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Amyotrophic lateral sclerosis is a neurodegenerative disease caused by the loss of motor neurons in the brain and spinal cord. There is currently no effective cure. The emergence of gene therapy brings hope to treatment, which can be achieved by delivering transgenes to replace or correct defective genes, as well as the expression of neurotrophic factors. The vectors of gene therapy can be viral vectors and non-viral vectors. Lentiviral vectors can be used to deliver therapeutic sequences to motor neurons in the central nervous system. Adeno-associated viruses can effectively mediate gene expression and delivery of neurotrophic factors. Gene editing and antisense oligonucleotides therapy are also perspective treatment options. This article summarizes gene therapy for amyotrophic lateral sclerosis from basic experiments and clinical trials.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which is associated with genetic and environmental factors, though the pathogenesis is still unclear and there is also a lack of effective treatment. With the rapid advance of genetic testing techniques, over 30 genes have been associated with the disease. Some ALS patients harboring genetic variants may present unique clinical characteristics and particular mode of inheritance, but the correlation between genotype and phenotype is still not very clear. Studies have shown that research on the pathogenic genes of ALS is important for the diagnosis and selection of potential drug targets. Here the pathogenic genes of ALS, in particular the newly discovered genes, and their underlying mechanisms are reviewed. The necessity of genetic testing for ALS patients is also stressed.
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Humans , Amyotrophic Lateral Sclerosis/genetics , Genetic Testing , Genotype , Neurodegenerative Diseases/genetics , PhenotypeABSTRACT
Objective To analyze the hemodynamic parameters of anomalous origin of the right coronary artery from the left coronary artery sinus (AORL) based on computational fluid dynamics (CFD), so as to make an evaluation of the disease. Methods A normal right coronary artery (RCA) case and an AORL case were selected. Two models were reconstructed in Mimics software and imported into ANSYS CFX software for hemodynamics simulation. The hemodynamics of normal RCA model and AORL model were compared. Results AORL model had a smaller volume flow (9.35 cm3/s), which might lead to insufficient blood supply downstream of the RCA; the pressure at the acute corner of AORL model (13.78 kPa) was lower than normal RCA model (14.9 kPa); the wall shear stress (WSS) of AORL model (12.83 Pa) was larger than that of normal RCA model (9.74 Pa); the total deformation of AORL model was relatively large. Conclusions The entrance velocity and pressure of AORL were lower than those of normal RCA, which might lead to ischemic symptoms. The research findings are of theoretical significance for the effective evaluation of ischemia and other diseases in clinic.
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Objective To investigate the interaction between traditional Chinese medicine syndromes of patients with chronic heart failure (CHF) and the primary pathogenesis of CHF, so as to grasp the distribution regularity of TCM syndrome caused by different primary diseases and provide reference for better intervention of CHF. Methods A total of 580 patients with CHF were included in the clinical cross-sectional study. The baseline data of the patients, the primary disease and the four diagnosis information of TCM were collected. The syndromes of TCM were judged and the logistic regression method was used to analyze the correlation of CHF and the distribution of syndromes. Results Analysis of TCM Syndromes of CHF showed that the main syndromes were Qi deficiency syndrome, blood stasis syndrome, water retention syndrome, yin deficiency syndrome, phlegm syndrome, and yang deficiency syndrome. Further analysis showed that the above causes of CHF were related to the distribution of TCM syndromes. When coronary heart disease is the primary disease, blood stasis syndrome, yang deficiency syndrome, and yin deficiency syndrome are related to the occurrence of CHF (χ2 values are 0.480, 4.445, 0.192, P<0.05). When hypertension is the primary disease, blood stasis syndrome and phlegm syndrome are related to the occurrence of CHF (χ2 values are 12.344, 10.990, P<0.05); dilated cardiomyopathy is the primary disease, blood stasis syndrome and yang deficiency syndrome and chronic heart failure It is related (χ2=5.222, 3.456, P<0.05). Conclusions The distribution patterns of TCM Syndromes of CHF caused by different primary diseases were different, which was related to the pathogenesis of CHF. It is of great significance for better application of traditional Chinese medicine CHF syndrome differentiation during treatment, so as to form optimal treatment to reduce re-admitted into hospitalization rate and mortality in patients with CHF.
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Establishing a suitable animal model is important for studying the mechanism of inflammatory bowel disease (IBD) and exploring new therapeutic approaches. Although a large number of IBD single gene knockout animal models have been established, single knockout of certain genes associated with human IBD susceptibility does not manifest symptoms of IBD or manifest extremely milder symptoms, while composite animal models based on other modeling factors can better simulate the clinical features of IBD. This article mainly introduces three novel composite animal models and elaborates the possible pathogenesis of each composite model:animal models established by gene double knockout have more obvious and earlier symptoms than single-knockout models; single gene knockout model with Helicobacter infection can help to study the role of microbial infections in the pathogenesis of IBD; on the basis of gene knockout, specific deletion of certain immune cells can be used to study the role of the immune cells in the development of IBD. Among the above composite animal models, double knockout mice may be important animal models for IBD study.
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Animals , Humans , Disease Models, Animal , Gene Knockout Techniques , Inflammatory Bowel Diseases , Genetics , Allergy and Immunology , Mice, Knockout , ResearchABSTRACT
Objective To explore the clinical efficacy and toxicity of standard-dose IA regimen as induction chemotherapy in treating initially diagnosed acute myeloid leukemia (AML) patients ≥55 years old. Methods A total of 32 patients were enrolled in this study. The remission, survival time and adverse effects after IA regimen were retrospectively analyzed. Results The complete remission (CR) rate, partial remission (PR) rate and overall response (OR) rate were 71.9%(23/32), 9.4%(3/32), 81.3%(26/32) after IA regimen. In favorable, intermediate and poor prognosis groups (grouped by cytogenetic or molecular factors), 6, 14 and 3 cases achieved CR (χ2= 5.571, P= 0.067), 1, 2 and 0 cases achieved PR, while OR rates were 100.0 %(7/7), 84.2 % (16/19), 50.0 % (3/6) (χ2= 2.114, P= 0.359). The median overall survival (OS) time of three groups were 28.07 months (6.57-46.33 months), 16.93 months (0.40-87.57 months) and 3.03 months (2.00-6.00 months) (Z=9.630, P=0.008) and the 2-year OS rates were 83.33%, 46.80%and 0, respectively (χ2=12.206, P< 0.001). Myelosuppression and infections due to neutropenia were the main adverse effects and severe non-hemotologic toxicities were not observed. Conclusion The standard-dose IA regimen can increase CR/OR rate and prolong the median OS time of patients with favorable and intermediate prognosis and it can be used as the first induction chemotherapy regimen for elderly AML patients of ≥55 years old.
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Objective To evaluate the effect of interventions for improving the management of cardiovascular risk factors in general practitioners. Methods Interventions were conducted in thirty-five community health service centers in Chaoyang District of Beijing using simplified clinical pathways,clinical decision support systems, service quality evaluation index and feedback mechanism, and quality-related motivation system. The research was divided into three periods, which were indicated as before the interventions (2014.1-6), after the first intervention (2014.8-10), and after the second intervention (2014.12-2015.2), according to the community service center outpatient clinic, the computer randomly selected 2 100, 2 089 and 2 052 subjects. With the method of retrospective case review, historical case records of each selected case were extracted, and the changes in KPIs before and after interventions were evaluated.Results After two cycles of intervention,compared with before the interventions,the capability of general practitioners to record hypertension(99.9% vs.70.5%,χ2=708.9),diabetes(99.6% vs.41.5%,χ2=1691.1),hyperlipidemia(99.5% vs.37.0%,χ2=1854.9),coronary atherosclerotic heart disease(CHD)(99.6% vs. 54.3%, χ2=1190.9), and cerebral hemorrhagic stroke (99.4% vs. 39.7%, χ2=1736.2) had significantly increased (P<0.001). Records of other risk factors, for instance, height and weight (81.4% vs. 72.2%, χ2=50.3),smoking(70.0% vs.0.1%,χ2=2 179.2),and health education including recommended physical activity (75.0% vs. 68.2%, χ2=24.0) and weight control (75.4% vs. 16.2%, χ2=1 467.1) significantly increased (P<0.001). The proportion of patients with hypertension who did not use antihypertensive drugs was 31.6% before the intervention;in the first period of intervention,it reduced to 20.2%,and in the second period after the intervention it was 25.8%. Cases of CHD, stroke, diabetes, patients taking aspirin, beta blockers, angiotensin converting enzyme inhibitors(ACEI)or angiotensin receptor blockers(ARB)in proportion to the class of drugs, and statins increased (P<0.05); the coronary atherosclerosis heart disease patients with beta-blockers utility ratio was 20.2% before the intervention, and in the second cycle it was up to 27.9% after the intervention;for patients with diabetes statins utility ratio was 32.1% before the intervention,and in the second cycle it was up to 40.9% after the intervention.Conclusion Adoption and implementation of a series of interventions such as simplified clinical pathways,clinical decision support systems,service quality evaluation index and feedback mechanism, and quality-related motivation system will be beneficial to improve the capability of general practitioners to manage the cardiovascular disease risk factors,which are implied to be effective methods for managing chronic diseases.
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<p><b>OBJECTIVE</b>To correlate the clinical features of patients with acute myeloid leukemia (AML) with mutations of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 genes as well as chromosomal aberrations.</p><p><b>METHODS</b>Somatic mutations of aforementioned genes in 412 newly diagnosed AML patients were detected with PCR and direct sequencing. All patients were also subjected to R-banding chromosomal analysis. The results were correlated with the clinical features and prognosis of the patients.</p><p><b>RESULTS</b>The mutation rates of FLT3-ITD, NPM1, CEBPA, c-KIT, DNMT3A and ND4 were 9.0% (26/289), 19.1% (50/262), 18.9% (34/180), 3.4% (7/208), 6.6% (9/137) and 6.9% (4/58), respectively. Patients with poor prognosis based on genetic mutations had lower blood platelet count than those with intermediate and good prognosis (P=0.001 and P=0.001, respectively). None of the three groups attained median overall survival (OS) (P> 0.05). The complete remission (CR) was similar among the three groups (P> 0.05). For patients with different prognosis based on cytogenetic findings, white blood cell count in those with intermediate prognosis was higher than those with good and poor prognosis (P< 0.001 and P=0.004, respectively), while the blood platelet count of the intermediate group was higher than that of the group with good prognosis (P=0.018). No significant difference was found among the three groups in terms of hemoglobin level (P> 0.05). The group with poor prognosis has attained shorter OS compared with those with good and intermediate prognosis (P< 0.001 and P=0.003, respectively). However, the CR rate of the group with good prognosis was higher than that of the intermediate group (P=0.001). For the group with intermediate prognosis, presence of genetic mutations did not correlate with the clinic characteristics such as white blood cell count, blood platelet count, hemoglobin level, OS and CR rate (P> 0.05 for all comparisons).</p><p><b>CONCLUSION</b>Genetic mutations combined with cytogenetic analysis can facilitate the prognosis and personalized treatment for patients with AML.</p>
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Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Leukemia, Myeloid, Acute , Genetics , Mortality , Mutation , PrognosisABSTRACT
Elderly acute myeloid leukemia (AML) accounted for 35 % of all AML with the increased incidence year by year, and the median onset age is 67 years old. Generally, AML patients require strong chemotherapy, but older patients often cannot tolerate intense chemotherapy due to the viscera dysfunction. It is still lack of unified treatment clinically. Reports on treatment of elderly AML in the 57th American Society of Hematology (ASH) annual meeting covered multiple fields, in which the traditional induction chemotherapy, demethylation drug alone or in combination with other drugs, and novel drugs were an involved. This article reviewed the latest research on the elderly AML in the 57th ASH annual meeting.
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Objective To explore the biological basis of TCM syndromes from a biomolecules network perspective with qi deficiency syndrome as the breakthrough point. Methods A data dictionary of neuro-endocrine-immune (NEI) related genes and qi deficiency syndrome characterization terminology thesaurus were established. Literature about qi deficiency syndrome characterization was retrieved by using Genclip, to excavate the characteristic NEI gene, thereby to explore different bioactive substances of syndromes. Results The analysis of the genetic data, showed qi deficiency related cluster with the relevance of endocrine, signal transduction, hematopoietic cell and immune deficiencies etc. It is confirmed that the intrinsic biological features of TCM syndrome can effectively identify in the NEI level. Conclusion Literature mining method as a new way to discover syndromes biological indicators has certain feasibility, and it is recommended to be further expanded into other studies on syndromes to validate the universality and reliability of this method.
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Objective To establish the decision tree model of Yang deficiency syndrome and clinical conventional indexes in type 2 diabetes mellitus patients.Methods Syndrome decision and clinical indexes collection from 249 type 2 diabetes mellitus patient were observed and analyzed.Tree structure model were built to summarize the correspondence between Yang deficiency syndrome and clinical conventional indexes based on T test,nonparametric analysis,and Spearman correlation analysis.Results The Yang deficiency syndrome accounted for 31.33％ of 249 type 2 diabetes mellitus patients.The accuracy identification rate of tree structure model of Yang deficiency syndrome with four core index,such as LPa、FT3、TSH、FINS was 84.74％,the sensitivity and specificity were 74.36％ and 89.47％.Conclusion Decision tree model can identify Yang deficiency syndrome of type 2 diabetes mellitus patients clearly and more intuitive.Decision tree model can provide the chance of syndrome objective.
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Erythropoietin (EPO),which is routinely used in clinic to treat anemia,has been implicated in a wide range of activities on diverse tissues.Recently,accumulating evidence shows that EPO has antidepressant-like effects and may be a po-tential drug candidate for treating mood symptoms and memory dysfunction in depression.This review summarizes the current progress on EPO’s antidepressant-like effects,and explores its potential mechanism and clinical application in the future,provi-ding a general view of the research and application status of EPO in depression.
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Medical education of PhD candidates is of great importance to medical personnel training in our country. With the development of society, the progress of science and technology and renewal of knowledge, cultivation of innovative talents and improvement of graduate education quality is priority nowadays. This paper reflects on the progress we’ve made on medical education of PhD candidates. Though efforts have been made to improve the innovative ability of talents in our country gradually, we still need to be more innovative, more consistent and more scientific in the future. According to the state Degree Requirements and our goal of talent training, we should combine courses with scientific research systematically, pay more attention to scientific methodology and academic training, finally form a better training mode of PhD candidates majoring in medical science.
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Objective To explore the risk factors of Qi deficiency syndrome of type 2 diabetes mellitus and to provide evidence for prevention and cure diabetes mellitus with TCM.Methods On the basisof the epidemiological survey,147 cases of Type 2 diabetes mellitus were collected and divided into Qi deficiency syndrome group and non-Qi deficiency syndrome group.The relationships between risk factors and Qi deficiency syndrome were analyzed by unconditional univariate and multivariate Logistic regression.Results Two hours postprandial blood sugar[2PPBS (β value is-0.764,OR (95％CI) is 0.466 (0.236 ～ 0.919)],apolipoprotein-B [APo-B (β value is-1.005,OR (95％CI)is 0.366 (0.140～0.959)],urine glucose [β value is-1.300,OR(95％CI)is 0.273 (0.127～0.584)] were inverse correlation with Qi deficiency syndrome of type 2 diabetes mellitus.Conclusion Qi deficiency syndrome of type 2 diabetes mellitus was inverse correlation with 2PPBS、APo-B and urine glucose.
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ObjectiveTo research the intestinal absorption characteristics in rats of multiple constituents,when Wuwei-Jiangya recipe was used in rats and showed reducing blood pressure effects.Methods ① After extracting Wuwei-Jiangya recipe,we fed it to rats once daily,until the blood pressure reduced; ②Establish Wuwei-Jiangya recipe and intestinal absorption of multiple constituents fingerprint by using reverted gut sac method and RP-HPLC fmgerprint.ResultsAfter one week's administration,there was the hypotensive effects and multiple constituents can be absorbed by intestine.ConclusionWhen the drug works,reverted gut sac method for studying intestinal absorption constituents can be used for locking the exposure constituents.
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The primary aim of this research is to systematically sort out and analyze available clinical documents for chronic congestive heart failure in traditional Chinese medicine (TCM) and integrated traditional Chinese and Western medicine, and to explore the diagnosis and treatment rule of TCM syndrome factors with data mining method.
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This paper is devoted to discussing two research patterns of biological basis of traditional Chinese medicine syndrome and presenting a research strategy for data mining methods. It points out that data mining methods which are based on feature selection are better fit for investigating biological basis of traditional Chinese medicine syndrome. Based on such a discussion, the concept of "characteristic pattern" is proposed to bridge the gap between "golden index" and biological basis of traditional Chinese medicine syndrome. This paper presents a novel research avenue for investigating biological basis of traditional Chinese medicine syndrome.
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OBJECTIVE: To investigate the effects of tetrandrine (Tet) on nuclear factor kappaB (NF-kappaB) expression in leukemia cell line K562 and multidrug-resistant K562/A02 cell line. METHODS: The activations of NF-kappaB in K562 and K562/A02 cells and the effects of 1 micromol/L Tet on NF-kappaB expression were determined by immunocytochemistry and Western blot assay. RESULTS: Tet had no effect on NF-kappaB expression in K562 cells after 6- and 12-hour treatment (P>0.05), and K562/A02 cells displayed higher level of NF-kappaB protein expression than their parental K562 cells (P<0.01). Tet could significantly down-regulate NF-kappaB protein expression and nuclear translocation in K562/A02 cells shown by immunocytochemistry and Western blot, and this decrease became more significant after 12-hour treatment than after at 6-hour treatment (P<0.05). CONCLUSION: Activation of NF-kappaB may be related to multidrug resistance of K562/A02 cell line. And the inhibition of NF-kappaB activation by Tet leads to multidrug resistance reversal in K562/A02 cell line.
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Objective Chromatography fingerprint of Radix Codonopsis of different age from Shanxi province was studied to provide the reference for the science appraisal of intrinsic quality of Radix codonopsis. Method A RP-HPLC method was applied on GraceSmart-RP18 (250 mm?4.6 mm, 5 ?m) column with acetonitrile-0.1% acetic acid gradient elution as mobile phase, and the flow-rate was 0.6 mL/min. The detection wavelength was at 268 nm and the column temperature was at 30 ℃. Result Chromatography fingerprint of Radix Codonopsis can demonstrate obviously the difference and the similarity of Radix Codonopsis of different age. The RSD were lower than 3% in the precision, stability and the repetitiveness trial, and the codonopsis pilosula alkyne glucoside can be used as the reference to identify the active composition of Radix Codonopsis. Conclusion The method was simple, reproducible and reliable. The integrity of fingerprint can be used to supply the reference for the quality control of Radix Codonopsis from Shanxi provice.
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Object: To observe the influence of different combinations of Chinese medicine on rat diabetic index so as to optimize formula. Method: Diabetic rats were induced by high fat food and low dose of streptozotocin, modified uniform design was used to combine different effective fractions, five kinds of combinations were given by intragastric administration for 30 days, glucose, triglyceride, cholesterol, creatinine clearance rate, urinary albumin were detected, the results were analyzed by regression analysis. Results: Glucose, triglyceride, cholesterol, urinary albumin in the five experimental group reduced significantly(P