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AIM: To compare the differences in choroidal structure between hyperopic amblyopia and normal children of the same age by the enhanced depth imaging optical coherence tomography(EDI-OCT)technique.METHODS: There were 35 cases in 50 eyes of children with hyperopic amblyopia visiting our hospital in January 2021 to December 2021 selected in the amblyopic group, and 30 cases in 51 eyes of healthy children who matched general data in the same period were selected in the control group. EDI-OCT examination was performed to measure the choroidal thickness(CT). After image processing, the total choroidal area(TCA), luminal area(LA), stromal area(SA)and choroidal vascularity index(CVI)were obtained.RESULTS: TCA(except inferior quadrant), SA(except inferior quadrant of the outer ring), LA and CT(except inferior and temporal quadrant )in the amblyopic group of each area were significantly larger than that in the control group(P<0.05), and there was no significant difference in CVI between the two groups except the temporal quadrant of the outer ring(P>0.05). There was no significant difference in CT for all degrees of hyperopic amblyopia, with the exception of the nasal quadrant(P>0.05).CONCLUSION: Hyperopic amblyopia is accompanied with abnormal choroidal structure. As the degree of hyperopia increases, TCA, LA and SA exhibit increasing trends. The changes in choroidal structure are presumed to be related to hyperopic amblyopia.
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Objective: To observe the therapeutic efficacy of warm needling moxibustion plus intra-articular injection of sodium hyaluronate in treating chondromalacia patellae and its effect on inflammatory factors in knee joint fluid. Methods: Sixty-eight patients with chondromalacia patellae were randomized into a control group and an observation group, with 34 cases in each group. The control group was treated with intra-articular injection of sodium hyaluronate, while the observation group was given additional warm needling moxibustion treatment. Before and after treatment, the two groups were scored using Western Ontario and McMaster Universities osteoarthritis index (WOMAC) and visual analog scale (VAS), examined by magnetic resonance imaging (MRI) and determined for the levels of nuclear factor-κB (NF-κB), tumor necrosis factor (TNF)-α and interleukin (IL)-1β in knee joint fluid. Clinical efficacy was estimated after treatment. Results: The effective rate was higher in the observation group than in the control group (P<0.05). After treatment, the scores of pain, stiffness and daily activities, as well as the general score of WOMAC declined significantly in both groups (all P<0.05), and were lower in the observation group than in the control group (all P<0.05); the time cost for climbing up and down one staircase and VAS score decreased markedly in both groups (all P<0.05), and were shorter or lower in the observation group than in the control group (both P<0.05); the MRI grading showed no significant change in the control group after intervention (P>0.05), while the grading in the observation group showed notable improvement (P<0.05), and was better than that in the control group (P<0.05); the levels of NF-κB and IL-1β in knee joint fluid dropped significantly in the control group after treatment (both P<0.05), while the levels of NF-κB, TNF-α and IL-1β in knee joint fluid all decreased significantly in the observation group (all P<0.05) and were lower than those in the control group (all P<0.05). Conclusion: Warm needling moxibustion plus intra-articular injection of sodium hyaluronate can produce definite efficacy in treating chondromalacia patellae; it can mitigate the clinical symptoms, improve the lesion extent of chondromalacia and down-regulate the levels of NF-κB, TNF-α and IL-1β in knee joint fluid.
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OBJECTIVE@#To assess the efficacy and safety of the Chinese medicine Dingkun Pill (, DKP) on insulin resistance in women with polycystic ovary syndrome (PCOS).@*METHODS@#A total of 117 women with PCOS were randomly assigned to Group A (38 women), Group B (40 women), or Group C (39 women) in a randomization sequence with SAS software and a 1:1:1 allocation ratio using random block sizes of 6, and were given 7 g of oral DKP daily (Group A), 1 tablet of Diane-35 orally daily (Group B), or 7 g of oral DKP daily plus 1 tablet of Diane-35 orally daily (Group C). Patients took all drugs cyclically for 21 consecutive days, followed by 7 drug-free days. The treatment course for the 3 groups was continued for 3 consecutive months. Oral glucose tolerance tests (OGTT) were performed before treatment and again after 2 and 3 months of therapy, respectively, and homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were calculated.@*RESULTS@#Of 117 women with PCOS, 110 completed the entire course of therapy: 35 in Group A, 36 in Group B, and 39 in Group C. After treatment, all three groups showed significant decreases in fasting glucose: at 1 h glucose decreased significantly in Group A (by 0.5 ± 1.4 mmol/L, P=0.028) and Group C (by 0.5 ± 1.2 mmol/L, P=0.045); while showing a tendency to increase in Group B (by 0.4 ± 1.9 mmol/L, P=0.238). HOMA-IR decreased significantly in Group C [by 0.5 (-2.2 to 0.5) mIU mmol/L, P=0.034]. QUICKI was significantly increased in Groups A and C (by 0.009 ± 0.02, P=0.033 and by 0.009 ± 0.027, P=0.049, respectively), while no change was observed in Group B. Repeated-measure ANOVA showed that the absolute changes in all parameters (except for glucose at 1 h), including glucose and insulin levels at all time-points during OGTT and in HbA1c, HOMA-IR, and QUICKI, were not significantly different among the 3 groups after treatment (P>0.05).@*CONCLUSION@#DKP or DKP combined with Diane-35 produce a slight improvement in insulin sensitivity compared with Diane-35 alone in PCOS patients (Trial Registration: ClinicalTrials.gov, NCT03264638).
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Objective To investigate the influence of body mass index(BMI) on the prognosis of patients who had received elective PCI.Methods The study population consisted of 2964 consecutive patients with electivePCIs performed between July 2009 and September 2011. The patients were divided into three groups based on their preoperative BMI levels:the normal group( BMI<24.0 kg/m2,n=810); the overweight group( 24.0 kg/m2≤BMI<28.0 kg/m2,n=1454) and the obese group(BMI≥28.0 kg/m2,n=700). We examined the association between baseline BMI levels and postoperative mortality through a mean(571.5±130.8)days of follow up.Results Patients with high BMI had a higher percentage of comorbidities compared with the normal BMI group. The results of multivariate Cox regression analysis revealed that preoperative BMI was inversely associated with mortality after adjustment for other factors (HR 0.896,95% CI 0.821-0.977,P=0.031). Compared with the obese group, the hazard ratios for risk of mortality in the overweight and the normal groups were 1.908(95%CI 0.689-5.291,P=0.213) and 2.241(95%CI 1.154-4.350,P=0.017).Conclusions For patients undergoing elective PCI, individuals with obesity and overweight had the better prognosis than those with normal BMI.
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OBJECTIVE Cloves(Syzygium aromaticum L.)have been used as both a spice and a traditional Chinese medicinal herb for thousands of years. However, relatively little is known about its potential anticancer activity and mechanisms.In this study,we investigated the in vitro and in vivo anti-tumor effects and mechanisms of water extract of cloves(WEC)against colorectal cancer. METHODS MTS assay and Colony-formation assay were used to detect the anti-tumor activity of WEC on HT-29 cells.The in vivo anti-tumor effect of WEC was detected in a subcutaneous transplantation tumor model of human HT-29 cells.Autophagy was detected by flow cytometry and the expressions of autophagy related proteins(Beclin-1 and LC-3a/b)were determined by western blot. RESULTS MTS result showed that WEC significantly inhibited the viability of HT-29 cells,with the IC50values of 150 μg·mL-1.The colony-formation assay showed that the WEC significantly suppressed colon cancer cells proliferation.WEC also exhibited significant antitumor activity in tumor bearing nude mice. Flow cytometry result showed that WEC significantly induced autophagy, and the averaged relative values of fluorescence intensity were 206,251,341 and 356 in cells treated with 0,100,150 and 200 μg·mL-1WEC for 48 h.Western blot result showed that WEC treatment significantly increased Beclin-1 expression and ratios of LC3-II/LC3-I. CONCLUSION These result showed that WEC inhibited the growth of colon tumor both in vitro and in vivo, which might be related with autophagy induction, and WEC has potential to be developed as a novel anticancer agent for the treatment of colon cancer.
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OBJECTIVE Zn-doped CuO nanocomposites (Zn-CuO NPs) are novel nanoparticles synthesized by our research group.In this study,we assessed the in vitro and in vivo antitumor effects of Zn-CuO NPS on pancreatic cancer cells,as well as the potential mechanisms. METHODS MTS assay was used to detect the effects of Zn-CuO NPS on proliferation pancreatic cancer cells(Panc-mia and Aspc-1). The in vivo antitumor effects of Zn-CuO NPs were detected by xenografts model in nude mice. The effects of Zn-CuO NPS on autophagy were detected bytransmission electron microscopy (TEM) andflow cytometry. Autophagy related proteins were detected by Western blotting. RESULTS Zn-CuO NPS significantly inhibited the proliferation of Panc-mia cells and Aspc-1 cells.In vivo experi-ments showed that Zn-CuO NPS significantly inhibited the tumor growth in nude mice without affecting the body weight of the mice. TEM and flow cytometry showed that Zn-CuO NPS induced autophagy, and significantly increased the number of autophagosome.Western Blot showed that Zn-CuO NPS alterd the expression of autophagy related proteins,such as AMPK,mTORand Beclin-1.Also,AMPK inhibitor could significantly reduce Zn-CuO NPS-induced autophagy pathwayas analyzed byWestern blotting. CONCLUSION The findings suggested that Zn-doped CuO nanocomposites inhibited the in vitro and in vivo growth of pancreatic cancer by inducing autophagy through AMPK/mTOR pathway.
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OBJECTIVE Granulin A (GRN A), a cytokinesis protein, is derived from proteolysis of progranulin. The previous study in our laboratory has shown that GRN A is able to inhibit cancer cell growth significantly. This study aimed to investigate the effect of combination of GRN A and cisplatin on in vitro and in vivo on the growth of hepatocellular carcinoma. METHODS The in vitro and in vivo antitumor effects of combination of GRN A and Cisplatin were evaluated with MTS assay and subcuta-neous transplantation tumor model.Chou-Talalay method was used to calculate the combination index (CI). Colony formation assay and flow cytometry were used to detect the effects of GRN A on apoptosis. The expression of apoptosis-related proteins were detected by Western blot. RESULTS MTS assay showed that GRN A significantly inhibit hepatocellular carcinoma cells growth with the IC50of 5.6 μmol·L-1, and GRN A combined with cisplatin synergistically inhibit hepatocellular carcinoma proliferation, with the CI<1.The colony-formation assay showed that GRN A significantly enhanced the inhibitory effects of cisplatin on cellular anchorage-independent growth. Flow cytometry showed that GRN A combined with cisplatin synergistically induced apoptosis,with the apoptotic rates of 5.87%,32.74%,35.67% and 67.15% in control, GRN A, Cisplatin, and combination of GRN A and Cisplatin groups, respectively. Western blot confirmed that the two drugs synergistically changed the expressions of proteins related to apoptosis.In vivo experiment indicated that combination of GRN A and cisplatin significantly suppressed tumor growth compared with single drug treatment groups.CONCLUSION The combination of GRN A and cisplatin resulted in synergistic antitumor effects against hepatocellular carcinoma both in vitro and in vivo.
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<p><b>OBJECTIVE</b>Osteosarcoma is the most common type of malignant bone tumor in children and adolescents. The role of E3 ligases in tumorigenesis is currently a focus in tumor research. In the present study, we investigated the role of the E3 ligase tripartite motif 21 (TRIM21) in osteosarcoma cell proliferation.</p><p><b>METHODS</b>3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays were used to assess osteosarcoma cell viability. U2-OS cells stably carrying a recombinant lentivirus expressing tetracycline-regulated TRIM21 were screened. Co-immunoprecipitation was coupled with LCMS/MS analysis to identify novel interacting partners of TRIM21. Co-immunoprecipitation and bimolecular fluorescence complementation (BIFC) were performed to validate the interactions between TRIM21 and its novel partner YWHAZ. A TRIM21-ΔRING construct was generated to test the effects of TRIM21 ligase activity on YWHAZ.</p><p><b>RESULTS</b>TRIM21 positively regulated osteosarcoma cell proliferation. Overexpression of TRIM21 enhanced osteosarcoma cell tolerance toward various stresses. YWHAZ protein was identified as a novel interacting partner of TRIM21 and its expression levels were negatively regulated by TRIM21. The RING domain of TRIM21 was required for TRIM21 negative regulation of YWHAZ expression. However, overexpression of YWHAZ did not affect positive regulation of osteosarcoma cell proliferation by TRIM21.</p><p><b>CONCLUSION</b>Our results further clarify the molecular mechanisms underlying the pathogenesis of osteosarcoma.</p>
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Humains , Protéines 14-3-3 , Génétique , Métabolisme , Prolifération cellulaire , Génétique , Ostéosarcome , Génétique , Ribonucléoprotéines , Génétique , Métabolisme , Cellules cancéreuses en cultureRésumé
<p><b>OBJECTIVE</b>Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem.</p><p><b>METHODS</b>Nuclear and cytoplasmic protein extraction and immuno?uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene expression of XIAP was tested by quantitative RT-PCR.</p><p><b>RESULTS</b>Previously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation. In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells.</p><p><b>CONCLUSION</b>Taken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.</p>
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Humains , Apoptose , Physiologie , Lignée cellulaire tumorale , Régulation de l'expression des gènes , Physiologie , Ribonucléoprotéine nucléaire hétérogène K , Génétique , Métabolisme , Mitogen-Activated Protein Kinase 1 , Génétique , Métabolisme , Mitogen-Activated Protein Kinase 3 , Génétique , Métabolisme , Ligand TRAIL , Génétique , Métabolisme , Régulation positive , Physiologie , Protéine inhibitrice de l'apoptose liée au chromosome X , Génétique , MétabolismeRésumé
<p><b>OBJECTIVE</b>Coronary artery calcification (CAC) is a well-established risk predictor of coronary heart disease events and is recognized as an indicator of subclinical atherosclerosis.</p><p><b>METHODS</b>A cross-sectional study consisting of 2999 participants aged ⋝40 years from the Jidong community of Tangshan City, an industrial and modern city of China, was conducted between 2013 and 2014 to examine the association between the ideal cardiovascular health (CVH) metrics and CAC. The ideal CVH metrics were determined based on the definition of the American Heart Association (AHA). The participants were then grouped into 4 categories according to the quartiles of their CVH metric scores as follows: first quartile (0-2), second quartile (3), third quartile (4), and fourth quartile (5-7). CAC was assessed by using high-pitch dual-source CT, and patients were identified based on thresholds of 0, 10, 100, or 400 Agatston units, as per common practice.</p><p><b>RESULTS</b>The prevalence of subclinical atherosclerosis was 15.92%, 13.85%, 6.76%, and 1.93%, determined by using the CAC scores at thresholds of 0, 10, 100, and 400 Agatston units, respectively. Compared with the group in the first quartile, the other three CVH groups had a lower odds ratio of CAC >0 after adjusting for age, sex, income level, education level, and alcohol use in the logistic regression analysis. The odds ratios in these groups were 0.86 [95% confidence interval (CI), 0.63-1.17; P<0.05], 0.75 (95% CI, 0.55-1.02; P<0.05), and 0.49 (95% CI, 0.35-0.69; P<0.05), respectively. These associations of CAC with the CVH metrics were consistent when different CAC cutoff scores were used (0, 10, 100, or 400).</p><p><b>CONCLUSION</b>The participants with more-ideal cardiovascular metrics had a lower prevalence of subclinical atherosclerosis determined according to CAC score. Maintaining an ideal cardiovascular health may be valuable in the prevention of atherosclerosis in the general population.</p>
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Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Athérosclérose , Épidémiologie , Anatomopathologie , Phénomènes physiologiques cardiovasculaires , Chine , Épidémiologie , Maladie des artères coronaires , Épidémiologie , Anatomopathologie , Études transversales , Comportement en matière de santé , État de santé , Plaque d'athérosclérose , Épidémiologie , Facteurs de risque , Calcification vasculaire , AnatomopathologieRésumé
Sonoclot analyzer has been widely used in many countries. But the reference intervals provided by the manufacturer were derived from only 45 participants, and there was no cut-off value for transfusion for Sonoclot analysis. This study aimed to establish reference intervals and transfusion criterion for Sonoclot analysis. Volunteers were recruited from healthy Chinese adults and patients undergoing cardiac surgery. Blood samples were withdrawn from forearm vein and measured for activated clotting time (ACT), clot rate (CR), platelet function (PF), activated partial thromboplastin time (APTT), fibrinogen concentration (FIB), and platelet count (PLT). The reference intervals were determined by the nonparametric method. Cut-off values were determined by the receiver operating characteristics curve. A total of 135 healthy volunteers and 281 patients were enrolled. The 95% reference intervals were 96-195 s, 22-51 signal U/min, >1.6 for ACT, CR, PF respectively. In the 281 patients, the results of APTT, FIB, PLT, ACT, CR, and PF ranged from 20.5-300.0 s, 0.28-4.11 g/L, (19.0-387.3)×109/L, 80-514 s, 2.9-74 signal U/min, and 0.1-5.1 respectively. The cut-off values for transfusion were >208, ≤14, and ≤1.3 for ACT, CR, PF respectively. The cut-off values of Sonoclot analysis were within the manufacturer's reference intervals, while they were outside the reference intervals established in this study. The results suggested that the manufacturer's reference intervals were not suitable for Chinese. The reference intervals and cut-off values established in this study will be helpful to Chinese patients.
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Adolescent , Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Coagulation sanguine , Pontage cardiopulmonaire , Chine , Fibrinogène , Métabolisme , Temps partiel de thromboplastine , Méthodes , Numération des plaquettes , Systèmes automatisés lit malade , Valeurs de référenceRésumé
<p><b>OBJECTIVE</b>To investigate the effects of Chinese medicine (CM) herbal treatment based on syndrome differentiation on patients with unresectable hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A total of 94 patients with unresectable HCC were reviewed between June 2008 and June 2011. Survival analysis was performed between patients who received CM with/without non-curative antitumor treatments of Western medicine (WM) (CM group, 30 cases) and patients who were not treated with CM but with non-curative antitumor treatments of WM or supportive treatment alone (non-CM group, 64 cases). Then, survival analysis was performed between patients treated with CM combined with non-curative antitumor treatments of WM (combination therapy group, 25 cases) and patients with non-curative antitumor treatments of WM alone (non-curative antitumor treatments group of WM, 52 cases). The survival analysis was performed by Kaplan-Meier method and prognostic factors for overall survival (OS) were assessed by the Cox proportional hazards regression model.</p><p><b>RESULTS</b>The median survival time (MST), 1- and 2-year survival rates of the CM group and the non-CM group were 36 months, 76.7%, 56.1% and 12 months, 48.4%, 26.6%, respectively. The Log-rank test revealed significant difference between the two groups in OS (P<0.01). Cox proportional multivariate analysis revealed that CM was an independent favorable prognostic factor for OS. The MST, 1- and 2-year survival rates of combination therapy group and non-curative antitumor treatments group of WM were 36 months, 76.0%, 55.5% and 13 months, 55.8%, 30.8%, respectively. There was significant difference in OS between the two groups (P=0.004).</p><p><b>CONCLUSIONS</b>CM herbs based on syndrome differentiation have positive effects on survival of patients with unresectable HCC. Furthermore, combination therapy of CM and WM are recommended in HCC treatment.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Carcinome hépatocellulaire , Traitement médicamenteux , Mortalité , Chirurgie générale , Association thérapeutique , Médicaments issus de plantes chinoises , Utilisations thérapeutiques , Estimation de Kaplan-Meier , Tumeurs du foie , Traitement médicamenteux , Mortalité , Chirurgie générale , Analyse multifactorielle , Pronostic , Analyse de survie , SyndromeRésumé
<p><b>OBJECTIVE</b>The protozoan Toxoplasma gondii expresses large amounts of a 37 kDa Type 2C serine-threonine phosphatase, the so-called TgPP2C which has been suggested to contribute to parasite growth regulation. Ectopic expression in mammalian cells also indicated that the enzyme could regulate growth and survival. In this study, we aimed to investigate the interaction of TgPP2C with human SSRP1 (structure-specific recognition protein 1) and the effects of TgPP2C on cell viability.</p><p><b>METHODS</b>The yeast two hybrid system, His-tag pull-down and co-immunoprecipitation assays were used to confirm the interaction of TgPP2C with SSRP1 and determine the binding domain on SSRP1. The evaluation of cell apoptosis was performed using cleaved caspase-3 antibody and Annexin-V/PI kit combined with flow cytometry.</p><p><b>RESULTS</b>We identified human SSRP1 as an interacting partner of TgPP2C. The C-terminal region of SSRP1 including the amino acids 471 to 538 was specifically mapped as the region responsible for interaction with TgPP2C. The overexpression of TgPP2C down-regulated cell apoptosis and negatively regulated apoptosis induced by DRB, casein kinase II (CKII) inhibitor, through enhanced interaction with SSRP1.</p><p><b>CONCLUSION</b>TgPP2C may be a parasitic factor capable of promoting cell survival through interaction with the host protein SSRP1, thereby creating a favorable environment for parasite growth.</p>
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Humains , Apoptose , Technique de Western , Protéines de liaison à l'ADN , Génétique , Métabolisme , Cytométrie en flux , Cellules HeLa , Protéines HMG , Génétique , Métabolisme , Immunoprécipitation , Phosphoprotein Phosphatases , Génétique , Métabolisme , Protein phosphatase 2C , Toxoplasma , Facteurs d'élongation transcriptionnelle , Génétique , Métabolisme , Techniques de double hybrideRésumé
<p><b>OBJECTIVE</b>To assess healthy related quality of life in patients with HBV induced liver cirrhosis.</p><p><b>METHODS</b>A total of 103 cases of patients with HBV induced liver cirrhosis were recruited from shenzhen Third People's Hospital during January 2009 to January 2012. The health related quality of life were assess using the most commonly used SF-36 scale questionnaire in all 103 patiemts. Sixty patients were further chosen for health related quality assessment using qualitive research method.</p><p><b>RESULTS</b>The quality of life of chronic hepatitis B patients with cirrhosis Child classification, four score of each group general health, vitality, social functioning, mental health was statistically significant (P < 0.05). Depth interviews found that the disease affects the psychological burden of the social needs of the three major affect quality of life factors.</p><p><b>CONCLUSION</b>Qualitative research with the SF-36 scale associated to a better understanding of the needs of life of patients with chronic hepatitis B cirrhosis, provide a reference for subsequent targeted medical services.</p>
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Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Hépatite B chronique , Cirrhose du foie , Psychologie , Recherche qualitative , Qualité de vieRésumé
N6-(2-Hydroxyethyl) adenosine, HEA (1), an active ingredient isolated from cultured mycelia of cordyceps species which is a famous traditional tonic in China, showed brain protective, sedative hypnotic activity in pharmacological tests. In order to explore novel non-benzodiazepine sedative-hypnotic agents, HEA was treated as the lead compound. Twenty three target compounds were designed and synthesized. Their chemical structures were characterized by 1H NMR, MS and elemental analysis. Pharmacological test in vivo showed that target compounds 8, 4, 13 were more active than HEA on locomotor and gasping activities of mice. Structure-activity relationships showed that the ribose moiety at N-9 position of adenine base was critical for activity.
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Animaux , Mâle , Souris , Adénosine , Chimie , Pharmacologie , Hypnotiques et sédatifs , Chimie , Pharmacologie , Souris de lignée ICR , Structure moléculaire , Activité motrice , Répartition aléatoire , Relation structure-activitéRésumé
<p><b>OBJECTIVE</b>To investigate the effect of up-regulated expression of tumor suppressor gene p14(ARF) on apoptosis of chronic myeloid leukemia (CML) cells and its interaction with imatinib.</p><p><b>METHODS</b>Tumor suppressor gene p14(ARF) was transduced into K562 (K562-p14(ARF)) and 4 blast crisis primary CML cells (CML-BC 1-4) using vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped lentiviral vector with cells transduced by empty vector as control. Fluorescence microscopy and flow cytometry were applied to measure transduction efficiency, and Western blotting assay was used to detect p14(ARF) protein of K562 cells. WST-8 method was used to determine cell growth inhibition rate of K562 cells transduced by the target gene under different concentrations of imatinib (0, 0.015, 0.062, 0.125, 0.25, 0.5, 1.0, 2.0 μmol/L). Cell apoptosis and leukemic cellular colony-forming ability were detected by Annexin V-FITC/PI dyeing using flow cytometry (FCM) and semi-solid culture method respectively.</p><p><b>RESULTS</b>Fluorescence microscopy and FCM showed that transduction efficiency (GFP positive cells) of K562-p14(ARF), K562-VSV and CML-BC1 cells were close to 100%, and CML-BC 2-4 cells were 80% to 90% on average. Results of Western blotting showed that the levels of ARF protein expression of K562 cells transduced by p14(ARF) were significantly higher than of untransduced cells; the apoptosis rate of K562-p14(ARF) was 20%; the mean apoptosis rate of 4 primary leukemic cells transduced by the p14(ARF) [(71.1±22.4)%] was significantly higher than of control group [(12.4±6.2)%] (P<0.05). Imatinib significantly inhibited the proliferation of K562-p14(ARF) cells in a dose-dependent manner. The mean leukemic cellular colony-forming unit of 4 primary leukemic cells transduced by the p14(ARF) (41.5±13.2) was significantly lower than of the control group (88.5±7.9) (P<0.05).</p><p><b>CONCLUSION</b>Increased p14(ARF) gene expression could induce apoptosis of CML cells; Moreover, it could enhance inhibitory effect on cell proliferation when combined with imatinib.</p>
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Humains , Apoptose , Régulation de l'expression des gènes dans la leucémie , Vecteurs génétiques , Cellules K562 , Leucémie myéloïde chronique BCR-ABL positive , Métabolisme , Anatomopathologie , Protéine p14(ARF) suppresseur de tumeur , Métabolisme , Régulation positiveRésumé
The aim of this study was to verify the presence of multipotential mesenchymal stem cells in peripheral blood (PBMSC) of rabbits. For mobilization, granulocyte-colony-stimulating factor 30 µg/(kg·d) was injected into New Zealand White rabbits subcutaneously for 6 d, then the PBMSC were isolated from peripheral blood of rabbits by density gradient centrifugation and adhesive culture. The morphology of cell proliferation was observed by microscopy, the proliferative curve of cells was drawn. The phenotypes of PBMSC were detected by flow cytometry, the differential capability of PBMSC into osteocytes, chondrocytes and adipocytes was identified. The results showed that the morphology of subcultured PBMSC were spindle or polygonal shaped, and cell population doubling time was 37.4 h. The isolated PBMSC expressed mesenchymal marker CD29, but not expressed hematopoietic marker CD14. Under specific induction conditions, PBMSC demonstrated multipotency to differentiate into osteocytes, chondrocytes and adipocytes. It is concluded that PBMSC are successfully isolated from peripheral blood and cultured, and their multipotential capability of differentiation into osteocytes, chondrocytes and adipocytes are verified.
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Animaux , Lapins , Adipocytes , Biologie cellulaire , Adipogenèse , Animaux nouveau-nés , Différenciation cellulaire , Chondrocytes , Biologie cellulaire , Cellules souches mésenchymateuses , Biologie cellulaire , Cellules souches multipotentes , Biologie cellulaire , Ostéocytes , Biologie cellulaireRésumé
Background Platelet-derived growth facto(PDGF) affectthe proliferation of human lenepithelial cell(LECs),and human LECexpresPDGF-α recepto(PDGFR-α) throughoutheilifetime.The binding of activated PDGF-α receptowith PDGF promotethe synthesiof DNA.Othestudiedemonstrated thasilencing of PDGFR-α by antisense oligodeoxynucleotide(ASODN) inhibitthe growth of RPE cellin proliferative vitreoretinopathy (PVR),buwhethethitechnique ifeasible foLECiunclear.Objective Thistudy wato investigate the effecof the knockdown of the PDGFR-α on the proliferation of human LECin vitro,and to offean experimental basifothe gene therapy of posteriocapsule opacification.MethodHuman LECstrain SRA01/ 04 wacultured in α-MEM containing fetal bovine serum.The cellwere incubated in 6-well platea5 × 104 cells/ well and transfection of ASODN-containing liposome waperformed.The cellwere divided into the blank control group (with blank liposome),PDGFR-α missense oligodeoxynucleotide(MSODN) group (with PDGFR-α MSODN + liposome),0.5 μmol/L PDGFR-α ASODN group (with 0.5 μmol/L PDGFR-α ASODN+liposome) and 1.0 μmol/L PDGFR-α ASODN group (with 1.0 μ mol/L PDGFR-α ASODN+liposome).The morphology of LECwaexamined undean inverse microscope 24 houraftetransfection.The expression of PDGFR-α mRNin the cellwadetected by reverse transcription-PC(RT-PCR).The rate of proliferation (A490) of the cellwaassayed using Mtand the inhibitory rate of PDGFR-α ASODN on proliferation wameasured.The percentage of LECin G1 phase waanalyzed by flow cytometer.ResultThe LECgrew well and exhibited polygonal shape in the blank control group and PDGFR-α MSODN group 24 houraftetransfection.Buin the 0.5 μmol/L and 1.0 μmol/L PDGFR-α ASODN groups,the cellappeared round in shape and the numberof cellwere obviously decreased.The expression of PDGFR-α mRNdetected by RT-Pcdemonstrated highelevel in the blank control group and PDGFR-α MSODN group;however,the PDGFR-α mRNexpression waobviously lowein the 0.5 μmol/L and 1.0 μmol/L PDGFR-α ASODN groups.The A490 value wa0.661 ± 0.036,0.655 ± 0.016,0.529 ± 0.030 and 0.441 ± 0.039 in the blank control group,PDGFR-α MSODN group,0.5 μmol/L PDGFR-α ASODN group and 1.0 μmol/L PDGFR-α ASODN group,respectively,showing significandecline in the 0.5 μmol/L PDGFR-α ASODN group and 1.0 μ mol/L PDGFR-α ASODN group in comparison with the blank control group (F=34.08,P<0.01).The percentageof LECin G1 phase were (47.73±1.18)%,(49.48±1.09)%,(53.31±1.30)% and (59.98±0.95) % in the blank control group,PDGFR-α MSODN group,0.5 μmol/L PDGFR-α ASODN group and 1.0 μmol/L PDGFR-α ASODN group,showing significandifference among them (F =68.41,P<0.01),and thain the 0.5 μmol/L PDGFR-α ASODN group o1.0 μmol/L PDGFR-α ASODN group showed significantly increase in comparison with the blank control group (P<0.05).ConclusionPDGFR-α silencing could inhibithe proliferation of human LECin vitro.
Résumé
<p><b>BACKGROUND</b>The optimal revascularization strategy in patients with heart failure with preserved ejection fraction (HFPEF) remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with HFPEF.</p><p><b>METHODS</b>From July 2003 through September 2005, a total of 920 patients with coronary artery disease (CAD) and HFPEF (ejection fraction ≥ 50%) underwent PCI (n = 350) or CABG (n = 570). We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events (MACCE), including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days.</p><p><b>RESULTS</b>In-hospital mortality was significantly lower in the PCI group than in the CABG group (0.3% vs. 2.5%, adjusted P = 0.016). During follow-up, there was no significant difference in the two groups with regard to mortality rates (2.3% vs. 3.5%, adjusted P = 0.423). Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG (13.4% vs. 4.0%, adjusted P < 0.001), mainly due to higher rate of repeat revascularization (adjusted P < 0.001). Independent predictors of mortality were age, New York Heart Association (NYHA) class and chronic total occlusion.</p><p><b>CONCLUSION</b>Among patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.</p>
Sujets)
Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Angioplastie coronaire par ballonnet , Mortalité , Pontage aortocoronarien , Mortalité , Défaillance cardiaque , Thérapeutique , Mortalité hospitalière , EndoprothèsesRésumé
<p><b>BACKGROUND</b>HATCH score is an established predictor of progression from paroxysmal to persistent atrial fibrillation (AF). The purpose of this study was to determine if HATCH score could predict recurrence after catheter ablation of AF.</p><p><b>METHODS</b>The data of 488 consecutive paroxysmal AF patients who underwent an index circumferential pulmonary veins (PV) ablation were retrospectively analyzed. Of these patients, 250 (51.2%) patients had HATCH score = 0, 185 (37.9%) patients had HATCH score = 1, and 53 (10.9%) patients had HATCH score ≥ 2 (28 patients had HATCH score = 2, 23 patients had HATCH score = 3, and 2 patients had HATCH score = 4).</p><p><b>RESULTS</b>The patients with HATCH score ≥ 2 had significantly larger left atrium size, the largest left ventricular end systolic diameter, and the lowest ejection fraction. After a mean follow-up of (823 ± 532) days, the recurrence rates were 36.4%, 37.8% and 28.3% from the HATCH score = 0, HATCH score = 1 to HATCH score ≥ 2 categories (P = 0.498). Univariate analysis revealed that left atrium size, body mass index, and failure of PV isolation were predictors of AF recurrence. After adjustment for body mass index, left atrial size and PV isolation, the HATCH score was not an independent predictor of recurrence (HR = 0.92, 95% confidence interval = 0.76 - 1.12, P = 0.406) in multivariate analysis.</p><p><b>CONCLUSION</b>HATCH score has no value in prediction of AF recurrence after catheter ablation.</p>