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Objective To evaluate the correlation between alterations in DNase1 and DNase1L3 enzyme activities and impairment of NET degradation in patients with sporadic SLE, and to investigate the underlying mechanism. Methods 46 sporadic SLE patients and 30 age- and sex-matched healthy individuals were recruited. Serum levels of DNase1, DNase1L3 and corresponding autoantibodies were detected by ELISA. DNase1 and DNase1L3 were isolated by immunoprecipitation; NETs and enzyme degradation activities were detected using a modified immunofluorescence. DNase1L3 secretion by PBMCs was analyzed by ELISPOT, Western blotting and reverse transcription PCR. Results Levels of H3-dsDNA and Ela-dsDNA complexes were significantly elevated in SLE patients. LDGs in SLE population was significantly higher than in the control group, and LDGs was positively correlated with H3-dsDNA and Ela-dsDNA NETs complexes. The ability of SLE patients to degrade NET in vitro was significantly lower than that of the control group. Degradation experiments of DNase1 and DNase1L3 in different proportions showed that the decrease in DNase1L3 activity was the primary contributor to the elevated NET residue level. The concentration of DNase1L3 autoantibodies in SLE patients was significantly elevated compared to the control group. In addition, the capacity of PBMCs to secrete DNase1L3 was significantly lower in the SLE patients compared to the control group. Conclusion Decreased secretion of DNase1L3 and the presence of relevant autoantibodies notably impede NET degradation in patients with SLE, offering new directions for the monitoring and treatment of SLE patients.
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Humans , Autoantibodies , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Extracellular Traps , Lupus Erythematosus, SystemicABSTRACT
BACKGROUND:Ischemic stroke is a serious threat to human health.After ischemia and hypoxia,astrocyte expresses lipocalin-2 in large amounts to aggravate brain injury,but the specific mechanism is not clear.Hydroxysafflor yellow A has anti-ischemia,anti-oxidation,anti-thrombosis and anti-inflammatory effects.However,whether hydroxysafflor yellow A affects the expression of lipocalin-2 in astrocytes after cerebral ischemia and hypoxia and its mechanism are not clear. OBJECTIVE:To investigate the effect and mechanism of hydroxysafflor yellow A on the expression of lipocalin-2 in astrocytes after cerebral ischemia and reperfusion. METHODS:(1)Thirty adult SD rats were randomly divided into three groups:sham operation group,middle cerebral artery occlusion and reperfusion group,and hydroxysafflor yellow A group.The middle cerebral artery occlusion and reperfusion model was established in the latter two groups,and hydroxysafflor yellow A group was intraperitoneally injected with 12 mg/kg hydroxysafflor yellow A after reperfusion.Longa score was used to evaluate the degree of neurological impairment.Infarct volume was determined by TTC staining.JAK2/STAT3 pathway and lipocalin-2 expression were detected by western blot assay and immunofluorescence.Levels of interleukin 1β,interleukin 6 and tumor necrosis factor α were detected by ELISA.(2)Astrocytes were divided into four groups:Normal group,glucose-oxygen deprivation group,hydroxysafflor yellow A group and AG490 group.In the latter three groups,glucose-oxygen deprivation and glucose-oxygen recovery models were established.Astrocytes were treated with 75 μmol/L hydroxysafflor yellow A and 10 μmol/L tyrosine phosphorylation inhibitor AG490 for 8 hours during glucose-oxygen deprivation,respectively.The mechanism of hydroxysafflor yellow A on lipocalin-2 was further verified. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,cerebral infarction was significantly increased in the middle cerebral artery occlusion and reperfusion group,accompanied by aggravated neurological impairment(P<0.01).Hydroxysafflor yellow A treatment could reduce cerebral infarction volume and improve neurological function(P<0.01).(2)The expressions of p-JAK2,p-STAT3 and lipocalin-2 in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A treatment reduced the expressions of JAK2,STAT3 and lipocalin-2(P<0.01).(3)The expression levels of interleukin 1β,interleukin-6 and tumor necrosis factor α in the middle cerebral artery occlusion and reperfusion group were higher than those in the sham operation group(P<0.01).Hydroxysafflor yellow A inhibited the expressions of interleukin 1β,interleukin-6 and tumor necrosis factor α(P<0.01).(4)In vitro,the expressions of p-JAK2,p-STAT3 and lipocalin-2 in the glucose-oxygen deprivation group were significantly higher than those in the normal group(P<0.01).After adding AG490,the phosphorylation of JAK2 and STAT3 decreased,and the expression of lipocalin-2 was inhibited(P<0.01).The results suggest that hydroxysafflor yellow A may inhibit the expression of lipocalin-2 in astrocytes after ischemia and hypoxia by regulating the JAK2/STAT3 signaling pathway,thereby reducing brain injury.
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BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway. METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.
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Objective:To investigatethe heterogeneity of career growth recognition amongphysicians at the stage of standardized training and the growth characteristics of clinical physicians in the early stage, and to provide a reference for improving the quality of standardized training.Methods:The trainees who received standardized residency trainingwere randomly selected from three grade A tertiary hospitals in Chongqing, China. Mplus7.4 was used for latent profile analysis to explain the relationship between explicit continuous indicators, and the subtypes of career growth recognition were analyzed.Results:Career growth recognition at the stage of standardized training was classifiedinto three subtypes of all-round growth recognition, high resource and expectation recognition, and unclassified growth recognition, among which the subtype of unclassified growth recognition accounted for the highest percentage of 40.27% (207 trainees).Conclusions:Physicians at the stage of standardized training show obvious uncertainty aboutcareer growth recognition, and it is necessary to strengthen the education on career growth recognition during standardized training and design a development pathway based on the characteristics of career growth recognition.
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OBJECTIVE：To study the effect and potential mechanism of the total flavonoids from Marchantia convoluta on anti-hepatic fibrosis in the mice. METHODS ：Seventy-two mice were randomly divided into blank group ，model group ，positive control group （colchicine 0.2 mg/kg）and M. convoluta total flavonoids high-dose ，medium-dose and low-dose groups （300，150， 75 mg/kg），with 12 mice in eac group. Except for blank group ，other groups were subcutaneously given 25％ CCl4-peanut oil solution on the back to induce liver fibrosis model. At the same time ，blank group and model group were given water intragastrically，while other groups were given relevant medicine intragastrically 20 mL/kg，once a day ，for consecutive 10 weeks. After last administration ，the serum levels of ALT and AST were detected . Histopathological changes of liver tissue in mice was observed. The levels of COL- Ⅰ，COL-Ⅲ and TGF-β1 in liver tissue were detected . The protein expression levels of α-SMA and TGF-β1，Smad2，Smad4 and Smad 7 in liver tissue were detected . The expression levels of TGF-β1，Smad2，Smad4 and Smad 7 mRNA in liver tissue were detected . RESULTS ：Compared with blank group ，the serum levels of ALT and AST in model group，the levels of COL- Ⅰ，COL-Ⅲ and TGF-β1 in liver tissue，protein expression levels of α-SMA，TGF-β1，Smad2 and Smad 4，mRNA expression levels of TGF-β1，Smad2 and Smad4 were increased significantly （P＜0.05 or P＜0.01）.The mRNA and protein expression levels of Smad 7 in liver tis sue were decreased significantly （P＜0.05）. The degree of liver tissue injury and collagen fiber hyperplasia were serious. Compared with model group ，above indexes of mice were reversed significantly in positive control group and M. convoluta total flavonoids high-dose group （P＜0.05 or P＜0.01）. Serum level of ALT ，the levels of COL- Ⅰ，mRNA and protein expression of TGF-β1，Smad2 and Smad 4 in liver tissue were decreased significantly in M. convoluta total flavonoids medium-dose group （P＜0.05 or P＜0.01）. Protein expression of Smad 2 and Smad 4 in liver tissue were decreased significantly in M. convoluta total flavonoids low-dose group （P＜0.05）. The liver injury and fibrosis of mice were relieved in administration groups. CONCLUSIONS ：M. convoluta total flavonoids possess the effect of anti-hepatic fibrosis ，the mechanism of which is related to the regulation of mRNA and protein expression of TGF-β1，Smad2，Smad4 and Smad 7 in the signaling pathway of TGF-β/Smad.
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Objective:To investigate the implementation of surgical dressing change standard and related factors influencing the implementation in a hospital, and to formulate the corresponding countermeasure for improving the dressing change standardization of clinicians.Methods:From February to September, 2018, the quality control circle (QCC) was comprehensively exerted and QCC activities were implemented through selecting topic, making plans, controlling current status, setting goals, analyzing causes, proposing and practicing countermeasures, confirming effects and standardizing the process. The quality was continuously improved on the basis of the PDCA cycle and effects were evaluated. In this study, self-control study was used; QCC activity team of "hand-in-hand circle" was set up; quality management tools were used; self-designed assessment table of dressing change skills and questionnaire for nonstandard reasons of dressing change were used to conduct the questionnaire survey and observation for 77 clinicians, and improvement of standard rate before and after the QCC intervention was compared. SPSS 20.0 was used to perform the t-test and χ2 test. Results:After QCC activity, relative quality indexes of dressing change were significantly increased. The pre-activity average score was (80.45±9.42) and the post-activity average score was (90.06±3.43) ( P<0.01). The standard rate of dressing change of the clinical physician was increased from pre-activity 57.14% to post-activity 98.70% ( P<0.01), which reached the target value of 90.98%. After QCC activity, dress standard rate, enforced rate of hand hygiene measures, qualification rates of disinfection isolation measures, aseptic operation and disposed items were improved significantly. In addition, the ability of circle members also improved differently. Conclusion:QCC activities can continuously improve the quality, obtaining good results. Quality management of QCC can effectively solve problems in infection management, which is an effective tool in the standardization, normalization and scientization of infection management.
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Objective@#To investigate the values of T lymphocyte-bound complement activation products such as T-C3d and T-C4d, B lymphocyte-bound complement activation products such as B-C3d and B-C4d and erythrocyte-bound complement activation products such as E-C3d and E-C4d in the diagnosis of systemic lupus erythematosus (SLE). @*Methods@#Peripheral blood samples from 68 SLE patients, 70 patients with non-SLE autoimmune diseases and 68 healthy controls were collected randomly, and the expression levels of T-C4d, B-C4d, E-C4d, T-C3d, B-C3d and E-C3d in these samples were detected by flow cytometry. Meanwhile, antinuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), peripheral blood cell count and other markers were also detected. The differences of cell-bound complement activation products in three groups were analyzed with the area under the receiver operating characteristic curve (AUC), nonparametric test, sensitivity and specificity. @*Results@#The specific median fluorescence intensity (SMFI) of T-C4d, B-C4d, E-C4d, T-C3d, B-C3d and E-C3d in SLE patients were significantly higher than those in the patients with non-SLE autoimmune diseases and healthy controls (all P＜0.05). The SMFI (median \[P 25, P 75\]) of T-C4d, B-C4d and E-C4d in SLE patients were 3.8(1.2, 13.1), 22.1(6.2, 67.9) and 19.6(1.8, 52.4), respectively. The SMFI of T-C4d, B-C4d and E-C4d in SLE patients with reduced red blood cells and/or lymphocytes were significantly higher than that with normal red blood cell and lymphocyte count (all P＜0.05). The AUCs of T-C4d, B-C4d, E-C4d, T-C3d, B-C3d and E-C3d were 0.711, 0.763, 0.663, 0.631, 0.611 and 0.615, respectively (all P＜0.05). The sensitivity of the combination of T-C4d with B-C4d (73.5%) in the diagnosis of SLE was superior to that of anti-dsDNA (36.8%). @*Conclusion@#The cell-bound complement activation products (CB-CAPs) are specifically expressed in SLE patients, and their combination detection is helpful for the diagnosis of SLE.
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OBJECTIVE:To optimize the water-extraction technology of Yao medicine Jasminum lanceolarium and study the anti-inflammatory and analgesic effect of its water extract. METHODS:The single factor test and orthogonal test were used to investigate the effects of extraction time,liquid-solid ratio and extraction times on water-extraction technology and optimize extraction technology using ferulic acid content and dry extract yield as index. The validation test was also conducted. With aspirin as positive control,the method of ear edema induced by xylene and paw edema induced by carrageenan in mice were used to observe the anti-inflammation effects of low-dose,medium-dose and high-dose(3,6,12 g/kg,by crude drug)of J. lanceolarium water extract;the analgesic effect of those was investigated by hot-plate induced pain response test and mice writhing response test. The contents of TNF-α and IL-1 β were determined by ELISA after carrageenan induced inflammation in mice. The contents of PGE2in serum and inflammation tissue were detected by UV spectrophotometry.RESULTS:The optimal extraction technology was as follows as extraction time of 120 min,liquid-solid ratio of 16:1(mL/g),extracting for 3 times.Compared to model group,the ear edema degree and paw edema rate of mice were raduced,writhing response times were lessened,and pain response threshold was enhanced significantly in low-dose,medium-dose and high-dose groups of J. lanceolarium water extract(P<0.05 or P<0.01). Compared to model group,the contents of TNF-α,IL-1β and PGE2in serum and the content of PGE2in inflammation tissue of mice were raduced significantly in low-dose,medium-dose and high-dose groups of J. lanceolarium water extract(P<0.05 or P<0.01). CONCLUSIONS:The optimized water-extraction technology of Yao medicine J. lanceolarium shows high efficiency,stable and feasible.Water extract shows significant anti-inflammatory and analgesic effects through reducing the contents of TNF-α,IL-1β and PGE2.
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Objective@#To understand the prevalence of dyslipidemia and risk factors among coal miners under different work conditions.@*Methods@#The survey was conducted from April 2016 to June 2016. 759 mine workers were divided into three groups (group of the front line miner, underground auxiliary and ground) . Questionnaire and physical examination were used to collect related information of workers. Logistic regression model was used to analyze relative factors.@*Results@#The overall prevalence of dyslipidemia was 43.2% in coal miners. The prevalence rate of the front line miner and underground auxiliary miners was 46.6%. Ground workers had the lowest prevalence rate of 36.4%. Multiple Logistic regression analysis showed that higher body mass index (BMI) was risk factors for underground workers (OR=2.18, 95%CI:1.51~3.13) . Smoking (OR=1.99, 95%CI:1.17~3.38) , drinking (OR=1.85, 95%CI:1.11~3.06) , hypertension (OR=1.79, 95%CI:1.00~3.22) and higher waist and hip ratio (OR=1.06, 95%CI:1.04~1.09) were risk factors for underground auxiliary workers. For ground workers, those with higher BMI (OR=2.64, 95%CI:1.68~4.16) were at higher risk of dyslipidemia and female workers had lower risk (OR=0.35, 95%CI:0.18~0.65) than male workers.@*Conclusion@#The dyslipidemia rate of coal mine workers is related to work environment and behavior. Health education may be needed to reduce the dyslipidemia rate of coal mine workers.
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Integrated medical education, namely medical education under the concept of integration, is an important trend in the development of global medical education, and also an important task in the re-form of medical universities and colleges in China. The integrated medical education abroad originated from Europe and America, and developed relatively well. It started late in China and was limited to integration of some subjects. At present, the reform of integrated medical education in domestic colleges and universities is still facing the problems and challenges such as lag of teaching ideas, limited content of reform, insufficient teachers' ability, difficulty to change learning habits, deviations of learning purposes, lack of integrated learning, lack of system, poor mechanism, weak guarantee and so on. In the future, we should make efforts to teach, learn and manage, give full play to the leading role of "teaching", improve the main position of"learning", and constantly improve the guarantee function of "management".
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Objective To discuss the microsurgical anatomy of carotid bifurcation and external branch of the superior laryngeal nerve (EBSLN),and to explore the operative techniques in carotid endarterectomy.Methods The carotid bifurcation (20 sides) of 10 cadaveric heads was studied by using microanatomy from January 2017 to January 2018.The distance between bifurcation of carotid artery to peripheral bone structure,and the distances between point of EBSLN to medial margin of the carotid artery to mandibular angle,most prominent point of the larynx,apex of the mastoid,and bifurcation of carotid artery were measured.Results (1) The vertical distance from carotid bifurcation to larynx point and mandibular angle was 24.32 (18.8-35.78) mm and 13.55 (9.26-19.60) mm.The straight distance from carotid bifurcation to mastoid tip was 68.59 (49.48-76.94) ram.According to the vertical distance of larynx point to carotid bifurcation,the height of bifurcation of the carotid artery was consistent with the results of wain measurement (K=0.90),and the difference was statistically significant (P＜0.05).(2) The distances between the point of EBSLN to medial margin of the carotid artery to carotid artery bifurcation,upper thyroid artery bifurcation,mandibular angle and mastoid process were 17.81 (15.24-25.58) mm,19.42 (17.08-29.12) mm,20.51 (17.98-22.20) mm,71.00 (69.00-74.50) mm in normal bifurcations.Those in the high bifurcation specimens were 6.40 (2.44-9.20) mm,8.84(4.74-10.88) mm,12.15(10.64-13.54),60.90 (59.80-66.50) mm,respectively.Conclusions The position of the laryngeal prominence is fixed,which can be used as a marker for surgical incision.When the vertical distance from the larynx point to the bifurcation of the carotid artery is greater than or equal to 2.5 cm,it is highly bifurcated;the bifurcation is normal when less than 2.5 cm.In patients with normal carotid bifurcation,1.5 cm of the carotid artery bifurcation can be used as a safety mark limit during the operation.For patients with high carotid artery,the EBSLN is almost parallel to or down the superior thyroid artery,and it should be closely attached to the bifurcation of the carotid artery and the outer membrane of the superior thyroid artery,and there is no safety margin.
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In this study,with the mechanism for teaching supervision in military colleges and universities construction as the starting point,the author makes an in-depth analysis of the problems existing in the current teaching supervision system of military academies,such as the imperfect mechanism,the limitation of the function,the lack of full-time staff,the lag of information technology and so on,and investigates and surveys the status quo of teaching supervision at home and abroad.It also puts forward some countermeasures,such as constructing the comprehensive supervision system,realizing the function transformation,promoting the innovation of the mode,expanding the connotation of the supervision,optimizing the structure of the team,developing the professional training,and strengthening the information construction and so on.
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Objective To investigate the effects of mitochondrial DNA (mtDNA) copy number in peripheral blood and related factors on the risk of hypertension in coal miners.Methods A case-control study was conducted in 378 coal miners with hypertension and 325 healthy coal miners recruited from Datong Coal Mine Group.A standard questionnaire was used to collect their general information,such as demographic characteristics,habits and occupational history.Fluorescence quantitative PCR was performed to detect the copy number of mtDNA.Logistic regression model was applied for identifying the related risk factors of hypertension and analyzing the interaction between mtDNA copy number and risk factors.Results The prevalence of hypertension of high mtDNA copy number was lower than mtDNA copy numberin 0-5.67 group,but the difference was not statistically significant (P=0.414).Alcohol drinking (OR=1.80,95％CI:1.26-2.56),family history of hypertension (OR=1.74,95％ CI:1.20-2.50),work shifts (OR=0.69,95％ CI:0.48-0.99),education level (P=0.012) and family monthly income level (P=0.001) were related to the prevalence of hypertension.There were potential interactions between mtDNA copy number and alcohol drinking,family monthly income level,family history of hypertension,respectively.Alcohol drinking was a risk factor for hypertension [1.77(1.25-2.50)].Potential interactions between mtDNA copy number and alcohol drinking reduced the risk of hypertension (OR=1.20,95％CI:1.07-1.35).Family history of hypertension was a risk factor for hypertension [1.81(1.26-2.59)].Potential interactions between mtDNA copy number and family history of hypertension reduced the risk of hypertension (OR=1.24,95％ CI:1.09-1.41).Family monthly income level was a protect factor for hypertension [0.55(0.46-0.66)].Potential interactions between mtDNA copy number and family monthly income level increased the protection role of hypertension (OR=0.90,95％CI:0.86-0.94).Conclusion mtDNA copy number variation was not significantly associated with the prevalence of hypertension in coal miners,but mtDNA copy number shewed multiplication interaction on the prevalence of hypertension with alcohol drinking,family monthly income level as well as family history of hypertension and made their influences weaken.
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Objective To investigate the effects of mitochondrial DNA (mtDNA) copy number in peripheral blood and related factors on the risk of hypertension in coal miners.Methods A case-control study was conducted in 378 coal miners with hypertension and 325 healthy coal miners recruited from Datong Coal Mine Group.A standard questionnaire was used to collect their general information,such as demographic characteristics,habits and occupational history.Fluorescence quantitative PCR was performed to detect the copy number of mtDNA.Logistic regression model was applied for identifying the related risk factors of hypertension and analyzing the interaction between mtDNA copy number and risk factors.Results The prevalence of hypertension of high mtDNA copy number was lower than mtDNA copy numberin 0-5.67 group,but the difference was not statistically significant (P=0.414).Alcohol drinking (OR=1.80,95％CI:1.26-2.56),family history of hypertension (OR=1.74,95％ CI:1.20-2.50),work shifts (OR=0.69,95％ CI:0.48-0.99),education level (P=0.012) and family monthly income level (P=0.001) were related to the prevalence of hypertension.There were potential interactions between mtDNA copy number and alcohol drinking,family monthly income level,family history of hypertension,respectively.Alcohol drinking was a risk factor for hypertension [1.77(1.25-2.50)].Potential interactions between mtDNA copy number and alcohol drinking reduced the risk of hypertension (OR=1.20,95％CI:1.07-1.35).Family history of hypertension was a risk factor for hypertension [1.81(1.26-2.59)].Potential interactions between mtDNA copy number and family history of hypertension reduced the risk of hypertension (OR=1.24,95％ CI:1.09-1.41).Family monthly income level was a protect factor for hypertension [0.55(0.46-0.66)].Potential interactions between mtDNA copy number and family monthly income level increased the protection role of hypertension (OR=0.90,95％CI:0.86-0.94).Conclusion mtDNA copy number variation was not significantly associated with the prevalence of hypertension in coal miners,but mtDNA copy number shewed multiplication interaction on the prevalence of hypertension with alcohol drinking,family monthly income level as well as family history of hypertension and made their influences weaken.
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AIM To establish an HPLC method for the simultaneous content determination of four constituents in Xiaojie'an Capsules (Forsythiae Fructus,Leonuri Herba,Spatholobi Caulis,etc.).METHODS The analysis of chloroform extract of this drug was carried out on a 30 ℃ thermostatic Diamond C1scolumn(250 mm ×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile (A)-0.05 mol/L monosodium phosphate (B) flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 278 nm.RESULTS Berberine hydrochloride,palmatine chloride,phillyrin and rutin showed good linear relationships within the ranges of 0.033 7-0.337 2 μg (r =0.999 1),0.054 8-0.548 3 μg (r =0.999 0),0.025 9-0.258 8 μg (r=0.999 2) and 0.008 4-0.084 2 μg (r =0.999 6),whose average recoveries were 98.8％ (RSD =1.3％),99.8％ (RSD =0.7％),98.8％ (RSD =1.3％) and 96.8％ (RSD =1.0％),respectively.CONCLUSION This sensitive and accurate method can be used for the quality control of Xiaojie'an Capsules.
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Through analyzing the connotation and current situation of the innovation ability training,the paper lists the main problems existing in the cultivation of medical students' innovation ability.With medical undergraduate education as the starting point,it summarizes the experience and practice of strengthening the cultivation of medical undergraduates' innovation ability from the following aspects as set-ting up the innovation education idea,promoting the innovation of teaching contents with minus three,three bases,three stresses,promoting the reform of teaching methods with innovation as the core,constructing new type teachers staff with science and education as one,improving training system innovation,accelerating the construction of integrated test system,and establishing and improving the innovation of educational system and mechanism and so on.
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Objective To investigate and clarify the effect of Stat5a on proliferation of human breast cancer cells (MCF‐7) and to detect the changes of epigenetic signature on the promoter region of p53 gene .Methods Stat5a was over expressed in human breast cancer cells (MCF‐7) by using adenovirus mediated gene transfer technology .The cell proliferation was examined by MTS assay .ChIP assay was used to check the trimethylation of lysine 27 on histone 3 (H3K27Me3) of p53 gene promoter region .Fur‐thermore ,qRT‐PCR and western blot were also applied to confirm the expression of p53 gene .Results The number of MCF 7 in‐creased in a dose dependent manner .Compared with that of control group ,the cell density of MCF‐7 increased 7 .603 1% , 18 .123 7% and 24 .898 7% when the MOI were 10 ,20 and 30 .Chromatin Immunoprecipitation showed that Stat5a significantly in‐creased H3K27Me3 and down regulated the expression level of p53 gene .Conclusion Stat5a promotes proliferation of breast cancer cells through trimethylation of H3K27 and inhibition of p53 gene expression .
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AIM:To evaluate the effect of lipoic acid ( LA) on LPS-induced Parkinson disease ( PD) model of mice.METHODS:Female C57BL/6 mice of 10-month-old were randomly divided into saline control group , PD group and LA group.The PD mouse model was induced by intranasal instillation of LPS .Assays of tyrosine hydroxylase , microglia and nuclear factor kappa B ( NF-κB) were performed by the methods of immunohistochemistry and Western blotting .RE-SULTS:Intranasal LPS instillation exhibited basic characteristics of PD model .However, LA administration significantly improved motor dysfunction , protected dopaminergic neurons from damage , and inhibited NF-κB activation in inflammatory microglia in the substantia nigra area of the brain .CONCLUSION:LA may exert a profound neuroprotective effect by an-ti-neuroinflammatory reaction to arrest the progression of PD .
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[ ABSTRACT ] AIM: To investigate the molecular mechanisms of cytotoxicity induced by dihydroartemisinin ( DHA) in non-small cell lung cancer ( NSCLC) cells.METHODS:NSCLC cell lines A549 and NCI-H1650 were treated with various concentrations of DHA for indicated time.Subsequently, the effects of DHA on the cell activity, colony forma-tion ability and apoptosis were determined by MTT assay, colony formation assay, Annexin V-FITC/PI staining and flow cy-tometry, respectively.At the same time, the effects of DHA on glucose, ATP and lactate levels were assessed, and the PI3K pathway activation and glucose transporter 2 ( GLUT2) expression were detected by Western blot in the A549 cells and NCI-H1650 cells.Overexpression of GLUT2 and Rheb was established in A549 and NCI-H1650 cells by transfection with GST-GLUT2 and GST-Rheb plasmids, respectively, and the effects of DHA on cell activity, apoptosis, glucose level, ATP content and PI3K pathway activation were analyzed in A549 cells and NCI-H1650 cells.The effect of glucose depriva-tion on the cytotoxicity triggered by DHA in NSCLC cells was also determined.RESULTS:Compared with control group, DHA significantly inhibited cell activity and colony formation ability, and induced remarkable cell apoptosis in the A549 cells and NCI-H1650 cells.At the same time, DHA reduced ATP and lactate contents, and hindered glucose uptake in a time-and dose-dependent manner in A549 cells and NCI-H1650 cells.The activity of PI3K pathway and GLUT2 expression were downregulated, while upregulated GLUT2 expression and activated PI3K pathway reduced the cytotoxicity induced by DHA in NSCLC cells.Glucose deprivation increased DHA-mediated cytotoxicity in NSCLC cells.On the contrary, high levels of glucose inhibited DHA-mediated cytotoxicity in NSCLC cells.CONCLUSION: DHA restrains cell activity and colony formation, and induces apoptosis.DHA induces cytotoxicity via inhibiting PI3K pathway activation and GLUT2 ex-pression, leading to inhibit glycolytic metabolism in NSCLC cells.
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<p><b>BACKGROUND</b>Prolactin (PRL) is a pituitary polypeptide hormone characterized by multiple biological actions including stimulation of growth in the prostate and formation of secretory alveoli and stimulation of milk protein gene expression in the mammary gland. PRL exerts its effect by dimerizing its receptor (PRLR) on the plasma membrane and regulating gene expression through the JAK-Stat signal pathway. We have previously described a natural variant of the PRLR in which the S2 subdomain of the extracellular domain is missing (Delta S2). Delta S2 PRLRs are dimerized in the absence of PRL and have constitutive activity in the promotion of breast cancer cell growth. Enhancer of zeste homolog 2 (EZH2), as one of the histone-modifying enzymes, is a key factor regulating gene expression by epigenetic modification. We hypothesized that these constitutive activated Delta S2 PRLRs played a pathogenic role in breast cancer in part through alterations in the expression of EZH2 and the trimethylation of histone 3 on lysine 27 (H3K27Me3).</p><p><b>METHODS</b>In order to verify the clinical significance and to establish the link between Delta S2 PRLR expression and epigenetic change, EZH2, H3K27Me3, and Delta S2 PRLR were detected in both normal and cancerous human breast tissues. Also, overexpression of Delta S2 PRLR in breast epithelial cells was achieved by infection with adenovirus carrying the cDNA. Western blotting and chromatin immunoprecipitation (ChIP assay) and acid histone extraction were applied to detect the expression of EZH2 and the trimethylation of histone 3, respectively.</p><p><b>RESULTS</b>In breast tissue, higher EZH2 expression and higher H3K27Me3 were found associated with higher Delta S2 expression in breast cancer samples. In breast epithelial cells, overexpression of Delta S2 PRLR increased EZH2 methyltransferase mRNA and protein, induced EZH2 methyltransferase recruitment to chromatin, increased the trimethylation of H3K27Me3, and decreased the expression of p53 gene.</p><p><b>CONCLUSIONS</b>Delta S2 PRLR plays an important pathogenic role in breast cancer through epigenetic modification. Elevated expression of Delta S2 PRLR, achieved by alternate splicing of the pre-mRNA of the full-length form, is a new mechanism contributing to human breast cancer.</p>