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1.
Neuroscience Bulletin ; (6): 677-691, 2022.
Article in English | WPRIM | ID: wpr-929119

ABSTRACT

Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer's disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an "X" to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.

2.
Neuroscience Bulletin ; (6): 290-302, 2022.
Article in English | WPRIM | ID: wpr-929083

ABSTRACT

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.


Subject(s)
Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Cognition , Disease Models, Animal , Mice , Mice, Transgenic , Monocytes/pathology , Polysaccharides/therapeutic use , Proteoglycans
3.
Acta Pharmaceutica Sinica ; (12): 392-398, 2022.
Article in Chinese | WPRIM | ID: wpr-922919

ABSTRACT

Numerous in vitro studies have shown that most pyrrolizidine alkaloids (PAs) are hepatotoxic after being metabolically activated by cytochrome P450 (CYP) 3A4. However, the key role of CYP3A4 has not been confirmed in vivo. Therefore, the CYP3A4 chemical inhibitor ritonavir was employed in this work and the effect of ritonavir on Gynura japonica-induced liver injury in rats was investigated. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Acute liver injury was induced by a single gavage of Gynura japonica extracts (GJE, 8 g·kg-1); rats in the protection group were gavaged with ritonavir (RIT, 30 mg·kg-1) 1 h before GJE treatment. The results show that RIT could significantly attenuate GJE-induced liver injury in rats. Rats in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase, as well as lower total bile acids. In addition, the infiltration of inflammatory cells, sinusoidal hemorrhage, and hepatic necrosis in GJE-treated rats were markedly attenuated in the protection group. The content of pyrrole-protein adducts (PPAs), a recommended biomarker for PA-induced hepatotoxicity in clinics, was determined at 10 min to 24 h after GJE treatment. The content of 13 bile acids was also quantified. RIT treatment reduced the content of PPAs in serum dramatically and restored the impaired bile acid homeostasis caused by GJE. These studies indicate that RIT attenuated Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs and the regulation of bile acid metabolism. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work will also be helpful in developing effective treatments for PA-induced liver injury and making a reasonable evaluation of the safety of drugs containing PAs in clinic.

4.
Article in Chinese | WPRIM | ID: wpr-907979

ABSTRACT

Objective:To compare the disease outcome, quality of life score [evaluated by child health assessment questionnaire - disability index(CHAQ-DI)] and medical expenses of children with systemic juvenile idiopathic (sJIA) combined with macrophage activation syndrome (MAS) diagnosed by two different criteria.And to analyze the impacts of early MAS diagnosis criteria on the prognosis of sJIA combined with MAS in children.Methods:From January 2016 to December 2020, children with high disease activity of sJIA who were diagnosed and initially treated in the Department of Rheumatology of Beijing Children′s Hospital were enrolled in this study.Clinical characteristics on admission were recorded as baselines.Patients were divided into 2 groups according to different diagnostic criteria.Children diagnosed as MAS based on the 2016 The European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation MAS diagnostic criteria were included in MAS control group(38 cases), and those diagnosed as early MAS based on the sJIA combined MAS early warning scale but did not meet the 2016 diagnostic criteria were included in MAS early warning group(38 cases). Basic information, clinical manifestations and laboratory test results were collected.According to the clinical manifestations and laboratory results in different periods of follow-up at 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months after treatments, the di-sease activity, CHAQ-DI and medical expenses were compared between the two groups.Results:There were no signi-ficant differences in the disease activity, duration of sJIA and medical expenses between the two groups (all P>0.05). In terms of laboratory results, serum ferritin in MAS early warning group were significantly lower than that of MAS control group at 4 weeks after treatment[(333.97±186.66) μg/L vs.(389.66±221.76) μg/L]( t=-83.47, P<0.05). In terms of disease activity, after 12 months of treatment, the evaluation of American College of Rheumatology pediatric indexes 70 in MAS early warning group was better than that in MAS control group [34.2%(13/38 cases) vs.7.9% (3/38 cases)]( χ2=6.067, P<0.05). In terms of CHAQ-DI, at 4 weeks, 8 weeks, 12 weeks and 6 months of treatment, CHAQ-DI in MAS early warning group were better than those in MAS control group, and the difference were statistically significant ( t=-0.34, -0.27, -0.23, -0.09; all P<0.05). In terms of cumulative medical expenditure at 12 months of treatment, the MAS early warning group was lower than the MAS control group [(114.3±80.7) thousand yuan vs.(157.9±111.7) thousand yuan]( t=-3.97, P<0.05). Conclusions:Quickly judge the condition through the quantitative integral of clinical examination and test indexes, screening and treatment of MAS in early stage are helpful to improve the prognosis and reduce the medical consumption.

5.
Acta Pharmaceutica Sinica ; (12): 432-444, 2021.
Article in Chinese | WPRIM | ID: wpr-873767

ABSTRACT

Transporters have a great influence on the transportation and distribution of drugs in the body. On the one hand, solute carrier transporters could transport drugs into tissues and organs, which may improve the oral bioavailability or change the tissue-distribution of the drugs. On the other hand, the ATP-binding cassette could pump some drugs out of the cell, which decreases the intracellular drug concentrations and leads to drug resistance. This paper summarizes the distribution, substrate characteristics and drug design strategies of several important drug transporters, such as improving bioavailability by prodrug design, introducing acid group to improve hepatic selectivity and adjusting the polarity of compounds to decrease efflux ratio.

6.
Acta Pharmaceutica Sinica ; (12): 2528-2535, 2021.
Article in Chinese | WPRIM | ID: wpr-886936

ABSTRACT

Modern pharmacological studies have shown that Cistanche deserticola (C. deserticola) has a protective effect on the liver, but its active fraction and mechanism are not clear. In order to identify the effective fraction of C. deserticola Y. C. Ma, an acute alcoholic liver injury model in mice was established with 56-proof Erguotou and different fractional extracts of C. deserticola Y. C. Ma (total glycosides, polysaccharides, and oligosaccharides) were administered. After 14 days of oral administration, liver pathology and lipid deposition were measured and the expression of nuclear factor E2-related factor (Nrf-2), kelch-like ECH-associated protein-1 (Keap-1), and plasmalemma vesicle-associated protein-1 (PV1) were measured by immunofluorescence. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) in serum, and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and malondialdehyde (MDA) in liver were measured by ELISA. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Peking University Health Science Center. The results show that the total glycosides of C. deserticola Y. C. Ma (400 mg·kg-1) could decrease liver pathology, decrease serum endotoxin, diamine oxidase, and D-lactic acid, and reduce hepatic lipid deposition. Total glycosides also promoted Nrf-2 transfer into the nucleus and decreased the expression of Keap-1 and PV1. In summary, the total glycosides of C. deserticola Y. C. Ma had a protective effect in acute alcoholic liver injury and the mechanism may be related to the activation of the Nrf-2/Keap-1 pathway, improvement of intestinal wall integrity, and inhibition of the transport of harmful substances into the liver.

7.
Article in Chinese | WPRIM | ID: wpr-886765

ABSTRACT

Objective To investigate the prevalence and changing trend of Enterobius vermicularis infections among children in Shandong Province, so as to provide the scientific evidence for the adjustment and development of the enterobiasis control strategy. Methods Soil-borne nematodiasis surveillance sites were assigned in 51 counties (districts, cities) in Shandong Province from 2016 to 2020, and the E. vermicularis infections were detected using a modified Kato-Katz technique and the cellophane tape method among children at ages of 3 to 9 years living in these surveillance sites. The epidemiological profiles of E. vermicularis-infected children were descriptively analyzed. Results A total of 5 060 children at ages of 3 to 9 years were detected in 51 soil-borne nematodiasis surveillance sites in Shandong Province from 2016 to 2020, and the overall prevalence of E. vermicularis infections was 2.23%. The annual prevalence of E. vermicularis infections was 3.99% (26/651), 1.70% (14/824), 0.96% (8/837), 2.90% (45/1 552) and 1.67% (20/1 196) from 2016 to 2020, respectively, with a significant difference detected among years ( χ2 = 21.455, P < 0.01). The prevalence of E. vermicularis infections was 1.25% (15/1 198), 1.85% (14/755), 3.18% (84/2 640) and 0 (0/467) among children from central, eastern, southern and northern Shandong Province (χ2 = 27.326, P < 0.01). In addition, there was no significant difference in the prevalence of E. vermicularis infections between male (1.98%, 56/2 831) and female children (2.56%, 57/2 229) (χ2 = 1.916, P > 0.05); however, there was age-specific prevalence of E. vermicularis infections among children (χ2 = 16.448, P < 0.05), with the greatest prevalence detected among children at ages of 6 years (3.18%, 25/786), and the lowest prevalence seen among children at ages of 3 years (0.75%, 6/800). Conclusions The prevalence of E. vermicularis infections remained at a medium level among children at ages of 3 to 9 years in Shandong Province from 2016 to 2020, with region-specific prevalence found across the province. An integrated strategy is required for enterobiasis control.

8.
Article in Chinese | WPRIM | ID: wpr-828378

ABSTRACT

We used exogenous GA_3 to break the seed dormancy of Thesium chinense. We used high-throughput sequencing technology was used to sequence the transcriptome of dormant seed embryos and dormancy breaking seed embryos of Th. chinense, and the data was analyzed bioinformatically and systematically. The results showed that exogenous GA_3 could effectively break the seed dormancy of Th. chinense; 73 794 up-regulated genes and 42 776 down regulated genes were obtained by transcriptome sequencing; 116 570 diffe-rential genes were annotated by GO function to GO items such as metabolism process, cell process, cell, cell component, binding and catalytic activity. A total of 133 metabolic pathways were found by Pathway analysis of 26 508 differentially expressed genes. In the process of dormancy release, DEGs were mainly enriched in translation, carbohydrate metabolism, folding, classification, degradation and amino acid metabolism. Based on the annotation results in KEGG database, 20 metabolic pathways related to dormancy release were found. Dormancy release of Th. chinense seeds is a complex biological process, including cell morphology construction, secondary metabolite synthesis, sugar metabolism and plant signal transduction, among which plant hormone signal transduction is one of the key factors to regulate dormancy release. The results of qRT-PCR showed that the sequencing results were consistent with the actual results.


Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Plant , Plant Dormancy , Plant Growth Regulators , Santalaceae , Seeds , Transcriptome
9.
Article in English | WPRIM | ID: wpr-827789

ABSTRACT

Inthomycins are polyketide antibiotics which contain a terminal carboxamide group and a triene chain. Inthomycin B (1) and its two new analogues 2 and 3 were isolated from the crude extract of Streptomyces pactum L8. Identification of the gene cluster for inthomycin biosynthesis as well as the N-labeled glycine incorporation into inthomycins are described. Combined with the gene deletion of the rare P450 domain in the NRPS module, a formation mechanism of carboxamide moiety in inthomycins was proposed via an oxidative release of the assembly chain assisted by the P450 domain.

10.
Journal of Experimental Hematology ; (6): 1381-1385, 2020.
Article in Chinese | WPRIM | ID: wpr-827108

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics and prognostic risk factors of HLH children with central nervous system (CNS) involvement so as to provide more reference for further improving the prognosis of HLH children.@*METHODS@#The clinical data of 45 HLH children with CNS involvement treated in our hospital from January 2006 to October 2016 were collected and analyzed retrospectively. The clinical characteristics of HLH children with CNS involvement were recorded, moreover the possible factors influencing the prognosis of HLH children with CNS involvement were analyzed using univariate and multivariate analysis through the establishment of Cox risk ratio model.@*RESULTS@#Among 45 HLH children with CNS involvement, male was 19 cases and female was 26 cases. The median age of 4.0 years old (1.0-15.1). The detection showed that EBV found in 38 cases (84.44%), CMV infection in 1 case (2.22%), bacterial infection in 3 cases (6.67%), connection tissue disease in 1 case (2.22%) and indefinite etiology infection in 2 cases (4.44%). After lumbar puncture of 27 HLH children with CNS involvement, 10 cases (37.04%) showed cerebrospinal fluid abnormality. In addition, 22 cases showed the craniography abnormality. The follow-up results showed that the OS rate of 1 year was 46.67% (21/45), the OS rate of 3 years was 44.44% (20/45); the median survival time was 5.0 months. The OS analysis indicated that 1 years OS rate of diseased children with cerebrospinal fluid abnormality was significantly lower than that of diseased children with cerebrospinal fluid normality (10/45 vs 17/45) (P<0.05), and 1 years OS rate of diseased children who not received intrathecal injection was significantly lower that of diseased children who received intrathecal (10/45 vs 17/45) (P<0.05). The univariate analysis showed that the symptoms of nervous system, abnormal cerebrospinal fluid, absence of intrathecal injection and treatment schedule all were the risk factors affecting the prognosis of HLH children with CNS involvement (P<0.05). The multivariate analysis by Cox risk model showed that abnormal cerebrospinal fluid and absence of intrathecal injection were independent risk factors for of HLH children with CNS involvement (P<0.05).@*CONCLUSION@#The clinical prognosis of HLH children with CNS involvement is relatively poor, moreover some of HLH children with CNS involvement have neural sequelae. The cerebrospinal fluid abnormality and absence of intrathecal injection are independent risk factors leading to poor prognosis for HLH clildren with CNS involvement.


Subject(s)
Child , Child, Preschool , Cytomegalovirus Infections , Female , Humans , Male , Nervous System , Prognosis , Retrospective Studies , Risk Factors
11.
Neuroscience Bulletin ; (6): 696-704, 2020.
Article in English | WPRIM | ID: wpr-826799

ABSTRACT

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

12.
Chinese Medical Journal ; (24): 173-177, 2020.
Article in English | WPRIM | ID: wpr-878026

ABSTRACT

BACKGROUND@#Recent studies suggest that a healthy diet helps to prevent the development of Alzheimer disease (AD). This study aimed to investigate whether spicy food consumption is associated with cognition and cerebrospinal fluid (CSF) biomarkers of AD in the Chinese population.@*METHODS@#We enrolled 55 AD patients and 55 age- and gender-matched cognitively normal (CN) subjects in a case-control study, as well as a cohort of 131 participants without subjective cognitive decline (non-AD) in a cross-sectional study. Spicy food consumption was assessed using the Food Frequency Questionnaire (FFQ). Associations of FFQ scores with cognition and CSF biomarkers of AD were analyzed.@*RESULTS@#In the case-control study, spicy food consumption was lower in AD patients than that in CNs (4.0 [4.0-8.0] vs. 8.0 [4.5-10.0], P < 0.001); FFQ scores were positively associated with Mini-Mental Status Examination scores in the total sample (r = 0.218, P = 0.014). In the cross-sectional study, the association between spicy food consumption and cognition levels was verified in non-AD subjects (r = 0.264, P = 0.0023). Moreover, higher FFQ scores were significantly associated with higher β-Amyloid (1-42) (Aβ42) levels and lower phospho-tau/Aβ42 and total tau/Aβ42 ratios in the CSF of non-AD subjects (P < 0.05).@*CONCLUSION@#Spicy food consumption is closely related to higher cognition levels and reversed AD biomarkers in the CSF, suggesting that a capsaicin-rich diet might have the potential to modify the cognitive status and cerebral pathologies associated with AD.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Biomarkers , Case-Control Studies , Cognition , Cross-Sectional Studies , Humans , Peptide Fragments , tau Proteins
13.
Acta Pharmaceutica Sinica ; (12): 427-445, 2020.
Article in Chinese | WPRIM | ID: wpr-815846

ABSTRACT

Most peptides have high binding affinity and good selectivity for endogenous receptors and are good lead compounds to develop into drugs. Many approved drugs are derived from the structural optimization of peptide molecules, such as the antihypertensive drug captopril and the anti-hepatitis C drug telaprevir. At present, the main problems in the development of peptide drugs include poor stability, short half-life, and high plasma clearance rate; lack of oral availability and poor patient compliance, a complex production process, and high production cost. Therefore, rational modification of peptides can not only reduce the production cost, but also improve the druggability of the peptides. Here we review structural modification strategies for peptides from the perspective of improving their physicochemical properties. These modification strategies are divided into two parts: one is modification of the peptide backbone, including unnatural amino acid modification, pseudopeptide strategy, inverse-peptide strategy, cyclization strategy, and terminal structure modification. Another is modification of the side chains of peptides, including fatty acid conjugation, polyethylene glycol conjugation, protein fusion strategy, and cholesterol conjugation.

14.
Acta Pharmaceutica Sinica ; (12): 473-477, 2020.
Article in Chinese | WPRIM | ID: wpr-815839

ABSTRACT

Recently, hepatic sinusoidal obstruction syndrome (HSOS) induced by misuse of Gynura japonica has increased and gained global attention. Large amounts of pyrrolizidine alkaloids (PAs) are present in G. japonica; these PAs are metabolically activated to generate pyrrole-protein adducts (PPAs). In this study, male SD rats were treated orally with a single dose of G. japonica extract (GJE) at 0.062 5, 0.25, 0.5, 1, and 2 g·kg-1. Blood was collected from the orbital venous plexus at 2, 12, 24 and 48 h, and at 48 h after treatment the rats were anesthetized with isoflurane and livers were collected for hematoxylin & eosin staining. The kinetics of PPAs at different doses were studied at 10, 20, 30 min, 1, 2, 4, 6, 12, 24 h, and 48 h, after a single gavage of GJE. The experimental scheme was approved by the ethics committee of animal experiments of Shanghai University of Traditional Chinese Medicine (PZSHUTCM190912019). The concentration of PPAs in serum was determined by liquid chromatography-mass spectrometry (LC-MS). Kinetic data were processed by using the non-compartmental pharmacokinetics data analysis software program PK solutions 2™. The results demonstrate that the concentration of PPAs increased with the dose of GJE and positively correlated with the severity of liver injury. The elimination rate of PPAs in rats was significantly prolonged at higher doses. The level of PPAs and their clearance rate may serve as useful references for the detoxification of PAs-induced injuries.

15.
Article in Chinese | WPRIM | ID: wpr-872762

ABSTRACT

Objective:This study intends to study the regulatory effect and mechanism of the effective components of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos on inflammatory factors related to cerebral ischemia-reperfusion injury in rats through multiple levels of neuropathology, molecular neurobiology and functional behavior. Method:The 32 male rats were randomly divided into four groups: sham group, model group, Danhong components compatibility group(720 mg·kg-1), nimodipine (0.5 mg·kg-1)groups,each group of eight male rats.Cerebral ischemia was established by middle cerebral artery occlusion (MCAO) approach. The treatment was performed immediately and at 6 hour after MCAO.Hematoxylin-eosin (HE)staining was used to check the changes of brain histopathology, immunohistochemistry and Real time polymerase chain reaction (Real-time PCR) were used to check the expression of IL-1β and Nrf2 in brain tissue,Western blot was used to detect the protein expression of Nrf2 in brain tissue. The aim is to investigate the treatment mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos components in a rat model of cerebral ischemic-reperfusion injury. Result:HE staining results showed, compared with sham group, the surviving neurons amount in the model group was significantly reduced(P<0.01),compared with the MCAO group,the number of surviving neurons in the brain tissue of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and nimodipine group was significantly increased(P<0.05,P<0.01).The results of immunohistochemistry and Real-time PCR showed that,compared with normal group,IL-1β and Nrf2 expression in model group were significantly increased (P<0.01),compared with MCAO group, the expression of IL-1β and Nrf2 in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and the nimodipine group was significantly decreased (P<0.05,P<0.01). Western blot results showed that, compared with sham group, Nrf2 positive expression in model group was much more increased (P<0.01), compared with MCAO group, the expression of Nrf2 in Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos component compatibility group and the nimodipine group was significantly decreased (P<0.01). Conclusion:The combination of effective components of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos can significantly down-regulate the expression of IL-1β and Nrf2 proteins.The mechanism is to activate the protein expression of inflammatory pathways, reduce the apoptosis of nerve cells, and finally inhibit the inflammatory response in the process of ischemic stroke injury.

16.
Article in Chinese | WPRIM | ID: wpr-869784

ABSTRACT

Objective:To evaluate the role of hypoxia-inducible factor-1α (HIF-1α)/Bcl-2/E1B-19kDa interacting protein 3 (BNIP3) signaling pathway in sevoflurane-induced attenuation of myocardial ischemia-reperfusion (I/R) injury in rats and the relationship with autophagy.Methods:Ninety healthy adult male Sprague-Dawley rats, weighing 300-350 g, were randomly divided into 5 groups ( n=18 each): sham operation group (Sham group), I/R group, sevoflurane group (SEV group), HIF-1a inhibitor 2ME2 group (2ME2 group), and 2ME2+ sevoflurane group (MSP group). Myocardial I/R injury model was established by ligating the left anterior descending branch of coronary artery for 40 min followed by 120-min reperfusion in anesthetized rats.In SEV group, 2.4% sevoflurane was inhaled for 15 min starting from the beginning of reperfusion.In 2ME2 group and MSP group, 2ME2 (15 mg/kg) was intraperitoneally injected at 1 h before ligation of the left anterior descending branch of coronary artery, and the other treatments were similar to those previously described in group I/R or in group SEV.Animals were sacrificed at 120 min of reperfusion, and the left ventricular myocardium was taken for determination of the expression of HIF-1α and BNIP3 (by Western blot), activity of ROS (by DHE), and myocardial infarct size (by TTC)and for observation of autophagosome (with an electron microscope). Results:Compared with Sham group, the activity of ROS, the number of autophagosome and myocardial infarct size were significantly increased in the other four groups, the expression of HIF-1α and BNIP3 was up-regulated in I/R group and SEV group ( P<0.05). Compared with I/R group, the activity of ROS, the number of autophagosome and myocardial infarct size were significantly decreased in the other four groups, the expression of HIF-1α and BNIP3 was up-regulated in SEV group, and no significant difference was found in the activity of ROS, the number of autophagosome or myocardial infarct size ( P>0.05), and the expression of HIF-1α and BNIP3 was down-regulated in 2ME2 and MSP groups ( P<0.05). Compared with SEV group, the activity of ROS, the number of autophagosome and myocardial infarct size were significantly increased, and the expression of HIF-1α and BNIP3 was down-regulated in 2ME2 and MSP groups ( P<0.05). Conclusion:HIF-1α/BNIP3 signaling pathway is involved in sevoflurane-induced attenuation of myocardial I/R injury, which is related to inhibiting autophagy in rats.

17.
Chinese Journal of Rheumatology ; (12): 306-310, 2020.
Article in Chinese | WPRIM | ID: wpr-868207

ABSTRACT

Objective:To investigate the clinical characteristics and follow-up of thrombosis of pediatric patients with systemic lupus erythematosus (SLE).Methods:In this retrospective study, inpatients who were diagnosed in Beijing Children's Hospital with SLE complicated with arterial or venous thrombosis from January 2006 to December 2019 were collected, the clinical characteristics and outcomes were analyzed. Statistical product and Service solutions (SPSS) 25.0 was used for statistical analysis. T test or χ2 test (counting data) was used to compare the differences between groups, and Kaplan-Meier survival curve was used to analyze the time of thrombus endpoint events in lupus children. Results:A total of 1 395 newly diagnosed SLE patients were admitted. Twenty-seven cases were diagnosed with thrombosis, accounting for 1.9% of all the lupus patients. The median course from diagnosis to thrombosis was 20 days (49 days before diagnosis to 1 year after dia-gnosis). Among the 27 patients, 22(81%) cases had renal involvement. The mean SLE disease activity index (SLEDAI) score was (14±6) and (11±4) at the diagnosis of lupus and at onset of thrombosis, respectively ( t=2.547, P=0.017). 30% (8/27) of the patients had no apparent clinical manifestations of thrombosis. The patients received standard anticoagulant therapy after the diagnosis of thrombosis. During follow-up, 6 patients stopped taking medications due to the severity of the primary disease. Twenty-one patients were followed up regularly for 1-3 years. Thrombosis disappeared in 12 cases (44%), thrombolysis time ranged from 16 days to 1 year. Thrombosis were getting smaller in 9 cases (33%). And the disease was stable during follow up. Conclusion:Thrombosis is not rare in pediatric patients with systemic lupus erythematosus patients. Some patients do not have apparent clinical manifestations related to thrombus. Pediatricians should be alert to patients with renal involvement need to be more vigilant for thrombosis. Early detection and active treatment are the keys to improve the prognosis of thrombosis in pediatric SLE patients.

18.
Chinese Journal of Rheumatology ; (12): 258-263, 2020.
Article in Chinese | WPRIM | ID: wpr-868200

ABSTRACT

Objective:To explore the clinical characteristic and prognosis of juvenile dermatomyositis (JDM) by retrospectively study of the clinical manifestations, laboratory examinations, treatment and follow-up results. The aim of this study was to improve the diagnosis and treatment of JDM and reduce the complications and mortality.Methods:Medical charts of 612 JDM cases hospitalized to Beijing children's hospital from July 2002 to July 2018. We retrospectively analyze the onset, clinical manifestations, laboratory examinations, treatment and the follow-up, and then summarize the clinical characteristics and assess the therapeutic effect and prognosis.Results:There were 278 male and 334 female. The maleto female ratio was 1∶1.2. Themedian age at symptoms onset was 5.4(2.9-8.4) years old (range 6 months to 14 years). Rash was the most common initial presentation. The main clinical manifestations were rash (100%, 612 cases) and muscles weakness (96.1%, 588 cases). The most commonly involved organs by JDM were lung (57.5%, 352 cases), digestive tract (38.5%, 236 cases) and heart (32.5%, 199 cases). Muscle enzymes elevated in 95.5% (584 cases) of the patients and 89.5%(534 cases) of the patients had typical changes on electromyography. Muscle biopsy was performed in 134 patients and pathologicresults were compatible with JDM. For the treatment, all of the patients were treated by steroids plus therapy combined with immunosuppressive agents. Mostof the patients got good effect and outcome. Twenty-four patients died, and acute respiratory failurewas the most common cause of death. 17.9%(105 cases) of patients had complications. The complications included calcinosis in 70 patients and amyotrophy in 35 patients.Conclusion:JDM is a rare disease of children, andis characterized by muscle weaknessand rash. Severe organ involvement may cause death. Treatments include corticosteroids and immunosuppressive agents, andthe outcome is generally good.

19.
Chinese Journal of Immunology ; (12): 230-235, 2019.
Article in Chinese | WPRIM | ID: wpr-744640

ABSTRACT

Interleukin ( IL) -38 is the most recently discovered cytokine, which is the tenth member of IL-1 cytokine family. IL-38 shares a high homology with IL-1 receptor antagonist ( IL-1 Ra) and IL-36 Ra. IL-36 R is the specific receptor of IL-38 which is the partial receptor antagonist of IL-36. Now, research has shown that IL-38 not only had relationship with intracellular infection and inflammation, but also with many clinical diseases such as autoimmune diseases, osteoarthritis, tumor and cardiopulmonary diseases. However, the molecular immune regulation mechanism of IL-38 is complicated, involving specific receptor recruitment, apoptosis mediated phagocyte regulation, regulation of Th17 cell differentiation and many other processes. It also provides several new clues to the treatment of diseases. IL-38 is a new cytokine research hot spot with extensive application prospects and need deep exploration.

20.
Article in Chinese | WPRIM | ID: wpr-742744

ABSTRACT

Objective:To discuss the clinic features and diagnosis of one case of hepatic angiomyolipoma (HAML) , and to analyze and summarize its diagnosis and treatment methods.Methods:The clinical materials of one case of HAML patient who was misdiagnosised as hepatocellcular carcinoma were analyzed retrospectively, and the related literatures were reviewed.Results:A middle-aged female patient visited our outpatient service because of low back discomfort.The upper abdominal CT and MRI suggested that a space occupying lesion located at the left lobe of liver inner lower segment, considering a high possibility of hepatocellular carcinoma.The patient underwent the left lobe of inner lower segmentectomy.The postoperative histopathological examination and immunohistochemical staining showed the tumour was HAML, After operation, the patient recovered well and the follow-up examination after hepatectomy found no tumor recurrence.Conclusion:HAML has no specific clinical characteristics or imaging features.The diagnosis of HAML mostly depend on the histopathological examination and hepatectomy is the effective treatment.

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