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The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.
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Chlamydia trachomatis (Ct) is the causative agent of bacterial sexually transmitted diseases (STDs) worldwide.The incidence of Ct infection has exceeded that of Neisseria gonorrhoeae,and becomes the highest in STDs in many countries.Ct infection can lead to urethritis,epididymitis,prostatitis and infertility in males,and cervicitis,endometritis,pelvic inflammatory disease,infertility in females,and neonatal conjunctivitis.Additionally,urogenital Ct infection is always ignored due to its concealed symptoms,leading to a long clinical course,recurrence or repeated infections.Furthermore,Ct infection can increase the risk of human immunodeficiency virus and human papilloma virus infections.Therefore,how to prevent and control the transmission of Ct has become one of the global public health issues.Currently,a growing body of researches have focused on the molecular epidemiological characteristics of Ct,which are aiming to identify the mutant strains,elaborate transmission dynamics,investigate the distribution of Ct serotypes in different populations,so as to provide molecular epidemiological evidence for the prevention and control of Ct infection.This review summarizes the epidemic status and research methods for molecular epidemiological characteristics of Ct,as well as application of Ct serotyping in clinical practice,providing references for the prevention,control and research of Ct infection.
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Objective:To explore the value of combined detection of PCT and IL-6 in differential diagnosis SIRSin ICU patients.Methods:100 patients with ICU admitted to our hospital from 2013 to 2016 were choosen,including 61 cases with non septic SIRS and 39 cases with sepsis,and 50 healthy persons over the same period were selected as control,and they were divided into non-septic group,sepsis group and control group.The levels of serum PCT and IL-6 were detected by electrochemiluminescence assay,and took PCT of 2 g/L and IL-6 of 50 ng/L for the critical value to identify non infectious SIRS and sepsis,to evaluate the clinical diagnostic value of combined detection.Results:The maximum values of PCT and IL-6in the non-septic group respectively were 0.91 ± 0.54 μg/L and 62.77± 11.75 ng/L,in the septic group respectively were 24.49± 5.00 μg/L and 1542.69± 361.66 ng/L,in the control group respectively were 0.08± 0.06 tμg/L and 3.68± 1.11 ng/L,the maximum values of PCT and IL-6 in the non-sepsis group and the sepsis group were significantly higher than control group (P＜0.05).Compared with the non-septic group,the maximum valuesin sepsis group were significantly increased (P＜0.05).The proportions of PCT ＞ 2 g/L and IL-6 ＜ 50ng/L in the non-septic group respectively were 21.31％ and 65.57％,in the septic group respectively were 92.31％ and 87.18％,the proportions of PCT＞2 g/L,IL-6＜50 ng/L in the sepsis groupwere significantly higher chan those in the non-septic group (P＜0.05).The positive predictive values,sensitivity and specificity of PCT were higher than IL-6,the positive value,specificity of combined detection was higher than IL-6 and PCT,while the sensitivity of combined detection was higher than IL-6,P＜0.05.Conclusions:Combined detection of PCT and IL-6 is helpful for differential diagnosis of sepsis and non-septic SIRS.
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Applying mitochondrial replacement technique to human assisted reproduction could benefit the fam-ilies with mitochondrial diseases and improve clinical outcomes of assisted reproduction in elderly patients. But it may also lead to a series of medical ethics issues such as the standardization and security of this technology, the conflict with the traditional ethical concepts, the determination of informed consent and confidentiality principles, the health development issues of the offspring, and commercial donation of eggs and so on. As for this, the relevant institutions should strictly control the indications when apply this technology, the government should formulate rele-vant laws and regulations. Simultaneously, it is important to strengthen supervision and management of social eth-ics, improve professional ethics of assisted reproductive personnel, and emphasize the correct guiding role of public opinion.
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Objective To investigate the distribution of scopolamine into brain following intranasal .Methods Adult Wistar rats were divided into two groups ,and administrated with scopolamine 0 .3 mg via intraperitoneal or intranasal respectively .Two groups of blood concentration and brain concentration of scopolamine were determined by solid phase extraction (SPE) and LC/MS assay at the time point of 5 ,10 ,20 ,30 ,60 ,120 ,240 ,480 min ,and their kinetic parameters were calculated and compared .Results Scopol-amine bioavailability of intranasal administration was 65% ,and the maximum concentration of scopolamine in brain following in-tranasal administration was much higher than that following intraperitoneal administration .Comparing the ratio of AUC in brain and in plasma ,ratio of intranasal administration is bigger than that of intraperitoneal administration significantly (P<0 .05) .Con-clusion It was concluded that scopolamine′s intranasal administration induced the agent targeting distribution into the brain .
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To clone and express the gene encoding chicken aminopeptidase N (chAPN), and analysis the biological function of chAPN expressed in Escherichia coli (E. coli). The chAPN gene was amplified by RT-PCR from the kidney cells of chicken embryo and then cloned into the prokaryotic expression vector pCOLD-TF. Recombinant expression plasmid of pCOLD-TF-chAPN was constructed and then transformed into the competent E. coli BL21(DE3) cells for expression under different conditions such as induction time and inductor concentrations. Purified soluble recombinant chAPN was obtained by Ni-NTA His Bind Resin affinity chromatography and identified by SDS-PAGE gel and Western blotting assay. Its biological function was detected by its reaction with Leu-PNA and Enzyme-Linked Immunosorbent Assay (ELISA). The results showed that the expression product of chAPN gene in E. coli was soluble. It was able to bind infectious bronchitis virus (IBV) dose-dependently. In conclusion, chAPN gene has been successfully cloned and expressed in E. coli, which will establish a basis for further research the enzymatic activity and antiviral function.
Subject(s)
Animals , CD13 Antigens , Genetics , Metabolism , Chickens , Cloning, Molecular , Escherichia coli , Genetics , Metabolism , Recombinant Proteins , Genetics , MetabolismABSTRACT
Objective:To develop an enzyme immunoassay for the detection of Osteogenic Growth Peptide in serum for clinical investigation.Methods:Two kinds of competitive Enzyme linked immununosorbent assay were employed,based on sensitivity and shape of dose-reaction curve,the most suitable testing pattern was selected for further application.Results:Purified antibody was better than salting-out antibody in competitive Enzyme linked immununosorbent assay in terms of standard curve.Modified competitive Enzyme linked immununosorbent assay was better than competitive Enzyme linked immununosorbent assay in sensitivity.Conclusion:Modified competitive Enzyme linked immununosorbent assay for Osteogenic Growth Peptide is sensitive enough for clinical investigation.
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@#Objective To observe the effect of consciousness-restoring obstruction-clearing needing technique combined with swallowing function training on pseudobulbar paralysis after stroke.Methods 80 stroke patients with pseudobulbar paralysis were randomly divided into the trial group and control group with 40 cases in each group.The patients of the trial group were treated with consciousness-restoring obstruction-clearing needing technique combined with swallowing function training and routine medicine,those of the control group were treated only with routine medicine.Results After treatment,the whole effective rate of the trial group was 92.5%,that of the control group was 60.0%,there was a significant difference between two groups(P<0.05).Conclusion The therapeutic effect of consciousness-restoring obstruction-clearing needing technique combined with swallowing function training and routine medicine on pscudobulbar paralysis after stroke is superior to simply routine medicine.