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OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.
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Objectives:To assess the effectiveness and safety of ivabradine for the treatment of chronic heart failure in the context of the new quadruple combination. Methods:Clinical data of 656 chronic heart failure patients hospitalized in Nanjing Drum Tower Hospital from March 2021 to June 2022 were retrospectively collected,and the patients were divided into control group(n=361)and observation group(n=295)according to ivabradine use,and both groups were treated with the new quadruple drug therapy.Propensity score matching was performed,268 patients in the observation group and 268 patients in the control group were successfully matched.The effectiveness(primary endpoint was the composite endpoint of cardiovascular death and rehospitalisation for worsening heart failure within 1 year of discharge;secondary endpoints were rehospitalisation for worsening heart failure,all-cause rehospitalisation,cardiovascular death,and all-cause death)and safety outcome measures(including bradycardia,atrial fibrillation,blurred vision,renal impairment,and hypertension)were compared between the two groups at 1 year after treatment. Results:After matching,there were no statistically significant differences at baseline characteristics between the two groups.Kaplan-Meier survival curve showed that the occurrence rates of primary endpoints(P=0.031),readmission for worsening heart failure(P=0.020),and all-cause readmission(P=0.036)were lower in the observation group than in the control group.Multivariate Cox proportional hazard regression analysis showed that the occurrence rates of primary endpoint events(P=0.045)and readmission for heart failure worsening(P=0.028)were lower in the observation group than in the control group. Conclusions:The ivabradine use on top of the new quadruple therapy regimen in patients with chronic heart failure is beneficial to improve one-year prognosis with favorable safety profile.
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OBJECTIVE To evaluate the clinical effectiveness and safety of domestic generic and imported original clopidogrel for antiplatelet therapy in patients with acute coronary syndrome （ACS）. METHODS The clinical data of ACS patients in Nanjing Drum Tower Hospital of China Pharmaceutical University from January 2020 to June 2021 were retrospectively collected by using electronic medical record system， and the patients were divided into original drug group （321 cases） and generic drug group （328 cases） according to the drug use. Both groups were given dual antiplatelet therapy with clopidogrel and aspirin. The effectiveness and safety outcomes of the two groups were followed up for 12 months and compared， the related influential factors were analyzed. RESULTS Major adverse cardiovascular events （MACE） occurred in 16 and 22 patients in original drug group and generic drug group respectively， including nonfatal myocardial infarction （4 and 5 cases）， stroke （2 and 4 cases）， revascularization （8 and 3 cases）， cardiovascular related death （2 and 4 cases）， and all-cause death （4 and 6 cases）. There were 12 and 7 patients with major bleeding events， 38 and 29 patients with minor bleeding events， and 33 and 21 patients with non-bleeding adverse events. There was no statistically significant difference in the cumulative incidence of related events （P values of Log-Rank tests were all greater than 0.05）. Cox regression analysis showed that the use of generic clopidogrel did not increase the risk of MACE and major bleeding events in ACS patients [hazard ratio of 1.305 and 0.416， 95% confidence interval of （0.678， 2.512） and （0.155， 1.117）， respectively， P＞0.05]， and the combination of proton pump inhibitors （PPI） could reduce the risk of major bleeding events [hazard ratio of 0.196， 95% confidence interval of （0.063， 0.611）， P＜0.05]. CONCLUSIONS Compared with imported original drug， domestic generic clopidogrel has similar clinical effectiveness and good safety. Combined use of PPI may be a beneficial factor to reduce the occurrence of major bleeding events in patients.
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At present, the teaching objects of clinical pharmacists have gradually changed from merely university students to complex and diverse groups including clinical pharmacist interns and others. However, the traditional teaching model cannot be tailored to different groups. In addition, it increases the burden of clinical pharmacists while not ensuring teaching quality. This study aims to classify teaching objects according to their characteristics, so as to provide individualized knowledge and service. Compared with the traditional way of teaching, this new method may make teaching more relevant and reduces the teaching load of teachers, which is of great significance to the training of clinical pharmacy personnel.
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Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/ DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.
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Liver， as a critical organ of metabolism and detoxification， can be damaged by viral infection， drug abuse， and heavy drinking. Liver diseases pose a serious threat to people's health and life in China.At present， drug therapy has been primarily adopted clinically in the treatment of the liver injury.In-depth investigation of the mechanism of liver-protective drugs is of great significance to the prevention and treatment of clinical liver diseases.In recent years， with the development of the medical industry in China， an increasing number of studies have focused on the treatment of liver injury with Chinese medicine.Compared with western medicine， Chinese medicine is advantageous in few side effects and overall regulation， which plays a pivotal role in liver protection.However， its underlying mechanism in liver protection still needs to be further studied due to its complex compositions and diverse targets.Metabolomics， a new approach to studying the metabolic pathway of biological systems， provides integral and systematic views in the investigation of liver protection with Chinese medicine. By virtue of metabolomics， the mechanism of Chinese medicine in multi-target and multi-pathway liver protection can be analyzed comprehensively， and the corresponding biomarkers can also be screened out. The authors analyzed the studies of the treatment of chemical liver injury models induced by carbon tetrachloride （CCl4）， dimethylnitrosamine （DMN）， α-naphthyl isothiocyanate （ANIT）， and alcohol by Chinese medicinal compounds， single herbal medicines， and monomers of Chinese medicine based on metabolomics， and summarized the biomarkers and related metabolic pathways of Chinese medicine in the intervention of each type of liver injury， aiming at providing a reference for the further research and clinical application in the treatment of different types of liver injuries by Chinese medicine.
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Liver disease is a kind of common and frequently occurring disease, which seriously threatens human life and health. The study of liver disease has become a hotspot and difficulty in the field of organic diseases. In recent years, scholars have found a close relation between liver disease and the metabolism of lipid compounds in body. Lipomics, an important branch of metabolomics, can evaluate liver diseases by analyzing the level of lipid changes in the body, find biomarkers of liver diseases, and study the possible mechanism of liver diseases. It plays an important role in the study of liver diseases. In order to provide reference for further study of liver diseases and their clinical treatment, the research methods of lipomics have been reviewed, and the application of lipomics in liver diseases summarized and analyzed based on different types of liver diseases in this paper.
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Objective To investigate the effects of moderate-to-vigorous intensity physical activity (MVPA) in early pregnancy on the onset of gestational diabetes mellitus (GDM) in Sichuan Province. Methods A case-control study was performed on 1 508 gravidas at 8-14 gestational weeks in Sichuan Provincial Hospital for Women and Children from February to July, 2017. Baseline information during early pregnancy was collected through questionnaires. Information on time and intensity of physical activity were collected through pregnancy physical activity questionnaire. The time spent in MVPA was calculated and was categorized as active ( ≥ 3.5 h/week) or inactive MVPA (<3.5 h/week). Based on self-reported pre-pregnancy weights collected by questionnaire as well as the measured heights, body mass index (BMI) before pregnancy was calculated. After a 75 g oral glucose tolerance test (OGTT) at 24-28 gestational weeks, all subjects were divided into GDM (n=561) or non-GDM group (n=947), according to the GDM diagnostic criteria of the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China (2014). Mann-Whitney U test and Chi-square test were used for statistical analysis. Multivariate unconditional logistic regression model was used to analyze the association between the time of MVPA in early pregnancy and GDM incidence. ResuLts The median time spent in MVPA [M(P25-P75)] in early pregnancy was 3.00 (0.50-3.12) h/week, and 345 gravidas (22.9%) were classified as active in MVPA. After the control of confounding factors such as age, gravidity and parity history, and pre-pregnancy BMI, the multivariate unconditional logistic regression analysis showed that compared with the inactive group, the risk of GDM of active MVPA gravidas was reduced by 26.1% (OR=0.739, 95%CI: 0.553-0.989, P=0.042). Among primigravidas and primiparae, the risk of GDM in active MVPA gravidas was decreased by 47.6% and 44.3% than the inactive ones, respectively (primigravidas: OR=0.524, 95%CI: 0.297-0.925, P=0.026; primiparae: OR=0.557, 95%CI: 0.357-0.868, P=0.010). ConcLusions Insufficient physical activity in early pregnancy is common in gravidas in Sichuan, China. The risk of GDM could be reduced if the frequency of MVPA during early pregnancy is no less than 3.5 h/week, especially in primigravidas and primiparae.
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<p><b>OBJECTIVE</b>To investigate the impact of dampness-heat (DH) on the development of mammary tumors in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rats.</p><p><b>METHODS</b>Forty rats were randomly divided into 3 groups in a randomized block design, including the control group (n=13), DMBA group (n=14), and DMBA plus DH group (n=13). Rats in the DMBA group and DMBA plus DH group were intragastrically administrated with DMBA (100 mg/kg) for twice, once per week, while rats in the control group were treated with equivalent volumes of sesame oil. After DMBA administration, rats in the DMBA plus DH group were exposed to a simulated climate chamber with ambient temperature (33.0±0.5°C) and humidity (90%±5%) for 8 weeks, 8 h per day. The body weight, time of tumor formation, and number of tumors were measured weekly to calculate tumor incidence, average latency period, average number of tumors, and average tumor weight. At the end of the experiment, the levels of matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in serum, and the contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β in serum and tumor tissue were measured, respectively. Some tumor tissues were processed for hematoxylin-eosin staining to determine the histopathological changes.</p><p><b>RESULTS</b>Compared with DMBA, DMBA plus DH significantly increased the average number of tumors, average tumor weight, levels of serum MMP-9, TIMP-1, TNF-α and IL-1β, and contents of tumor tissue TNF-α and IL-1β (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>DH could accelerate the development of mammary tumors through increasing the expressions of MMP-9, TIMP-1, TNF-α and IL-1β in DMBA-induced rats.</p>
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Objective: To explore the association between gestational weight gain (GWG) and adverse pregnancy outcomes. Methods: A prospective study was conducted among 1 220 healthy singleton pregnant women in the first trimester of pregnancy, from Chengdu city, Sichuan province. Pre-gestational body mass and other basic information were collected through a set of questionnaires. Weight at the last week before delivery was measured and GWG was classified by IOM criteria (2009). Related information on pregnancy outcomes was collected after delivery, through the hospital information system. Multiple non-conditional logistic regression models were used to test the association between GWG and adverse pregnancy outcomes. Results: In total, data on 1 045 pregnant women were analyzed. Compared with adequate GWG, excessive GWG was associated with the increased risks of cord entanglement and large for gestational age (OR=1.641, 95%CI: 1.197-2.252; OR=1.678, 95%CI: 0.132-2.488), respectively. Additionally, when compared with the adequate GWG, insufficient GWG was associated with the increased risk of preterm delivery (OR=3.189, 95%CI: 1.604-6.341). Conclusions: Both excessive and insufficient GWG appeared associated with the pregnancy outcomes. Weight monitoring should be strengthened for pregnant women to reduce related risks on adverse pregnancy outcomes.
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Adulte , Femelle , Humains , Nouveau-né , Grossesse , Poids de naissance , Indice de masse corporelle , Chine/épidémiologie , Prise de poids pendant la grossesse , Complications de la grossesse/épidémiologie , Issue de la grossesse/épidémiologie , Études prospectivesRÉSUMÉ
Objective To investigate the effect of telmisartan on the expression of peroxisome proliferator activated receptor gamma(PPARγ)and its regulation in myocardial remodeling in spontaneously type 2 diabetic male Otsuka Long-Evans Tokushima Fatty(OLETF)rats fed with high-fat diet.Methods Twenty-eight four-week-old male OLETF rats were fed with high-fat diet. From 22-week of age, the pre-diabetic OLETF rats were randomly assigned to three groups:telmisartan-treated group[O-T group,5 mg/(kg·d),n=10],pioglitazone-treated group[O-P group,10 mg/(kg·d),n=8]and untreated group ( O-C group, equal volume of normal saline, n=10), continuously administration for 22-week. Twelve sex and age matched Long-Evans Tokushima Otsuka(LETO)rats were used as control(LETO group).At 22 and 48-week of age, the glucose tolerance of the rats was assessed by the oral glucose tolerance test(OGTT).At 48 weeks of age,five rats were randomly selected from each group,and clamp experiments were carried out.The glucose infusion rate from 60 min to 120 min(GIR60-120)was measured.All rats were sacrificed and the myocardial tissues were dissected.The ratio of heart weight to body weight(HW/BW)was calculated.Blood samples were collected,and serum PPARγ,tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6)and adiponectin were measured using ELISA and radioimmunoassay.The mRNA expressions of IL-6,PPARγ1 and PPARγ2 were measured by real-time PCR.The protein expression levels of PPARγ,adiponectin,IL-6 and NF-κB were determined by Western blot assay.The myocardial pathological changes were observed under light microscope (HE staining, Masson staining and PAS staining), and ultrastructural changes were observed under transmission electron microscope.Results At 22-week of age,neither type 2 diabetes mellitus(T2DM)nor IGT were found in three groups.At 48-week of age,T2DM was found in seven rats of O-C group,and IGT was found in two rats.T2DM was found in one rat of O-C group,and IGT was found in three rats.Neither T2DM nor IGT was found in the other two groups.GIR60-120and HW/BW were all significantly lower in the O-P group and O-T group than those of the O-C group at 48-week of age (P<0.05). Systolic blood pressure(SBP)and diastolic blood pressure(DBP)were significantly lower in O-T group than those in other three groups(P<0.05).Compared with the O-C group,the serum levels of PPARγ and adiponectin were significantly up-regulated,whereas the serum levels of IL-6 and TNF-α were down-regulated by telmisartan administration in O-T group (P<0.05).There were no significant differences in the above indexes between O-P and O-T groups.The results of real-time PCR and Westen blot assay showed that the mRNA expression of PPARγ1 was increased,and IL-6 expression decreased in O-T group compared with those of O-C group. The protein expressions of PPARγ and adiponectin were increased, and protein expressions of NF-κB and IL-6 were significantly decreased in O-P group and O-T group compared with those of O-C group(P<0.05).In the O-C group,the arrangernent of myocardial cells was irregular,myocardial fibers were swollen,a large amount of fibrotic tissue in the myocardial interstitium, and glycogen accumulation under light and electron microscope. Besides, myofibril breakage and perinuclear space expansion, myocardial mitochondria were apparently damaged or even dissolved. Compared with the O-C group, myocardial fibers arranged neatly, no obvious glycogen deposition and the ultrastructural changes of myocardium were obviously reduced in O-T group and O-P group. Conclusion Telmisartan can increase the expression level of PPARγ in the serum and myocardial tissue, reduce myocardial fibrosis and alleviate cardiac remodeling in the high-fat-diet OLETF rats.
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Objective To explore the association between gestational weight gain (GWG) and adverse pregnancy outcomes.Methods A prospective study was conducted among 1 220 healthy singleton pregnant women in the first trimester of pregnancy,from Chengdu city,Sichuan province.Pre-gestational body mass and other basic information were collected through a set of questionnaires.Weight at the last week before delivery was measured and GWG was classified by IOM criteria (2009).Related information on pregnancy outcomes was collected after delivery,through the hospital information system.Multiple non-conditional logistic regression models were used to test the association between GWG and adverse pregnancy outcomes.Results In total,data on 1 045 pregnant women were analyzed.Compared with adequate GWG,excessive GWG was associated with the increased risks of cord entanglement and large for gestational age (OR=1.641,95％CI:1.197-2.252;OR=1.678,95％ CI:0.132-2.488),respectively.Additionally,when compared with the adequate GWG,insufficient GWG was associated with the increased risk of preterm delivery (OR=3.189,95％CI:1.604-6.341).Conclusions Both excessive and insufficient GWG appeared associated with the pregnancy outcomes.Weight monitoring should be strengthened for pregnant women to reduce related risks on adverse pregnancy outcomes.
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<p><b>OBJECTIVE</b>To investigate the effects of prebiotics supplementation for 9 days on gut microbiota structure and function and establish a machine learning model based on the initial gut microbiota data for predicting the variation of Bifidobacterium after prebiotic intake.</p><p><b>METHODS</b>With a randomized double-blind self-controlled design, 35 healthy volunteers were asked to consume fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS) for 9 days (16 g per day). 16S rRNA gene high-throughput sequencing was performed to investigate the changes of gut microbiota after prebiotics intake. PICRUSt was used to infer the differences between the functional modules of the bacterial communities. Random forest model based on the initial gut microbiota data was used to identify the changes in Bifidobacterium after 5 days of prebiotic intake and then to build a continuous index to predict the changes of Bifidobacterium. The data of fecal samples collected after 9 days of GOS intervention were used to validate the model.</p><p><b>RESULTS</b>Fecal samples analysis with QIIME revealed that FOS intervention for 5 days reduced the intestinal flora alpha diversity, which rebounded on day 9; in GOS group, gut microbiota alpha diversity decreased progressively during the intervention. Neither FOS nor GOS supplement caused significant changes in β diversity of gut microbiota. The area under the curve (AUC) of the prediction model was 89.6%. The continuous index could successfully predict the changes in Bifidobacterium (R=0.45, P=0.01), and the prediction accuracy was verified by the validation model (R=0.62, P=0.01).</p><p><b>CONCLUSION</b>Short-term prebiotics intervention can significantly decrease α-diversity of the intestinal flora. The machine learning model based on initial gut microbiota data can accurately predict the changes in Bifidobacterium, which sheds light on personalized nutrition intervention and precise modulation of the intestinal flora.</p>
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<p><b>OBJECTIVE</b>To investigate the regulatory effect of ATP?binding cassette transporter A1 (ABCA1) knockdown on inflammatory response induced by Pam3CSK4 in mouse mononuclear macrophage RAW264.7 cell line.</p><p><b>METHODS</b>A mouse mononuclear macrophage RAW264.7 cell line with stable ABCA1 knockdown was constructed and stimulated with Toll?like receptor 2 (TLR2) ligand Pam3CSK4, and the changes in the transcriptional levels of the proinflammatory and anti-inflammatory cytokines were analyzed in this cell model.</p><p><b>RESULTS</b>In RAW264.7 cells, ABCA1 knockdown significantly up-regulated Pam3CSK4 stimulation?induced expressions of IL?1β, TNF?α and IL?6 and also enhanced the expression of transcription factor cAMP?dependent transcription factor 3 (ATF3) without obviously affecting the expressions of the transcription factors ATF1, ATF2, ATF4 or ATF5.</p><p><b>CONCLUSION</b>ABCA1 knockdown in macrophages may have both proinflammatory and anti?inflammatory effects. ABCA1 knockdown up?regulates the transcription of ATF3 possibly through a mechanism that is different from that for the other members of the ATF protein family.</p>
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Objective To investigate the effects of Abnormal Phlegmatic Munziq on ability of learning and memory, and protein expressions of brain tissue RAGE and LRP1 of APP/PS1 transgenetic mice model of AD;To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control group, Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups, 18 mice in each group. Another 18 three-month-old C57BL/6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in ability of learning and memory of mice were detected by Step-down test; protein expressions of LRP1 and RAGE were detected by immunohistochemistry and Western blot. Results Compared with the normal control group, the reaction time of learning grades and the mistake times increased, incubation of memory grades decreased and the mistake times increased in the model control group (P<0.01);Compared with the model control group, the reaction time of learning grades and the mistake times decreased, incubation of memory grades increased and the mistake times decreased in all administration groups (P<0.05, P<0.01). Immunohistochemistry and Western blot results showed that compared with normal control group, the LRP1 expression decreased and RAGE increased in the model control group (P<0.05);Compared with the model control group, the LRP1 expression decreased and RAGE increased in Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups (P<0.05,P<0.01). Conclusion Abnormal Phlegmatic Munziq can improve ability of spatial learning and memory in APP/PS1 mice and regulate the expressions of RAGE and LRP1.
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Objective:To investigate the high risk factors of pelvic lymph node metastasis in patients with type Ⅰ endometrial carcinoma in order to provide the basis for making reasonable operation scope.Methods:Risk factors of pelvic lymph node metastasis were analyzed in 136 cases of type Ⅰ endometrial carcinoma.Univariate analysis was performed with Chi square test or Fisher's exact probability method,and multivariate analysis was performed with a logistic regression mode.Results:The positive rate of pelvic lymph nodes in 136 patients with type Ⅰ endometrial carcinoma was 9.56％ (13/136).Univariate analysis showed that histological grade,size of lesion,depth of myometrial invasion and vascular invasion were related to lymph node metastasis(P ＜0.05);Multivariate Logistic analysis showed that low differentiation,deep muscular invasion,tumor diameter≥2 cm and LVSI were independent risk factors of pelvic lymph node metastasis in patients with type Ⅰ endometrial carcinoma(P ＜0.05).Conclusions:The rate of pelvic lymph node metastasis is low in type Ⅰ endometrial carcinoma.Patients with low differentiation,deep muscular invasion,tumor diameter≥2 cm and LVSI are more likely to occur pelvic lymph node metastasis in type Ⅰ endometrial carcinoma.
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Objective To investigate the relationship between the homocysteine,sperm DNA fragmentation index and sperm counts of male with severe impaired spermatoqenesis.Methods From December 2015 to February 2017,56 male patients with severe impaired spermatoqenesis were enrolled in the study.The patients were divided into two groups according to the WHO criteria:severe oligozoospermia and azoospermia group (n =25) and oligoasthenoteratozoospermia group (n =31),and the control group was a male with no reproductive impairment (n=27).The sperm parameters were analyzed by using the computer automatic semen analyzer,sperm DNA fragmentation index and serum Hcy level were detected by sperm chromatin diffusion method and enzyme colorimetric method.Results The median of Sperm DNA fragmentation index and homocysteine level in control groups were 33％ [95％CI(29.0％ ～34.4％)] and 13.2 μmol/L [95％CI(12.4 μmol/L～14.2 μmol/L)],and in severe spermatogenesis groups in these two indicators were 21％ [95％CI(19.0％ ～24.0％)] and 8.9 mol/L [95％CI(8.4 μmol/L～ 9.4 μmol/L)],respectively.The results of these two items were higher than the control group,the difference was statistically significant (t=6.793～7.543,P=0.000).Sperm survival rate in normal control group and severe spermatogenesis group was 71％ [95％ CI(67.8％ ～75.1％)] and 57％[95％CI(52.3％ ～58.0％)],respectively,and the difference was statistically significant (t=-8.475,P=0.000).Sperm DNA fragmentation index was positively correlated with serum Hcy level and sperm concentration,Passing-Bablok regression analysis was:Y=10.705 +0.053X,Y=21.071+0.286X,and Hcy level was negatively correlated with sperm concentration.Conclusion The increase of Hcy level and sperm DNA fragmentation index may be an importantcause of male with severe impaired spermatoqenesis,but the specific mechanism remains to be further studied.
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Our previous study demonstrated that human KIAA0100 gene is a novel acute monocytic leukemia-associated antigen (MLAA) gene. But the functional characterization of human KIAA0100 gene has remained unknown to date. Here, firstly, bioinformatic prediction of human KIAA0100 gene was carried out using online software;Secondly, human KIAA0100 gene expression was downregulated by the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) 9 system in U937 cells. Cell proliferation and apoptosis were next evaluated in KIAA0100-knockdown U937 cells. The bioinformatic prediction showed that human KIAA0100 gene was located on 17q11.2, and human KIAA0100 protein was located in the secretory pathway. Besides, human KIAA0100 protein contained a signal peptide, a transmembrane region, three types of secondary structures (alpha helix, extended strand, and random coil) , and four domains from mitochondrial protein 27 (FMP27). The observation on functional characterization of human KIAA0100 gene revealed that its downregulation inhibited cell proliferation, and promoted cell apoptosis in U937 cells. To summarize, these results suggest human KIAA0100 gene possibly comes within mitochondrial genome; moreover, it is a novel anti-apoptotic factor related to carcinogenesis or progression in acute monocytic leukemia, and may be a potential target for immunotherapy against acute monocytic leukemia.
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Monoclonal antibodies (MAbs) are important tools for the study of proteins′ function and structure. But there has been no report on the preparation of MAbs against human KIAA0100 protein up to date. Here, first, we generated the mouse MAb against human KIAA0100 protein using purified recombinant 6×Histidinc (6×His)- tagged human KIAA0100 protein segment (1557–2234) as an antigen; then, the mRNA expression of human KIAA0100 gene was detected in U937 cells using Northern blot analysis. The results showed that the mouse MAb against human KIAA0100 protein could sensitively recognize the human KIAA0100 protein using Western blot analysis and immunocytochemistry analysis. Besides, Western blot analysis revealed that human KIAA0100 gene possibly encoded two different protein products (254 kDa and < 250 kDa) in U937 cells. Moreover, Northern blot analysis confirmed that human KIAA0100 gene might produced two different mRNA products (6000–10000 bp and 5000–6000 bp) in U937 cells. The results provide a basis for large-scale production of the MAb against human KIAA0100 protein, which will be useful for the study of human KIAA0100 protein′s function/structure and MAb-targeted drugs in the future.
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<p><b>OBJECTIVE</b>To investigate the relationship between miR-144 and Toll-like receptor 2 (TLR2).</p><p><b>METHODS</b>RT-qPCR was used to determine the expression of TLR2 and its downstream inflammatory cytokine TNF-α in rat macrophage cell line NR8383 transfected by a mimic miR-144 or miR-144 inhibitor. The fragments of 3'UTR region of rat TLR2 mRNA including wild or mutant miR-144 binding site obtained by PCR using rat liver cDNA were ligated to pmirGLO report gene vector digested with SacI and XbaI to construct the recombinant vectors of pmir-TLR2-3'UTR and pmir-mutant-TLR2-3'UTR. The miR-144 targeting TLR2 was further determined by dual luciferase reporter assay and miR-144 mimics.</p><p><b>RESULTS</b>TLR2 and TNF-α in NR8383 cells were decreased after transfection with 100 nmol/L mimic miR-144 for 24 h and increased after transfection with 100 nmol/L miR-144 inhibitor. PCR and double-enzyme digestion with SacI and XbaI confirmed successful insertion of the target fragments. Dual luciferase reporter assay suggested the binding of miR-144 to the 3'UTR of rat TLR2 mRNA.</p><p><b>CONCLUSION</b>miR-144 negatively regulates the expression of TLR2 and its down-stream cytokine TNF-α by targeting TLR2 in NR8383 cells.</p>