Despite the availability of six classes of antihypertensive agents, control of blood pressure and improving patients' quality of life remain far from ideal. There is a wide variability in terms of the hypotensive effect and side effect profile for the same antihypertensive agent used in different patients. How to select the right agent to provide the most beneficial results in terms of efficacy and improvement of quality of life as well as to decrease clinical symptoms and minimize adverse reactions is an important therapeutic challenge. It has been suggested that clinical usage of pattern (Zheng) diagnosis of traditional Chinese medicine may improve the accuracy in selecting the right antihypertensive agents with improved efficacy and deceased adverse effects. Limited research in this area suggested the calcium channel blocker may work better in treating phlegmatic damp excess pattern and blood stasis pattern while beta-blockers may be more beneficial in the liver yang rising pattern. On the other hand, angiotensin converting enzyme inhibitors may be more suitable in a yin deficiency and yang hyperactivity pattern as well as combined liver and kidney yin deficiency pattern. More research studies using this innovative approach in improving the selection of antihypertensive agents including mechanistic studies are urgently needed.

Objective:To investigate the distribution characteristics of syndrome types of traditional Chinese medicine (TCM) in essential hypertension and to explore the distribution rule of TCM syndromes. Methods: A multicenter, large-sample survey method of clinical epidemiology was applied to choose the patients with essential hypertension from North, Middle, and South China. A questionnaire was designed and filled in, then 477 untreated patients with first-diagnosed essential hypertension were selected and the information was recorded into FileMaker database. A cluster analysis method was utilized to study the TCM syndrome distribution rule of essential hypertension. Results: Two-step cluster analysis was done from 3 to 7 clusters. Seven clusters were appropriate, which included deficiency of heart and kidney qi, hyperactivity of liver-yang, deficiency of yin and yang, stagnation of phlegm-dampness, phlegm-heat (subtype of stagnation of phlegm-dampness), blood stasis obstructing collaterals, and other syndromes. The symptoms presenting high percentage in each cluster were more significant in TCM theory. The syndromes of hyperactivity of liver-yang (24.1%) and stagnation of phlegm-dampness (27.1%) presented the high percentages, and deficiency of heart and kidney qi (10.1%), deficiency of yin and yang (8.4%), and blood stasis obstructing collaterals (9.0%) presented the low percentages. Conclusion: As compared with the current syndrome differentiation criteria, two-step cluster analysis results not only include the syndromes of deficiency of yin and yang, hyperactivity of liver-yang, stagnation of phlegm-dampness, but also cover qi deficiency and blood stasis.

ObjectiveTo explore the relationship between the negative co-inhibitor programmed death-1 ( PD-1 ) and the pathogenesis of myasthenia gravis ( MG), by detecting the expression of PD-1 and programmed death ligand-1 ( PD-L1 ) on peripheral blood mononuclear cells (PBMCs) and soluble PD-1 (sPD-1) in plasma from myasthenia gravis patients. MethodsPeripheral blood samples were collected from 45 MG patients and 33 healthy persons without prednisone or other immunodepressant treatment during the half year ahead of withdrawal.The expression of PD-1 and PD-L1 on PBMCs were detected using immuno-fluorescence labeling and flow cytometry, and the concentrations of sPD-1 in plasma were measured using an ELISA kit. Results(1) The proportion of CD4+ PD-1 + T cells, as well as CD14+ PD-L1 +monocytes of the MG group was higher than that of the control group. There were no significant differences in the proportion of CD4+ PD-1 + T cells or CD14+ PD-L1 + monocytes in the MG sub-groups between different genders or MG types. While the proportion of CD4+ PD-1 + T cells of the late-onset MG (age ≥40) group was higher than that of the early-onset MG group (age ＜40). And it was higher in the MG patients with thymoma or thymus hyperplasia than that from the MG patients with normal thymus. The proportion of CD14+ PD-L1 +monocytes from the MG patients with thymoma or thymus hyperplasia group decreased obviously compared with that of the patients with normal thymus group; but no difference could be found between the late-onset group and early-onset group. (2)The concentration of sPD-1 in the plasma from the group of MG patients was(6. 92 ±0. 72) ng/ml,which was higher than that of the healthy control group ( (3.28 ±0. 42) ng/ml),even more, it was significantly higher in the early-onset MG group than that of the late-onset MG group,there was a negative correlation( r =-0. 526, P =0. 000) between the age of onset and the concentration of sPD-1. ConclusionsThe increased expressions of PD-1 on CD4+ T cells and PD-L1 on CD14+ monocytes in MG patients suggested the involvement of the couple of molecules in the pathogenesis of MG.Higher concentration of soluble PD-1 in the plasma of patients with MG suggested that it might disturb the ligation of PD-1 and PD-L1 on T cells and antigen presenting cells, which might result in the abnormal transportation of the negative modulating signal, and accelerate the pathological progress of MG.

Objective To investigate the role and mechanism of B7-H4, a negative costimulatory molecule, in mediating the immunomodulatory effects of mesenchymal stem cells C3H10T1/2 (C3H10) on T cell polarization. Methods The lentiviral vectors that carried the shRNA targeting mouse B7-H4 were transfected into mouse mesenchymal stem cells (C3H10-B7-H4). The cells were co-cultured with PHA-acti-vated mice spleen lymphocytes before and after the transfection. ELISA was performed to detect the concen-trations of cytokines in supernatants of cell culture in order to elucidate the effects of B7-H4 expressed by C3H10 on T cell polarization. A mouse model of experimental allergic encephalitis (EAE) was established. Fifty C57BL/6 mice were divided into five groups including control group, EAE group, C3H10 group (injec-ting EAE mice with C3H10 cells), C3H10-NC group ( injecting EAE mice with C3H10-NC cells) and C3H10-B7-H4 group (injecting EAE mice with C3H10-B7-H4 cells). ELISA was performed to detect the soluble form of IL-2, IL-17, IFN-γ and IL-4 in plasma samples. Results Knocking down the B7-H4 gene with shRNA significantly decreased the expression of B7-H4 on C3H10 cells, which weakened the inhibitory effects of C3H10 cells on the secretion of IL-2, IL-17 and IFN-γ by spleen lymphocytes. The therapeutic effects of C3H10-B7-H4 cells on mice with EAE were weakened after silencing the B7-H4 gene expression, which was manifested as higher nerve function score and earlier onset and bring forwarded peak time of EAE than those of the C3H10 group. Treating EAE mice with C3H10-B7-H4 cells was less efficient in inhibiting the expression of IL-2, IL-17 and IFN-γin plasma. However, knocking down the B7-H4 gene had no signif-icant effect on the expression of IL-4 in terms of treating EAE with C3H10 cells. Conclusion The co-inhib-itor molecule B7-H4 expressed on C3H10 cells mediated the treatment of EAE with C3H10 cells by regula-ting Th1 and Th17 effector T cells.

Objective To evaluate the effect of mesenchymal stem cell (MSC) coated-islets on instant blood-mediated inflammatory reaction (IBMIR) after islet transplantation. Methods MSC labeled with tracer and human islets were placed into an ultra-low adsorption cell culture dish, shaken and mixed twice at an interval of 0.5 h, and then incubated at 37 ℃ and 5% CO₂ for 24 h to obtain MSC-coated islets. The coating effect of MSC and in vitro function of the islets were assessed. A blood circulation tube-shaped model was established in vitro. In the blank control group, 0.2 mL of islet culture solution was added. In the islet group, 800 islet equivalent quantity (IEQ) of uncoated islets were supplemented. In the MSC-coated islets group, 800 IEQ of MSC-coated islets were added, and circulated for 60 min at 37 ℃. A portion of 0.5 mL blood sample was taken for routine blood test at 0, 30 and 60 min, respectively. After 60 min circulation, the blood sample was filtered with a 70 μm filter to collect plasma, blood clots and islets. Blood clots and islets were subject to hematoxylin-eosin (HE) staining and immunohistochemical staining. Morphological changes and the aggregation of CD11b-positive cells surrounding the islets were observed. The contents of plasma thrombin-antithrombin complex (TAT), tissue factor (TF), C3a, C5b-9, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1 and IL-8 were determined by enzyme-linked immune absorbent assay. Results After 24 h co-incubation, the islets were coated by MSC, with a coating degree of approximately 80%. In the islet and MSC-coated islet group, a large quantity of neutrophils and monocytes were observed surrounding the blood clots and islets, and the quantity of CD11b-positive cells in the MSC-coated islet group was less compared with that in the islet group. After co-incubation with the whole blood for 0, 30 and 60 min, the quantity of platelets, neutrophils and monocytes was declined in the MSC-coated and islet groups, and gradually decreased over time. Compared with the blank control group, the quantity of platelets, monocytes and neutrophils was lower, whereas the TF content was higher in the MSC-coated islet group. Compared with the islet group, the quantity of platelets, monocytes and neutrophils was higher, whereas the TAT and TF contents were less in the MSC-coated islet group, the differences were statistically significant (all P < 0.05). Compared with the blank control group, the expression levels of C3a, C5b-9, IL-6, TNF-α and IL-8 were up-regulated in the MSC-coated islet group. Compared with the islet group, the expression levels of C3a, C5b-9, IL-1β, IL-6, TNF-α, IL-8 and MCP-1 were down-regulated in the MSC-coated islet group, and the differences were statistically significant (all P < 0.05). Conclusions MSC-coated islets may reduce the exposure of islet TF in the blood and prevent the incidence of IBMIR during the coagulation response stage, thereby mitigating the injury and loss of islet allograft in the early stage of islet transplantation.

Islet transplantation is one of the effective therapies for diabetes mellitus. Nevertheless, multiple issues still exist, such as shortage of donors and adverse reactions caused by long-term use of immunosuppressants, which limit the islet survival post-transplantation. Microencapsulated islet transplantation may overcome these difficulties to certain extent, whereas many factors, such as the destruction of immune isolation microenvironment within the microcapsules and insufficient supply of oxygen and nutrients, constrain the application of microencapsulated islet transplantation in clinical practice. In recent years, how to enhance the effect of microencapsulated islet transplantation has been gradually studied. The application of stem cells in microencapsulated islet transplantation has steadily become a research hot spot. Therefore, the optimizing strategies for microencapsulated islet transplantation and the application of stem cells in microencapsulated islet transplantation were reviewed, and the potential improvement techniques of microencapsulated islet transplantation were investigated in this article, aiming to provide reference for further clinical application of microencapsulated islet transplantation.

Objective To compare the accuracy of dynamic contrast-enhanced magnetic resonance (DCE-MRI) and SPECT in the measurement of glomerular filtration rate (GFR) in renal allografts.Methods Sixty renal transplant recipients were enrolled in this study.DCE-MRI and SPECT were used to measure the GFR of the transplanted kidneys,and compared with the endogenous creatinine clearance rate (Ccr).Bias,precision,correlation and Bland-Altman agreement were calculated for each modality compared with the endogenous Ccr.Results In 60 renal transplant recipients,the corrected Ccr was (60.63 ± 24.83) ml · min-1 · 1.73 m-2.The GFR measured by SPECT was (65.31 ± 17.08) ml · min-1 · 1.73 m-2,and (50.44 ± 22.78) ml · min-1 · 1.73 m-2 by MRI,respectively.The bias of GFR-SPECT was 4.69 ml·min-1 · 1.73 m-2,and the precision was 23.76 ml·min-1 1.73 m-2.The bias of GFR-MRI was-10.18 ml·min-1 ·1.73 m-2,and the precision was 13.87 ml·min-1 · 1.73 m-2.Correlation analysis showed that GFR-MRI and the endogenous Ccr had a good correlation (r=0.833,P＜0.01),GFR-SPECT and the endogenous Ccr had a moderate correlation (r=0.406,P＜0.01),and GFR-MRI and GFR-MRI had a poor correlation (r=0.342,P ＜0.01).Bland-Altman analysis showed a confidence interval of 95.3 ml·min-1 ·1.73 m-2 for GFR-SPECT and 62.3 ml· min-1 · 1.73 m-2 for GFR-MRI.Conclusion DCE-MRI can be used as confidently as SPECT to evaluate the renal function of transplanted kidneys in the same time of determining anatomical information.

Objective To identify the key genes and targeted protection methods affecting the survival of human islets. Methods Using bioinformatics method, the gene expression profile (GSE53454) was selected through screening and comparison from Gene Expression Omnibus(GEO) database. GEO2R tool was employed to screen the differentially expressed gene(DEG) between the human islets exposed (exposure group) and non-exposed (non-exposure group) to interleukin (IL)-1β and interferon (IFN)-γ for 24, 48 and 72 h, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID. Protein-protein interaction (PPI) network was constructed by STRING and Cytoscape apps. Results A total of 69 up-regulated DEGs and 2 down-regulated DEGs were identified. GO analysis showed that during the biological process, DEGs were enriched in the aspects of virus defense and inflammatory response. In cellular components, DEGs were significantly enriched in extracellular space, outside plasma membrane and extracellular regions. Regarding molecular functions, DEGs were significantly enriched in chemokine activity and cytokine activity. KEGG analysis revealed that DEGs were mainly enriched in multiple signaling pathways, such as cytokine-cytokine receptor interaction, virus protein-cytokine and cytokine-receptor interaction, etc. Ten key genes (STAT1, CXCL10, IRF1, IL6, CXCL9, CCL5, CXCL11, ISG15, CD274, IFIT3) with high connectivity were selected by STRING analysis, all of which were significantly up-regulated in human islets exposed to IL-1β and IFN-γ. Six genes (STAT1, CXCL10, CXCL9, CXCL11, CCL5, IL6) were screened by KEGG enrichment analysis, mainly in Toll-like receptor signaling pathway. Conclusions STAT1, CXCL10, CXCL9, CXCL11, CCL5 and IL6 are the key genes affecting the survival of human islets, which are mainly enriched in Toll-like receptor signaling pathway and act as important targets for islet protection.

Objective To discuss the clinical significance of programmed cell death-1 (PD-1) in neuromyelitis optica spectrum disorder (NMOSD) patients by analyzing PD-1 and programmed death 1-1igand (PD-L1) expressions.Methods Sixteen patients with NMOSD,16 patients with longitudinally extensive transverse myelitis (LETM),13 patients with opticneuritis (ON),20 with other diseases of the central nervous system (OTH) and 16 health controls (CONs) were chosen in our hospital from April 2015 to July 2016;their peripheral blood was separately collected.The PD-1 expression in the CD4+r lymphocytes,and PD-L1 expressions in the CD14+ mononuclear leucocytes and CD19+B lymphocytes of peripheral blood were detected by flow cytometry.ELISA was performed to analyze the levels of soluble PD-1 and soluble PD-L1 in plasma samples.Results The PD-1 level from the peripheral blood of NMOSD patients was significantly higher than that from LETM,ON,and OTH patients and CONs (P＜0.05).The PD-L1 level of NMOSD patients was significantly higher than that of the other 4 groups (P＜0.05).ELISA indicated that levels of soluble PD-1 and soluble PD-L1 in plasma samples from NMOSD patients were significantly higher than those in LETM,ON,and OTH patients and CONs (P＜0.05).Conclusion The PD-1/PD-L1 pathway is an important immune response approach and takes part in the earlier stage of the NMOSD pathological process.

Objective To discuss the risk factors on short-term prognosis after kidney transplantation from donors after cardiac death (DCD). Methods We retrospectively analyzed the information of donors and recipients who performed DCD donor kidney transplantation in our center between January 2011 and August 2015, including 64 donors and 95 recipients. Also, we analyzed the potential relationship among donors' clinical characteristics and the early recovery of graft function, including the incidence of delayed graft function(DGF)and the serum creatinine (SCr) on the 90th day, and infection rate after kidney transplantation.Results We found that when donors had the factors of WIT>10 min, urine volume<100 ml/h, SBP≤100 mmHg or a history of CPR, the incidence of recipients' DGF were 55.6%,73.3%,62.5%,77.8% respectively with a significant difference. Recipients would have more chance to be infected if donors have the following characteristics: male, older than 50 years, died of cerebral hemorrhage which was caused by cardiovascular diseases, WIT>30 min, treated in ICU for more than 10 days or infection. Conclusions Nowadays, DCD has become the main graft source in Chinese kidney transplantation. This research indicates that the donors' factors may affect the recovery of graft function and the incidence of infection after kidney transplantation to some extent.By evaluating rigorously and preserving quality of renal grafts carefully, DCD would become more safe and valid.