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OBJECTIVE To study the immunomodulatory effect of Guipi pills on D-galactose（D-gal）-induced aging mice. METHODS The immune-related targets and related pathways for Guipi pills to exert immune effects were screened by network pharmacology and verified through pharmacodynamic experiments. Totally 105 male ICR mice were randomly divided into blank control （CON） group， model control （MOD） group， positive control （POS） group， Guipi pills low-dose （GD） group and Guipi pills high-dose （GG） group. Except for the CON group， other groups were subcutaneously injected with 400 mg/kg D-gal to induce the aging model； CON group and MOD group were given distilled water， POS group was given 300 mg/kg pidotimod oral solution intragastrically， GD group and GG group were given Guipi pills 300， 600 mg/kg intragastrically， once a day， for 8 weeks. After medication， the serum and spleen were collected， and the contents of interleukin 2 （IL-2）， IL-4， IL-6 and tumor necrosis factor α （TNF-α）， and the contents of immunoglobulin G （IgG）， IgM and IgA were detected. The spleen index was calculated and the histopathological changes in the spleen were observed. The activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH- Px） and malondialdehyde （MDA）， and the content of 8-hydroxy-2 deoxyguanosine （8-OHdG） in spleen were detected； the expression of TNF/phosphoinositide-3-kinase-threonine protein kinase （PI3k-Akt）-related proteins in spleen was detected except for POS group. RESULTS The results of network pharmacology showed that TNF， IL-6 and Akt1 were core targets. The results of pharmacodynamic study showed that compared with MOD group， the contents of IL-2， IL-4， IgG， IgM and IgA were increased significantly in Guipi pills groups， while the contents of TNF-α and IL-6 were decreased significantly； the spleen index was increased significantly （P＜0.05 or P＜0.01）. The phenomenon of diffuse proliferation of lymphocytes was improved， the spleen cells were closely arranged， and the line between the white pulp and red pulp was clear. The activities of SOD and GSH-Px in spleen were increased significantly， while the activity of MDA， the content of 8-OHdG， and the protein expressions of TNF-α， PI3K and p-Akt were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Guipi pills can regulate the immune function of D-gal-induced aging mice， which is related to regulating the TNF/PI3k-Akt pathway， thereby reducing oxidative stress damage in spleen tissue of mice， and regulating protein expressions of TNF-α， PI3K and p-Akt.
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Drugs have both therapeutic and toxic side effects. How to quickly determine the toxicity of the test substance is very important for drug development. In vitro cytotoxicity testing compensates for the shortcomings of using animal models for toxicity evaluation. Its role in toxicity evaluation is increasingly important. The development of computer technology and in-depth research in proteomics, genomics, and metabolomics provide a method for in vitro cytotoxicity evaluation towards a faster and more accurate direction. This paper reviews the commonly used cells, evaluation indicators, and detection techniques for in vitro cytotoxicity evaluation, in order to provide some reference for related research.
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@#Objective To compare the clinical outcomes of transcatheter aortic valve implantation (TAVI) in oncology and non-oncology patients with severe aortic stenosis (AS). Methods A computer-based search in PubMed, The Cochrane Library, EMbase, CBM, CNKI and Wanfang databases from their date of inception to December 2021 was performed, together with reference screening, to identify eligible clinical trials. Two investigators screened the articles, extracted data, and evaluated quality independently. RevMan 5.3 and Stata 12.0 softwares were used for meta-analysis. Results The selected 8 cohort studies contained 57 988 patients, including 12 335 cancer patients and 45 653 non-cancer patients. The results of meta-analysis showed that in patients with cancer, the 30-day mortality [OR=0.74, 95%CI (0.65, 0.84), I2=0%, P<0.000 01], stroke [OR=0.87, 95%CI (0.76, 0.99), I2=0%, P=0.04] and acute kidney injury [OR=0.81, 95%CI (0.76, 0.85), I2=49%, P<0.000 01] were lower than those in patients without cancer. The 1-year mortality [OR=1.46, 95%CI (1.15, 1.86), I2=62%, P=0.002] and late mortality [OR=1.51, 95%CI (1.24, 1.85), I2=61%, P<0.000 1] were higher in patients with cancer. Conclusion It is effective and safe in cancer patients with severe AS undergoing TAVI. However, compared with patients without cancer, it is still high in long-term mortality, and further study of the role of TAVI in cancer patients with AS is necessary.
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Objective:To investigate the clinical efficacy and safety of ixazomib-based therapy in patients with relapsed or refractory multiple myeloma (RRMM) .Methods:A retrospective analysis was performed on the efficacy and adverse reactions of 53 RRMM patients treated with a combined regimen containing ixazomib in the Hematology Department of Beijing Jishuitan Hospital from July 8, 2018 to November 30, 2020. Among them, 6 patients received ID regimen (ixazomib + dexamethasone) , 30 patients received ID regimen + immunomodulator, and 17 patients received ID regimen + other chemotherapy drugs.Results:Fifty-three patients with RRMM received ixazomib-based therapy. The median previous treatment line was 3, the median treatment course was 6 (2-30) , and the median follow-up time was 21 months (2-32 months) . The overall response rate (ORR) was 54.7% (29/53) after 2 courses of treatment. Among them, 26.4% (14/53) had very good partial response (VGPR) and 28.3% (15/53) had partial response (PR) . The ORR of the ID regimen group, ID regimen + immunomodulator group and ID regimen + other chemotherapy group were 83.3% (5/6) , 56.7% (17/30) and 41.2% (7/17) respectively, with no statistically significant difference among the three groups ( P=0.208) . The median time to progression (TTP) of 53 patients was 8 months (1-24 months) . The most frequent adverse events of ixazomib treatment were gastrointestinal reactions such as nausea, vomit and diarrhea, with an incidence of 37.7% (20/53) , and the incidence of grade 3-4 was 5.7% (3/53) . The most common hematological adverse events were thrombocytopenia (15.1%, 8/53) , neutropenia (11.3%, 6/53) and anemia (9.4%, 5/53) . Grade 1-2 peripheral neurotoxicity occurred in only 7.5% (4/53) of patients. Conclusion:Ixazomib has good efficacy and safety for the patients with RRMM in the real world.
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Objective:To investigate the clinical efficacy and safety of bendamustine combination regimen in the treatment of patients with relapsed or refractory multiple myeloma (RRMM).Methods:From March 2020 to December 2020, 16 patients with RRMM were treated with bendamustine combination regimen in Beijing Jishuitan Hospital. The efficacy and adverse events (AEs) of bendamustine combination regimen were retrospectively analyzed in the 16 patients.Results:The median treatment lines for 16 patients with RRMM who received bendamustine combination regimen was 4 lines, and the median course of treatment was 3 (1-8). The median follow-up time after bendamustine treatment started was 5.3(1.3-9.2)months. Among the 16 cases, the disease control rate (DCR), overall response rate(ORR), and ≥ very good partial remission (VGPR) rate were 13/16, 5/16, 4/16 respectively. The median PFS was 4.9 months. Among them, the ORR of bendamustine combined with immunomodulators was higher. AEs were anemia, leukopenia, neutropenia, thrombocytopenia and fatigue. No patients who stopped treatment and adjusted the dose due to AEs.Conclusions:Bendamustine combination regimen is an effective and safe regimen for relapsed/refractory multiple myeloma.
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Extrachromosomal DNA (ecDNA) is a small segment of circular DNA located outside the chromosome, which has the function of self-replication. Recently, amplification of oncogenes on ecDNA has been proved to be a common phenomenon in tumor cells, and has some characteristics worth studying, such as correlation with patients' poor prognosis. Multiple chromosomal events are involved in the formation of ecDNA, and its amplification can directly increase the number of DNA copies of extra-chromosomal oncogenes and accelerate the generation and development of tumors. Moreover, the segregation pattern of unequal transmission of parental ecDNA cells to offspring not only increases tumor heterogeneity, but also enhances tumor adaptation to environment and response to therapy. This article reviews the current status and potential significance of ecDNA in tumor cells. .
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Objective@#To evaluate the cost-utility of different immunization strategies for rabies in China, and to provide a reference for determining the optimal immunization strategy.@*Methods@#The system dynamics model was used to simulate the epidemic of canine rabies and a decision tree model was conducted to analysis different immune strategies. Relevant probabilities were obtained through literature search and on-site investigation. Sensitivity analysis was used to explore the important influenced factors.@*Results@#At baseline, from a social perspective, 70% vaccination of dogs was the optimal strategy compared to current vaccination strategy (43% vaccination in dogs, human category-Ⅱ exposure vaccination/category-Ⅲ exposure vaccination combined with RIG). The total cost was 14 084 354 CNY, and the total utility value was 22 078 616.23 QALYs, and the incremental cost-utility ratio was-62 148 147 CNY/QALY; if human vaccination was considered, 55% vaccination of dogs combined with strategy one was the optimal strategy, its incremental cost-utility ratio was-444 620 557 CNY/QALY. The probability that an injured dog carries rabies virus was the most sensitive parameter. When it was greater than 0.005 03, strategy four was the optimal strategy. When it was less than 82/100 000, strategy one was the optimal strategy; when it was between 82/100 000 and 120/100 000, strategy two was the optimal strategy; when it was between 120/100 000 and 503/100 000, strategy two was the optimal strategy.@*Conclusion@#It was conducive to increase the vaccination coverage of canine for the prevention and control of rabies.
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Objective To investigate the changes of mechanoreceptors in the different state remnant stumps after anterior cruciate ligament(ACL)rupture.Methods From March 2013 to December 2015,fifty-seven cases of complete ACL rupture were collected to record the time interval from injury to surgery.The patients were divided into two groups according to preoperative kneelax joint measurement results:≤6 mm group (group 1)and>6 mm group(group 2).The morphology of each ligament stump in the two groups was recorded.After H&E staining and immunohistochemical labeling,the morphology,type,and quantity of the mechanoreceptors in the ligament stump were observed under an optical microscope.The relationship among the changes of the mechanoreceptors in the remnant stumps and the morphology of the ligament stump,the affected knee stability and the time from injury to surgery were analyzed.Results Twenty specimens were included in group 1.While 37 specimens were included in group 2.There was significant difference between the two groups in the distributions of the 4 types of the remnant stumps(P=0.000).There was significant difference between the two groups in the distributions of the 4 types of mechanoreceptors(P= 0.002).The number of the mechanoreceptors was positively correlated with the affected knee stability(r=0.63,P=0.018).There was no significant correlation between the number of the mechanoreceptors and the time from injury to surgery in group1 (r=-0.37,P=0.136),while the number of the mechanoreceptors was negatively correlated with the time from injury to surgery in group 2(r=-0.51,P =0.022).Conclusion After ACL rupture,the ligament stump in some patients still connect the femur and the tibia in the joint cavity,and exert mechanical stability function, which can retain the mechanoreceptors in the tissue for a long time.
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Objective To study to take the oxidized Mannan?modified 786?0 in renal clear cell carcinom as tumor cells antigen to sensitize Dendrit?ic cells(DC)and to observe the its killing effect on renal clear cell carcinoma of CTLs induced. Methods Getting the peripheral blood mononucle?ar cells from the volunteers,and then to be stimulated to turn to be maturation by GM?CSF and IL?4 in vitro. Taking the clear renal carcinoma cell as the tumor antigen,and then making it to be modified by oxidized Mannan to acquire the tumor cell vaccine.Experimental groups include:blank group:DC?PBS group,control group:control?DC?786?0,experimental group:DC?Ox?Mannose?786?0 group. Taking the flow cytometry to detect the changes of DC phenotype,then taking the ELISA to detect the sencretion levels of supernatant of IL?12 of DC,then taking the CCK to detecte the cytotoxicity of lymphocytes(CTL)induced by DC of these experiment groups. Results Results by flow cytometry:the mature phenotype of DCs sensitized by Ox?Mannose?786?0 group included CD80,CD83,CD86 and HLA?DR expressed significantly higher than the other groups. As well as the secretion levels of IL?12. Meanwhile the cytotoxicity activity of lymphocytes(CTLs)induced by DCs which are sensitized by Ox?Mannose?786?0 increased more significantly than the other groups. Conclusion Glycosylated Antigens can be more effective in sensitizing antigen?presenting cells DC,and stimulating them to be maturation,while the killing effect to tumor cells also have noticeably improved.
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Objective To establish a capillary gas chromatography( GC)method for the determination of residual organic solvents in poly( lactic-co-glycolide)( PLGA),including methanol,acetone,dichloromethane,and toluene. Methods A capillary GC method was carried out. DB-624 capillary column(30 m× 0. 32 mm,1. 80 μm)with programmed temperature chromatography was employed. The initial temperature was kept at 40 ℃ for 8 min. Then the temperature was raised to 200 ℃ at a rate of 10 ℃·min-1 . The injection port temperature was 180 ℃,and the split ratio was 10:1. The carrier gas was nitrogen. The temperature of FID was set at 250 ℃,and the sample volume was set at 3 μL. Results Four residual organic solvents consisting of methanol,acetone,dichloromethane and toluene in PLGA were completely separated. The linear range of concentration of methanol,acetone,dichloromethane and toluene was within 10. 0-50. 0( r=0. 999 8 ),16. 7-83. 3( r=0.9998),2.0-10.0(r=0.9993),and3.0-14.8(r=0.9997)μg·mL-1,respectively.Therecoveryofmethanol,acetone, dichloromethane and toluene was 99. 9%( RSD=1. 5%),100. 8%( RSD=0. 9%),100. 1%( RSD=1. 1%),and 99. 5%(RSD=0. 6%),respectively. Six batches of samples met the requirements. Conclusion The method is proven to be sensitive and accurate after the validation. It is suitable for the determination of residual organic solvents in PLGA.
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This article pointed out the purposes and significances of establishing a standardized clinical simulated education system and introduced the way adopted by general hospital of Tianjin medical university based on the status and problems of practical ability cultivation for students in clinical simulated education.Meanwhile,teaching methods were improved timely and teaching contents were replenished.
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National Outline Program for Medium and Long-term Education Reform and Development (2010 -2020) points out the importance of cultivating the ‘excellent physicians' and the idea of ‘ constructing high-qualified and high-leveled clinical faculty is at the top priority' was put forward clearly at the ‘ working conference of the national mdical education reform' sponsored by both the ministry of education and the ministry of health.From the perspective of constructing clinical faculty adaptable to the new situation,this essay explored the importance of constructing clinical faculty under the new situation of medical education reform,summarized the achievements and experiences in the general hospital of Tianjn medical university and proposed some suggestions.
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Objective This study was to evaluate the usefulness of the model of end-stage liver disease (MELD) score in comparison with the Child-Pugh classification to predict postoperative mortality and short-term survival in liver transplant patients. MethodsMELD score and Child-Pugh score were computed for each patient according to the original formula on admission day. Kaplan-Meier survival curves were made using the cut-off points calculated by Youden index. ResultsSix out of 40 patients died within three months, MELD scores and Child-Pugh scores for non-survivors (32.2?8.0, 12.3?2.0) were higher than those for survivors (13.4?6, 9.12?2.31) significantly (P