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Multiple myeloma (MM) is a plasma cell malignant proliferative hematological tumor. At present, a variety of drugs including immunomodulators (IMiD) and proteasome inhibitors (PI) have been used to treat MM, and the progression-free survival time of patients has been significantly prolonged. Because the immune dysfunction of MM patients has not been fundamentally corrected, most of them will eventually relapse and develop drug resistance. Pomalidomide, a third-generation IMiD, has achieved a high response rate in clinical trials of patients with relapsed/refractory multiple myeloma (RRMM) who did not respond to lenalidomide or bortezomib. This article reviews the mechanism of pomalidomide and the efficacy and safety of relevant clinical trials, so as to investigate the treatment measures for RRMM.
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This review summarized the importance of return to work to patients with hematologic malignancies and their families, the research status at home and abroad, the factors affecting return to work and their intervention status, in order to provide reference for more current research and intervention measures in China.
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Objective:To investigate the therapeutic effect and safety of pomadomide combined with cyclophosphamide and dexamethasone (PCD) in the treatment of relapsed/refractory multiple myeloma (MM).Methods:The clinical data of 20 relapsed/refractory MM patients receiving PCD regimen in the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College from March 2021 to June 2022 were retrospectively analyzed; and 29 relapsed/refractory MM patients receiving other regimens including DECP (dexamethasone+etoposide+cyclophosphamide+cisplatin, 13 cases) and VCD (bortezomib+ cyclophosphamide+ dexamethasone, 16 cases) during the same period were treated as the control group. The efficacy and adverse effects of both groups were compared after 4 cycles of treatment.Results:After 4 cycles of treatment, the overall response rate (ORR) and the clinical benefit rate (CBR) of 20 cases in PCD group was 70.0% (14/20) and 85.0% (17/20), respectively; among 20 cases, there were 5 cases of complete response (CR), 4 cases of very good partial remission (VGPR), 5 cases of partial remission (PR), 3 cases of minimal remission (MR), 2 cases of stable disease (SD), 1 case of the progression of the disease (PD). ORR and CBR of 29 cases in the control group was 41.4% (12/29) and 65.5% (19/29), respectively; among 29 cases, there were 2 cases of CR, 3 cases of VGPR, 7 cases of PR, 7 cases of MR, 5 cases of SD, 5 cases of PD. There was a statistically significant difference in ORR of both group ( χ2 = 3.89, P = 0.048), while the difference in CBR of both group was not statistically significant ( χ2 = 2.30, P = 0.129). There were 2 patients with renal impairment achieving CR in PCD group and 1 patient with renal impairment achieving CR in the control group ( P = 0.152); 1 genetically high-risk patient achieved CR in PCD group and none of patients in the control group achieved CR, and the difference was statistically significant ( P>0.05). The common hematological adverse effects of two groups were anemia, neutropenia, thrombocytopenia; the common non-hematological adverse effects were malaise, infection and fatigue, and the differences were statistically significant (all P>0.05). The incidence of grade 3-4 infection was 25.0% (5/20) in PCD group and the disease was under the control after anti-infective therapy, and the incidence of grade 3-4 infection was 24.1% (7/29) in the control group; and the difference was not statistically significant ( P > 0.05). Conclusions:PCD regimen has good clinical efficacy and safety in treatment of relapsed/refractory MM.
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OBJECTIVE@#To investigate the regulatory effect of metformin on regulatory T cells (Treg) in acidic environment.@*METHODS@#CD4 CD25 Treg cells were obtained by magnetic bead sorting. Treg and conventional T cells (Tcon) cells were cultured for 24-72 h in pH 7.4 or pH 6.7 medium, and the cell proliferation, apoptosis and Foxp3 expression were detected by flow cytometry. Real-time PCR was used to detect the expression levels of the genes related with glucose metabolism. Thirty-two C57BL/6 male mouse models bearing subcutaneous prostate cancer xenograft derived from RM-1 cells were randomized into 4 equal groups for treatment with PBS, metformin, tumor vaccine, or both metformin and the vaccine. The treatment started on the 4th day following tumor cell injection, and metformin (100 mg/kg) or PBS was administered by intraperitoneal injection on a daily basis; the vaccine was intramuscularly injected every 4 days. The tumor size was continuously monitored, and the mice were euthanized on day 25 after tumor implantation to obtain tumor and blood samples. Flow cytometry was used to detect the changes in CD4, CD8, CD4Foxp3 cell subsets in the tumor tissue and peripheral blood.@*RESULTS@#Treg cells showed significantly enhanced proliferation ( < 0.05) while the proliferation of Tcon cells was suppressed in acidic medium ( < 0.001). Treg cells cultured in acidic medium showed significantly increased expressions of OXPHOS-related genes pgc1a ( < 0.001) and cox5b ( < 0.01), which did not vary significantly in Tcon cells in acidic medium. Treg cells exhibited significantly decreased apoptosis in acidic medium ( < 0.01) with increased Foxp3 cells ( < 0.001) and intracellular alkaline levels ( < 0.01). Metformin obviously reversed the acid tolerance of Treg cells without producing significant effect on Tcon cells. In the animal experiment, both metformin ( < 0.05) and vaccine ( < 0.01) alone reduced the tumor volume, but their combined treatment more potently reduced the tumor volume ( < 0.001). Metformin alone did not obviously affect CD4 cells or CD8 cells but significantly decreased the percentage of CD4Foxp3 ( < 0.05); the vaccine alone significantly increased CD4 cells and CD8 cells ( < 0.001) and also the percentage of CD4Foxp3 cells ( < 0.05). The combined treatment, while reducing the percentage of CD4Foxp3cells to a level lower than that in the vaccine group ( < 0.01), produced the strongest effect to increase CD4 cells and CD8 cells ( < 0.01).@*CONCLUSIONS@#Metformin can inhibit the proliferation and function of regulatory T cells in an acidic environment and enhance the effect of tumor vaccine by reducing the proportion of Treg cells to achieve the anti-tumor effect.
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Animals , Male , Mice , Cell Proliferation , Forkhead Transcription Factors , Metformin , Mice, Inbred C57BL , T-Lymphocytes, RegulatoryABSTRACT
Objective To examine the teaching effects of case-based learning in the class of functional experiment. Methods Students (n=139) of five-year clinical medicine specialty were ran-domly divided into control group (n=70) and case group (n=69). The students of control group were taught with traditional teaching method and the case-based learning was adapted in the case group. Namely the clinical cases were led into teaching and the teaching process was completed through case import, problem sets, and the literature review and discussion. The teaching effects were evaluated through questionnaire survey (Analysis by the χ2-test, the test level is 0.05) and the analysis of test scores (Analysis by the t-test, the test level is 0.05). Results The score of the case group was better than the control group in the operation test (P=0.042 0). The total evaluating score and test score were also better in the case group in comparing to the control group (P=0.007 8 or P=0.008 2). As indicated by the questionnaire survey, more than 80%students thought the case teaching method could improve their learning interests and the independent learning abilities. Moreover, the skills of problem analysis and knowledge application were increased through case teaching. Conclusion The teaching effects of case-based learning were superior to the traditional teaching.
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In medical colleges, it is difficult to effectively carry out design experiment teach-ing in functional experiment because of the limitation of many factors such as the large number of stu-dents and the shortage of teachers and teaching resources. This study explored the multi-level teaching of designing experiment. Through gradually increasing the difficulty of the teaching content, the center position of the students was improved. Besides, the students' knowledge expanded from books to the subject research frontiers and their awareness of innovation was gradually enhanced. The survey showed that students' satisfaction with the teaching was up to 90% and their self-learning ability was en-hanced. However, it should be noticed that teaching time should be arranged reasonably and the teach-ing process should be supervised in design experiment to ensure the effective experiment teaching.
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The present study prepared the pulmonary fibrosis model in mice by using Bleomycin and carry out the investigations on the effects of taurochenodeoxycholic acid [TCDCA] in preventing pulmonary fibrosis in mice. Expression profiles of the bile acid receptors in the lung of mice FXRalpha and TGR5 were examined, and pulmonary coefficient, pathohistology as well as expression of TNF-alpha, MMP-2, MMP-9 and TIMP-2 in pulmonary fibrosis mice. The results showed that FXRalpha and TGR5 simultaneously expressed in the lung of the mice; TCDCA in dosages of 0.05 and 0.1g/kg can extremely significantly decrease the pulmonary coefficient in the model mice [P<0.01], TCDCA in a dosage of 0.2g/kg significantly decreased the pulmonary coefficient in the model mice [P<0.05]; TCDCA in dosages of 0.05 and 0.1g/kg significantly reduce the pathological damages on their lungs; TCDCA can extremely significantly decrease the expression levels of TNF-alpha and TIMP-2 in pulmonary tissues in the pulmonary fibrosis mice [P<0.01], the expression level of MMP-9 extremely significantly increased [P<0.01], while it has no significant effects on MMP2. The results as mentioned above indicated that TCDCA had antagonistic actions on pulmonary fibrosis in mice
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Animals, Laboratory , Pulmonary Fibrosis/prevention & control , Mice , Bleomycin , Receptors, G-Protein-Coupled , Tumor Necrosis Factor-alpha , Tissue Inhibitor of Metalloproteinase-2ABSTRACT
How to test and assess is related to the teaching objectives,teaching ideas,teaching effectiveness and development.And it's also the key factor of experiment teaching reform.Formative evalution system was researched and practiced in the functional experiment.It was tested through questionnaire survey and analysis of paper.
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margin from CTV to PTV.
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Objective To analyze the efficacy of kaolin intake amount as an index for motion sickness (MS)induced by different motion patterns stimulating the vestibular receptors of rats.Methods Rats were randomly divided into 5 groups.Three groups were subjected to one of the following stimulations,respectively-linear acceleration along either the interaural axis(IA)or body axis (AP),and double rotation(DR)stimulation.Other 2 groups were used as control.Kaolin intake was recorded for consecutive 6 d,3 d before and 3 d after stimulation,and the data were statistically analyzed.Results It was found that:1)following IA,AP and DR stimulations,25%,17% and 58% of the rats in each group increased mean kaolin intake by 1 g in the 3 d phase post-stimulation compared with that in the same duration of pre-stimulation,respectively;2)in contrast to some prewous reports,the present observation showed that high Ievel of kaolin intake post-stimulation may persist for more than one day.Conclusion All 3 tvpes of stimulation methods can serve as ways of specifically stimulating vestibular end-organs to induce kaolin intake increase,and double rotation iS the most effective.
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With the aim to examine the distribution of high-affinity neurotrophin receptors (tyrosine kinase receptors, TrkA, TrkB and TrkC)in the rat Scapa's ganglion ( vestibular ganglion, VG), Avidin-Biotin-peroxidase Complex ( ABC ) method of immunohistochemistry with diaminobenzidine (DAB) as the chromogen to identify the immunoreactivities was employed in the present study. The results showed that many VG neurons were immunoreactive to each Trk isoform. The receptors were localized in the neuronal somata. The intensity of immunoreactivity for each Trk receptor was different among neurons, ranging from weak, moderate to intense. For each individual Trk receptors, the labelled neurons were of different size; the result sfatistical of analysis showed that the mean areas for neurons immunoreative to TrkA, B and C were 330.8 ± 7.6, 303.89 ± 10.6 and 355.05 ± 8.3 μm2 , respectively. The present study provids morphological substrate for the important roles played by Trk receptors in maintaining the survival and stabilizing the phenotype of VG neurons.
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To investigate the relationship of the rotation stimulation with motion sickness, the expression of Fos protein in the whole brain of the rat stimulated by complex double rotation on two axes was observed in the present study. The rats were randomly divided into four groups: normal contral group; double-axes rotation stimulation group; the bilateral labyrinthectomy group; group of two-axes rotation stimulation after the bilateral labyrinthectomy. Immunohistochemical staining method was used to detect the expression of Fos protein in different regions of whole brain of the rat. The present results showed that: (1) No Fos-like immunoreactivity was detected in the brain of the rats in control group and the bilateral labyrinthectomy group; (2) In the double-axes rotation stimulation group, the Fos-like immunoreactive neurons were observed in many regions of the brain and brainstem of the rats following complex double-axes rotation stimulation, and the Fos-immunoreactivities were expressed in the nucleus. These Fos-immunopositive neurons were intensively distributed in different subnuclei of the vestibular nucleus complex (including medial, superior and spinal nuclei), nucleus of the solitary tract, locus coeruleus, medial and lateral parabrachial nucleus of the brainstem, paraventricular nucleus of the diencephalons and the amygdala of the limbic system; (3) The expression of Fos protein can be scarcely detected around forementioned regions in brains of the rats following complex two-axes rotation stimulation after the bilateral labyrinthectomy. The present results suggest that the double-axes rotation stimulation can activate effectively the vestibular neurons and many neurons of other region of the brain and brainstem are further activated through direct or indirect connections with vestibular nuclei after complex double rotation stimulation. These activated neurons may be related to the complex mechanism of the motion sickness.
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Objective To set up a method for determining the content of Salvianolic acid B in Qianggan Syrup.Methods HPLC was adopted.A mixture of methanol-acetonitrile-1.5% formic acid(30:10:60) served as the mobile phase with a flow rate of 1.00 mL/min.The detection wavelength was 286 nm.Results The linear range was 0.145～1.747 ?g,r=0.999 9.The average recovery rate was 99.79%,RSD= 0.23%.Conclusion The method is highly effective,quick and sensitive,and suitable for quality control of the preparation.
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Laboratory opening pattern was researched in order to increase the practical ability and spirit of innovation. The study focused specifically on teaching form,teaching method and evaluation systems in laboratory opening.Surver research was made in students and showed good effects.
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The purpose of this study was to investigate the changes of calcitonin gene-related peptide (CGRP) expression in the trigeminal motor nucleus (Vmo) following mandibular nerve transection. The expression of CGRP and glial fibrillary acidic protein (GFAP) were detected at 3, 7, 14, 21, 28, 35 and 42 days post-axotomy (dpa) by using immunohistochemical and double-immunofluorescence histochemical methods. And the number of CGRP-positive surviving motoneurons was examined by using image analysis system. The present results showed that there was a "biphasic" up-regulation of CGRP-immunoreactivity at 3 and 35 dpa on the ipsilateral side of the Vmo, and significant changes were also observed on the contralateral side. Quantitative analysis revealed that there was almost no loss of motoneurons in the Vmo but there was an evident increase in GFAP expression around the Vmo neurons on the ipsilateral side after axotomy. The present results suggest that the up-regulation of CGRP may exert its trophic effects in both the acute stress reaction and the recovery of the injured motoneurons, and the activated astrocytes may be well involved in this process.
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Immunofluorescence histochemistry combined with retrograde tracing technique was employed to observe the effects of masseteric nerve transection on the expression of Trk ( tropomyosin-related kinase) receptor proteins, namely TrkA, TrkB and TrkC in the trigeminal mesencephalic nucleus ( Me5 ) of the rat. At 7 and 14 days following transection of masseteric nerve through which Fluorogold (FG) was applied to identify the Me5 neurons innervating masseter, brain sections were immunohistochemically processed to detect the three Trk isoforms in FG-labeled Me5 neurons. With the percentage of double-labeled neurons to the total number of FG-labeled neurons as the index,we demonstrated ( 1 ) a significant increase in the percentage of TrkA-immunoreactive (IR) Me5 neurons at both 7 and 14 days after nerve transection, (2) no significant, but gradual, increase in the percentage of TrkB-IR Me5 neruons with longer survival time post transection and ( 3 ) little change of TrkC expression. The current findings indicate that axotomy differently affected the expression of the individual Trk receptors and these expression patterns may reflect an adaptation of the Me5 neurons to the peripheral nerve injury.
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The possible relationship of vesicular glutamate transporters ( VGluT1 and VGluT2 ) - and 5-HT-like immunoreactive (LI) terminals with mesencephalic trigeminal nucleus (Vme) neurons in the rat was examined by using triple-immunofluorescence histochemistry and double-labeled electron microscopic immunohistochemistry. Under confocal laser-scanning microscope, many neuronal cell bodies of Vme showed phosphate-activated glutaminase (PAG) -LI and the vast majority of them were large pseudounipolar neurons. A considerable number of VGluT1 -LI and VGluT2-LI terminals were widely distributed in Vme, the density of VGluT2-LI terminals was higher than that of VGluT1-LI. 5-HT-LI axonal varicosities had dense distribution in Vme, and some 5-HT-LI terminals also showed immunoreactivity for VGluT2. Some VGluT1-LI, VGluT2-LI, 5-HT-LI and VGluT2/5-HT-LI terminals were frequently observed in close apposition to the cell bodies of Vme neurons showing PAG-LI. Under electron microscope, VGluT1/VGluT2-LI and 5-HT-LI were visualized with silver grains and peroxidase products, respectively. Some terminals in Vme showed both VGluT2- and 5-HT-LI, these dual labeled varicosities usually made asymmetric contact with Vme neurons. Synaptic terminals that showed VGluT1-LI was also observed, but no coexpression of VGluT1 and 5-HT was found in Vme. The present results suggest that in the transmission of the proprioceptive sensory information from the orofacial regions to the higher center, glutamate and 5-HT may play important roles on the regulation of Vme neurons through complicated integration.
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Experimental technicians are indispensable team to fulfill experimental teaching.With the process of medical experimental teaching reform and the foundation of functional experiment course,experimental technicians face more challenges.In the new experimental teaching mode,experimental technicians should modulate themselves from multiple aspects,in order to be more competent for the job.
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Aim To investigate the impact of UVA on expression of tumour necrosis factor related apoptosis inducing ligand (TRAIL) and study the role of TRAIL in UVA-induced apoptosis of HaCaT cells as well as the influence of Polypeptide from Chlamys farreri(PCF)on TRAIL apoptotic pathway induced by UVA.Methods Cells were divided into five groups: control group, UVA model group,UVA+5.69 mmol?L-1 PCF group, UVA+2.84 mmol?L-1 PCF group, UVA+1.42 mmol?L-1 PCF group.Expression level of TRAIL mRNA was assayed by Real-Time PCR.Western blot analysis was used to determine the protein level of TRAIL and caspase-8 activation. The effect of TRAIL neutralization antibody on UVA-induced apoptosis was also investigated.Results TRAIL mRNA and protein levels increased after 8 J?cm-2 UVA radiation and the discrepancy was significant compared with control group(P
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Aim To study the effect of Taurochenodeoxycholic Acid (TCDCA) on immunologic cell in vitro and in vivo in mice. Methods Five doses were used , including 0.043, 0.065, 0.1, 0.153, 0.189 g?kg-1 in vivo and 0.01, 0.05, 0.1, 1, 10 mg?L-1 in vitro. Effects of TCDCA on peritoneal macrophage in mouse in vitro,splenic lymphocyte, normal organism, immunologic functional inhibiting model and nerve-endocrine-immunoregulation system were investigated. Results TCDCA had the obvious immunoregulation effect on normal organisms in mouse. 0.1 g?kg-1 TCDCA had the obvious anastated effects on the immunological inhibiting model made up by the cyclosporine A and cyclophosphamide. TCDCA may affect the peritoneal macrophage and splenic lymphocyte in vitro directly, meanwhile two kinds of immunological cells showed the obvious immunoregulation effects on the whole. 0.1 g?kg-1 TCDCA can increase the hydrocortisone contents of the nerve-endocrine-immunoregulation system in mouse most remarkably. Conclusion TCDCA had the adjustment effect on the immunoregulation function in mouse.