ABSTRACT
To screen novel anti-dengue virus (DENV) NS5 RdRp enzyme inhibitors, a series of 5-cyano-2-thiacetoaryl pyrimidinone compounds were designed and synthesized by molecular hybridization method with HCV NS5B RdRp inhibitor 3jc and ZIKV NS5 RdRp inhibitor 4w as lead compounds. The anti-DENV activity of these compounds was evaluated by MTT assay and plaque assay and five compounds showed anti-DENV activity. The most active compound 7a'k showed better anti-DENV activity than that of the positive control ribavirin (EC50 = 7.86 μmol·L-1 vs EC50 = 18.07 μmol·L-1), and the other four compounds showed almost the same anti-DENV activity as ribavirin. Finally, the prediction and simulation of the binding mode through molecular provided new ideas for the further development of this new DENV NS5 RdRp inhibitor.
ABSTRACT
Objective: To calculate and compare the healthy life expectancy (HLE) of the middle-aged and elderly in China, the United States, and developing and developed countries in the European Union(EU) and analyze the impact of socioeconomic factors on HLE in different countries or regions. Methods: Four surveys from 2010 to 2019 were brought into the research. The data were collected from the China Health and Retirement Longitudinal Study, Health and Retirement Study, and the Survey of Health, Ageing and Retirement in Europe. Developed and developing countries in the EU were divided into two groups for calculation. Education level, total family wealth, and work retirement status were selected to measure socioeconomic status, and activities of daily living were used as health status indicators. We used the multi-state life cycle table method to calculate the transition probability between different health states and estimate life expectancy and HLE. Results: A total of 69 544 samples were included in the study. In terms of age, the middle-aged and elderly in the United States and developed countries of the EU have higher HLE in all age groups. In terms of gender, only Chinese women have lower HLE than men. Regarding socioeconomic factors, the middle-aged and elderly with higher education levels and total family wealth level have higher HLE. In China, working seniors have higher HLE, while for USA women and developed countries of the EU, retired or unemployed seniors have higher HLE. Conclusions: Demographic and socioeconomic factors impact HLE in different countries or regions. China should pay more attention to the health of women and the middle-aged and elderly retired with lower education and less total family wealth.
Subject(s)
Aged , Male , Middle Aged , Female , Humans , United States , Healthy Life Expectancy , European Union , Activities of Daily Living , Longitudinal Studies , Socioeconomic Factors , China/epidemiologyABSTRACT
Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.
Subject(s)
Animals , Zebrafish/metabolism , Embryo, Nonmammalian/metabolism , Transcriptome , Oxidative Stress , Water Pollutants, Chemical/metabolismABSTRACT
AIM: To explore the effect of flipped classroom combined with team-based learning(TBL)in ophthalmology practice teaching by applying directly observed procedural skills(DOPS). METHODS: A total of 54 students of clinical medicine “5+3” integration and clinical medicine for five years, interned at the department of ophthalmology from June 15th to November 14th, 2021 were divided into traditional teaching group(group A)and flipped classroom combined with TBL group(group B). The teaching effects of slit lamp microscopy and direct ophthalmoscopy in group A and group B were compared by DOPS score, and Mann-Whitney U test was used for statistical analysis.RESULTS: Total DOPS score for slit-lamp microscopy in group A was 59(58.00, 60.00)points,which was significantly lower than that of group B 63(61.00,65.00)points(P<0.001). The DOPS score for direct ophthalmoscopy in group A was 63(61.00, 63.75)points, which was significantly lower than that of group B, 66(63.75,66.25)points(P<0.001). In the two operations and especially in the aspects of “understanding of complications,relevant anatomical structure and proficiency in operation”“preparatory work” and “technical ability of operation”, the scores of group B was significantly higher than those of group A(P<0.05).CONCLUSION: Flipped classroom combined with TBL has significant advantages in clinical practice teaching for interns in ophthalmology, which is worthy of promotion and application compared with traditional teaching.
ABSTRACT
The United Nations Sustainable Development Goal proposes to achieve universal health coverage by 2030， and the key element is that everyone can enjoy high-quality healthcare services. Cardiovascular diseases， predominantly acute coronary syndromes， have become the largest disease burden on global health. However， the quality of healthcare services for acute coronary syndromes varies significantly across the populations and regions. This study aimed to investigate the difference in the quality of acute coronary syndrome services in multiple countries， regions， hospitals， and patient populations， and then determine the impact of quality improvement initiatives on quality disparity， which may facilitate further improving the equity of clinical service quality for acute coronary syndromes and promoting health equity and universal health coverage.
ABSTRACT
Suicide,a major public health problem,is the death caused by injuring oneself with the intent to die.In this paper,we reviewed the genes encoding serotonin system,calcium voltage-gated channel subunit alpha1 C,γ-aminobutyric acid,and spindle and kinetochore associated complex subunit 2,as well as their related brain regions,from the perspective of imaging genetics,aiming to provide new ideas for the research and intervention on suicidal behavior.
Subject(s)
Humans , Brain , Suicidal Ideation , SuicideABSTRACT
<p><b>OBJECTIVE</b>To study the changes of T lymphocyte subsets and immunoglobulin in peripheral blood of patients with acute lymphoblastic leukemia (ALL) and non-acute lymphocytic leukemia (N-ALL) before and after treatment and their value for monitoring of disease and evaluation of prognosis.</p><p><b>METHODS</b>One hundred and six cases of leukemia were selected in our hospital, including 48 cases of ALL (ALL group) and 58 cases of N-ALL (N-ALL group); 54 peoples of normal physical examination were selected as the normal control group in the same period. The IgA, IgG and IgM levels of peripheral blood were detected, and the absolute value of T lymphocyte subsets was determined by cell slide method. According to whether the patients' status was improved or not by treatment, the 106 patients were divided into the unimproved group (55 cases including 25 ALL, 30 N-ALL) and improved group (51 cases including 23 ALL, 28 N-ALL).</p><p><b>RESULTS</b>The levels of IgA, IgG and IgM in 106 cases of leukemia were significantly lower than those in the control group (all P<0.05), and the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells in the peripheral blood were significantly lower than those in the control group(all P<0.05); the absolute value of CD3CD8T cells showed no significant difference in comparison with the control group (P >0.05). After treatment, IgA,IgG and IgM levels in the improved group were significantly higher than those before therapy (all P<0.05), while their levels were not significantly different from that in the control group (all P>0.05); the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells in the peripheral blood were significantly higher than those before therapy (all P<0.05), while those were not significantly different from the control group (all P>0.05). Compared with levels before treatment, the levels of above mentioned indicators in the unimproved group after treatment were not significantly different (all P>0.05); and the CD3level, CD3CD4/CD3CD8ratio and the absolute value of CD3CD4T cells were significantly lower than those in the control group (all P<0.05), and the absolute value of CD3CD8T cells were higher than that in the control group (P<0.05).</p><p><b>CONCLUSION</b>After the treatment, the T lymphocyte subsets (CD3, CD3CD4T cells) and immunoglobulin (IgA, IgG, IgM) levels in peripheral blood of patients with ALL and N-ALL have been improved significantly, and the detection of these indexes is helpful for disease monitoring and prognosis evaluation.</p>
ABSTRACT
BACKGROUND: We have found that mouse nerve growth factor has the ability to induce differentiation of umbilical cord blood mesenchymal stem cells (UCB-MSCs) into neurons in vitro. In order to further explore the method of improving the induction efficiency of nerve cells, we attempt to combine a variety of cell growth factors for cell induction. OBJECTIVE: To explore the effect of mouse nerve growth factor combined with brain-derived neurotrophic factor on the differentiation of UCB-MSCs into neuron-like cells in vitro . METHODS: After the donated primary UCB-MSCs were resuscitated and cultured, the passage 5 UCB-MSCs were divided into five groups. The first four groups served as pre-induced groups, and fibroblast growth factor and epidermal growth factor were added to pre-induce cells for 24 hours, and mouse nerve growth factor and brain-derived neurotrophic factor, alone or in combination, were used thereafter to induce UCB-MSCs, while in control group, only the same amount of cell medium was added. The last group was non-pre-induced group, in which the cells were cultured in the cell culture medium for 24 hours, and then mouse nerve growth factor and brain-derived neurotrophic factor were both added to induce UCB-MSCs. The morphological changes of cells were observed under inverted microscope. The expression of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) was detected by immunocytochemistry technique. Real-time qPCR was used to detect the relative expression of NSE and GFAP at mRNA level. RESULTS AND CONCLUSION: (1) The cell morphology of UCB-MSCs was in long shuttle shape and spindle shape with unequal size. After induction, the cell bodies gradually retracted and became rounded, and the projections extended to one-side or multi-sides, presenting with the neuron-like changes. (2) Immunocytochemistry and real-time qPCR results showed that NSE and GFAP were positive in each experimental group, and the positive rate and mRNA expression of NSE and GFAP in the combined induction group were higher than those in the other groups. (3) Either mouse nerve growth factor or brain-derived neurotrophic factor could induce UCB-MSCs to differentiate into neuron-like cells. Moreover, there was a cumulative effect between the two cytokines, and their combined use could effectively improve the efficiency of induction.
ABSTRACT
BACKGROUND: Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are a kind of adult stem cells in the human umbilical cord blood, which have the potential to differentiate into neuron-like cells and can be used for the treatment of a variety of nervous system diseases. How to effectively induce hUCB-MSCs differentiation into neuron-like cells is always a hotspot in the stem cell research, which is of high scientific research value. OBJECTIVE: To explore the induction effect of mouse nerve growth factor (mNGF) on the differentiation of human umbilical cord blood-derived mesenchymal stem cells into neuron-like cells in vitro. METHODS: The donated hUCB-MSCs were resuscitated and the cell morphology after culture was observed to draw a cell growth curve. Passage 5 cells were cultured in the culture medium containing 0 (blank control), 50, 100, 150, 200 μg/L mNGF, and the cell morphology was observed and recorded daily under inverted phase contrast microscope. Immunocytochemistry detection was used to examine the expression of neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP) at 7 days of induction, and then the NSE and GFAP positive expression was calculated by Image-Pro Plus 6.0 software. RESULTS AND CONCLUSION: The viability of resuscitated hUCB-MSCs was up to over 90%. The cell morphology was in long shuttle shape and spindle shape with unequal size, and the cells presented with "S"-shaped growth curve and entered the logarithmic growth phase at 3-6 days. Typical neuron-like changes were observed after induction by mNGF; however, there was no change in the cell morphology in the control group. Immunocytochemical staining showed that the induced cells were positive for both NSE and GFAP, and the highest positive rates of NSE and GFAP were observed after induction by 100 μg/L mNGF (P < 0.05). In the control group, there was no positive expression of NSE and GFAP.To conclude,mNGF can induce the in vitro differentiation of hUCB-MSCs into neuron-like cells,and 100 μg/L mNGF can achieve the best induction effect.
ABSTRACT
Objective· To observe the progression of left ventricular hypertrophy (LVH) in maintenance hemodialysis (MHD) patients,and to analyse risk factors of the progression of LVH.Methods· Stable MHD patients of Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were enrolled in July 2012.These patients were followed for 1 year.Clinical characteristics and laboratory indices were collected at baseline and 1-year followup.Left ventricular mass (LVM) was evaluated by ultrasonic cardiogram.Left ventricular mass index (LVMI) increased more than 5％ was defined as LVH progression.Results · Totally 71 MHD patients were enrolled in this study.44 patients were males,with median age 55.9 years old,median dialysis vintage 152.1 months.22 (30.99％) patients had LVH at enrollment.A significant higher percentage of MHD patients used calcium-channel binder (CCB) and angiotensin-converting-enzyme inhibitor (ACEI) in LVH group,while a significant higher NT-proBNP level was also showed in LVH group.31 patients had LVH progression while 40 patients didn't after 1 year.Patients in progression group had significant higher levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C).In univariable and multivariable Logistic regression,total cholesterol and LDL-C were independent risk factors of LVH progression (OR=2.515,95％ CI 1.219-5.910,P=0.013;OR=1.950,95％ CI 1.127-3.375,P=0.017).Conclusion · LVH is one of the common cardiovascular complications in MHD patients.The proportion of use of antihypertensive drugs is higher in the patients with LVH.Higher LDL-C and total cholesterol levels are risk factors for the progression of LVH.
ABSTRACT
<p><b>OBJECTIVE</b>To explore a method for combining Fluoro-Jade B (FJB) staining with immunofluorescent staining in rats with focal cortical infarction.</p><p><b>METHOD</b>Permanent distal middle cerebral artery occlusion (dMCAO) was induced in rats by electrocoagulation. The rat models were randomized into two groups, and frozen sections of the brain tissues from each group were stained with FJB followed by immunofluorescent staining or in the reverse order.</p><p><b>RESULTS</b>FJB staining followed by immunofluorescence staining clearly visualized both FJB-positive and immunofluorescence-positive cells in the frozen sections, but the staining protocol in the reverse sequence failed to clearly show the immunofluorescence-positive cells.</p><p><b>CONCLUSION</b>FJB staining prior to immunofluorescence staining does not affect the staining effect of protein immunofluorescent staining and better visualizes the positive cells.</p>
Subject(s)
Animals , Rats , Brain , Pathology , Fluoresceins , Chemistry , Fluorescent Antibody Technique , Methods , Fluorescent Dyes , Chemistry , Infarction, Middle Cerebral Artery , Staining and Labeling , MethodsABSTRACT
The international cooperated research projects of the Human Microbiome Project (HMP) and Metagenomics of The Human Intestinal Tract (MetaHIT) were officially launched in 2007, which indicated the era of metagenomics research of microorganisms in human gastrointestinal tract had been coming. Each human body is a superorganism which is composed of 90% commensal microorganisms, especially the intestinal microorganisms. The intestinal microorganisms play an important role on health maintenance since they are involved in the absorption and metabolism of nutrients in the human bodies. Herein, we review the research progress in the mechanism of intestinal microorganisms in human diseases. Our purpose is to provide novel ideas on human health and therapeutic targets of diseases.
ABSTRACT
<p><b>BACKGROUND</b>This study was to investigate the relationship among aortic artery calcification (AAC), cardiac valve calcification (CVC), and mortality in maintenance hemodialysis (MHD) patients.</p><p><b>METHODS</b>All MHD patients in Shanghai Ruijin Hospital in July 2011 were included. To follow up for 42 months, clinical data, predialysis blood tests, echocardiography, and lateral lumbar X-ray plain radiography results were collected. Plasma FGF23 level was measured using a C-terminal assay.</p><p><b>RESULTS</b>Totally, 110 MHD patients were involved in this study. Of which, 64 (58.2%) patients were male, the mean age was 55.2 ± 1.4 years old, and the median dialysis duration was 29.85 (3.0-225.5) months. About 25.5% of the 110 MHD patients had CVC from echocardiography while 61.8% of the patients had visible calcification of aorta from lateral lumbar X-ray plain radiography. After 42 months follow-up, 25 (22.7%) patients died. Kaplan-Meier analysis showed that patients with AAC or CVC had a significant greater number of all-cause and cardiovascular deaths than those without. In multivariate analyses, the presence of AAC was a significant factor associated with all-cause mortality (hazard ratio [HR]: 3.149, P = 0.025) in addition to lower albumin level and lower 25-hydroxy Vitamin D (25(OH)D) level. The presence of CVC was a significant factor associated with cardiovascular mortality (HR: 3.800, P = 0.029) in addition to lower albumin level and lower 25(OH)D level.</p><p><b>CONCLUSION</b>Lateral lumbar X-ray plain radiography and echocardiography are simple methods to detect AAC and CVC in dialysis patients. The presence of AAC and CVC was independently associated with mortality in MHD patients. Regular follow-up by X-ray and echocardiography could be a useful method to stratify mortality risk in MHD patients.</p>
Subject(s)
Female , Humans , Male , Middle Aged , Aortic Diseases , Blood , Calcinosis , Blood , China , Fibroblast Growth Factors , Blood , Follow-Up Studies , Heart Valve Diseases , Blood , Heart Valves , Pathology , Proportional Hazards Models , Renal Dialysis , MortalityABSTRACT
In the post-genomic era, biological studies are characterized by the rapid development and wide application of a series of "omics" technologies, including genomics, proteomics, metabolomics, transcriptomics, lipidomics, cytomics, metallomics, ionomics, interactomics, and phenomics. These "omics" are often based on global analyses of biological samples using high through-put analytical approaches and bioinformatics and may provide new insights into biological phenomena. In this paper, the development and advances in these omics made in the past decades are reviewed, especially genomics, transcriptomics, proteomics and metabolomics; the applications of omics technologies in pharmaceutical research are then summarized in the fields of drug target discovery, toxicity evaluation, personalized medicine, and traditional Chinese medicine; and finally, the limitations of omics are discussed, along with the future challenges associated with the multi-omics data processing, dynamics omics analysis, and analytical approaches, as well as amenable solutions and future prospects.
Subject(s)
Biomedical Research , Methods , Gene Expression Profiling , Genomics , Metabolomics , Pharmacology , ProteomicsABSTRACT
Objective To evaluate the role of c-Jun N-terminal kinase (JNK) signaling pathway in paclitaxel-induced apoptosis in hippocampal neurons of rats, and the relationship with nuclear factor kappa B (NF-κB) pathway.Methods The primarily cultured hippocampal neurons were seeded in 96-well plate at a density of 1×106 cells/ml (200 μl/hole) , and were randomly divided into 4 groups (n=8 each) using a random number table: control group (C group), paclitaxel group (P group), JNK inhibitor SP600125 group (S group), and SP600125 + paclitaxel group (S+P group).Paclitaxel 2 ml (1 μmol/L) was added to group P.SP600125 2 ml (10 μmol/L) was added to group S.In group S+P, SP600125 2 ml (10 μmol/L) was added, the cell were then incubated for 1 h, and then paclitaxel 2 ml (1 μmol/L) was added.The cells were then incubated for 24 h.At 24 h of incubation, the apoptosis in hippocampal neurons was detected by flow cytometry, and the expression of NF-κB p65 was measured by Western blot.The apoptosis rate was calculated.Results Compared with group C, the apoptosis rate was significantly increased, and the expression of NF-κB p65 was up-regulated in P and S+P groups, and the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S (P＜0.05).Compared with group P, the apoptosis rate was significantly decreased, and the expression of NF-κB p65 was down-regulated in group S+P (P＜0.05).Conclusion JNK signaling pathway mediates paclitaxel-induced apoptosis in hippocampal neurons of rats, and the mechanism is likely related to inhibition of NF-κB pathway activation.
ABSTRACT
<p><b>OBJECTIVE</b>The purpose of the present study was to observe the changes in CD4+CD25+Nrp1+Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved.</p><p><b>METHODS</b>ICR mice and mouse lymphoma cell line (EL-4 cells) was used. The expressions of CD4, CD25, Nrp1, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-β1, IL-10, PKA and cAMP were estimated with ELISA.</p><p><b>RESULTS</b>At 12 h after irradiation, the expression of Nrp1 increased significantly in 4.0 Gy group, compared with sham-irradiation group (P<0.05) in the spleen and thymus, respectively, when ICR mice received whole-body irradiation (WBI). Meanwhile the synthesis of Interleukin 10 (IL-10) and transforming growth factor-β1 (TGF-β1) increased significantly after high dose irradiation (HDR) (> or = 1.0 Gy). In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4+CD25+Nrp1+Treg cells after ionizing radiation.</p><p><b>CONCLUSION</b>These results indicated that HDR might induce CD4+CD25+Nrp1+Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.</p>
Subject(s)
Animals , Female , Male , Mice , Calcineurin , Genetics , Metabolism , Cyclic AMP , Metabolism , Dose-Response Relationship, Radiation , Gene Expression Regulation , Radiation Effects , Immunosuppression Therapy , Interleukin-10 , Genetics , Metabolism , Lymphocyte Subsets , Physiology , Neuropilin-1 , Genetics , Metabolism , Phosphoinositide Phospholipase C , Genetics , Metabolism , Protein Kinases , Genetics , Metabolism , Signal Transduction , Transforming Growth Factor beta , Genetics , Metabolism , Whole-Body IrradiationABSTRACT
BACKGROUND: Groundwater is believed to possess many beneficial effects due to its natural source of various minerals. In this study, we examined the effects of natural Jeju groundwater S1 (Samdasoo(TM)), S2 and S3 pumped up from different locations of Jeju Island, Korea, along with local tap water, on body weight gain, serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced hyperlipidemic rats. MATERIALS/METHODS: Rats were randomly and equally divided into 6 groups. Different water samples were supplied to the hyperlipidemic rats as their daily drinking water and the widely-used anti-hyperlipidemic drug simvastatin was used as a positive control. Body weight, serum lipids and lipoproteins were measured weekly. Liver weight, liver index and liver histopathology were examined after the execution of the rats. RESULTS: After drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced weight growth and serum triglycerides levels and increased high density lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and particularly S2 significantly reduced the severity of liver hypertrophy and steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous ions. CONCLUSION: Jeju Groundwater S1 and particularly S2 exhibit protective effects against hyperlipidemia and fatty liver and hypothesize that the beneficial effect of Jeju Groundwaters may be contributed from blockade of autoxidation of ferrous ions rather than their high contents of vanadium.
Subject(s)
Animals , Rats , Body Weight , Cholesterol , Drinking , Drinking Water , Fatty Liver , Groundwater , Hyperlipidemias , Hypertrophy , Ions , Korea , Lipid Metabolism , Lipoproteins , Liver , Minerals , Simvastatin , Triglycerides , Vanadium , WaterABSTRACT
An enzyme-displaying yeast as a whole-cell biocatalyst is an alternative to immobilized enzyme, due to its low-cost preparation and simple recycle course. Here, lipase-displaying Pichia pastoris whole-cell was used as a biocatalyst to synthesize diisooctyl adipate in the non-aqueous system. The maximum productivity of diisooctyl adipate was obtained as 85.0% in a 10 mL reaction system. The yield could be reached as high as 97.8% when the reaction system was scaled up to 200 mL. The purity obtained is 98.2% after vacuum distillation. Thus, the lipase-displaying P. pastoris whole-cell biocatalyst was promising in commercial application for diisooctyl adipate synthesis in non-aqueous phase.
Subject(s)
Adipates , Metabolism , Industrial Microbiology , Lipase , Metabolism , Pichia , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and progression-free survival of erlotinib after progression of disease to gefitinib in patients with advanced pulmonary adenocarcinoma who previously obtained a disease control with gefitinib.</p><p><b>METHOD</b>In this retrospective study, 12 patients with advanced or metastatic pulmonary adenocarcinoma,who were previously obtained a partial response or a stable disease with gefitinib,were treated with erlotinib after gefitinib failure. Erlotinib efficiency, progression-free survival and overall survival were analyzed.</p><p><b>RESULTS</b>Nice (75%)achieved stable disease and three (25%) achieved progression disease with erlotinib treatment after gefitinib failure. No complete response or partial response was observed. The disease control rate was 75%. The median progression-free survival and overall survival of erlotinib were 180 days and 831 days.</p><p><b>CONCLUSION</b>Erlotinib seems to be an optional treatment after gefitinib failure for advanced pulmonary adenocarcinoma patients,who previously responded to gefitinib.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Adenocarcinoma , Drug Therapy , Antineoplastic Agents , Therapeutic Uses , Drug Tolerance , Erlotinib Hydrochloride , Feasibility Studies , Kaplan-Meier Estimate , Lung Neoplasms , Drug Therapy , Quinazolines , Therapeutic Uses , Retrospective Studies , Treatment OutcomeABSTRACT
This study was aimed to investigate the protective effects of dimethylsulfoxide (DMSO) combined with trehalose on the cryopreserved platelets. The platelets were preserved at -80 degrees C. The experiments were divided into 5 groups: blank control group composed of apheresis platelet suspension; trehalose group composed of apheresis platelet suspension and 0.25 mol/L trehalose; DMSO group composed of apheresis platelet suspension and 5% DMSO; 5% combined group composed of apheresis platelet suspension, 5% DMSO and 0.25 mol/L trehalose; 2.5% combined group composed of apheresis platelet suspension, 2.5% DMSO and 0.25 mol/L trehalose. All the groups were thawed at 37 degrees C in a waterbath. The recovery rate of platelets and mean platelet volume (MPV) were assayed by using hemocytometer; the ultrastructural changes were examined by electron microscopy; the expressions of CD41, CD42b, CD61 and CD62p on platelets were detected by flow cytometry. The results indicated that single use of trehalose had no strong effect in increasing the recovery rate of platelets, but the morphology of platelets was close to normal. The DMSO showed significant effect in increasing the recovery rate of platelets and maintaining the intact property of platelets, however, the shape of platelets tended to sealing, and partial platelets still displayed heteromorphic changes. The combination of DMSO and trehalose revealed the protective effect on the external morphology and internal structure of platelets to be close to the normal homeostasis, and ensured an ideal recovery rate of the cryopreserved platelets and higher expression levels of CD41, CD42b, CD61 and CD62p in the same time. It is concluded that the combined use of DMSO and trehalose possesses the synergistic protective effect on the cryopreserved platelets, therefore, the combined use of both as the protective agent is hopeful to further raise the effectiveness of clinical infusion of the cryopreserved platelets.