and carcinogenic gene (c-Kit), in peripheral blood, spleen and lung tissues of mice were determined by flow cytometry. The contents of interleukin-IL-1α (IL-1α) and interleukin-6 (IL-6) were detected by the enzyme linked immunosorbent assay (ELISA). After 21 days of treatment, tumors were surgically removed, weighed and the tumor volume was measured with vernier caliper and the antitumor effect of co-administration was evaluated. After 45 days of administration, the survival of mice was recorded. The results of flow cytometry showed that the percentage of neutrophils in gefitinib group, SJZ group, and co-treatment group was significantly decreased in the lung tissue compared to the model group (P<0.05 or P<0.01), but there was no significant difference between three treatment groups (P>0.05). In the mouse peripheral blood and lung tissue, compared with the model group, the expression levels of CXCR1, CCR2 and c-Kit on the surface of neutrophils and monocytes in SJZ group and co-treatment group decreased or decreased significantly (P<0.01 or P<0.05). However, there was a significant increase in the expression level of c-Kit on the surface of monocytes (P<0.05). In the mouse spleen tissue, the expression levels of CXCR1, CCR2 and c-Kit in the gefitinib group increased significantly (P<0.05), while decreased significantly in SJZ or co-treatment group (P<0.05). The results of ELISA showed that the content of IL-1α in SJZ group decreased significantly in the plasma of the mice compared with the model group (P<0.01) and the content of IL-6 in co-treatment group decreased significantly (P<0.05). Compared with the gefitinib group, the content of IL-1 in the co-treatment group decreased significantly (P<0.05). In the tumor tissues of mice, compared with the model group, the content of IL-1α in the co-treatment group decreased significantly (P<0.05). Furthermore, the content of IL-1α in co-administrated group and IL-6 in SJZ or co-treatment group decreased significantly compared with the gefitinib group (P<0.05). After 21 days of continuous administration, the tumor inhibition rates of gefitinib group, SJZ group and co-administrated group were 45.7%, 38.4%, and 84.8%, respectively. After 45 days of administration, the survival rate of the model group was 0%, whereas the gefitinib, SJZ or co-treatment group has a survival rate of 40%, 60%, or 60%, respectively. In summary, our study illustrated that Sijunzi Tang could improve the anti-tumor effect of gefitinib by regulating pre-metastatic niche.
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With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.
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<p><b>OBJECTIVE</b>To investigate the safety and efficacy of decitabine combined with CAG regimen in the treat-ment of newly diagnosed elderly patients with acute myeloid leukemia(AML).</p><p><b>METHODS</b>Fourty-nine patients with newly diagnosed acute myeloid leukemia (except M3) who were admitted to our hospital were selected. All the patients were older than 50 years old, and allogeneic hematopoietic stem cell transplantation could not be performed for various reasons. Decitabine-based chemotherapy regimens were used during induction therapy including single decitabine therapy(DAC), decitabine combined with CAG regimen(DAC-CAG) and decitabine combined with HAAG regimen(DAC-HAAG). Most of patients continued to use the original treatment after complete remission, while others were given the standard "3+7" regimen chemotherapy. A total of 2-4 courses of treatment was conducted in the majority of patients.</p><p><b>RESULTS</b>All of the 49 patients completed the induction therapy, in which 26 cases achieved complete remission(CR), 7 cases achieved partial remission(PR) and no response(NR) existed in 16 cases. The complete remission and the overall response rate(ORR) were 53% and 67% respectively. The overall response rate of DAC group, DAC-CAG group and DAC-HAAG group were 17%, 77% and 63% respectively. 14 patients were infected and 1 patients died of pulmonary infection during the induction therapy. The median number of suspended red blood cells and platelet infused were 9 units and 69 units respectively. Neutrophil recovery time was 15.1 days while the platelet recovery time was 20.1 days during the induction therapy. The mean follow-up time was 21 months. Overall survival(OS) was 75% at 6 months, 30% at 1 year, and 26% at 2 year, while disease-free survival(DFS) was 83% at 3 months, 54% at 1 year, and 47% at 2 year. The induction therapy could reach CR that was an independent prognostic factor, however, the initial white blood cell count, platelet count, age, chemotherapy regimen, prognostic stratification and whether complical by pnenmonia during chemotherapy were not independent prognostic factors.</p><p><b>CONCLUSION</b>The induction efficacy of decitabine combined with chemotherapy is superior to that of decitabine alone. The outcome of induction chemotherapy is an independent prognostic factor, however, the high white blood cell count, poor karyotype, complications and AML with myelodysplasia-related changes do not affect long-term survival. DAC-CAG regimen is effective and have relatively few adverse reactions in AML. It is suitable for the patients who are ineligible for conventional chemotherapy.</p>
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Sujet âgé , Humains , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique , Azacitidine , Cytarabine , Décitabine , Chimiothérapie d'induction , Leucémie aigüe myéloïde , Induction de rémission , Résultat thérapeutiqueRésumé
<p><b>BACKGROUND</b>The aim of this study was to assess the efficacy and safety of vinorelbine and cisplatin (NP chemotherapy) alone or in combination with Aidi injection for the treatment of advanced nonsmall cell lung cancer (NSCLC).</p><p><b>METHODS</b>Pertinent publications were identified in PubMed, EMBASE, Cochrane Library, CNKI, CQVIP, and Wanfang databases, up to December 8, 2015. After quality assessment of all included randomized controlled trials evaluating Aidi injection combined with NP chemotherapy for the treatment of advanced NSCLC, a meta-analysis was performed by Review Manager 5.2 and STATA 12.0 for statistical analyses.</p><p><b>RESULTS</b>Twelve studies including 509 and 503 cases in the experimental and control groups, respectively, were finally analyzed. The meta-analysis revealed that when cisplatin dose ranging from 20 to 40 mg/m 2 , combination of Aidi injection and NP chemotherapy was statistically different compared with NP chemotherapy alone in enhancing efficiency (relative risk [RR] = 1.24, 95% confidence interval [CI] [1.05-1.47], P = 0.010) and reducing the incidence of Grade II or above nausea and vomiting (RR = 0.49, 95% CI [0.30-0.80], P = 0.005). Meanwhile, with cisplatin ranging from 80 to 120 mg/m 2 , no significant differences in efficiency (RR = 1.11, 95% CI [0.87-1.42], P = 0.390) and Grade II or above nausea and vomiting (RR = 0.88, 95% CI [0.71-1.10], P = 0.260) were obtained. In addition, Aidi injection combined with NP chemotherapy was superior to NP chemotherapy alone in improving the quality of life, alleviating Grade II or above leukopenia and thrombocytopenia.</p><p><b>CONCLUSIONS</b>Aidi injection combined with NP chemotherapy can enhance efficiency, improve the quality of life, and decrease adverse effects in patients with advanced NSCLC.</p>
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Humains , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Carcinome pulmonaire non à petites cellules , Traitement médicamenteux , Psychologie , Cisplatine , Médicaments issus de plantes chinoises , Injections , Tumeurs du poumon , Traitement médicamenteux , Psychologie , Biais de publication , Qualité de vie , VinblastineRésumé
To observe the effect of geniposide on non-alcoholic fatty liver disease (NAFLD), and discuss the mechanism of geniposide for NAFLD from the aspect of free fatty acid, forty healthy Wistar male rats were randomly divided into normal group, model group, geniposide and Xuezhikang group. The rats in normal group were fed with normal diets, and the rats in other 3 groups were given with high-fat diet for 8 weeks to induce the NAFLD models. From the week 5 to end of week 8, the rats in geniposide and Xuezhikang group were intervened with corresponding medicines. The body weight, liver wet weight, and fat weight of the rats were recorded. Visual and pathological changes in hepatic tissues were observed with HE staining. The contents of TG, FFA, FAS, AMPK, ACCase and Malonyl-CoA in hepatic tissue, contents of CHO and LDL-C in serum and activities of AST and ALT in serum were detected by using corresponding methods. The results showed that the body weight, liver wet weight, and fat weight of the rats, CHO, LDL-C, ALT and AST levels in serum, TG, FFA, FAS, ACCase and Malonyl-CoA levels in hepatic tissues of the rats in model group were significantly higher than those in normal group (P<0.01), while AMPK activity was significantly lower than that of the normal group (P<0.01), with obvious visual and pathological steatosis in hepatic tissues, and inflammatory injury occurred in model group. Compared with the model group, body weight of the rat, fat weight, levels of FFA in hepatic tissues, ALT and AST activities in serum, liver wet weight, TG, FAS, ACCase and Malonyl-CoA levels were significantly decreased in geniposide group (P<0.01), while the AMPK activity in hepatic tissues was significantly increased (P<0.05),with improvement in visual and pathological performance. Compared with the model group, liver wet weight, fat weight, TG and FFA levels in hepatic tissues, and LDL-C level in serum were significantly decreased in Xuezhikang group (P<0.05). Compared with Xuezhikang group, the body weight of rat, fat weight and FFA level in hepatic tissues were significantly lower in geniposide group (P<0.01), but with no significant difference in other aspects. These findings indicated that geniposide was highly effective in improving the pharmacological effect of NAFLD induced by high-fat diet, and the mechanism was achieved through AMPK-ACCase-Malonyl-CoA-FFA axis.
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<p><b>BACKGROUND</b>Hyperglycemia is associated with poor clinical outcomes and mortality in several patients. However, studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition (TPN) are scarce. The aim of this study was to assess the relationship between glycemia and tumor kinds with TPN by monitoring glycemic variation in tumor patients.</p><p><b>METHODS</b>This retrospective clinical trial selected 312 patients with various cancer types, whose unique nutrition treatment was TPN during the monitoring period. All patients had blood glucose (BG) values assessed at least six times daily during the TPN infusion. The glycemic variation before and after TPN was set as the indicator to evaluate the factors influencing BG.</p><p><b>RESULTS</b>The clinical trial lasted 7.5 ± 3.0 days adjusted for age, gender, family cancer history and blood types. There were six cancer types: Hepatic carcinoma (HC, 21.8%), rectal carcinoma (17.3%), colon carcinoma (CC, 14.7%), gastric carcinoma (29.8%), pancreatic carcinoma (11.5%), and duodenal carcinoma (DC, 4.8%). The patients were divided into diabetes and nondiabetes groups. No statistical differences in TPN glucose content between diabetes and nondiabetes groups were found; however, the tumor types affected by BG values were obvious. With increasing BG values, DC, HC and CC were more represented than other tumor types in this sequence in diabetic individuals, as well as in the nondiabetic group. BG was inclined to be more easily influenced in the nondiabetes group. Other factors did not impact BG values, including gender, body mass index, and TPN infusion duration time.</p><p><b>CONCLUSIONS</b>When tumor patients are treated with TPN, BG levels should be monitored according to different types of tumors, besides differentiating diabetes or nondiabetes patients. Special BG control is needed for DC, HC and CC in both diabetic and nondiabetic patients. If BG overtly increases, positive measurements are needed to control BG values. The ClinicalTrials.gov ID is NCT02024321.</p>
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Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Glycémie , Études cas-témoins , Tumeurs , Sang , Nutrition parentérale totale , MéthodesRésumé
This study was purposed to construct prokaryotic expression vector and to investigate the expression of Notch ligand Jagged1 in E.coli. An expression vector pET-hJagged1 was constructed, which can be inserted in Jagged1 with different lengths, but the DSL domain of human Jagged1 should be contained. Then the recombinant plasmids were transformed into the competent cell of E.coli BL21, and the expression of the fusion protein was induced by IPTG. Fusion protein was purified from the supernatant of cell lysates via the Nickel affinity chromatography. The results showed that prokaryotic expression vectors pET-hJagged1 (Bgl II), pET-hJagged1 (Hind I) and pET-hJagged1 (Stu I) were successfully constructed, but only pET-hJagged1 (Stu I) could express the soluble TRX-hJagged1. The purified TRX-Jagged1 protein could be obtained via the Nickel affinity chromatography, and then confirmed by Western Blot. It is concluded that prokaryotic expression vector pET-hJagged1 is successfully constructed, but only pET-hJagged1 (Stu I) can express the soluble TRX-hJagged1 and the TRX-Jagged1 fusion protein is obtained through the prokaryotic expression system, which laid a solid foundation for further to explore the effects of Jagged1 in hematopoietic and lymphoid system.
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Protéines de liaison au calcium , Génétique , Métabolisme , Clonage moléculaire , Escherichia coli , Métabolisme , Vecteurs génétiques , Protéines et peptides de signalisation intercellulaire , Génétique , Métabolisme , Protéine jagged-1 , Protéines membranaires , Génétique , Métabolisme , Plasmides , Protéines de fusion recombinantes , Génétique , Protéines serrate-jaggedRésumé
Objective: To study the dynamic variation of Mn, Cu, Zn, Fe, K, Ca, and Mg in velamen and stem bark of Periploca sepium and their correlation with the elements such as periplocin and 4-methoxysalicylic aldehyde in different harvesting periods, and to reveal dominant factors on the accumulation of two active components. Methods: The contents of periplocin and 4-methoxysalicylic aldehyde were detected by FAAS and electric heating wet digestion, and the data were analyzed by SPSS 19.0. Results: The seven elements were varied widely in velamen and stem bark. The variation trends of Ca and periplocin, Fe and 4-methoxysalicylic aldehyde in velamen were similar, equally, those of Fe and 4-methoxysalicylic aldehyde, Ca and Mg in stem bark were similar and like double peaks. Periplocin has highly significant positive correlation with Ca in velamen and significant negative correlation with Zn in stem bark. To 4-methoxysalicylic aldehyde, when in velamen, it has highly significant positive correlation with 4-methoxysalicylic aldehyde and Fe in stem bark, significant negative correlation with Mn in stem bark, and significant positive correlation with Fe in velamen; when in stem bark, it has highly significant positive correlation with Fe in both velamen and stem bark. Conclusion: Ca, Zn, Fe, and Mn are dominant elements of accumulation, the key factors for periplocin are Ca in velamen and Zn in stem bark, and Mg in velamen is indierect acting factors; The key factors for 4-methoxysalicylic aldehyde are Mn in stem bark and Fe, Ca and Mg in stem bark are indirect acting factors.
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<p><b>OBJECTIVE</b>To investigate the regulatory effects of lanthanum chloride (LaCl3) on the activation of nuclear factor kappa B inhibitor (IκB) kinase beta (IKKβ) induced by tumor necrosis factor alpha (TNF-α).</p><p><b>METHODS</b>(1) Hela cells were cultured routinely in vitro. One portion of cells were collected and divided into TNF-α group (cultured with serum-free RMPI 1640 medium containing 20 ng/mL TNF-α for 30 min), low-dose LaCl3 + TNF-α group, moderate-dose LaCl3 + TNF-α group, high-dose LaCl3 + TNF-α group, LaCl3 group (cultured with serum-free RMPI 1640 medium containing 100 µmol/L LaCl3 for 30 min), and control group (cultured with serum-free RMPI 1640 medium for 30 min) according to the random number table. Cells in low-dose LaCl3 + TNF-α group, moderate-dose LaCl3 + TNF-α group, high-dose LaCl3 + TNF-α group were first cultured with serum-free RMPI 1640 medium containing 5, 25, 100 µmol/L LaCl3 for 4 h, and then stimulated with serum-free RMPI 1640 medium containing 20 ng/mL TNF-α for 30 min. There were 3 samples in each group. Cells were collected for detection of intracellular location of NF-κB/p65 protein by immunofluorescence staining. (2) Another portion of cells were collected and divided into TNF-α group, low-dose LaCl3 + TNF-α group, moderate-dose LaCl3 + TNF-α group, high-dose LaCl3 + TNF-α group, and control group with the same treatment as above. There were 3 samples in each group. The protein levels of NF-κB/p65 in nuclei, and the protein levels of IκBα, phosphorylated IκBα (p-IκBα) as well as IKKβ and phosphorylated IKKβ (p-IKKβ) in cytoplasm were determined by Western blotting. The binding activity between NF-κB/p65 in the nuclear and target gene was determined by NF-κB/p65 transcription factor kit (denoted as absorption value). Data were processed with analysis of variance or LSD-t test.</p><p><b>RESULTS</b>(1) High expression of NF-κB/p65 was observed in cytoplasm of control group. High expression of NF-κB/p65 was observed in nuclei of TNF-α group. The expression of NF-κB/p65 in cytoplasm of LaCl3 group was lower than that of control group. In groups treated with LaCl3 and TNF-α, NF-κB/p65 expression levels in nuclei and cytoplasm were decreased along with the increase in the concentration of LaCl3, which were all lower than those in TNF-α group. (2) There was certain amount of NF-κB/p65 protein expressed in nuclei of control group. The expression of NF-κB/p65 protein in nuclei of TNF-α group was higher than that of control group. In groups treated with LaCl3 and TNF-α, the expressions of NF-κB/p65 protein in nuclei were decreased along with an increase in the concentration of LaCl3. The level of IκBα in TNF-α group was significantly decreased but that of p-IκBα increased as compared with those in control group. Along with the increase in the concentration of LaCl3, the levels of IκBα gradually increased and the levels of p-IκBα gradually decreased in groups treated with LaCl3 and TNF-α. There were no statistical differences in expression levels of IKKβ among the 5 groups. The expression of p-IKKβ could be hardly observed in control group, but it was obviously increased in TNF-α group. The expression levels of p-IKKβ in groups treated with LaCl3 and TNF-α were gradually decreased along with the increase in the concentration of LaCl3. The absorption value in TNF-α group was 0.39 ± 0.03, which was higher than that in control group (0, t = -7.23, P<0.01). The absorption values in low-dose LaCl3 +TNF-α group, moderate-dose LaCl3 + TNF-α group, and high-dose LaCl3 +TNF-α group were respectively 0.17 ± 0.03, 0.15 ± 0.03, and 0, which were obviously lower than that in TNF-α group (with t values respectively -6.54, -5.92, -7.23, P values all below 0.01).</p><p><b>CONCLUSIONS</b>LaCl3 can block the activation of NF-κB signaling pathway by blocking the phosphorylation of IKKβ of Hela cells.</p>
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Humains , Milieux de culture , Cellules HeLa , I-kappa B Kinase , Métabolisme , Protéines I-kappa B , Métabolisme , Lanthane , Pharmacologie , Inhibiteur alpha de NF-KappaB , Transduction du signal , Facteur de transcription RelA , Métabolisme , Facteur de nécrose tumorale alpha , PharmacologieRésumé
OBJECTIVE: To evaluate the therapeutic effect and safety of Ruyi Jinhuang Powder for phlebitis. METHODS: The Cochrane Library, PubMed database, Embase database, ISI database, CBM database, CNKI database, VIP Database, and Wanfang database were searched. Randomized controlled trials (RCT), systematic reviews (SR)and meta-analysis of treating phlebitis by Ruyi Jinhuang Powder and 50% magnesium sulfate were included. Methodological quality assessment and meta-analysis of randomized controlled trials were carried out, and the conclusions of the included systematic reviews and meta-analyses were referred to. RESULTS: Ten RCTs comparing Ruyi Jinhuang Powder and 50% magnesium sulfate for treatment of phlebitis were included into the analysis. The total efficiencies of the two drugs had statistical significance [RR 12.96, 95% CI (5.81, 28.89), P 0.05]. CONCLUSION: Ruyi Jinhuang Powder is effective for treating phlebitis, the therapeutic effect is better than 50% magnesium sulfate, and no adverse drug reaction has been reported.
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<p><b>OBJECTIVE</b>To understand the demographic, occupational and clinic characteristics of occupational poisoning case due to trichloroethylene in Dongguan in recent years for the purpose of prevention.</p><p><b>METHODS</b>Using the trichloroethylene patients of poisoning diagnosed in the years between 2002 to 2009 as subjects, their age, sex, industry, job, working duration and exposure level were analysed.</p><p><b>RESULTS</b>In Dongguan between 2002 and 2009 altogether 82 cases were reported, among the 82 cases 8 patients were dead with case fatality rate of 9.8%. among them there were 12 cases of poisonings(8 females ,4 males); 9 cases were classified as mild poisonings and the rest serious ones, among the 12 cases 3 patients were dead with case fatality rate of 25.0%; Dermatitis caused by TCE there were 70 cases (37 males and 33 females), among the 70 cases 5 patients were dead with case fatality rate of 7.1%. 11 persons (91.7%) were engaged in the job of cleaning and 1 (8.3%) in water gun, and they performed the job only for 3 days in shortest and for 450 days in longest. The cases were distributed in the jobs as the following: 29 (41.4%), 12 (17.1%), 8 (11.4%), 5 (7.1%), 4 (5.7%), cases respectively in the job of cleaning, parts hanging, board washing, painting, gun water spraying; a job duration of 1-50 d (27.4 days in average).</p><p><b>CONCLUSION</b>In summary the TCE poisonings in Dongguan were two types of poisoning, i.e., systematic poisonings and drug rash-like dermatitis, occupational TCE poisonings took place mainly in the cleaning workers. Dermatitis caused by TCE can cure but hard to prevent, we should strengthen the early examination of new works.</p>
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Adolescent , Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Chine , Épidémiologie , Dermatite professionnelle , Épidémiologie , Exposition professionnelle , Trichloroéthylène , IntoxicationRésumé
ObjectiveTo investigate the methods and effects on the mobilization and collection of peripheral hematopoietic stem cells.MethodsPeripheral hematopoietic stem cells of 198 cases of healthy donors were selected and mobilized by subcutaneous recombinant human granulocyte colony stimulating factor (rhG-CSF) by (5-10) μg·kg-1 ·d-1 and collected on the 5th day. The effects of gender, height, age and WBC count of donors on mobilization and collection were analyzed. ResultsAll the peripheral hematopoietic stem cells of donors were successfully mobilized.The average counts of mononuclear cells(MNC)and CD34+ cells were (4.19±1.96)×108/kg and (2.98±1.40)×106/kg, respectively, which had no correlation with gender, height and age.The counts of MNC and CD34+ cells collected were positively correlated with the WBC count of peripheral blood (r =0.9201, P =0.0035; r =0.8420, P =0.0149). The donors with WBC ≥20.0×109/L had moresignificant effect than thoseWBC<20.0×109/L (F =4.688, P =0.0013; F =4.622, P =0.0006). Conclusion The WBC count of peripheral blood from healthy donors is a simple and feasible indicator to predict the quantity of CD34+ cells.
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<p><b>OBJECTIVE</b>To study the effects of genistein on the proliferation, apoptosis induction and expression of related gene proteins of human colon cancer cells in vitro and in vivo, and its mechanisms of action.</p><p><b>METHODS</b>MTT colorimetric assay was used to detect the effects of genistein on the proliferation of human colon adenocarcinoma SW480 cells. Light and transmission electron microscopy were used to study the histological and ultrastructural changes. Flow cytometry was used to determine the effects of genistein on cell cycle and apoptosis. Flow cytometry and immunohistochemistry were used to determine the effects of genistein on apoptosis induction and expression of related gene proteins of colon cancer cells.</p><p><b>RESULTS</b>The MTT colorimetric assay showed that genistein inhibited the proliferation of SW480 cells in a dose-dependent and time-dependent manner, and the highest inhibition rate was 60.2% after 80 microg/ml genistein treatment for 72 h. The light microscopy revealed that many genistein-treated cancer cells were shrunken, disrupted, or showing cytoplasmic vacuolization. The electron microscopic examination showed cell shrinkage, nuclear fragmentation and pronounced chromatin condensation, sometimes formed crescent chromatin condensation attached to the nuclear membrane. The results of flow cytometry showed that: after SW480 cells were treated with 0, 20, 40, 80 microg/ml genistein for 48 h, the FI values of PCNA were 1.49 +/- 0.02, 1.28 +/- 0.04, 1.14 +/- 0.03, and 0.93 +/- 0.08; the FI values of VEGF were 1.75 +/- 0.02, 1.34 +/- 0.06, 1.32 +/- 0.04, and 1.23 +/- 0.04; the fluorescence index (FI) values of p21 were 1.26 +/- 0.05, 1.36 +/- 0.06, 1.61 +/- 0.03, and 1.73 +/- 0.03, respectively. There were statistically significant differences between the control group and each treatment group (P < 0.05 or P < 0.01). The scores of immunohistochemical staining of PCNA and VEGF proteins were decreased, while p21 increased. There were statistically significant differences between the control group and each treatment group (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>Genistein can inhibit the growth of colon cancer cells via apoptosis induction and cell cycle arrest at G(2)/M phase. The anti-tumor mechanisms of genistein may be related with the down-regulation of expression of VEGF and PCNA, and up-regulation of the expression of p21.</p>
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Animaux , Humains , Mâle , Souris , Adénocarcinome , Métabolisme , Anatomopathologie , Anticarcinogènes , Pharmacologie , Apoptose , Cycle cellulaire , Lignée cellulaire tumorale , Prolifération cellulaire , Tumeurs du côlon , Métabolisme , Anatomopathologie , Inhibiteur p21 de kinase cycline-dépendante , Métabolisme , Relation dose-effet des médicaments , Régulation de l'expression des gènes tumoraux , Génistéine , Pharmacologie , Souris de lignée BALB C , Transplantation tumorale , Antigène nucléaire de prolifération cellulaire , Métabolisme , Facteur de croissance endothéliale vasculaire de type A , MétabolismeRésumé
<p><b>OBJECTIVE</b>To investigate the effects of arginine enriched enteral nutrition (EN) on nutritional status and cellular immunity of severely burned patients.</p><p><b>METHODS</b>Randomized, single blind, parallel and positive control investigation was employed in the study. Thirty severely burned patients were divided into enteral immune nutrition (EIN) group and EN group. Sixteen patients in EIN group received enteral nutrition enriched with arginine, while the other 14 patients in EN group received standard enteral nutrition. Nutritional support was continued for 14 days. Gastrointestinal reaction of patients in 2 groups was observed. Fasting venous blood was drawn from patients of both groups before receiving nutrition treatment and on the morning of 7th, 14th day of treatment. Level of serum protein, hepatic function parameters, renal function parameters, fasting-blood glucose, and subpopulations of T lymphocytes in peripheral blood were determined.</p><p><b>RESULTS</b>(1) Incidence of gastrointestinal side effect in EIN group (25.0%) was close to that of EN group (21.4% , P > 0.05). (2) Compared with pre-treatment days, levels of prealbumin and transferrin in serum of patients in 2 groups on 7th and 14th post-treatment days were significantly increased (P < 0.05 or P < 0.01), but there was no significant difference between 2 groups. The level of total serum protein on 14th day of treatment of patients was significantly increased in both groups, and that of EIN group (66 +/- 7 g/L) was significantly higher compared with that in EN group (64 +/- 11 g/L, P < 0.05). The level of serum albumin (29 +/- 5, 32 +/- 5 g/L, respectively) of patients in EIN group on 7th and 14th day of treatment were significantly higher than that (26 +/- 4 g/L, P < 0.05) in pre-treatment days, however there was no significant difference in EN group. (3) There was no significant difference in respect of hepatic function, renal function, and fasting-blood glucose between pre-treatment and post-treatment periods in both groups (P > 0.05). (4) The ratio of CD4(+), CD8(+) on 14th day of treatment in EIN group was close to that of pretreatment level. In EN group, cell percentage of CD4(+) significantly decreased, while that of CD8(+) significantly increased (P < 0.05), and CD4(+) was significantly higher [(56 +/- 8)%] in EIN group than that in EN group [(55 +/- 12)%, P < 0.05]. In both groups, cell percentage of CD3(+) was significantly higher than that in pre-treatment days (P < 0.05), while there was no obvious change in CD4(+)/CD8(+).</p><p><b>CONCLUSIONS</b>Arginine enriched enteral nutrition can effectively improve nutritional status and cellular immune function of burn patients.</p>