OBJECTIVE: To explore the protective effect of glycosaminoglycans (GAG) on vascular endothelium in patients with sepsis. METHODS: A prospective study was conducted on adult patients with sepsis admitted to the intensive care unit (ICU) of Hangzhou Normal University Affiliated Hospital from December 2022 to December 2023. Patients were randomly divided into conventional treatment group and GAG intervention group. Both groups were treated according to the 2021 Surviving Sepsis Campaign Guidelines. The GAG intervention group was additionally treated with GAG (2 mL of sulodexide intramuscular injection once daily for 7 days) on the basis of conventional treatment. Venous blood was collected from patients at 0, 6, 24, 48, 72 hours and 7 days after enrollment to detect serum vascular endothelial glycocalyx [heparan sulfate (HS) and syndecan-1 (SDC-1)], inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)], and coagulation markers [prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin-III (AT-III), fibrinogen (Fib), D-Dimer], and to perform acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and International Society on Thrombosis and Haemostasis (ISTH) scores. The prognosis of patients (length of hospital stay, ICU and 28-day mortality) was observed. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the value of HS in predicting the prognosis of sepsis patients, and the correlation between endothelial glycocalyx degradation products and various clinical indicators was analyzed. RESULTS: A total of 50 adult patients with sepsis meeting the inclusion criteria were enrolled, with 25 in the conventional treatment group and 25 in the GAG intervention group. In terms of degradation products of endothelial glycocalyx, compared to baseline, both groups showed an increasing trend in HS and SDC-1 levels post-treatment. However, the GAG intervention group exhibited significantly lower HS levels at 72 hours and 7 days, as well as lower SDC-1 levels at 6, 24, 48, 72 hours and 7 days compared to the conventional group. Among the surviving patients, the HS levels at 72 hours and SDC-1 levels at 6 hours of treatment in the GAG intervention group were significantly reduced compared to the conventional treatment group. In terms of severity score, compared with before treatment, the GAG intervention group showed a significant decrease in APACHE II, SOFA, and ISTH scores after 7 days of treatment. The SOFA scores of the GAG intervention group after 48 hours and 7 days of treatment were significantly lower than those of the conventional treatment group. In terms of inflammatory indicators, compared with before treatment, the GAG intervention group showed a significant decrease in IL-6 levels after 48 hours of treatment. With the prolongation of treatment time, the CRP levels of both groups of patients showed a significant downward trend, and at 7 days of treatment, the CRP level in the GAG intervention group was significantly lower than that in the conventional treatment group. In terms of coagulation function, with prolonged treatment time, PT and APTT of both groups of patients showed an increasing trend, while Fib showed a decreasing trend. The GAG intervention group showed a significant prolongation of PT after 72 hours of treatment compared to the conventional treatment group. In terms of prognosis, there were no statistically significant differences in ICU and 28-day mortality rates between the two groups. The GAG intervention group had significantly shorter hospital stays than the conventional treatment group. ROC curve analysis showed that HS, CRP, APTT, IL-6, APACHE II, SOFA, and ISTH scores were predictive factors for the prognosis of sepsis patients (all P < 0.05). Compared to a single indicator, the combined detection of multiple indicators has a higher value in predicting the prognosis of sepsis patients [area under the curve (AUC) = 0.911, 95% confidence interval (95%CI) was 0.817-1.000], with a sensitivity of 76.9% and a specificity of 91.9%. Correlation analysis showed that HS was significantly negatively correlated with Fib, PT, TNF-α, IL-6, and PCT (r values were -0.338, -0.396, -0.288, -0.319, and -0.340, all P < 0.05), while HS was significantly positively correlated with D-Dimer and CRP (r values were 0.347 and 0.354, both P < 0.05); SDC-1 was significantly negatively correlated with Fib, PT, APTT, TNF-α, IL-6, and ISTH scores (r values were -0.314, -0.294, -0.408, -0.353, -0.289, -0.287, all P < 0.05). CONCLUSIONS Early glycocalyx degradation can occur in sepsis patients. GAG have a protective effect on,the vascular endothelium, reducing the severity of sepsis and providing organ protection. HS, CRP, APTT, IL-6, APACHE II score, SOFA score, and ISTH score are independent predictive factors for the prognosis of sepsis patients. The combination of HS and the above indicators can significantly improve the accuracy of prediction.
Humans ; Sepsis/blood* ; Glycocalyx/drug effects* ; Glycosaminoglycans/pharmacology* ; Prospective Studies ; Endothelium, Vascular/metabolism* ; Syndecan-1/blood* ; Male ; Female ; C-Reactive Protein/metabolism* ; Interleukin-6/blood* ; Heparitin Sulfate/blood* ; Middle Aged ; Adult ; Tumor Necrosis Factor-alpha/blood* ; Procalcitonin/blood*

OBJECTIVE: To investigate the correlation between the pulse pressure (PP) and functional outcome in acute middle cerebral arterial (MCA) ischemic stroke. METHOD: We reviewed the medical records of 52 first-ever hemiplegic MCA ischemic stroke patients (age 61.5+/-9.7 years; 35 men, 17 women). Functional outcomes were evaluated with Korean-modified Barthel index (K-MBI), functional independence measure (FIM), Korean-national institutes of health stroke scale (K-NIHSS), and Korean-mini mental state examination (K-MMSE) on 3 days and 3 months after the onset of stroke in all the subjects. The PP was measured six times within initial 24 hours after stroke onset and then the highest PP was selected for the analysis. RESULTS: The degree of PP elevation revealed the significant correlations with male gender, over the age of 55 years, diabetes mellitus, and current smoking history, respectively (p<0.05). In TOAST (Trial Org 10172 in Acute Stroke Treatment) classification, the large artery atherosclerosis group showed significantly the higher PP rather than the other groups (p<0.05). There were inverse correlations between the PP and each of FIM and K-MBI scores on 3 months after stroke onset (p=0.000, 0.009; r=- 0.479, -0.358). There was an inverse correlation between the PP and the change of FIM (p=0.000, r=-0.532). CONCLUSION: The PP within initial 24 hours after stroke onset revealed significant correlation with functional outcome. The management for the proper PP gives the favorable effect on the functional outcome in acute MCA territory ischemic stroke.
Academies and Institutes ; Arteries ; Atherosclerosis ; Blood Pressure ; Chondroitin Sulfates ; Dermatan Sulfate ; Diabetes Mellitus ; Hemiplegia ; Heparitin Sulfate ; Humans ; Male ; Medical Records ; Middle Cerebral Artery ; Smoke ; Smoking ; Stroke

Adenoid cystic carcinoma is malignant tumor in salivary gland, and its behavior is very invasive. Of all malignant tumor adenoid cystic carcinoma is occured in frequency of 4.4% in major salivary gland, and 1.29% in minor salivary gland. Histopathologically, adenoid cystic carcinoma is characterized by a cribriform appearance, and tubular form and solid nest type tumor can be seen. The tumor cell structure composed of modified myoepithelial cell, and basaloid cell. Extracellular matrix of this tumor cell contains variable ground substance with basement membrane component. Basement membrane matrix composed of collagen fibers, glycoproteins, proteoglycans, and its function is well known that it participate in differentiation, proliferation, and growth of tumor cell. Basement membrane molecule is essential for invasion of peripheral nerve, blood vessel, skeletal muscle in tumor cell of adenoid cystic carcinoma. In many studies, the tumor cell of adenoid cystic carcinoma containing modified myoepithelial cell participate in synthesis of proteoglycan. In this study, tissue sample of adenoid cystic carcinoma of human salivary gland were obtained from 15 surgical specimen, and all specimen were routinely fixed in 10% formalin and embedded. Serial 4-micrometer thick sections were cut from paraffin blocks. the histopathologic evaluation was done with light microscopy. And, the immunohistochemical staining, characteristics of glycosaminoglycan were observed. For biochemical analysis of glycosaminoglycan, isolation of crude glycosaminoglycan from tumor tissue and Western bolt analysis were carried out. With transmission electomicroscopy, tumor cell were observed. Biologic behavior of adenoid cystic carcinoma was observed with distribution and expression of basement membrane of glycosaminoglycan in tumor cells, The results obtained were as follows: 1. In immunohistochemical study, chondroitin sulfate is postively stained in tumor cell and interstitial space, dermatan sulfate is weakly stained in ductal cell. But keratan sulfate is negatively stained. 2. In immunohistochemical study, heparan sulfate is strong positive stained in tumor cell and basement membrane, especially in invasion area to peripheral nerve tissue. 3. In transmission electromicroscpic view, the tumor cells are composed modifed myoepithelial cells, and contains many microvilli and rough endoplasmic reticulum. 4. In Western blot analysis, the expression of glycosaminoglycan is expressed mostly in heparan sulfate. From the results obtained in this study, tumor cell of adenoid cystic carcinoma is composed modified myoepithelial cell, and glycosaminoglycan of basement membrane molecule of heparan sulfate and chondroitin sulfate mostly participate in the development and invasiveness of adenoid cystic carcinoma by immunohistochemical study and western blot analysis.
Adenoids* ; Basement Membrane ; Blood Vessels ; Blotting, Western ; Carcinoma, Adenoid Cystic* ; Chondroitin Sulfates ; Collagen ; Dermatan Sulfate ; Endoplasmic Reticulum, Rough ; Extracellular Matrix ; Formaldehyde ; Glycoproteins ; Heparitin Sulfate ; Humans ; Keratan Sulfate ; Microscopy ; Microvilli ; Muscle, Skeletal ; Paraffin ; Peripheral Nerves ; Proteoglycans ; Salivary Glands ; Salivary Glands, Minor

OBJECTIVETo explore the synergic effect of heparan sulfate (HS) and cytokines on the growth of human umbilical cord blood (UCB) hematopoietic cells.

METHODSHematopoietic cells from human UCB were cultured with (1) cytokines (rhIL-3, rhIL-1beta, rhIL-6 and SCF) or (2) SN (supernatant from cultured human marrow stromal cells) and cytokines, or (3) SN, or (4) HS and cytokines. Cellular proliferation, CFU-GM yields and changes of cell immunophenotype were observed.

RESULTSHematopoietic cell proliferation reached peak at the 14th day. The number of total nucleated cells increased 134.5-, 171.3-, 81.5- and 167.2-fold in (1), (2), (3) and (4) groups, respectively, at the 21th day, the (3) group significantly decreased. CD(34)(+) cells increased at the 7th day and reached peak, at the 14th day with a percentage of 68.4%, 82.5%, 69.8% and 79.3%, and at the 21th day 56.2%, 71.7.%, 12.3% and 73.3%, respectively. CD(33)(+) cells reached peak at the 14th day and increased by 80.2%, 68.6%, 81.6% and 70.3%, respectively, and remained these levels at the 21th day. CD(38)(+) cells increased by 66.6%, 73.8%, 70.4% and 71.9% at the 7th day and remained this level at the 14th and the 21th day. From the first week of culture, the percentage of CFU-GM increased in all of the four groups, at the second week of culture, it increased by 250%, 279%, 217% and 273%, and at the third week still increased by 151%, 240%, 145% and 231%, respectively.

CONCLUSIONThe combination of SN and cytokines have a synergic effect in promoting proliferation of hematopoietic cell from human UCB. The synergic effect remained the same when SN was replaced by heparan sulfate.

ADP-ribosyl Cyclase ; analysis ; ADP-ribosyl Cyclase 1 ; Antigens, CD ; analysis ; Antigens, CD34 ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Cell Division ; drug effects ; Cells, Cultured ; Cytokines ; pharmacology ; Drug Synergism ; Fetal Blood ; cytology ; drug effects ; immunology ; Heparitin Sulfate ; pharmacology ; Humans ; Infant, Newborn ; Interleukin-1 ; pharmacology ; Interleukin-3 ; pharmacology ; Leukocytes, Mononuclear ; cytology ; drug effects ; immunology ; Membrane Glycoproteins ; Recombinant Proteins ; pharmacology ; Sialic Acid Binding Ig-like Lectin 3 ; Time Factors