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In recent years,great progress has been achieved in the application of immune checkpoint inhibitors (ICI) in tumor immunotherapy.However,a variety of adverse reactions induced by ICI have been reported.Despite the high overall incidence of adverse reactions caused by ICI,some adverse reactions,such as immune-related pancreatitis,are rare in clinical practice.In this paper,a case of immune-related pancreatitis after treatment of advanced gastric cancer with nivolumab was identified.We analyzed the cause,treatment,incidence,and risk factors of the adverse reaction,aiming to improve the clinical diagnosis,treatment,and safe medication of rare adverse reactions associated with ICI.
Subject(s)
Humans , Nivolumab/adverse effects , Immune Checkpoint Inhibitors/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Pancreatitis/drug therapy , Stomach NeoplasmsABSTRACT
Objective: To explore the effect of emotional optimization of workplace employees in immersive virtual natural environment. Methods: In July 2020, 15 subjects were selected to complete two groups of treadmill walking training experiments in virtual natural environment and daily environment respectively. At the same time, the subjects' skin electrical (EDA) , pulse frequency (Pf) , respiratory frequency (Rf) physiological data and Self-Assessment Manikin (SAM) data before and after walking were collected; the mean value of three dimensions of SAM and the emotion difference before and after the experiment were calculated. The differences of physiological indexes and subjective mood changes of subjects were tested by paired sample t-test. Results: Compared with the daily environment, the ΔEDA, ΔPf and ΔRf of the subjects in the virtual natural environment were all decreased , and the differences were statistically significant (P<0.05). There were statistically significant differences in pleasure and arousal between subjects before and after using the virtual natural environment (P <0.05). Compared with the daily environment, the Δpleasure degree of subjects using the virtual natural environment increased, and the Δarousal degree and Δdominance degree decreased, and the differences were statistically significant (P <0.05). Conclusion: Walking in virtual natural environment can help subjects improve their mood, relax and improve the regulation ability of autonomic nervous system.
Subject(s)
Humans , Arousal , Emotions/physiology , Heart Rate , Virtual Reality , WorkplaceABSTRACT
The pathogenesis of autoimmune disease is complex, lacking in specific markers and new therapeutic targets. Traditional Chinese medicine (T C M) is effective in treating chronic complex diseases such as autoimmune diseases, but the specific mechanism of action remains unclear. The core idea of network pharmacology has much in common with the overall philosophy of TCM. As a new discipline, it provides a new research mode for TCM to transform from empirical medicine to evidence-based medicine. Network pharmacology has been applied in many fields of research, but its application in a certain kind of disease is rarely reviewed. Through searching domestic and foreign literature, this paper reviews the application of network pharmacology in the prevention and treatment of rheumatoid arthritis, psoriasis, systemic lupus erythematosus with traditional Chinese medicine and identification of related biological targets.
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OBJECTIVE@#To investigate the down-regulation effect of let-7b-5p on the expression of FTO in acute myeloid leukemia cell line THP-1 and inhibitory effect on THP-1 proliferation via m@*METHODS@#The acute myeloid leukemia cell line THP-1 and the normal human peripheral blood mononuclear cells (PBMNC) were selected as subjects. The expression of let-7b-5p and FTO mRNA in those cells was detected by qPCR, further the expression of FTO protein in those cells was detected by Western blot. And, the luciferase reporter gene assay was used to verify the targeting effect of let-7b-5p on FTO. Finally, THP-1 cells were transfected respectively with let-7b-5p mimic, and PBMNC with let-7b-5p inhibitor, there after the C-MYC mRNA m@*RESULTS@#Compared with PBMNC, the expression of let-7b-5p in THP-1 significantly decreased, while the expression of FTO was significantly increased (P<0.05). After transfection with let-7b-5p mimic combined with FTO 3'-UTR, the luciferase activity of transfected THP-1 cells significantly decreased, but the luciferase activity significantly increased after transfection with mutant 3'-UTR, which was significantly different from the negative control group(blank vector) (P<0.05). Let-7b-5p inhibitor down-regulated c-MYC mRNA m@*CONCLUSION@#Human acute myeloid leukemia cell line THP-1 low expresses the let-7b-5p, which regulates c-MYC expression through let-7b-5p-/FTO-/m
Subject(s)
Humans , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Cell Line, Tumor , Cell Proliferation , Leukemia , Leukocytes, Mononuclear , MicroRNAs/genetics , Signal Transduction , THP-1 CellsABSTRACT
<p><b>OBJECTIVE</b>To compare clinical efficacy of complete and incomplete radical debridement for spinal tuberculosis by Meta-analysis.</p><p><b>METHODS</b>The literatures of RCT or non-RCT with complete and incomplete radical debridement for spinal tuberculosis from Medline, EMBASE, Cochrane Library, Web of Science, CBM, CNKI and Wanfang were searched from the time of creating database to July, 2017. Two independent reviewers identified eligible studies, extracted data and evaluated risk of bias of included studies. Meta analysis were performed by Revman 5.3 and GRADE system were used to grade evidence. Recurrence rate, adverse effects, healing time, chemotherapy duration, spinal deformity by correction angle, bone fusion time in interface of intervertebral, erythrocyte sedimentation rate and C-reaction protein were compared between two groups.</p><p><b>RESULTS</b>Totally 9 literatures were chosen, including 5 RCT and 4 non-RCT with 1 302 patients. Compared with incomplete radical debridement, complete radical debridement had lower recurrence rate [=0.14, 95%CI(0.08, 0.22), <0.000 01], lower rate of adverse effects[=0.18, 95%CI(0.12, 0.27), <0.000 01], shorter healing time[MD=-4.80, 95%CI(-5.14, -4.45), <0.000 01]and chemotherapy duration [MD=-5.25, 95%CI(-5.64, -4.86), <0.000 01], larger spinal deformity by correction angle[MD=4.88, 95%CI(3.55, 6.27), <0.000 01], smaller erythrocyte sedimentation rate[MD=-8.74, 95%CI(-11.99, -5.49), <0.000 01] and C-reaction protein [MD=-4.75, 95%CI(-8.61, -0.88), =0.02] . However, there was no difference on bone fusion time in interface of intervertebral between two groups[MD=-0.19, 95%CI(-0.50, 0.12), =0.23].</p><p><b>CONCLUSIONS</b>Compared with incomplete radical debridement, complete radical debridement has advantages of lower incidence of recurrence, lower rate of adverse reaction, shorten healing time and chemotherapy time, recovered faster. Techniques are selected according to indication of patients individual, complete radical debridement is recommended at the same indications.</p>
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Objective To evaluate the effects of lentivirus-delivered short hairpin RNA (shRNA) targeting human papillomavirus 16 (HPV16) E7 gene on the expression of 4 kinds of DNA methyltransferases (DNMTs),including DNMT1,DNMT3A,DNMT3B and DNMT3L,in HPV16-positive cervical cancer cell line SiHa.Methods The recombinant plasmid containing HPV16 E7 gene-targeting shRNA was constructed firstly.Then,the BLOCK-iTTM lentiviral RNAi expression system kit was used to package the lentiviral vector,which was transfected into 293T cells.The lentivirus-containing supernatants were collected at 48 and 72 hours after transfection.The SiHa cells were divided into 3 groups to be cultured with lentiviral supernatant containing HPV16 E7 gene-targeting shRNA recombinant plasmids mixed with complete medium at a ratio of 1:1 (shRNA group),lentiviral supernatant containing empty plasmids mixed with complete medium at a ratio of 1:1 (negative control group),and complete medium alone (blank control group),respectively.Real-time fluorescence-based quantitative PCR (qRT-PCR) was performed to measure mRNA expression of HPV16 E7 and 4 kinds of DNMTs in the above 3 groups at 0,48,96 hours after infection,and Western blot analysis to determine protein expression of the 4 DNMTs at 48,96 hours after infection.Results There were no significant differences in the mRNA expression of HPV16 E7 and the 4 DNMTs among the shRNA group,negative control group and blank control group at 0 hour after infection (all P ＞ 0.05).At 48,96 hours after infection,the mRNA expression of HPV16 E7 and the 4 DNMTs decreased significantly in the shRNA group compared with the negative control group and blank control group (all P ＜ 0.05),but did not differ between the negative control group and blank control group (all P ＞ 0.05).Additionally,E7,DNMT1,DNMT3A,DNMT3B and DNMT3L gene-silencing efficiencies in the shRNA group were 71.13％,50.53％,13.72％,46.27％ and 17.92％ at 48 hours,and 83.50％,74.2％,47.8％,64.7％ and 48.9％ at 96 hours after infection,respectively.Western blot analysis showed that the protein expression of the 4 DNMTs significantly decreased in the shRNA group compared with the negative control group and blank control group at 48,96 hours after infection (all P ＜ 0.01).Moreover,the protein expression of DNMT1,DNMT3A,DNMT3B and DNMT3L in the shRNA group gradually decreased over time,and was inhibited by 84％,37.2％,59.8％ and 49.3％ at 48 hours respectively,and by 73.1％,68.7％,55.5％ and 65.5％ at 96 hours after infection respectively.Conclusion Targeted silencing of E7 gene in HPV16-positive SiHa cells can interfere with the mRNA and protein expression of DNMT1,DNMT3A,DNMT3B and DNMT3L.
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Objective To evaluate effects of human papilloma virus(HPV)16E7 on expressions of six tumor suppressor genes(including MT1G, NMES1, RRAD, SFRP1, SPARC and TFPI2)in a cell line SiHa, as well as on its proliferation and apoptosis. Methods SiHa cells were divided into two groups to be transfected with a small interfering RNA targeting HPV16E7(E7SiRNA, experimental group)and an empty vehicle(negative control group) respectively, with SiHa cells receiving no treatment serving as the blank control group. After 48 hours, qPCR was performed to measure the mRNA expressions of E7 and six tumor suppressor genes, CCK?8 assay to evaluate cellular proliferative activity, and flow cytometry to assess apoptosis of SiHa cells. Results At 48 hours after the transfection, the experimental group showed significantly decreased E7 mRNA expression(0.25 ± 0.036, P0.05). Conclusion E7 may participate in HPV16?induced cellular malignant transformation by suppressing the mRNA expressions of 6 tumor suppressor genes, including MT1G, NMES1, RRAD, SFRP1, SPAR and TFPI2.
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The molecular mechanism of DNA damage induced by hydroquinone (HQ) remains unclear. Poly(ADP-ribose) polymerase-1 (PARP-1) usually works as a DNA damage sensor, and hence, it is possible that PARP-1 is involved in the DNA damage response induced by HQ. In TK6 cells treated with HQ, PARP activity as well as the expression of apoptosis antagonizing transcription factor (AATF), PARP-1, and phosphorylated H2AX (γ-H2AX) were maximum at 0.5 h, 6 h, 3 h, and 3 h, respectively. To explore the detailed mechanisms underlying the prompt DNA repair reaction, the above indicators were investigated in PARP-1-silenced cells. PARP activity and expression of AATF and PARP-1 decreased to 36%, 32%, and 33%, respectively, in the cells; however, γ-H2AX expression increased to 265%. Co-immunoprecipitation (co-IP) assays were employed to determine whether PARP-1 and AATF formed protein complexes. The interaction between these proteins together with the results from IP assays and confocal microscopy indicated that poly(ADP-ribosyl)ation (PARylation) regulated AATF expression. In conclusion, PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of AATF through PARylation.
Subject(s)
Humans , Antioxidants , Toxicity , Apoptosis Regulatory Proteins , Genetics , Metabolism , Cell Line , DNA Damage , Gene Expression Regulation , Gene Silencing , Histones , Genetics , Metabolism , Hydroquinones , Toxicity , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases , Genetics , Metabolism , Protein Transport , Repressor Proteins , Genetics , MetabolismABSTRACT
In China, Monascus spp., a traditional fungus used in fermentation, is used as a natural food additive. Monascus spp. can produce a secondary metabolite, monacolin K namely, which is proven to be a cholesterol-lowering and hypotensive agent. Hence, recently, many researchers have begun focusing on how to increase the production of monacolin K by Monascus purpureus. In the present study, we investigated the effect of the fungal elicitor and the mutagenesis of UV & LiCl on the amount of monacolin K produced by Monascus purpureus. The fugal elicitor, Sporobolomyces huaxiensis, was isolated from tea leaves and its filtrate was added into the culture filtrate of Monascus purpureus during growth to induct the production of monacolin K. The results showed that the highest amount of monacolin K produced by the liquid fermentation was 446.92 mg/mL, which was produced after the fungal elicitor was added to the culture filtrate of Monascus purpureus on the day 4; this amount was approximately 6 times greater than that of the control culture filtrate, whereas the highest amount of monacolin K produced by the mutated strain was 3 times greater than the control culture after the irradiation of UV light in the presence of 1.0 % LiCl in the medium.
Subject(s)
Basidiomycota/physiology , Lovastatin/biosynthesis , Mutation , Monascus/metabolism , China , Culture Media , Lithium Chloride , Monascus/genetics , Monascus/radiation effects , Ultraviolet RaysABSTRACT
Objective Discuss propofol in aged patient do not have painful gastroscope inspection in calm ease pain effect and safety.Methods Inspect gastroseope divide into observation group(propofol group) with compare group(conventional gastroscope group).Observe each group of record to receive the gastroscope operating time.nar- cotic thing role time and reaction in skill,before inspecting in rear BP,HR,SpO_2 and skill rear questionnaire investi- gation.Results The case owned is inspected all consummately,observe group to have negative role less,patient is more easy to accept.Conclusion It is rapid to have effect in propofol inspects without painful gastroscope,recovery time short,negative role lose,is comfortable and safe.
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To clone KGF-2 gene, get hKGF-2 protein and detemine its activity. The cNDA of human KGF-2 was isolated from fetal lung by RT-PCR and cloned into pBV220 plasmid. The recombinant pBV220-hKGF-2 plasmid was transformed into E. coli (BL21), induced at 42 degrees C for the expression of hKGF-2. Recombinant human KGF-2 was purified from the ultrasonic-treated BL21 by heparin-Sepharose CL-6B treated column chromatography and cation exchange column chromatography. MTT method was used for the determination of its biological activity. SDS-PAGE showed that rhKGF-2 was expressed in E. coli BL21 as soluble protein of approximately 20kD. The rhKGF-2 protein can stimulate the proliferation of NIH3T3 cells significantly from 1 ng/mL to 10 ng/mL. HKGF-2 cDNA wasclned and highly expressed in E. coli BL21 and the purified rhKGF-2 showed the mitogenic activity on NIH3T3 cells.
Subject(s)
Humans , Cloning, Molecular , Escherichia coli , Genetics , Metabolism , Fetus , Fibroblast Growth Factor 10 , Genetics , Genetic Vectors , Genetics , Lung , Chemistry , Recombinant Proteins , GeneticsABSTRACT
Objective To investigate the effects of anti-cell membrane associated DNA (mDNA) antibodies in the diagnosis of systemic lupus erythematosus (SLE) lacking of specific autoantibodies including anti Sm,anti ds-DNA,and anti-nucleosome antibodies.Methods Indirect immunofluorescence assay was used to measure anti-mDNA antibodies in serum of 145 SLE patients,and indirect immunofluorescence,Western-blot and ELISA were used to detect the anti-dsDNA ,anti-Sm and anti- nueleosome antibodies respectively to analysis the value of anti-mDNA antibodies on the specific autoantibodies negative patients with SLE.Results The sensitivity for anti-mDNA antibodies (69.7%) in SLE was significantly higher than anti-Sm (19.7%),anti-dsDNA ( 31.9% ) and anti-nucleosome (45.8% ).The incidences of anti-mDNA antibodies in SLE lacking of anti-dsDNA,Sm and anti-nueleosome antibodies (AnuA) were 64.3% ,70.2% and 60.3% respectively.Conclusion Anti-mDNA antibodies are serologic marker of SLE and important in diagnosis of SLE lacking of anti-dsDNA,Sm and nucleosome antibodies.
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Objective To investigate the effects of ischemic postconditioning (Post) on myocardial cell apoptosis and expres- sion of Bcl-2 and Bax protein during ischemia/reperfusion period in rabbits.Methods Eighteen rabbits were randomly allocated to three groups (6 in each group),sham operation (group S),ischemia/reperfusion group(group IR) and ischemic postconditioning group(group Post).Group IR and group Post were subjected to 15 minutes of left anterior descending coronary artery occlusion followed for 30 minutes of reperfusion.Ischemic postconditioning was achieved by three 30 seconds cycles of reperfusion,each followed by 30 seconds ischemia.Cardiomyocyte apoptosis were determined by in situ TDT-mediated dUTP nick end labeling (TUNEL) and DNA electrophoresis.The expression of Bcl-2 and Bax proteins in apoptotic myocardial cells were detected by immunohistochemistry sepa- rately.Results Compared with group IR,apoptotic index was significantly reduced in group Post [(28.06?2.92) % vs.(55.70? 13.96)%,P