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Objective:To investigate the effect of amlodipine/benazepril tablets on blood pressure control and cardiac function improvement in older adult patients with hypertension complicated by coronary heart disease.Methods:A randomized controlled clinical study was conducted on 98 older adult patients with hypertension complicated by coronary heart disease who were diagnosed and treated at Liaoning Jinqiu Hospital between February 2020 and February 2022. The patients were randomly divided into an observation group and a control group, with 49 patients in each group using a random lottery method. The control group was treated with amlodipine tablets, while the observation group was treated with amlodipine/benazepril tablets for 3 months. Blood pressure levels and cardiac function improvement were compared between the two groups.Results:Prior to treatment, there were no statistically significant differences in diastolic blood pressure, systolic blood pressure, cardiac function indices, and inflammatory factor levels between the two groups (all P > 0.05). After treatment, the observation group exhibited lower levels of diastolic blood pressure and systolic blood pressure [(88.74 ± 4.26) mmHg, (125.47 ± 6.23) mmHg, 1 mmHg = 0.133 kPa] compared with the control group [(95.71 ± 4.55) mmHg, (134.28 ± 6.10) mmHg, t = 7.07, 7.82, both P < 0.001]. After treatment, the observation group showed lower levels of endothelin 1 and higher levels of nitric oxide compared with the control group ( t = 5.02, 4.96, both P < 0.05). After treatment, the observation group demonstrated lower left ventricular end-systolic diameters [(44.04 ± 3.26) mm vs. (48.58 ± 3.19) mm, t = 6.96, P < 0.001], lower left ventricular end-diastolic diameters [(52.07 ± 4.11) mm vs. (60.12 ± 4.30) mm, t = 9.47, P < 0.001], and higher levels of left ventricular ejection fraction [(54.08 ± 3.06)% vs. (47.50 ± 3.22)%, t = 10.36, P < 0.001] compared with the control group. The levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in the observation group were significantly lower than those in the control group ( t = 5.53, 12.48, 13.45, all P < 0.001). Conclusion:Amlodipine/benazepril tablets are effective in facilitating the recovery of cardiac and vascular endothelial function in older adult patients with hypertension complicated by coronary heart disease. Furthermore, they improve blood pressure control and mitigate the inflammatory response in the body.
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Understanding of a variety of membranous structures throughout the body,such as the fascia,the serous membrane,is of great importance to surgeons. This is especially valuable in abdominal surgery. With the rise of membrane theory in recent years,membrane anatomy has been widely recognized in the treatment of abdominal tumors,especially of gastrointestinal tumors. In clinical practice. The appropriate choice of intramembranous or extramembranous anatomy is appropriate to achieve precision surgery. Based on the current research results,this article described the application of membrane anatomy in the field of hepatobiliary surgery,pancreatic surgery,and splenic surgery,with the aim of blazed the path from modest beginnings.
Тема - темы
Humans , Mesentery/surgery , Digestive System Surgical Procedures , Fascia/anatomy & histologyРеферат
We analyzed the anticancer effect and mechanism of the novel indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor NLG-919 combined with temozolomide (TMZ) on human glioma cell lines. The anti-tumor activity of NLG-919 and temozolomide after single and combined treatments was detected by MTT assay. Colony formation assay, invasion assay and migration assays were used to detect the effects of NLG-919 and temozolomide alone or in combination on proliferation, invasion and migration of human glioma cells. A flow cytometry assay was used to detect cell apoptosis, cell cycle arrest, reactive oxygen species (ROS) production and mitochondrial membrane potential damage (JC-1). An immunofluorescence assay was used to detect the expression level of IDO1 and HPLC was used to detect the expression level of L-kynurenine (Kyn) to explore the anti-tumor mechanism of NLG-919 and temozolomide. The results show that NLG-919 had a weak in vitro inhibitory effect compared to that of temozolomide. The IC50 of NLG-919 on U251 cells and U87 after 72 h was 26.9 and 30.7 μmol·L-1, respectively. However, when NLG-919 was used in combination with temozolomide, its anti-glioma activity was significantly increased. Compared with the single treatment, the combination treatment had a potent ability to inhibit proliferation, invasion and migration of glioma cells. Combination treatment improved the capacity of temozolomide to induce cell cycle arrest and inhibit the growth of glioma cells. NLG-919 significantly down-regulated the expression and activity of IDO1 in glioma cells, and the inhibitory effect was improved after combination with temozolomide, and effectively blocked the production of Kyn through the metabolism of L-tryptophan (Trp). In conclusion, the IDO1 inhibitor NLG-919 and temozolomide showed synergistic effects in the anticancer therapy of human glioma cell lines.
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This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.
Тема - темы
Animals , Chlorocebus aethiops , Drugs, Chinese Herbal/pharmacology , Enterovirus A, Human/physiology , Hand, Foot and Mouth Disease , Vero CellsРеферат
Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.
Тема - темы
Adolescent , Child , Child, Preschool , Female , Humans , Male , Body Mass Index , China/epidemiology , Cross-Sectional Studies , Obesity/epidemiology , Overweight/epidemiology , Puberty , Puberty, Precocious , Sexual DevelopmentРеферат
Clinical practice using associating liver partition and portal vein ligation for staged hepatectomy(ALPPS) or its modified procedures in treatment of primary hepatocellular carcinoma(HCC) with insufficient future liver remnant(FLR) in the past 10 years has failed to meet our expectations both in achieving decreased perioperative complications and mortality.The efficacy of ALPPS in improving long-term survival outcome of HCC still remains poor.Due to the trauma of two surgery within a short period,and patients with inadequate FLR are all diagnosed at advanced disease stages,ALPPS can only achieve surgical rather than biological tumor-curability.Previous studies have demonstrated comparable 5-year survival rates between early and advanced stages of HCC who underwent regional treatments.Therefore,tumor biological conversion is the key strategy prior to liver remnant volume conversion in improving treatment outcomes for HCC patients with insufficient FLR.Target therapy,immunotherapy together with locally treatment were expected to improve the conversion efficacy.Looking back at the development of ALPPS for the last decade,the rapid proliferation of FLR should be passed on,while the technology costs high risks and result in poor long-term outcome must be cautiously selected.
Тема - темы
Humans , Carcinoma, Hepatocellular/surgery , Hepatectomy , Ligation , Liver , Liver Neoplasms/surgery , Portal Vein/surgery , Technology , Treatment OutcomeРеферат
Glypican-3 (GPC3) is an oncofetal protein anchored on the plasma membrane and highly expressed in hepatocellular carcinoma (HCC).GPC3 could he used as a biomarker for the diagnosis of HCC and the serum levels of GPC3 in liver cancer patients has a significant role for their prognosis.Moreover, GPC3 in HCC cells is immunoreactive, rendering it a suitable target for the treatment of HCC.Nowadays, several clinical trials targeting GPC3 for HCC therapy have already been conducted: new anti- GPC3 antibodies are generated; the clinical trials about its combination administration with other targeted medicines are being in progress; (tP(3-targeted TRAB, GPC3 vaccines and GPC3-based chimeric antigen receptor T-cells (CAR-T) therapy are under investigation.In this review, we briefly discuss the structure of GPC3, its role in HCC pathogenesis and summarize the recent development in the clinical application of GPC3.We firmly believe that GPC3 would be a promising target for HCC therapy.And further studies focusing on GPC3 should provide us more solid evidence.
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Objective:To compare the clinical manifestations of ocular toxoplasmosis (OT) in adult and children, and to preliminarily explore the role of intraocular fluid detection in the early diagnosis of OT.Methods:A retrospective study. From January 2018 to October 2019, 60 cases of OT patients with 60 eyes diagnosed in the Department of Ophthalmology of Beijing Chaoyang Hospital Affiliated of Capital Medical University were included in the study. The medical history information of patients was collected in parallel with slit-lamp microscopy, indirect ophthalmoscope examination, and canine toxoplasma antibody detection in aqueous or vitreous fluid. Fifty-eight cases underwent visual inspection; 2 cases did not underwent visual inspection, who were children. The visual acuity examination was carried out using the new version of the standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution(logMAR) visual acuity during statistics. According to age, the patients were divided into adult group and child group, with 12 eyes in 12 cases and 48 eyes in 48 cases, respectively. The clinical characteristics and main points of diagnosis and treatment of the two groups of patients were compared and observed. The comparison among the measurement data groups conforming and the normal distribution was performed by the independent t test. The comparison between the measurement data groups of the skewed distribution was performed by the Kruskal- Wallis test. The qualitative data were compared with χ 2 test. Results:Among the adult group and the child group, 7 (58.3%, 7/12) and 34 (70.8%, 34/48) patients with a clear history of contact with dogs and cats were in the adult group and the child group, respectively. The adult group was significantly lower than the child group, however, there was no different statistical significance ( χ 2=0.236, P=0.627). At the first visit, the self-reported blurred vision of the adult group and the child group was 10 (83.3%, 10/12) and 22 (45.8%, 22/48) cases, respectively. In the adult group and the child group, 3 (25.0%, 3/12) and 20 (43.5%, 20/46) eyes with logMAR visual acuity greater than 1.85, 8 (66.7%, 8/12) and 22 (45.8%, 22/46) eyes with logMAR visual acuity less than 0.3. The visual acuity of the adult group was better than that of the child group, and the difference was statistically significant ( Z=2.162, P=0.031). There was no statistically significant difference in the composition ratio of different clinical types of the two groups of eyes ( χ 2=1.908, P=0.385). The incidence of inflammation in the anterior segment of the eye in the adult group and the child group were 25.0% (3/12) and 56.3% (27/48), respectively; there was no statistically significant difference between the two groups ( χ 2=3.750, P=0.053). The concentration of antibodies in the vitreous humor of the affected eye in the adult group and the child group was greater than that of aqueous humor. The antibody concentrations of vitreous humor and aqueous humor were 36.51 (22.58) and 19.94 (21.78) U/ml in the children group; 45.95 (56.44) and 32.20 (38.64) U/ml in the adult group. Comparison of antibody concentrations in the vitreous humor and aqueous humor of the affected eyes in the child group showed statistically significant differences ( Z=-1.984, P=0.047). Conclusions:Compared with children with OT, adult patients with OT have better vision and mild inflammation or hyperplasia of the vitreous cavity. The detection of antibodies related to toxoplasma in the intraocular fluid is helpful for early diagnosis.
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OBJECTIVE@#To observe the effect of electroacupuncture (EA) pretreatment on inflammatory reaction, apoptosis and expression of Yes-associated protein (YAP) of ischemic penumbra of cerebral cortex in cerebral ischemia reperfusion injury rats, and to explore the possible mechanism of its neuroprotection effect.@*METHODS@#A total of 84 SD rats were randomized into a sham operation group (12 rats), a model group (18 rats), an EA group (18 rats), an EA+YAP virus transfection group (18 rats) and an EA+virus control group (18 rats). Except for the sham operation group, thread embolization method was adopted to establish the middle cerebral artery occlusion (MCAO) model in rats of the other groups. EA was applied at "Baihui" (GV 20) and "Dazhui" (GV 14) for 30 min in the 3 EA intervention groups 2 h before model establishment, disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in intensity. Adenovirus transfection technique was used to induce gene silencing of YAP in the EA+YAP virus transfection group, and adenovirus vectors was injected as negative control in the EA+virus control group 4 d before model establishment. Twenty-four hours after model establishment, neurological function score was evaluated, the relative cerebral infarction area was observed by TTC staining, the apoptosis in the ischemic penumbra of cerebral cortex was detected by TUNEL staining, the levels of inflammatory factors IL-1β, IL-6 and TNF-α in the ischemic penumbra of cerebral cortex was detected by ELISA method, the expression of YAP was detected by Western blot and immunofluorescence.@*RESULTS@#Compared with the sham operation group, the expression of YAP was increased in the model group (@*CONCLUSION@#Electroacupuncture pretreatment can effectively improve the ischemia reperfusion injury, its mechanism may be related to up-regulating the expression of YAP in the ischemic penumbra of cerebral cortex and relieving the apoptosis and inflammatory reaction.
Тема - темы
Animals , Rats , Brain Ischemia/therapy , Electroacupuncture , Infarction, Middle Cerebral Artery , Rats, Sprague-Dawley , Reperfusion Injury/therapyРеферат
Objective:To investigate the therapeutic effect of polydatin on ulcerative colitis (UC) in mice and its regulation of protein kinase C<italic>θ</italic>(PKC<italic>θ</italic>)/signal transducer and activator of transcription 3(STAT3) signaling on T helper cell 17(Th17) and its mechanism in the treatment of UC. Method:The 32 male C57BL/6 mice were randomly divided into normal group, model group, polydatin group (0.045 g·kg<sup>-1</sup>) and sulfasalazine group (0.5 g·kg<sup>-1</sup>). The UC model was established by giving 3% dextran sodium sulfate (DSS) solution to free drinking water in mice. Polydatin and sulfasalazine groups were given by gavage 0.5 h before modeling for 7 days. The normal group and model group were given the same amount of normal saline. After the last administration, the colonic tissue was taken and hematoxylin-eosin (HE) was used to observe the pathological changes of colonic tissue. Flow cytometry was used to detect the proportion of Th17 in the lamina propria of colonic mucosa. The expression of interleukin-17A (IL-17A) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Polydatin was added to CD4<sup>+ </sup>T cells purified from spleen of C57BL/6 mice by magnetic-activated cell sorting (MACS) under the stimulation of cell stimulation cocktail <italic>in vitro </italic>in order to detect its impact on PKC<italic>θ</italic> and STAT3 phosphorylation. Result:Compared with normal group, the body weight was significantly decreased, and disease activity index (DAI) scores of the model group was significantly increased (<italic>P</italic><0.01), the colonic mucosal epithelium was damaged and inflammatory cells infiltration in the mucosa and submucosa was obvious, the proportion of Th17 in the lamina propria of colonic mucosa was significantly increased (<italic>P</italic><0.01), and the content of serum IL-17A was significantly increased (<italic>P</italic><0.01). Compared with the model group, the weight and DAI score of polydatin and sulfasalazine groups were significantly improved (<italic>P</italic><0.01), the degree of colon tissue damage was significantly improved, the proportion of Th17 in colon mucosa lamina propria was significantly decreased (<italic>P</italic><0.01), and the content of IL-17A in serum was significantly decreased (<italic>P</italic><0.01). <italic>In vitro</italic> experiments showed that polydatin could significantly inhibit the phosphorylation of PKC<italic>θ</italic> and STAT3 in Th17 (<italic>P</italic><0.01) as well as IL-17A secretion. Conclusion:Polydatin can improve the ulcerative colitis in mice via inhibiting the phosphorylation of PKC<italic>θ</italic> and STAT3 to preclude IL-17A secreting in Th17.
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OBJECTIVE@#To study the association of body fat ratio with precocious puberty in girls. Previous studies have shown that body mass index (BMI) is associated with the girls' age of puberty but have not revealed the association of body fat ratio with age of puberty.@*METHODS@#Based on the consensus on the diagnosis and treatment of central precocious puberty (CPP), 128 children with precocious puberty who were admitted to the hospital from July to August, 2017, were divided into a CPP group with 87 children and a peripheral precocious puberty (PPP) group with 41 children. A total of 51 girls without any puberty development signs were enrolled as the control group. Dual-energy X-ray absorptiometry was used to measure the body fat ratios of upper limbs, legs, trunk, android area, gynoid area, and the whole body. The association between body fat ratios and precocious puberty was analyzed with reference to age, BMI, BMI-Z score, bone age, ovarian volume, and hormone levels.@*RESULTS@#Compared with the control group, the CPP and PPP groups had significantly higher body fat ratios of upper limbs, legs, trunk, android area, gynoid area, and the whole body, legs/whole body fat ratio, and (upper limbs+legs)/trunk fat ratio (P0.05). For the girls with precocious puberty, the high body fat ratio group had significantly higher luteinizing hormone (LH) base value, luteinizing hormone releasing hormone (LHRH)-stimulated LH peak value, and LH/follicle-stimulating hormone peak value than the low body fat ratio group (P<0.05). Compared with the control group, both the high body fat ratio and low body fat ratio groups had a significantly higher LH base value (P<0.05).@*CONCLUSIONS@#The increase in body fat may be a factor inducing precocious puberty in girls, but further studies are needed to determine the mechanism.
Тема - темы
Child , Female , Humans , Adipose Tissue , Follicle Stimulating Hormone , Gonadotropin-Releasing Hormone , Luteinizing Hormone , Puberty, Precocious , Sexual MaturationРеферат
To investigate the value of diffusion-weighted imaging(DWI)and apparent diffusion coefficient(ADC)in the diagnosis and differential diagnosis of posterior fossa solid hemangioblastoma(PFSH). We retrospectively analyzed the clinical data of 15 PFSH patients and 58 patients with other hypervascular tumors in the posterior fossa(the latter included 23 cases of meningioma,5 cases of medulloblastoma,8 cases of acoustic neuroma,4 cases of hemangiopericytoma,5 cases of lymphoma,9 cases of metastatic tumor,3 cases of astrocytoma,and 1 case of choroid plexus papilloma)confirmed by operation and pathology.All patients underwent axial DWI scans,and the mean ADC value of solid part of the tumors and the adjacent normal cerebellar white matter were measured,and then the normalized ADC was calculated.In addition, test was used to compare the differences in mean ADC and normalized ADC between these two groups,and receiver operating characteristic(ROC)curve was applied to analyze the diagnostic performance of normalized ADC. Of all the 15 PFSH patients,DWI appeared hypointense in 12 patients and isointense in 3 patients;the signals on ADC maps were isointense or hyperintense;the mean ADC value of PFSHs was(1.881±0.445)×10 mm /s and the normalized ADC was 2.70±0.62.In contrast,in 58 patients with other tumors in the posterior fossa,DWI appeared hyperintense in 51 cases,isointense in 3 cases,and hypointense in 4 cases;the mean ADC value was(0.771±0.202)×10 mm /s,and the normalized ADC was 1.17±0.33.Thus,the ADC value and normalized ADC value were significantly higher in PFSH than in other tumors in the posterior fossa(=9.419,<0.001;=9.184,<0.001).The cut-off value of the normalized ADC for the diagnosis of solid hemangioblastoma was 1.89,with the sensitivity and specificity being 100%and 96.6%respectively,and the area under the ROC curve was 0.989. ADC and normalized ADC are valuable in the differential diagnosis of PFSH from other tumors with abundant blood supply.
Тема - темы
Humans , Diagnosis, Differential , Diffusion Magnetic Resonance Imaging , Hemangioblastoma , Diagnosis , ROC Curve , Retrospective StudiesРеферат
OBJECTIVE@#To investigate the effect of stably down-regulating the FMI expression of K562 cells on the sensitivity of K562 cells to Imatinib (IM) and its possible mechanism.@*METHODS@#Western-blot was used to detect the expression of FMI protein in K562 cells and peripheral blood mononuclear cells from the patients with chronic myelogenous leukemia, chronic myeloid blast crisis and healthy volunteers. The specific interference sequences targeting at the human FMI gene were designed and ligated into the lentiviral vector LV3; the three plasmid system-packaged lentivirus particles were used to transfect K562 cells to screen K562 cells that stably down-regulated FMI. CCK-8 assay and flow cytometry were used to determine effect of IM on cell proliferation and apoptosis. The transcription level of FMI and Fz8 in leukemia cells was detected by fluorescent quantitative PCR. The protein expression levels of FMI, Fz8, NFAT1, BCR-ABL and β-catenin in leukemia cells were detected by Western-blot.@*RESULTS@#The expression of FMI protein could be detected in peripheral blood mononuclear cells of the patients with CML-BC and K562 cells, the FMI expression could not be detected in all the patients with CML-CP and healthy volunteers. The recombinant lentiviral vector LV3/FMI had been successfully constructed the lentivirus was packaged, and the K562 cells stably down-regulating the FMI protein were screened. After stable down-regulation of FMI expression in K562 cells, the proliferation rate of leukemia cells decreased and the apoptosis rate was increased under the same drug concentration. Both the transcription and protein expression levels of Fz8 decreased. The NFAT1 total protein level increased, as well as the nuclear translocation of protein was enhanced. There was no significant change in the expression level of BCR-ABL fusion protein. The expression level of β-catenin protein decreased.@*CONCLUSION@#After the stable down-regulation of FMI expression, the sensitivity of K562 cells to IM and apoptosis of cells increase, which are performed possibly by inhibiting the FMI-Fz8 signaling pathway and activating the Ca-NFAT and Wnt/β-catenin signaling pathway.
Тема - темы
Humans , Apoptosis , Drug Resistance, Neoplasm , Fusion Proteins, bcr-abl , Imatinib Mesylate , K562 Cells , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukocytes, MononuclearРеферат
OBJECTIVE: To observe the effect of acupoint injection at "Yingxiang"(LI 20) and "Yintang"(GV 29) on nasal allergic reactions and the expression of histamine receptor H 1 and H 4 in nasal mucosa of allergic rhinitis (AR) rats, so as to reveal its mechanism underlying improvement of AR. METHODS: SD rats were randomized into normal, model, non-acupoint injection and acupoint injection groups (n=8 in each). The AR model was established by intraperitoneal (i.p.) injection of mixture of ovalbumin, aluminium hydroxide gel and normal saline (once every other day, for 7 times), and nasal drip of ovalbumin (on the following day of i.p.for 7 days). The mixture solution of lidocaine, dexamethasone (DXM) and transfer factor (0.1 mL/acupoint or non-acupoint) was injected into bilateral LI 20 and GV 29 in the acupoint injection group, or into the non-acupoints (about 5 cm below the armpit on both sides, and the middle point between the left "Houhai"[GV 1] and "Huantiao"[GB 30]), on the 1st , 5th, 9th, and 13th day after modeling. Symptoms of sneezing, nasal discharge, nose-rubbing, etc. were scored after the treatment. The expression levels of H1 R and H4 R proteins and genes in the nasal mucosa tissue were determined using immunohistochemistry and quantitative real-time PCR, respectively. RESULTS: Compared with the normal group, the symptom score and the expression levels of H1 R, H4 R proteins and genes in nasal mucosa were significantly increased in the model group (P0.05), suggesting a specificity of the effect of acupoint injection. CONCLUSION: Acupoint injection can relieve the allergic symptoms of AR rats, which may be related to its effects in down-regulating the over expression of H1 R and H4 R proteins and genes in the nasal mucosa.
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·AIM: To compare clinical effects and cost of panretinal photocoagulation (PRP) combined with Ranibizumab or triamcinolone acetonide (TA) for diabetic macular edema (DME). ·METHODS: Forty-eight patients (48 eyes) with DME and diabetic retinopathy ( DR) receiving PRP were randomly assigned to two groups, which were respectively intravitreally injected ranibizumab (0. 5mg) and TA (4mg). Ranibizumab (0.5mg) was intravitreal injected every 4wk for 3 times. The effects of injection for DME were evaluated using best-corrected visual acuity (BCVA ), central macular thickness ( CMT ) and intraocular pressure (IOP). During the follow-up, other injections were performed to eyes which had CMT greater than 400μ m. The medical costs were calculated at 12wk and 24wk.·RESULTS: BCVA and CMT between 2 groups were not significantly different (P>0.05); BCVA and CMT among different time points were significantly different(P<0.05);the treatments and the time points had significant interaction on BCVA (P<0.05). BCVA was improved in two groups at all the time after injection(P<0.05),except 1wk after injection of TA (P=0.33). There was significant difference between the two groups at 12wk and 16wk on BCVA and that injected with ranibizumab was better (P=0.03,0.045). CMT decreased in two groups at all the time after injection (P<0.05). There was significant difference only between the two groups at 1wk (P< 0. 01). All intraocular pressures were in the normal range, except one needed ocular hypotensive agents. The medical costs (yuan) of the ranibizumab group in 12wk and 24wk were 38 736 and 42 564,which of the TA group were 5 790 and 7 053,respectively. ·CONCLUSION:Both PRP combined with ranibizumab or TA for DME can effectively control disease progression in short time. Therapeutic effect is not significant between two methods, but PRP combined with TA is more economic.
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<p><b>OBJECTIVE</b>To investigate the effect of steadily down-regulating the expression of VE-cadherin on the chemotheraputic sensitivity of K562 cells, and explore its possible mechanism.</p><p><b>METHODS</b>Specifically targeting interference sequences carrying human VE-cadherin were designed, the recombinant lentiviral vector containing the IRES-GFP and NEO segment was constructed; recombinant lentivirus was generated by three-plasmids packing system, and transfected into K562 cells, then the cells steadily down-regulated were sorted. CCK-8 assay was performed to evaluate the VE-cadherin of chemotherapeutic (Imatinib) sensitivity of K562 cells. The apoptosis was analyzed by flow cytometry with Annexin V/7-AAD double labeling. The expressions of CD133 and ALDH1 mRNA were determined by real time PCR. The protein expressions of VE-cadherin, BCR-ABL and β-catenin were analyzed by Western blot.</p><p><b>RESULTS</b>The recombinant lentiviral vector pLB-shVEC-NEO-IRES-GFP was successfully constructed, packed into the lentivirus, then the K562 cells steadily down-regulating VE-cadherin expression was obtained. When VE-cadherin was down-rengulated in K562 cells, the proliferation rate was reduced while the the apoptosis rate was increased; the mRNA levels of CD133 and ALDH1 also were reduced; BCR-ABL fusion protein was not obviously changed; the total β-catenin protein, as well as the nuclear β-catenin protein were decreased in the K562/shVEC cells. Conclution: K562 cells are more susceptible to chemotherapy when VE-cadherin is down-regulated, that may be realized via reducing the stability and the nuclear transfer of β-catenin protein.</p>
Тема - темы
Humans , Antigens, CD , Metabolism , Apoptosis , Cadherins , Metabolism , Cell Proliferation , Fusion Proteins, bcr-abl , K562 CellsРеферат
AIM:To investigate the changes of cardiac structure and function in rats with type 2 diabetic melli-tus(T2DM),and to explore the mechanisms underlying diabetic cardiomyopathy.METHODS:The cardiac structure and function were measured by echocardiography in Zucker diabetic fatty(ZDF)rats and their control Zucker lean(ZL)rats. The size of the cardiomyocytes was determined by wheat germ agglutinin staining.The protein expression of atrial natriuretic peptide(ANP),β-myosin heavy chain(β-MHC), receptor for advanced glycation end products(RAGE), L-type cal-cium channel α1C subunit(CaV1.2)and Orai1 was assessed by Western blot.RESULTS:Compared with the ZL control rats,the thickness of left ventricular wall,ejection fraction(EF),fractional shortening(FS)and the sizes of cardiomyo-cytes were significantly increased,and diastolic function was decreased in the ZDF rats(P<0.05).The protein expression of β-MHC, ANP, RAGE and Orai1 was increased, while the expression of Ca V1.2 was decreased in ZDF rats(P <0.05).CONCLUSION:T2DM rats show the prominent features including cardiomyocyte hypertrophy,ventricular hyper-trophy and compensatory enhancement of cardiac function, and the Ca2+handling and increase in RAGE expression may play important roles in the processes.
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Objective: To explore the relationship between ABO blood group and acute non-ST-segment elevation myocardial infarction (NSTEMI) occurrence. Methods: Our research included 2 groups: NSTEMI group, 1039 relevant patients treated in Anzhen hospital from 2013-01 to 2014-12 were retrospectively enrolled; Control group, 1039 subjects with normal coronary artery which was confirmed by coronary angiography. The Baseline condition including age, previous disease history and ABO blood group was studied. Logistic regression model was used to conduct single and multivariate analysis. Results: In NSTEMI group and Control group, blood type A was 287/1039 (27.6%) vs 259 (24.9%), type B was 345 (33.3%) vs 356 (34.3%), type AB was 102 (9.8%) vs 114 (11.0%) and type O was 305 (29.4%) vs 310 (29.8%), ABO blood group distribution for A and non-A, B and non-B, AB and non-AB blood group, O and non-O had no statistic meaning between 2 groups, P>0.05. Logistic regression analysis indicated that with adjusted risk factors of MI such as age, gender, hypertension, diabetes, hyperlipemia, cerebrovascular disease and smoking, the patients with blood types A, B and AB had the similar risk for NSTEMI occurrence than type O patients; there was no relationship between ABO blood group and NSTEMI occurrence. Conclusion: ABO blood group had no relationship to NSTEMI occurrence.
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Objective To investigate the initiation pathway of corneal endothelial cell apoptosis induced by high-pression.Methods Primary rabbit corneal endothelial cells were identified by immunohistochemistry and cultured under high pressure 50 mmHg (1 kPa =7.5 mmHg) for 1 h,2 h,24 h,respectively,while cells cultured under the normal pressure 15 mmHg served as the normal pression group.In addition,the first generation of rabbits corneal endothelial ceils with 70% to 80% fusion were pretreated with 10-6 mol · L-1 anti-Caspase 8 and anti-Caspase 9 for lh,followed by 50 mmHg pression for the treatment of the cells;while cells cultured with no inhibitor in the same pression served as the control group.Then the expression of P53 and Bcl-2 protein was detected by Western blot,and cytochrome C in rabbit corneal endothelial cells was determined by immunofluorescence staining in all groups.Results The expression levels of P53 in the 50 mmHg group were 0.651 +0.007,0.805 ±0.006 and 0.839 ±0.011 after 1 h,2 h,24 h high-pression respectively,which were significantly higher than those in the normal pressure group (0.033 ± 0.004),and the difference approached statistical significance (all P < 0.01).The expression of P53 protein in corneal endothelial cells gradually increased as time went on,and the difference was statistically significant between each two time-points (all P < 0.01).Moreover,the expression of Bcl-2 in the 50 mmHg pressure group was 0.590 ± 0.009,0.724 ± 0.005 and 0.34 ± 0.016,respectively,which was higher than that in the normal pressure group (0.081 ±0.013),with signifi cant difference (all P < 0.01),and the difference approached statistical significance between each two time points in this group (all P < 0.01).The expression level of P53 in anti-Caspase 9 and anti-Caspase 8 group was 0.535 ± 0.007 and 0.703 ± 0.010,respectively,which was significantly lower than that in the control group (0.727 ± 0.021),and the difference was statistically significant (all P < 0.01).The expression of Bcl2 was 0.312 ± 0.003 and 0.442 ± 0.011,respectively,which were significantly lower than that in the control group (0.501 ± 0.011),with statistical difference (P < 0.01).Finally,the expression of P53 and Bcl-2 in anti-Caspase 9 group was lower than that of anti-Caspase 8 group (P < 0.01),indicating that anti-Caspase 9 had more enhanced inhibitory effect on the apoptosis of corneal endothelial cells than anti-Caspase 8.Conclusion AntiCaspase 9 inhibitor could effectively block the corneal endothelial cell apoptosis induced by high pressure.And the damage from high pressure on corneal endothelial cells mainly triggers the release of cytochrome C from chondriosome to activate the endogenous enzyme linked apoptotic pathway in which Caspase 9 involves.
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Objective:To explore clinical and fistula origin characteristics of congenital coronary artery fistula (CAF).Methods:Clinical and coronary angiographic (CAG)data of 37 congenital CAF patients,who were treated in our hospital from Apr 2011 to Aug 2016 and diagnosed by CAG,were retrospectively analyzed.Chief complaint symptoms were analyzed.According to fistula origin location,patients were divided into left anterior descending (LAD)group (n=23),right coronary artery (RCA)group (n=6),LAD & RCA group (n=2),left circumflex (LCX)group (n=5)and left main (LM)group (n=1).Characteristics of fistula origin and drainage location dis-tribution were analyzed.Results:Among the chief complaints of 37 congenital CAF patients,there were 24 cases (64.9%)of chest tightness and short of breath,six cases (16.2%)of chest pain,five cases (13.5%)of palpitations and two cases (5.4%)of heart murmur in physical examination.Compared with RCA group,LAD & RCA group, LCX group and LM group,there was significant rise in percentage of LAD fistula origin (16.2%,5.4%,13.5%, 2.7% vs.62.2%),P <0.01 all,but there were no significant difference among other groups,P >0.05 all.The 23 cases of LAD fistula origin included 22 cases of pulmonary artery fistulas (PAF)and one case of bronchial artery fis-tulas (BAF);the six cases of RCA fistula origin included three cases of PAF,two cases of right atrial fistulas (RAF) and one case of left ventricular fistulas (LVF);the five cases of LCX fistula origin included two cases of RAF,and one case of PAF,LVF and RVF respectively.Conclusion:Coronary angiography is the gold standard to diagnose congenital CAF.Percentage of congenital CAF originated from left coronary artery is significantly more than that of right coronary artery.