Objective To investigate the effect of hypoxia-inducible factor (HIF)-1α and vascular en-dothelial growth factor (VEGF) on the angioge-nesis of rheumatoid arthritis (RA). Methods The collagen-induced arthritis (CIA) model was set up in male Wistar rats. The pathological angiogenesis and expression of HIF-1α and VEGF in the synovia different time points were observed by H&E and immunohistochemistry staining. Results The expressions of HIF-1α and VEGF on CIA synovium were significantly elevated and their expression increased gradually with the prolonged disease course. Both synovial HIF-1α expression and VEGF expression were correlated significantly with the pathological angiogenesis score. Synovial lining and sublining HIF-1α expression were correlated significantly with VEGF expression respectively. Conclusion H1F-1α may play an important role in the pathogenesis of RA by upregulating the expression of VEGF and then promoting angiogenesis.

Objective To identity the risk factors for supine hypotension syndrome (SHS) after spinal anesthesia in parturients.Methods A total of 204 parturients,scheduled for elective cesarean section,were divided into either control group or SHS group depending on whether or not SHS (systolic blood pressure [SBP] in the upper extremity decreased by ＞ 30 mmHg or decreased to ＜ 80 mmHg) developed after spinal anesthesia.The baseline patient characteristics such as age,body height and weight,gestational weeks and biparietal diameter were recorded.Supine stress test (SST) was performed.Heart rate,blood pressure in upper and lower extremities,perfusion index,pleth variability index and intravesical pressure were recorded when patients were in supine position and in left lateral position before spinal anesthesia.The risk factors of which P values were less than 0.05 would enter the multi-factor logistic regression analysis to stratify the risk factors for SHS.Results Among the 204 patients,99 cases developed SHS after spinal anesthesia,and the incidence was 48.5％.Logistic regression analysis showed that maternal body weight,biparietal diameter,the difference in SBP between upper and lower extremities in supine position,the difference in SBP in upper extremities caused by changing position and positive SST were risk factors for SHS after spinal anesthesia (P＜0.05 or 0.01).Conclusion Maternal body weight,biparietal diameter,the difference in SBP between the upper and lower extremities in supine position,the difference in SBP in upper extremities caused by changing position and positive SST are risk factors for SHS after spinal anesthesia in parturients.

Objectives To observe the effect of Luoyutong capsule on neurological function following focal cerebral ischemia-reperfusion in rats and to preliminarily study the protective mechanism of Luoyutong capsule for focal cerebral ischemia-reperfusion in rats. Methods A rat model of middle cerebral artery occlusion (MCAO)was induced by the modified Longa method. After 1. 5 h of ischemia,reperfusion started. Ten male SD rats were selected as sham operation group,and forty male SD rats were randomly divided into 4 groups:Model (MCAO),Luoyutong moderate-dose (LYTM),Luoyutong high-dose (LYTH),and citicoline sodium (CS)groups (n=10 in each group). At day 3 and 7 after modeling,the neurological function of the rats was evaluated by using 12 neurological score and forelimb placing test. Western blotting was used to detect the expression levels of brain derived neurotrophic factor (BDNF),basic fibroblast growth factor (b-FGF),and phosphor/protein kinase (p-AKT/AKT)on the ischemic side of the rats and in the ipsilateral brain tissue at day 3 after modeling,as well as the expression level of Caspase-12 at day 7 after modeling in the ipsilateral brain tissue,and a comparison was performed among the groups. Results (1 )Neurological score:At day 3 after modeling,there was no significant difference between the 12 neurological score and the forelimb placing test score (all P>0. 05);At day 7 after modeling, there were obvious improvement in the LYTM,LYTH,and CS groups compared with model group (all P<0.05). (2)The results of western blot showed that①compare with the sham operation group,the expression levels of BDNF and b-FGF were reduced obviously (all P<0.05);compare with the MCAO group,the expression levels of the LYTM,LYTH and CS groups could be up-regulated,particularly in the LYTH group (P<0. 01);② compare with the sham operation group,the expression level of p-AKT/AKT in MCAO group was decreased obviously (P<0. 05);compare with the MCAO group,the expression levels of p-AKT/AKT of the LYTM,LYTH,and CS groups were increased,particularly in the LYTH and CS groups (all P<0. 05);③ compared with the sham operation group,the expression of cleavage Caspase-12 was increased obviously in the MCAO group (P<0. 05). Compared with the MCAO group,the expression levels of proCaspase-12 and cleavage Caspase-12 had a decreasing trend in the LYTM and LYTH groups,but there were no significant differences (all P >0. 05);the expression levels of proCaspase-12 and cleavage Caspase-12 in the CS group were obviously lower than those of the MCAO group (P<0. 05). Conclusion Luoyutong capsule may play a protective effect for focal cerebral ischemia-reperfusion injury in rats by promoting neural survival and regeneration,and this protective effect may be associated with the inhibition of neuronal apoptosis.

In mankind, the circulation system is a closed pressure-loaded system; the pressure in circulation flow field would change with the variation of natural or pathological geometry of the local bloodvessel, and the pressure shift induced by the variation of vascular geometry would lead to a series of physiological and pathological changes in the endothelial cells (ECs). This experiment is designed to elucidate the effects of different pressure shift on F-actin alignment and expression in cultured endothelial cells in vitro, and to investigate the relationship between the altered pressure shift and the expression intensity of Vascular adhesion molecule (VCAM) and Integrin alphaVbeta3. Non-activated cultured ECs and single shear stress loaded ECs as control group were set, the double-immuno-fluoro-cytochemistry, laser confocal scanning microscopy and image analysis system were used to observe the expression of VCAM, Integrin alphaVbeta3 and F-actin in endothelial cells which were exposed to levels of pressure shift in an improved parallel plate flow chamber. When exposed to different decreased pressure shift, the expression intensity of VCAM, Integrin alphaVbeta3 and F-actin showed regular changes. The decreased pressure shift resulted in changes in cell alignment and cytoskeleton F-actin, and also affected ECs adhesion function and transmembrane mechanotransduction function which were represented by VCAM and Integrin alphaVbeta3 respectively.
Actins ; genetics ; metabolism ; Cell Adhesion ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Hemodynamics ; Humans ; Integrin alphaVbeta3 ; genetics ; metabolism ; Pressure ; Umbilical Veins ; cytology ; Vascular Cell Adhesion Molecule-1 ; genetics ; metabolism

Inhibitory cells derived from bone marrow are a kind of inhibitory cells derived from bone marrow.These cells are not only related to tumor growth,but also participate in the inflammatory immune process.Therefore,we established a rat model of chronic osteomyelitis,and used gemcitabine to inhibit the cell growth ratio of MDSCs.We detected the ratio of MDSCs in bone marrow and spleen of rats by flow cytometry and immunofluorescence,detected the changes of inflammatory factors in peripheral blood by ELISA,and analyzed the inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-11)in peripheral blood of normal rats,osteomyelitis rats and rats after gemcitabine inhibition.The results showed that the proportion of MDSCs cells in bone marrow and spleen of osteomyelitis model rats was increased,but it was significantly decreased in gemcitabine group(P<0.05).Levels of inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-17,IFN-γ,TGF-β)were positively correlated with the change of MDSCs cell proportion(P<0.05).From the results,it can be inferred that the change of the proportion of MDSCs cells in rat osteomyelitis is positively related to the inflammatory factors,and gemcitabine can reduce inflammatory factors by inhibiting MDSCs.

PURPOSE: Previous studies have confirmed that microRNAs play important roles in the pathogenesis of acute aortic dissection (AAD). Here, we aimed to explore the role of miR-145 and its regulatory mechanism in the pathogenesis of AAD. MATERIALS AND METHODS: AAD tissue samples were harvested from patients with aortic dissection and normal donors. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with miR-145 mimic/inhibitor or negative control mimic/inhibitor. Gene and protein expression was measured in human aortic dissection tissue specimens and VSMCs by qRT-PCR and Western blot. Luciferase reporter assay was applied to verify whether connective tissue growth factor (CTGF) was a direct target of miR-145 in VSMCs. Methyl thiazolyl tetrazolium assay was used to detect VSMC viability. RESULTS: miR-145 expression was downregulated in aortic dissection tissues and was associated with the survival of patients with AAD. Overexpression of miR-145 promoted VSMC proliferation and inhibited cell apoptosis. Moreover, CTGF, which was increased in aortic dissection tissues, was decreased by miR-145 mimic and increased by miR-145 inhibitor. Furthermore, CTGF was confirmed as a target of miR-145 and could reverse the promotion effect of miR-145 on the progression of AAD. CONCLUSION: miR-145 suppressed the progression of AAD by targeting CTGF, suggesting that a miR-145/CTGF axis may provide a potential therapeutic target for AAD.
Animals ; Apoptosis ; Blotting, Western ; Connective Tissue Growth Factor ; Humans ; Luciferases ; MicroRNAs ; Muscle, Smooth, Vascular ; Rats ; Tissue Donors

Objective    To investigate the multidisciplinary management of patients with acute type A aortic dissection in late pregnancy. Methods    The clinical data of 3 patients admitted to the Second Affiliated Hospital of Army Medical University from 2018 to 2019 were analyzed. Their age ranged from 27 to 32 years, while gestational age was 34-37 weeks. Sudden chest pain was the main clinical symptom before operation. All 3 patients underwent Bentall surgery after cesarean section under general anesthesia, of whom 2 patients received total arch replacement (TAR) combined with frozen elephant trunk (FET) implantation and 1 received coronary artery bypass grafting (CABG) additionally. Results    No patient died during the perioperative period, and all the newborns were delivered successfully and survived healthily. The ICU stay was 3-5 d. The postoperative hospital stay was 15-18 d. The follow-up was 250-751 d. There was no recurrence or death. One patient who developed spontaneous pneumothorax and hydropneumothorax was cured in our center. Conclusion    The multidisciplinary diagnosis and treatment strategy plays a crucial role in saving the life of pregnant patients with acute type A aortic dissection.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.