Screening of GLP-1r agonists from natural products using affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology: a case study of Panax ginseng.

In our study, a method based on affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was established to select Glucagon-like peptide-1 receptor (GLP-1R) agonists from natural products, and as an example, the GLP-1R agonists from Panax ginseng was selected using our established method. As a result, total five GLP-1R agonists were selected from Panax ginseng for the first time. Our results indicated that activating GLP-1R to promote insulin secretion probably was another important hypoglycemia mechanism for ginsenosides in Panax ginseng, which had great influence on the study of the anti-diabetes effect of ginsenosides.

Screening of potential α-glucosidase inhibitors from astragalus membranaceus by affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS method.

Astragalus membranaceus is a traditional Chinese medicine with multiple pharmacological activities. Modern pharmacological research has found that Astragalus membranaceus extract has an inhibitory effect on α-glucosidase, however, which component can inhibit the activity of α-glucosidase and its degree of inhibition are unknown. To address this issue, this study used affinity ultrafiltration screening combined with UPLC-ESI-Orbitrap-MS technology to screen α-glucosidase inhibitors in Astragalus membranaceus. Using affinity ultrafiltration technology, we obtained the active components, and using UPLC-ESI-Orbitrap-MS technology, we quickly analyzed and identified them. As a result, a total of 8 ingredients were selected as α-glucosidase inhibitors.

Factors associated with clopidogrel resistance and clinical outcomes in ischemic cerebrovascular disease: A retrospective study.

OBJECTIVE: Clopidogrel resistance may lead to the recurrence of cerebrovascular diseases. We aimed to identify potential factors associated with clopidogrel resistance and evaluate the clinical outcomes of the patients. MATERIALS AND METHODS: In this retrospective study, patients with ischemic cerebrovascular disease treated with clopidogrel were included and classified into 2 groups according to the adenosine diphosphate (ADP)-induced platelet aggregation. Patients with the ADP inhibition rate of <30 % were included in clopidogrel resistance group, otherwise were included in clopidogrel sensitive group. CYP2C19 genotype and other clinical data were analyzed to identify factors and clinical features in the multivariate analysis. The outcomes were vascular events in 6 months. RESULTS: In total, 139 patients were enrolled with 81 (58.27 %) in clopidogrel sensitive group and 58 (41.73 %) in clopidogrel resistance group. Female and CYP2C19 *2*3 carrying were risk factors for clopidogrel resistance, and female was an independent risk factor (OR 2.481, 95 % CI 1.066-5.771, P=0.035). The clopidogrel resistance group showed a higher use rate of argatroban (P=0.030) and a lower arachidonic acid-induced inhibition of platelet aggregation (P=0.036). Clopidogrel resistance was related to the progressing stroke (HR 3.521, 95 % CI 1.352-9.170, P=0.010), but had no influence on the bleeding events (P>0.05). CONCLUSIONS: The risk of clopidogrel resistance increased significantly in female patients. Patients with clopidogrel resistance may have an increased incidence of stroke progression in the acute phase.

The benefits of rehabilitation exercise in improving chronic traumatic encephalopathy: recent advances and future perspectives.

Traumatic encephalopathy syndrome (TES) is used to describe the clinical manifestations of chronic traumatic encephalopathy (CTE). However, effective treatment and prevention strategies are lacking. Increasing evidence has shown that rehabilitation training could prevent cognitive decline, enhance brain plasticity, and effectively improve neurological function in neurodegenerative diseases. Therefore, the mechanisms involved in the effects of rehabilitation exercise therapy on the prognosis of CTE are worth exploring. The aim of this article is to review the pathogenesis of CTE and provide a potential clinical intervention strategy for CTE.

Factors affecting the scientific research ability and the corresponding countermeasures in clinical postgraduates.

BACKGROUND: Scientific research ability (SRA) is very important for clinical postgraduates. However, the factors affecting students' SRA are constantly changing with the development of medicine. The aim of this study was to investigate the current situation of SRA in clinical postgraduates and exploring the potential factors and the corresponding countermeasures under the background of new medical science. METHODS: A total of 133 postgraduates (first- or second-year) were investigated by questionnaire in the Second Affiliated Hospital of Fujian Medical University. All results were analyzed by R software. RESULTS: In terms of the SRA, academic-degree postgraduate students (ADPSs) were significantly better than professional-degree postgraduate students (PDPSs) (P = 0.001), the students with scientific research interest were remarkably better than those without scientific research interest (P = 0.004), the students who mastered statistical analysis methods were more prominent than those who did not (P = 0.007), the students with paper-writing skills were obviously superior to those without it (P = 0.003), and the second-year students were notably better than the first-year students (P = 0.003). Stratified analysis by the above factors except the degree type showed no significant difference in the first-year postgraduates. In the second-year postgraduates, the ADPSs were remarkably superior to the PDPSs (P = 0.002), the students with scientific research interest were obviously better than those without scientific research interest (P = 0.014), the students with more time investment in scientific research were more prominent than those with less time investment in scientific research (P = 0.025), the students with paper-writing skills were notably superior to those without it (P = 0.031), and the students with plotting ability were better than those without it (P = 0.013). CONCLUSION: The important factors affecting the SRA of clinical postgraduates include the degree type, the grade of student, scientific research interest, time investment in scientific research, statistical analysis methods, paper-writing skills, plotting ability. In short, earlier systematic SRA training contributes to the improvement of SRA in clinical postgraduates, especially in PDPSs.

Comprehensive Identification of Ginsenosides in the Roots and Rhizomes of Panax ginseng Based on Their Molecular Features-Oriented Precursor Ions Selection and Targeted MS/MS Analysis.

Panax ginseng is widely used in Asian countries and its active constituents-ginsenosides-need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG.

Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening.

Leucine and mTORc1 act independently to regulate 2-deoxyglucose uptake in L6 myotubes.

Chronic mTORc1 hyperactivation via obesity-induced hyperleucinaemia has been implicated in the development of insulin resistance, yet the direct impact of leucine on insulin-stimulated glucose uptake in muscle cells remains unclear. To address this, differentiated L6 myotubes were subjected to various compounds designed to either inhibit mTORc1 activity (rapamycin), blunt leucine intracellular import (BCH), or activate mTORc1 signalling (3BDO), prior to the determination of the uptake of the glucose analogue, 2-deoxyglucose (2-DG), in response to 1 mM insulin. In separate experiments, L6 myotubes were subject to various media concentrations of leucine (0-0.8 mM) for 24 h before 2-DG uptake in response to insulin was assessed. Both rapamycin and BCH blunted 2-DG uptake, irrespective of insulin administration, and this occurred in parallel with a decline in mTOR, 4E-BP1, and p70S6K phosphorylation status, but little effect on AKT phosphorylation. In contrast, reducing leucine media concentrations suppressed 2-DG uptake, both under insulin- and non-insulin-stimulated conditions, but did not alter the phosphorylation state of AKT-mTORc1 components examined. Unexpectedly, 3BDO failed to stimulate mTORc1 signalling, but, nonetheless, caused a significant increase in 2-DG uptake under non-insulin-stimulated conditions. Both leucine and mTORc1 influence glucose uptake in muscle cells independent of insulin administration, and this likely occurs via distinct but overlapping mechanisms.

Alterations of Interhemispheric Functional Connectivity and Degree Centrality in Cervical Dystonia: A Resting-State fMRI Study.

Background: Cervical dystonia (CD) is a neurological movement disorder characterized by involuntary head and neck movements and postures. Reports on microstructural and functional abnormalities in multiple brain regions not limited to the basal ganglia have been increasing in patients with CD. However, the neural bases of CD are unclear. This study is aimed at identifying cerebral functional abnormalities in CD by using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Using rs-fMRI data, voxel-mirrored homotopic connectivity (VMHC) and degree centrality were used to compare the alterations of the rs-functional connectivity (FC) between 19 patients with CD and 21 healthy controls. Regions showing abnormal FCs from two measurements were the regions of interest for correlation analyses. Results: Compared with healthy controls, patients with CD exhibited significantly decreased VMHC in the supplementary motor area (SMA), precuneus (PCu)/postcentral gyrus, and superior medial prefrontal cortex (MPFC). Significantly increased degree centrality in the right PCu and decreased degree centrality in the right lentiform nucleus and left ventral MPFC were observed in the patient group compared with the control group. Further correlation analyses showed that the VMHC values in the SMA were negatively correlated with dystonia severity. Conclusion: Local abnormalities and interhemispheric interaction deficits in the sensorimotor network (SMA, postcentral gyrus, and PCu), default mode network (MPFC and PCu), and basal ganglia may be the key characteristics in the pathogenesis mechanism of CD.

[Epidemiological characteristics of mumps in mainland China from 2004 to 2018 and key population for prevention and control].

OBJECTIVE: To investigate the epidemiological characteristics of mumps in mainland China from 2004 to 2018, and to provide data for the key population for prevention and control of mumps. METHODS: The epidemiological characteristics of mumps were analyzed with reference to the data of the cases of mumps reported in the National Scientific Data Sharing Platform for Population and Health and Disease Prevention and Control Bureau of National Health Commission of the People's Republic of China. Descriptive epidemiology was used to analyze the epidemiological characteristics of mumps. RESULTS: A total of 4 272 368 cases of mumps were reported in China during 2004-2018, with an average annual reported incidence rate of 21.44/100 000. A single dose of mumps-containing vaccine was added to the national Expanded Program of Immunization in 2008, but the annual incidence rate ranged from 12.84/100 000 to 35.59/100 000. The second dose of measles, mumps and rubella combined attenuated live vaccine was included in the routine immunization in Beijing, Tianjin and Shanghai, and then the average incidence rate of mumps reported in these three regions dropped to about 10/100 000. From 2004 to 2016, the population aged 3-14 years accounted for 81.16% of all patients with mumps. The children aged 6 years had the highest incidence rate of mumps during 2004-2013. CONCLUSIONS: A single dose of mumps-containing vaccine has no obvious effect on the incidence rate of mumps. Children aged 6 years have the highest incidence rate of mumps. A booster dose of mumps-containing vaccine should be given to preschool children.

Plasma Long Non-Coding RNA (lncRNA) GAS5 is a New Biomarker for Coronary Artery Disease.

Our study aimed to investigate the diagnostic value of long non-coding RNA (lncRNA) GAS5 for coronary artery disease (CAD) and to explore the mechanism of the role of GAS5 in CAD. A total of 30 patients with CAD were selected from January 2015 to January 2017 in The First Hospital of Tianmen. In addition, 30 healthy individuals were selected as a control group, and patients with various other types of cardiovascular diseases were also selected. Expression of GAS5 in plasma of all participants was detected by quantitative real-time PCR. Receiver operating characteristic (ROC) curve analysis was performed to investigate the diagnostic value of GAS5 for CAD. Levels of mammalian target of rapamycin (mTOR) and phospho-mTOR (p-mTOR) in human primary coronary artery endothelial cells (HCAECs) were detected by western blotting. Compared with normal healthy people, expression level of lncRNA Novlnc6 was significantly reduced in patients with CAD and diabetes mellitus, but not in patients with other types of cardiovascular diseases, such as hypertension, abnormal aortic aneurysm, viral myocarditis. In addition, the expression level of GAS5 was significantly lower in patients with CAD compared to patients with diabetes mellitus. ROC curve analysis showed that GAS5 may serve as a promising biomarker for CAD. GAS5 knockdown and overexpression showed no significant effect on the level of mTOR) in HCAECs. However, GAS5 knockdown significantly increased the level of phospho-mTOR (p-mTOR), and GAS5 overexpression significantly decreased the level of p-mTOR. Treatment with mTOR inhibitor and activator showed no significant effect on expression of GAS5 in HCAECs. GAS5 plays a role as upstream regulator of the mTOR pathway to participate in the development of CAD. GAS5 was specifically downregulated in patients with CAD, and it may serve as a promising biomarker for CAD.

Anti-rheumatoid arthritis effects of traditional Chinese medicine Fufang Xiaohuoluo pill on collagen-induced arthritis rats and MH7A cells.

Background: Fufang Xiaohuoluo pill (FFXHL) is a commonly used prescription in clinical practice for treating rheumatoid arthritis in China, yet its specific mechanism remains unclear. This study aims to elucidate the pharmacological mechanisms of FFXHL using both in vivo and in vitro experiments. Methods: The collagen-induced arthritis (CIA) rat model was established to evaluate FFXHL's therapeutic impact. Parameters that include paw swelling, arthritis scores, and inflammatory markers were examined to assess the anti-inflammatory and analgesic effects of FFXHL. Human fibroblast-like synoviocytes (MH7A cells) is activated by tumour necrosis factor-alpha (TNF-α) were used to explore the anti-inflammatory mechanism on FFXHL. Results: Our findings indicate that FFXHL effectively reduced paw swelling, joint pain, arthritis scores, and synovial pannus hyperplasia. It also lowered serum levels of TNF-α, interleukin-1ß (IL1ß), and interleukin-6 (IL-6). Immunohistochemical analysis revealed decreased expression of nuclear factor-kappa B (NF-κB) p65 in FFXHL-treated CIA rat joints. In vitro experiments demonstrated FFXHL's ability to decrease protein secretion of IL-1ß and IL-6, suppress mRNA expression of matrix metalloproteinases (MMP) -3, -9, and -13, reduce reactive oxygen species (ROS) levels, and inhibit NF-κB p65 translocation in TNF-α stimulated MH7A cells. FFXHL also suppressed protein levels of extracellular signal-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), p38 MAP kinase (p38), protein kinase B (Akt), p65, inhibitor of kappa B kinase α/ß (IKKα/ß), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) induced by TNF-α in MH7A cells. Conclusion: The findings imply that FFXHL exhibits significant anti-inflammatory and antiarthritic effects in both CIA rat models and TNF-α-induced MH7A cells. The potential mechanism involves the inactivation of TLR4/MyD88, mitogen-activated protein kinases (MAPKs), NF-κB, and Akt pathways by FFXHL.

Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

[The clinical characteristics of 10 cases of adrenocorticotropic hormone- independent macronodular adrenal hyperplasia].

OBJECTIVE: To evaluate the clinical characteristics of patients with adrenocorticotropin-independent macronodular adrenal hyperplasia (AIMAH). METHODS: A total of 10 AIMAH cases were enrolled in this retrospective study. The clinical and laboratory findings of all patients were collected and analyzed. RESULTS: All patients manifested some clinical features and biochemical evidence of Cushing's syndrome. The plasma adrenocorticotropic hormone (ACTH) level was undetectable in all the patients and their serum cortisol secretion rhythm was abnormal. Low and high-dose dexamethasone suppression tests failed to suppress the cortisol secretion. The bilateral macronodular adrenal enlargement was shown by CT/magnetic resonance imaging. The supine-upright posture test was positive in four patients. Three patients were performed bilateral adrenalectomy, five were unilateral adrenalectomy and the remaining two patients were taken propranolol. All the patients had followed up for 10 to 89 months. Contralateral adrenalectomy was performed in two patients with recurrent symptoms after unilateral adrenalectomy and two patients given propranolol were underwent bilateral adrenalectomy when their symptoms had not been improved or recurred. CONCLUSION: AIMAH is a relatively rare subtype of Cushing's syndrome with unique clinical and laboratory findings. Propranolol is a good choice if the supine-upright posture test is positive. Unilateral adrenalectomy appears to be an effective and safe alternative treatment for AIMAH. Bilateral adrenalectomy could be performed if the symptoms have not been improved or recurred after unilateral adrenalectomy.

Probiotic Escherichia coli Nissle 1917 propelled micro-robot with pH sensitivity for hypoxia targeted intestinal tumor therapy.

Poor drug penetration in hypoxia area of solid tumor is a big challenge for intestinal tumor therapy and thus it is crucial to develop an effective strategy to overcome this challenge. Compared with other bacteria used for construction of hypoxia targeted bacteria micro-robot, the Escherichia coli Nissle 1917 (EcN) bacteria are nonpathogenic Gram-negative probiotic and can especially target and identify the signal molecules in the hypoxic region of tumor, and thus, in this study, we choose EcN to construct a bacteria propelled micro-robot for targeting intestinal tumor therapy. Firstly, the MSNs@DOX with average diameter of 200 nm were synthesized and conjugated with EcN bacteria using EDC/NHS chemical crosslinking method to construct a EcN propelled micro-robot. The motility of micro-robot was then evaluated and the motion velocity of EcN-pMSNs@DOX was 3.78 µm/s. Compared with pMSNs@DOX without EcN driven, EcN bacteria propelled micro-robot transported much more pMSNs@DOX into the inner of HCT-116 3D multicellular tumor spheroids. However, the EcN bacteria are non-intracelluar bacteria which lead to the micro-robot can not directly enter into tumor cells. Therefore, we utilized acid-labile linkers of cis-aconitic amido bone to link EcN with MSNs@DOX nanoparticles to achieve the pH sensitive separation of EcN with MSNs@DOX from the micro-robot. At 4 h of incubation, the isolated MSNs@DOX began to enter into the tumor cells through CLSM observation. In vitro live/dead staining results show that EcN-pMSNs@DOX induced much more cell death than pMSNs@DOX at 24 and 48 h of incubation with HCT-116 tumor cells in acid culture media (pH 5.3). For the validation of the therapeutic efficacy of the micro-robot for intestinal tumor, we established the HCT-116 subcutaneous transplantation tumor model. After 28 days of treatment, EcN-pMSNs@DOX dramatically inhibit tumor growth with tumor volume was around 689 mm3, induce much more tumor tissues necrosis and apoptosis. Finally, the toxicity of this micro-robot was investigated by pathological analysis the liver and heart tissues. We expect that the pH sensitive EcN propelled micro-robot here we constructed may be a safe and feasible strategy for intestinal tumor therapy.

Improving natural products identification through molecular features-oriented precursor ion selection and targeted MS/MS analysis: a case study of Zhi-Ke-Yang-Yin capsule.

Chemical substance identification is an indispensable step in research on therapeutic materials based on traditional Chinese medicine and its formulas. The successful characterization of chemical substances mainly relies on high-quality MS/MS spectra. However, to date, relatively few studies have specifically addressed the issues of improving the acquisition of MS/MS spectra of compounds for characterization. The current auto-MS/MS mode, where the precursor ions are selected depending on their signal intensity, encounters a drawback when the sample contains many overlapping signals, leading to compounds with a lower or much lower abundance missing identification. To solve this problem, a strategy in which molecular features oriented precursor ion selection was followed by targeted MS/MS analysis for structure elucidation was proposed. The precursor ions were selected according to their first and second molecular features, namely m/z and retention time, irrespective of their intensities. By performing targeted MS/MS analysis, the MS/MS spectra of many more compounds of interest can be obtained, leading to an improvement in natural product identification. As an example, the chemical substances in the Zhi-Ke-Yang-Yin extract were analyzed using this strategy, and as a result, 431 ingredients were tentatively characterized, including both known and unknown or new compounds.

Hippocampal Glycerol-3-Phosphate Acyltransferases 4 and BDNF in the Progress of Obesity-Induced Depression.

Background: Obesity has been reported to lead to increased incidence of depression. Glycerol-3-phosphate acyltransferases 4 (GPAT4) is involved in triacylglycerol synthesis and plays an important role in the occurrence of obesity. GPAT4 is the only one of GPAT family expressed in the brain. The aim of this study is to investigate if central GPAT4 is associated with obesity-related depression and its underlying mechanism. Results: A high-fat diet resulted in increased body weight and blood lipid. HFD induced depression like behavior in the force swimming test, tail suspension test and sucrose preference test. HFD significantly up-regulated the expression of GPAT4 in hippocampus, IL-1ß, IL-6, TNF-α and NF-κB, accompanied with down-regulation of BDNF expression in hippocampus and ventromedical hypothalamus, which was attributed to AMP-activated protein kinase (AMPK) and cAMP-response element binding protein (CREB). Conclusion: Our findings suggest that hippocampal GPAT4 may participate in HFD induced depression through AMPK/CREB/BDNF pathway, which provides insights into a clinical target for obesity-associated depression intervention.

Abnormal Network Homogeneity in the Right Superior Medial Frontal Gyrus in Cervical Dystonia.

Background: Increasing evidence from modern neuroimaging has confirmed that cervical dystonia (CD) is caused by network abnormalities. Specific brain networks are known to be crucial in patients suffering from CD. However, changes in network homogeneity (NH) in CD patients have not been characterized. Therefore, the purpose of this study was to investigate the NH of patients with CD. Methods: An automated NH method was used to analyze resting-state functional magnetic resonance (fMRI) data from 19 patients with CD and 21 gender- and age-matched healthy controls (HC). Correlation analysis were conducted between NH, illness duration and symptom severity measured by the Tsui scale. Results: Compared with the HC group, CD patients showed a lower NH in the right superior medial frontal gyrus. No significant correlations were found between abnormal NH values and illness duration or symptom severity. Conclusion: Our findings suggest the existence of abnormal NH in the default mode network (DMN) of CD patients, and thereby highlight the importance of the DMN in the pathophysiology of CD.

[The effects of glucose fluctuation on resistin].

OBJECTIVE: To explore the effect of glucose fluctuation on resistin. METHODS: The phorbol-12-myristate-13-acetate(PMA)-activated and differentiated U937 cells were exposed to experimental condition for 3 days, three groups of cells were formed, each one receiving the following fresh medium every 6 hours, respectively: (1) continuous 11.1 mmol/L glucose concentration medium (Con group), (2) continuous 22.2 mmol/L glucose concentration medium (CHG group), (3) alternating 11.1 mmol/L glucose concentration and 22.2 mmol/L glucose concentration medium every 6 hours (IHG group). The supernatants of cell median at the last 6 hours were collected to test resistin concentration. Besides, 92 subjects were selected and classified into three groups according to the results of oral glucose tolerance test: normal glucose tolerance group (NGT group, n=30), impaired glucose tolerance patients (IGT group, n=31) and newly diagnosed type 2 diabetes patients (T2DM group, n=31). Blood glucose and serum resistin levels were measured at 0 h and 1 h during oral glucose tolerance test (OGTT) to compare the glucose fluctuation (ΔGlu1-0) and the change of serum resistin level (ΔlnRes1-0) among the three groups. RESULTS: Resistin concentration in the Con, CHG and IHG group was (73.62±5.07) ng/L, (97.78±7.00) ng/L and (212.49±28.81) ng/L respectively and in IHG group it was higher as compared with the other two groups (P<0.05). ΔGlu1-0 in NGT, IGT and T2DM group was (2.31±2.30) mmol/L, (5.70±2.08) mmol/L and (8.41±2.63) mmol/L respectively; ΔGlu1-0 increased gradually in all the three groups (P<0.05). Serum resistin level from 0 h to 1 h in the NGT group was 6.41 (1.52-15.76) µg/L to 6.96 (1.52-22.70) µg/L, in the IGT group 5.47 (1.49-24.09) µg/L to 9.12 (1.27-21.94) µg/L and in the T2DM group 5.77 (1.11-30.10) µg/L to 9.27(1.02-48.15) µg/L. In the IGT and T2DM group serum resistin level increased from 0 h to 1 h (P<0.05), but no difference was observed in the NGT group (P>0.05). ΔlnRes1-0 in these 3 groups was (0.05±0.05) µg/L, (0.25±0.04) µg/L and (0.37±0.03) µg/L respectively and the change in the T2DM group was significant as compared with that in the NGT group, ΔlnRes1-0 was positively correlated with ΔGlu1-0 (r=0.23, P=0.02). CONCLUSION: Glucose fluctuation induced monocyte/macrophage to secrete resistin, greater the glucose fluctuation, greater the change of amplitude of serum resistin.

Comparison of two regimens for patients with thyroid-associated ophthalmopathy receiving intravenous methyl prednisolone: A single center prospective randomized trial.

Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.