Osteoimmunology research in rheumatoid arthritis: From single-cell omics approach / 中华医学杂志(英文版)

Cellular immune responses as well as generalized and periarticular bone loss are the key pathogenic features of rheumatoid arthritis (RA). Under the pathological conditions of RA, dysregulated inflammation and immune processes tightly interact with skeletal system, resulting in pathological bone damage via inhibition of bone formation or induction of bone resorption. Single-cell omics technologies are revolutionary tools in the field of modern biological research.They enable the display of the state and function of cells in various environments from a single-cell resolution, thus making it conducive to identify the dysregulated molecular mechanisms of bone destruction in RA as well as the discovery of potential therapeutic targets and biomarkers. Here, we summarize the latest findings of single-cell omics technologies in osteoimmunology research in RA. These results suggest that single-cell omics have made significant contributions to transcriptomics and dynamics of specific cells involved in bone remodeling, providing a new direction for our understanding of cellular heterogeneity in the study of osteoimmunology in RA.

Serum and cerebrospinal levels of fluid progranulin in children with purulent meningitis and their relationship with prognosis / 中国医师进修杂志

Objective:To explore the relationship between serum and cerebrospinal fluid levels of progranulin (PGRN) and prognosis in children with purulent meningitis (PM).Methods:Sixty children with PM (PM group) and 60 children without central nervous system infection (suspected central nervous system infection, or having indications for lumbar puncture; control group) in Zhuji People′s Hospital of Zhejiang Province from January 2014 to December 2018 were selected. The serum and cerebrospinal fluid PGRN, C-reactive protein (CRP) and procalcitonin (PCT) levels were detected. The correlation was analyzed by Pearson method; the receiver operating characteristic (ROC) curve was drawn, and the prognostic value of serum and cerebrospinal fluid PGRN were evaluated.Results:The serum and cerebrospinal fluid PGRN, CRP and PCT in PM group were significantly higher than those in control group, serum: (42.61 ± 4.79) ng/L vs. (26.13 ± 4.26) ng/L, (58.46 ± 3.74) mg/L vs. (1.34 ± 0.37) mg/L, (7.48 ± 0.24) μg/L vs. (0.31 ± 0.06) μg/L; cerebrospinal fluid: (3.52 ± 0.43) ng/L vs. (1.47 ± 0.36) ng/L, (23.06 ± 0.67) mg/L vs. (2.17 ± 0.45) mg/L, (4.13 ± 0.25) μg/L vs. (0.18 ± 0.07) μg/L, and there were statistical differences ( P<0.01). The correlation analysis result showed that serum and cerebrospinal fluid PGRN were positively correlated with CRP and PCT in children with PM (serum: r = 0.517 and 0.546, P<0.01; cerebrospinal fluid: r = 0.541 and 0.528, P<0.01). Among the 60 children with PM, 44 had good prognosis and 16 had poor prognosis. The serum and cerebrospinal fluid PGRN, CRP and PCT in children with poor prognosis were significantly higher than those in children with good prognosis, serum: (48.78 ± 4.65) ng/L vs. (34.15 ± 5.12) ng/L, (67.15 ± 3.84) mg/L vs. (47.02 ± 4.23) mg/L, (8.46 ± 0.35) μg/L vs. (6.23 ± 0.31) μg/L; cerebrospinal fluid: (3.93 ± 0.49) ng/L vs. (3.12 ± 0.37) ng/L, (27.62 ± 0.74) mg/L vs. (18.53 ± 0.81) mg/L, (4.97 ± 0.28) μg/L vs. (3.24 ± 0.31) μg/L, and there were statistical differences ( P<0.01). ROC curve analysis result showed that the area under curve of serum and cerebrospinal fluid PGRN for assessing the prognosis of children with PM was 0.821 (95% CI 0.818 to 0.824) and 0.913 (95% CI 0.910 to 0.916), with a sensitivity of 81.23% and 89.46%, and a specificity of 72.34% and 79.58%, cut-off value of PGRN was 41.53 and 3.54 ng/L. Conclusions:Serum and cerebrospinal fluid PGRN levels in children with PM are significantly increased, which are closely related to the prognosis of children with PM, and are potential indicators for evaluating the prognosis of PM.

Research on inhibitory effect of celecoxib against migration of vascular endothelial cells / 医学研究生学报

Objective The mechanism of celecoxib in influencing the migration of vascular endothelial cells is still not clear.The aim of this study was to investigate the effect of celecoxib against migration of vascular endothelial cells and its mechanism.Methods Human umbilical vein endothelial cells (HUVECs) were obtained from the cell bank of Central Laboratory of Nanjing General Hospital of Nanjing Military Command.Transwell was used to measure the migration rate of HUVECs after the administration of 0μmol/L, 10μmol/L and 20μmol/L celecoxib.Immunofluorescence, western blot, and qRT-PCR were used to detect protein and mRNA expression of COX-2 and PTPRJ in HUVECs.Results The expression of COX-2, PTPRJ in HUVECs were detected by immunofluorescence.After the administration of 20μmol/L, 10μmol/L and 0μmol/L celecoxib, HUVEC migration rate was (12.35±3.61), (32.80±5.92) and (63.15±5.83) respectively, representing significant difference (P<0.01).COX-2 protein expression in 20μmol/L group (0.16±0.03) and 10μmol/L group (0.36±0.05) decreased significantly compared with that of 0μmol/L group (0.77±0.07) (P<0.01).Moreover, COX-2 protein expression in 20μmol/L group significantly decreased compared with that of 10μmol/L group(P<0.05).PTPRJ protein expression in 20μmol/L group (0.82±0.05) and 10μmol/L group (0.51±0.02) was respectively higher than that of 0μmol/L group (0.27±0.04) (P<0.01).Moreover, PTPRJ protein expression in 20μmol/L group significantly increased compared with that of 10μmol/L group (P<0.05).COX-2 mRNA expression in 20μmol/L group (0.06±0.02) and 10μmol/L group (0.22±0.05) decreased significantly compared with that of 0μmol/L group (1.05±0.13) (P<0.01).PTPRJ mRNA expression in 20μmol/L group (60.27±11.31) and 10μmol/L group (16.50±3.18) increased significantly compared with that of 0μmol/L group (0.99±0.25) (P<0.01).Conclusion Celecoxib inhibits the migration of vascular endothelial cells, which may be related to the inhibition of COX-2 expression and the up-regulation of PTPRJ expression in vascular endothelial cells.

Effect of alprostadil on early proinflammatory cytokines and its therapeutic effect in patients with severe acute pancreatitis / 解放军医学杂志

Objective To investigate the effects of alprostadil on expression of proinflammatory cytokines in patients with severe acute pancreatitis (SAP) and evaluate the clinical efficacy.Methods Seventy-three SAP patients were collected from January 2014 to May 2016,and then were randomly divided into control group (n=37) and experimental group (n=36).On the basis of routine treatment,the experimental group patient was given alprostadil at a dose of 15μg/d.The expression of C-reactive protein (CRP),white blood cell (WBC) count,amylase,alanine aminotransferase (ALT),aspartate aminotransferase (AST),creatinine,serum proinflammatory cytokine tumor necrosis factor alpha (TNF-α),interleukin-1 beta (IL-1[β),interleukin-6 (IL-6) were detected in serum on the 1st,3rd and 7th day.Results The biochemical indexes and expression ofproinflammatory cytokines were significantly increased in the two groups on the 1st day,and decreased gradually,with a significant difference between the time points (P＜0.05),but the between-group difference was not significant (P＞0.05).These indexes were decreased significantly with the passage of time and there were significant differences between the two groups at the 3rd and 7th day (P＜0.05).Conclusion Alprostadil can effectively reduce the severity of early inflammatory reaction in SAP patients,and has important significance for improving the prognosis.

Correlation between Simplified Endoscopic Score for Crohn's Disease (SES-CD) and Clinical and Laboratory Markers in Patients with Crohn's Disease / 胃肠病学

Endoscopic activity has been used as an endpoint in treatment of Crohn's disease (CD).Simplified Endoscopic Score for Crohn's Disease (SES-CD) is a simple and easy-to-use endoscopic scoring system for CD, however, studies evaluating the correlation between SES-CD and noninvasive inflammatory markers are scarce.Aims: To investigate the correlation between SES-CD and clinical and laboratory inflammatory markers for identifying a noninvasive surrogate marker for endoscopic activity of CD.Methods: Forty-two patients with CD were enrolled for detecting laboratory inflammatory markers including leukocyte and platelet count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), hemoglobin (Hb), albumin (Alb) and fecal calprotectin (FC);SES-CD and Crohn' disease activity index (CDAI) were assessed.Predictive performance of these markers for endoscopic activity of CD was analyzed by ROC curve, and the correlation of SES-CD with all these markers was evaluated.Results: The platelet count, CRP, ESR, FC and SES-CD were significantly higher in active CD than in inactive CD, while Hb and Alb were significantly lower in active CD (P all <0.05).In all the noninvasive markers, only CDAI and FC had an area under the curve (AUC) greater than 0.9 for predicting CD endoscopic activity.Taken 150 as the cut-off value of CDAI and 50 μg/g (the upper limit of normal, ULN) as the cut-off value of FC, the sensitivity of CDAI and FC were 58.8% and 100%, and the specificity were 100% and 60.0%, respectively.SES-CD had moderate correlation with CDAI, platelet count, CRP, ESR, Alb and FC, respectively (P all <0.05).Conclusions: SES-CD is correlated moderately with the clinical and laboratory inflammatory markers, however, when taken the ULN as cut-off value the conventional inflammatory markers such as CDAI, CRP and ESR are hard to predict sensitively and accurately the endoscopic activity of CD;while FC has fairly high accuracy and sensitivity and can be used as a noninvasive surrogate marker for evaluating endoscopic activity of CD.

Relationship between Peripheral Blood CD3 +,CD4 + and CD8 + T Cells and Inflammation Markers in Patients with Crohn’s Disease / 胃肠病学

Background:Abnormal immune response is involved in the pathogenesis of Crohn’s disease( CD),and T lymphocytes are the main players in the immune response. Aims:To investigate the relationship between peripheral blood CD3 + ,CD4 + and CD8 + T cells and inflammation-related markers in patients with CD. Methods:Proportions of peripheral blood CD3 + ,CD4 + and CD8 + T cells were measured by flow cytometry in 26 CD patients( including 14 patients in active stage and 12 in remission stage )and 8 healthy volunteers(control group),and their correlation with inflammation-related markers(including white blood cell count,platelet count,ESR,CRP,albumin and hemoglobin) were analyzed. Results:Proportions of CD3 + ,CD4 + and CD8 + T cells were significantly increased in patients with active CD than those with remission CD and controls( P ﹤ 0. 05),however,no significant differences were found between remission CD patients and controls(P ﹥ 0. 05). ESR and CRP in active CD patients were significantly higher than those in controls(P ﹤ 0. 05),while albumin and hemoglobin levels were significantly decreased(P ﹤ 0. 05);albumin in remission CD patients was significantly lower than that in controls(P ﹤ 0. 05). No significant differences in white blood cell count and platelet count were found between active,remission CD patients and controls(P ﹥ 0. 05). Proportions of CD3 + , CD4 + and CD8 + T cells were positively correlated with CRP,and negatively correlated with hemoglobin( P ﹤ 0. 05);CD3 + and CD4 + T cells were positively correlated with ESR(P ﹤ 0. 05). However,CD3 + ,CD4 + and CD8 + T cells were not correlated with white blood cell count,platelet count and albumin level( P ﹥ 0. 05). Conclusions:Proportions of peripheral blood CD3 + ,CD4 + and CD8 + T cells are increased with the increase of disease activity in CD,and are positively correlated with CRP,and negatively correlated with hemoglobin.

Changes in the Expression and Distribution of Claudins, Increased Epithelial Apoptosis, and a Mannan-Binding Lectin-Associated Immune Response Lead to Barrier Dysfunction in Dextran Sodium Sulfate-Induced Rat Colitis

BACKGROUND/AIMS: This animal study aimed to define the underlying cellular mechanisms of intestinal barrier dysfunction. METHODS: Rats were fed 4% with dextran sodium sulfate (DSS) to induce experimental colitis. We analyzed the sugars in 24-hour urine output by high pressure liquid chromatography. The expression of claudins, mannan-binding lectin (MBL), and MBL-associated serine proteases 2 (MASP-2) were detected in the colonic mucosa by immunohistochemistry; and apoptotic cells in the colonic epithelium were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method assay. RESULTS: The lactulose and sucralose excretion levels in the urine of rats with DSS-induced colitis were significantly higher than those in the control rats. Mannitol excretion was lower and lactulose/mannitol ratios and sucralose/mannitol ratios were significantly increased compared with those in the control group (p<0.05). Compared with the controls, the expression of sealing claudins (claudin 3, claudin 5, and claudin 8) was significantly decreased, but that of claudin 1 was increased. The expression of pore-forming claudin 2 was upregulated and claudin 7 was downregulated in DSS-induced colitis. The epithelial apoptotic ratio was 2.8%+/-1.2% in controls and was significantly increased to 7.2%+/-1.2% in DSS-induced colitis. The expression of MBL and MASP-2 in the intestinal mucosa showed intense staining in controls, whereas there was weak staining in the rats with colitis. CONCLUSIONS: There was increased intestinal permeability in DSS-induced colitis. Changes in the expression and distribution of claudins, increased epithelial apoptosis, and the MASP-2-induced immune response impaired the intestinal epithelium and contributed to high intestinal permeability.

Study on preparation and property of a new adsorbent for endotoxin removal in blood purification / 生物医学工程学杂志

In order to remove the endotoxin from the blood of endotoxemia patients, we prepared a new adsorbent with heparin space arm and polymyxin B (PMB) ligand. The carrier of chloromethyl polystyrene resin was activated and heparin space arm was grafted, and then PMB ligand was immobilized onto adsorbent with glutaraldehyde. We employed in vitro FITC-lipopolysaccharide (FITC-LPS) static adsorption to characterize the adsorption properties on the adsorbent, and conducted in vitro lipopolysaccharide (LPS) static adsorption to measure quantitavely the adsorption capacity and rate, and then evaluated the blood compatibility. The in vitro static adsorption indicated that the adsorbent had the removal rate of LPS above 70% with the adsorption equilibrium time for 2 hours. Blood compatibility experiment showed that the adsorbent had little negative effects on blood cells and plasma protein, and their adsorption rates were less than 10% for hemocytes and 20% for plasma protein respectively. This adsorbent exhibited high selectivity, high adsorption capacity and good biocompatibility, and presented a promising clinical application in the treatment of endotoxemia.

Effect of Comprehensive Rehabilitation on Facial Paralysis / 中国康复理论与实践

@#ObjectiveTo assess the effect of comprehensive rehabilitation on facial paralysis.Methods80 patients with facial paralysis were divided into observation group receiving comprehensive rehabilitation(medicine, physical therapy, functional exercise and psychological treatment), and control group with medicine and physical therapy.ResultsThere was a significant difference in the scores for Portmann's Simple Scale between before and after treatment in two groups (P<0.01). There was a significant difference in the clinical effect between observation group and control group (P<0.05).ConclusionComprehensive rehabilitation has a better effect on facial paralysis.

Endoscopic measurement by virtual internal standard:Feasibility and accuracy / 医学研究生学报

Objective: Endoscopic measurement mainly depends on visual estimation or open biopsy forceps,which have been proved lacking in accuracy due to the image barrel distortion caused by wide-angle lens in endoscope.This study aimed to validate a new concept of "virtual internal standard" proposed by ourselves and develop a new method for endoscopic measurement based on the concept.Methods: We photographed planar grid graphs printed with standard calibrations with an electronic endoscope at different object distances,obtained the information on the virtual internal standard from each photo at the corresponding object distance,and analyzed the digital characteristics of the barrel distortion photos,including the size of the visual field,the image compression ratio,and the credible area for measurement with the virtual internal standard.Based on the analyses,the method of endoscopic measurement by the virtual internal standard was established and experiments both in vivo and in vitro were conducted.Results: The ratio of the object distance to the visual field was 1 ∶ 2 when the former was between 10 mm and 40 mm.Calculation of the compression ratio showed that the credible area of measurement in the central area was 10 mm at the object distance of 10-15 mm,20 mm at 20-30 mm,and 30 mm at 30-50 mm.The credible area of measurement on various planes accounted for 2/5 to 3/5 of the total image width.There was a tendency of double-curve change in the arrangement of pixel values of the central grids on different planes.The differences between the pixel values per centimeter became slight at the object distance of 35-50 mm.Conclusion: Endoscopic measurement by the virtual internal standard is a objective,accurate,simple and practical method.

Renal injury in severe acute pancreatitis and its pathogenesis / 医学研究生学报

Acute pancreatitis,a multiple system disease was associated with distant organs injury such as the liver,lung and kidney,etc.Acute renal failure is one of the major death causes in severe acute pancreatitis.Renal injury in acute pancreatitis and its pathogenesis was reviewed to further understand the mechanisms of systemic inflammatory response and multiple organ failure

A study on the safety of tilt table test in elderly patients / 中华老年医学杂志

Objective To study the safety of tilt table test (TTT) in elderly patients. Methods Among the 785 subjects examined for TTT, 110 were elders with an average age of( 65?4) years, ranging from 60 to 82. Out of the 110 elder subjects, 39 syncope patients were due to unknown reasons, 13 due to heart or brain diseases and 58 were non syncope subjects. We conducted base tilt table test (BTTT) in all patients and additional isoproterenol tilt table test (ITTT) in 18 patients. The BTTT protocol included 60～80 degrees upright tilt for 25 minutes and the ITTT protocol included isoproterenol infusion at 2-4 ?g/min for 10 minutes. Results 13 out of 39 patients with unknown reasons had a positive BTTT and 6 out of 10 patients had a positive ITTT, respectively; Among the 31 out of 110 positive TTT patients, 17 (54.8%) showed a vasodepressor response, 4 (12.9%) a cardioinhibitory response and 10 (32.3%) mixed response. Serious abnormal responses were not observed. Conclusions (1) TTT is a safe and effective method for diagnosing the vasovagal syncope (VVS) in elderly patients; (2) Because of its safety, BTTT could be chosen for identifying the VVS in the elderly heart or brain disease patients complicated with syncope.

Off-pump coronary artery bypass in the diabet ic patient-Perioperative clinical analysis / 中国糖尿病杂志

ObjectiveDiabetes is an independent risk factor for coronary artery bypasss grafting(CABG). Off pump coronary artery bypasss (OPCAB) experience in 251 cases was reviewed to determine whether diabetes wou ld be applicable in OPCAB procedures.MethodsConsecutive 251 patients underwent OPCAB over 12 month period. This study included 71 diebetic patients (DM group) and 180 nondiabetic patients (NDM group). Preoperative v ariables were compared between the two groups by univariate analysis.R esultsNo differences were found regarding the length of stay in cardio intensive care unit [DM group(2.4?0.3)d; NDM group (2.4?0.3) d;P=0. 386], and sternal complication (DM group: 5.7%;NDM group: 3.9%;P=0.511) . In hospital complications were as follows: death rate(DM group: 2.8%; NDM gr oup: 1.1%; P=0.680); stroke (DM group: 2 8%; NDM group: 1 7%; P=0 623 ); hemofiltratioin renal failure (DM group: 2.8%; NDM group: 0.5%; P=0.194); myocardial infarction(DM group: 0%; NDM group: 0.5%;P=1.000); blood using were more frequent in DM group comparied with NDM group (P=0.111). ConclusionOPCAB in diabetic patients is as safe as in non diabetic patients.