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ObjectiveUsing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.MethodsThirty-nine patients with a genetic diagnosis of Fabry disease were included, and plasma levels of Lyso-GL3 were measured by LC-MS/MS analysis, and detailed clinical information of the patients was obtained including: α-galactosidase A activity, genetic variants, quantification of urine protein, mean arterial pressure, and estimation of glomerular filtration rate, and the differences in the levels of Lyso-GL3 in different clinical phenotypes and genotypes were statistically analyzed, as well as the association with clinical indicators.ResultsLyso-GL3 showed good linearity within 0.7856-400 ng/mL(r=0.9992).Further analysis of 39 Fabry disease patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine showed a median Lyso-GL3 concentration of 23.6 ng/mL(4.3-92.9 ng/mL); Lyso-GL3 levels were significantly higher in patients with both the frameshift and the splicing mutations, as well as in patients with the nonsense mutations, than in patients with the missense mutations (median value 119.7 ng/mL vs. 11.9 ng/mL, P=0.006, and median value 97.0 ng/mL vs. 11.9 ng/mL, P=0.015, respectively). Whereas, association analysis revealed that Lyso-GL3 was not significantly associated with urinary protein, mean arterial pressure and estimated glomerular filtration rate.ConclusionsThe using of LC-MS/MS to quantify plasma Lyso-GL showed significant differences in Lyso-GL3 concentrations between classical and atypical phenotypes, suggesting that plasma Lyso-GL3 may help with clinical phenotypes. However, Lyso-GL3 levels is found to be overlapped between genotypes. No significant linear correlation was found between Lyso-GL3 and renal clinical indicators, suggesting the urgent need in finding a more accurate tool to assess renal involvement and prognosis in patients with Fabry disease.
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Fabry disease is a X-linked inherited lysosomal storage disease. The pathogenesis is that mutations in the GLA gene lead to the decrease or lack of α-galactosidase A activity, followed by the accumulation of substrate and its intermediate metabolites in cells and tissues, eventually leading to multiple organ injury. The rise of specific treatment and gene technology pushes the application of precision medicine in patients with Fabry disease. As a milestone in the specific treatment of Fabry disease, enzyme replacement therapy can delay disease progression and improve quality of life, but not all carriers with GLA mutation need intervention immediately, and indeed individualized treatment is required. However, enzyme-enhanced therapy is only suitable for "amenable mutations" and has clinical application limitation. Therefore, new treatments such as substrate reduction therapy, second-generation enzyme replacement therapy, and gene therapy are already undergoing clinical trials, expected to bring new gospel to Fabry disease patients. This article will review development of precision treatment on Fabry disease, providing the basis of individualized treatment for the drug selection and prevention of side effect. The expectation is to drive future therapeutic strategies toward precision-based treatment.
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Objective:To establish a IgA nephropathy (IgAN) standard dataset for the structured and standardization of IgAN clinical information, which will be beneficial to the integration and utilization of clinical information among different medical institutions. Therefore, the IgAN Expert Collaboration Group composed the "IgA Nephropathy Standard Dataset".Methods:Referring to the domestic information standards, guidelines, data standard and consensus of related fields, based on electronic medical history, the patient identification number was used as the primary key of the system to collect information. By standardizing each data element in the data set, the standardization of the management system in data and information exchange, data collaboration and sharing was ensured, and a quality control system was developed.Results:This standard dataset included 607 data elements and 8 business domains, which were patient information, medical history information, physical examination, laboratory examination, assistant examination, renal pathology, drug treatment, and follow-up, respectively. Each module was composed of module name, data element name, English name, definition, range, reference standard, etc. At the same time, a corresponding quality control system was formulated to evaluate data quality from multiple dimensions such as completeness, standardization, accuracy, timeliness, and security for ensuring the high quality and security of the data.Conclusion:The IgAN standard dataset is established, which will contribute to the structuration and standardization of clinical information of IgAN patients.
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Objective:To estimate and summarize the evidence for the blood pressure in patients with ruptured intracranial aneurysm bleeding, to provide valuable reference for clinical care and improve the prognosis of patients.Methods:BMJ Best Practice, UpToDate, Chinese Guideline Website, Cochrane Library, PubMed, American Stroke Association, Chinese National Knowledge Infrastructure, Wanfang Database and VIP Database were utilized for screening out evidences of blood pressure management strategies for patients with ruptured intracranial aneurysm bleeding from database establishment to December 8, 2020. The source of evidences included guidelines, evidence summarization, information brochure of optimal clinical practice, recommended practice, systematic review and original research. Upon the assessment of the included literature, the evidences meeting the enrollment criterion would be identified and extracted.Results:There were 9 articles involved in this research and 20 evidences possessing clinical applicability were extracted. The evidences involved in clinical assessment, regulation tenets, intervention protocol, and nursing to prevent complications in patients with ruptured intracranial aneurysm bleeding.Conclusions:To summarize, we suggested strongly to evaluate the individual differences in age, underlying diseases and pharmacological tolerance, and to effectivelly control blood pressure in patients with ruptured intracranial aneurysm bleeding through scientific nursing methods, which could improve the nursing qualification.
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Patients in the perioperative period are often at risk of malnutrition due to the disease itself, surgical trauma, stress, and fasting. Oral nutritional supplementation is widely used in the perioperative period as the first choice for nutritional therapy. This article summarizes the effects, usage, adverse reactions and coping methods of oral nutritional supplementation during perioperative period, aiming to understand the current status of oral nutritional supplementation in perioperative period, and provide reference for subsequent application research of oral nutritional supplementation in perioperative period.
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Objective To explore the mechanism of tetramethylpyrazine (TMP) in preventing and treating inflammation and cell apoptosis in rats. Methods Totally 180 healthy male SD rats were selected and randomly divided into sham operation group (sham), cerebral ischemia reperfusion injury(CIRI) group, nimodipine group (nimodipine, N), and TMP subdivided into low-dose group (low). There were three subgroups: low-dose(L), medium dose (M), and high dose (H). In CIRI group a modified suture method was used to prepare the CIRI model; each TMP group was given tail injection 30 minutes before surgery. Intervention was given by intravenous injection of 5 mg/kg, 10 mg/kg, and 30 mg/kg TMP. N group was given tail vein injection of nimodipine (1 mg/kg), sham group and CIRI group were given the same dose of normal saline. SD rats in each group were scored for neurological deficits immediately after the CIRI model was constructed. At the same time, after 24 hours of reperfusion in each group,2,3,5-triphenyltetrazole chloride (TTC) staining, HE staining and Nissl staining were performed to detect the morphological changes of the parietal cortex ischemic penumbra; ELISA to detect the expression of IL-1β and IL-8 in the parietal cortex, TUNEL detects neuronal cell apoptosis in the parietal cortex, immunofluorescence detected the expression of β-catenin positive cells in the parietal cortex, and Western blotting detected the expression of Bax and Bcl-2 in the parietal cortex. Results Compared with the sham group, the neurological deficit score in the CIRI group was significantly higher(P<0.01). The HE and Nissl staining showed neuronal swelling and degeneration, some of which showed vacuole-like changes, pyknosis and deep staining of the nucleus, and a decrease in the number of neurons(P<0.01), the number of Nissl bodies was significantly reduced(P<0.01);the concentrations of inflammatory factors IL-1β and IL-8 increased significantly(P<0.01), apoptotic cells and β-catenin-positive cells and their average absorbance values both increased significantly(P<0.01);the expression of Bcl-2 protein decreased, while the expression of Bax protein increased significantly(P<0.01). Compared with the CIRI group, the neurological deficit scores of the rats in the N group and the TMP intervention group were reduced (P<0.01), HE and Nissl staining revealed that the edema of large neurons was reduced, a few nerve cells were destroyed, and the number of neurons increased(P<0.01), the number of Nissl bodies ncreased (P<0.01);the concentration of inflammatory factors IL-1β and IL-8 decreased significantly(P<0.01), apoptotic cells and β-catenin-positive cells and the average absorbance value decreased significantly (P<0.01)the expression of Bcl-2 protein increased, while the expression of Bax protein decreased significantly(P<0.01);compared with group N, as the concentration of TMP increased, nerve function, inflammatory response, and neuronal pathological changes showed dose-effects relationship (P<0.05). Conclusion TMP intervention treatment can alleviate the neurological deficit, neuronal damage, tissue edema, inflammatory factors and cell apoptosis after CIRI in rats. The mechanism may be related to the inhibition of the expression of β-catenin protein in the parietal cortex of rats.
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Aim To explore the effects of depression on tumors, as well as its molecular mechanisms. Methods The chronic unpredictable mild stress model (CUMS) was constructed. Tumor was inoculated after behavioral test, and the differences in serum norepinephrine and tumor volume between groups were detected. Breast cancer cells were stimulated by administration and invasion, migration, proliferation and cell cycle distribution were detected. Western blot and immunofluorescence were utilized to detect cell surface receptors and intracellular signaling pathways. Results Depression up-regulated the level of norepinephrine (N E) and increased the phosphorylation of p38 MAPK, resulting in increased malignancy of breast cancer cells. Conclusions Depression may increase the malignancy of breast cancer through norepinephrine-induced p38 MAPK signaling pathway, thus increasing the malignant degree of breast cancer.
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A large number of cancer patients suffer from pain. Growing evidence suggested that pain might be a serious risk factor for cancer patients. The shared modulators and modulation pathways between neural system and tumor cells, such as various neurotransmitters and neurogenic cytokines, provide essential basis for the effect of pain on tumor. In this article, we reviewed some possible mechanism of this process from two aspects: the systematic regulation of central nervous system on endocrine and immunity, and the regional regulation of peripheral nerves on tumor cells. The aim of this review is to provide more innovative knowledge about pain and cancer and to emphasize the importance of anti-pain in the therapy of cancer.
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Humans , Cancer Pain , Central Nervous System , Memory , Neurotransmitter Agents , Pain , Peripheral NervesABSTRACT
Objective To investigate the clinical efficacy of nimesulide in the treatment of chronic periodontitis patients,and analyze the effect of IL-8 and TNF-αlevels in the gingival sulcus fluid.Methods 88 patients with chronic periodontitis in our hospital between June 2014 to December 2015 were divided into control group and observation group by the random number method, 44 cases in each group, the control group patients were given metronidazole treatment, observation group patients were given nimesulide treatment,two groups therapeutic effect and the incidence of adverse reactions were observed, compared two groups of patients before and after treatment in gingival sulcus fluid IL-8 and TNF-αlevel, compared sulcus bleeding index (SBI), plaque index (PLI) and clinical attachment level (CAL),before and after treatment two weeks and four weeks of probing depth (PD) of two groups.Results The total effective rate of observation group patients was 95.55%, significantly higher than the control group patients’total efficiency (81.82%) (χ2 =4.06, P=0.04), after treatment in the observation group gingival sulcus fluid IL-8 factor and TNF-αlevels were significantly lower than the control group (P<0.05), After 2 weeks and 4 weeks of treatment, PD, SBI and CAL indicators observation group were significantly lower than the control group ( P <0.05 ) , the incidence of adverse reactions of observation group patients was 4.55%, significantly lower than the incidence of adverse reactions in control group patients(22.73%)(χ2 =6.18, P=0.01).Conclusion Nimesulide in the treatment of chronic periodontitis with a highly efficient clinical efficacy, while reducing gastrointestinal side effects, etc., can effectively reduce the gingival sulcus fluid IL-8 and TNF-αlevels, ease clinical symptoms, is a highly effective treatment.
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Long-chain acyl coenzyme A synthetase (ACSL) is a member of the synthetase family encoded by a multigene family; it plays an important role in the absorption and transport of fatty acid. Here we review the roles of ACSL in the regulating absorption and transport of fatty acid, as well as the connection between ACSL and some metabolic diseases.
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Cellular senescence refers to a process that cellular proliferation and differentiation modulated by the multiple stimulating factors gradually decline. Aging cells present the irreversible stop of proliferation and differentiation and change in secretory function because the cell cycle of aging cells is steadily blocked at some point. It has have been shown that cellular senescence plays an important role in the occurrence and development of liver diseases. In this paper, we review the advances in relations between cellular senescence and liver diseases.
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The lipids present in hepatic stellate cells (HSCs) lipid droplets include retinyl ester, triglyceride, cholesteryl ester, cholesterol, phospholipids and free fatty acids. Activation of HSCs is crucial to the development of fibrosis in liver disease. During activation, HSCs transform into myofibroblasts with concomitant loss of their lipid droplets and production of excessive extracellular matrix. Release of lipid droplets containing retinyl esters and triglyceride is a defining feature of activated HSCs. Accumulating evidence supports the proposal that recovering the accumulation of lipids would inhibit the activation of HSCs. In healthy liver, quiescent HSCs store 80% of total liver retinols and release them depending on the extracellular retinol status. However, in injured liver activated HSCs lose their retinols and produce a considerable amount of extracellular matrix, subsequently leading to liver fibrosis. Further findings prove that lipid metabolism of HSCs is closely associated with its activation, yet relationship between activated HSCs and the lipid metabolism has remained mysterious.
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Animals , Humans , Cholesterol , Metabolism , Hepatic Stellate Cells , Physiology , Lipid Metabolism , Triglycerides , Metabolism , Vitamin A , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To study the effect of cultivation techniques on the flower yield flavonoid content in Chrysanthemum flower grown in Hebei.</p><p><b>METHOD</b>Studied on flowers yield and three factors (transplanting date and plant density and fertilizer quantity) were examined in field experiment at 4 treatments levels.</p><p><b>RESULT AND CONCLUSION</b>The best results were obtained at following conditions: diammonium phosphate 300 kg x hm(-2) and potassium sulfate 150 kg x hm(-2) fertilized before transplanting, transplanting at the first ten days of May and the spacing 40 cm x 40 cm.</p>
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Biomass , China , Chrysanthemum , Metabolism , Fertilizers , Flavonoids , Metabolism , Flowers , Metabolism , Gardening , Methods , Phosphates , Plants, Medicinal , Metabolism , Seasons , SulfatesABSTRACT
group A by turns. (3) The concentrations of plasma endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) were significantly higher in group B than that in group A. However, the ET-1 and ACE were significantly lower in group C than those in group B. (4) The ET-1 and ACE had a significant positive correlation with R/L+S, mPAP and PI, respectively. The multivariate linear regression analysis revealed that ET-1 and ACE were major factor affecting PI. CONCLUSION: The pulmonary vascular and myocardial structural remodeling are one of the pathogenesis accompanied with excessive cell proliferation in hypoxic pulmonary hypertension (PH). Cilazapril effectively prevents and treats the hypoxic PH by inhibiting cell proliferation and structural remodeling of pulmonary circulation, as induced by ET-1 and ACE.
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Objective To investigate the present situation of living and living quality of the elderly living in communities of Xi'an City.Methods By using quality of life(QOL) questionnaire,the elders living in two communities in Xi'an were investigated regarding their physical,psychological,social and material functions as well as overall living quality.Results Psychological and social functions scored significantly higher in both male and higher-income groups than those in the others.The scores of physical and social functions in the lower-income elderly were significantly higher than those in high-income ones.The scores of overall living quality of those elderly having spouses,living with their family members,taking an active part in social activities,having hobbies and enjoying medical insurance were significantly higher than those of the others.The well-educated elderly scored significantly higher in social function than those with lower education level;adverse events prominently decreased the quality of life of the elderly.More than 80% of the elderly were satisfied with their living environment.The highest incidence of chronic diseases in the communities was hypertension.Conclusion The quality of life of the elderly living in communities of Xi'an City is good.Health status,family environment,educational level,income and marital status are the main factors that affect the quality of life of the elderly.