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Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4+T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.
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Humans , Arthritis, Rheumatoid/genetics , MicroRNAs/metabolism , Synoviocytes/pathology , Cytokines/metabolism , RNA, Messenger/metabolism , Fibroblasts/pathology , Cell ProliferationABSTRACT
OBJECTIVE@#To investigate the effect of folic acid coated-crosslinked urethane-doped polyester elastomer (fCUPE) nerve conduit in repairing long distance peripheral nerve injury.@*METHODS@#Thirty-six 3-month-old male Sprague Dawley rats weighing 180-220 g were randomly assigned to 3 groups, each consisting of 12 rats: CUPE nerve conduit transplantation group (group A), fCUPE nerve conduit transplantation group (group B), and autologous nerve transplantation group (group C), the contralateral healthy limb of group C served as the control group (group D). A 20-mm-long sciatic nerve defect model was established in rats, and corresponding materials were used to repair the nerve defect according to the group. The sciatic function index (SFI) of groups A-C was calculated using the Bain formula at 1, 2, and 3 months after operation. The nerve conduction velocity (NCV) of the affected side in groups A-D was assessed using neuroelectrophysiological techniques. At 3 months after operation, the regenerated nerve tissue was collected from groups A-C for S-100 immunohistochemical staining and Schwann cell count in groups A and B to compare the level of nerve repair and regeneration in each group.@*RESULTS@#At 3 months after operation, the nerve conduits in all groups partially degraded. There was no significant adhesion between the nerve and the conduit and the surrounding tissues, the conduit was well connected with the distal and proximal nerves, and the nerve-like tissues in the conduit could be observed when the nerve conduit stents were cut off. SFI in group A was significantly higher than that in group C at each time point after operation and was significantly higher than that in group B at 2 and 3 months after operation ( P<0.05). There was no significant difference in SFI between groups B and C at each time point after operation ( P>0.05). NCV in group A was significantly slower than that in the other 3 groups at each time point after operation ( P<0.05). The NCV of groups B and C were slower than that of group D, but the difference was significant only at 1 month after operation ( P<0.05). There was no significant difference between groups B and C at each time point after operation ( P>0.05). Immunohistochemical staining showed that the nerve tissue of group A had an abnormal cavo-like structure, light tissue staining, and many non-Schwann cells. In group B, a large quantity of normal neural structures was observed, the staining was deeper than that in group A, and the distribution of dedifferentiated Schwann cells was obvious. In group C, the nerve bundles were arranged neatly, and the tissue staining was the deepest. The number of Schwann cells in group B was (727.50±57.60) cells/mm 2, which was significantly more than that in group A [(298.33±153.12) cells/mm 2] ( t=6.139, P<0.001).@*CONCLUSION@#The fCUPE nerve conduit is effective in repairing long-distance sciatic nerve defects and is comparable to autologous nerve grafts. It has the potential to be used as a substitute material for peripheral nerve defect transplantation.
Subject(s)
Rats , Animals , Male , Rats, Sprague-Dawley , Polyesters , Peripheral Nerve Injuries/surgery , Elastomers , Urethane , Sciatic Nerve/injuries , Carbamates , Nerve Tissue , Nerve Regeneration/physiologyABSTRACT
OBJECTIVE@#To investigate the maximum dose of continuous mivacurium infusion for intraoperative neuromonitoring (IONM) and observe the adverse reactions during thyroid surgery under total intravenous anesthesia (TIVA).@*METHODS@#Thirty patients undergoing IONM during thyroid surgery received continuous infusion of mivacurium at the initial rate of 14.97 μg · kg@*RESULTS@#The EC@*CONCLUSIONS@#In patients undergoing thyroid surgery under TIVA, the EC
Subject(s)
Humans , Anesthesia, Intravenous , Mivacurium , Propofol , Remifentanil , Thyroid GlandABSTRACT
Objective:To investigate the threshold of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), synovial fluid white blood-cell count (WBC) and polymorphonuclear cells (PMN) proportion in the diagnosis of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA).Methods:The clinical data of 246 patients with RA and osteoarthritis (OA) who had previously undergone total knee and hip arthroplasty from January 2006 to December 2019 was retrospectively analyzed. The patients were divided into four groups according to the disease type and whether PJI occurred, namely 46 patients in the RA-PJI group, 64 patients in the RA-non-PJI group, 72 patients in the OA-PJI group, and 64 patients in the OA-non-PJI group. The receiver operating characteristics (ROC) curve was used to determine the optimum cut-off values of CRP, ESR, synovial fluid WBC and PMN proportion for diagnosing the RA-PJI and OA-PJI. The optimal cut-off values of serum and synovial fluid indexes were evaluated for the diagnostic efficacy of RA-PJI by comparing the area under curve (AUC) of each index. Further, the values were applied for joint test analysis.Results:For PJI prediction, the results of serological and synovial fluid indexes were different between RA-PJI group and OA-PJI group. The results of ROC curve analysis showed that the optimal cut-off values of each detection index were as follows. The optimal cut-off value of CRP for diagnosing RA-PJI was 14.4 mg/L, ESR was 39 mm/1 h, synovial fluid WBC was 3 654×10 6 /L, and PMN proportion was 0.659. The optimal cut-off value for diagnosing OA-PJI were 8.16 mg/L, 31 mm/1 h, 2 452×10 6 /L, and 0.625, respectively. In the RA-PJI group, the difference between the AUC of each detection index and AUC=0.5 was statistically significant ( P<0.05). Among them, the specificity of synovial fluid WBC was 92.3%, AUC was 0.879 (95% CI: 0.776, 0.982) with 87.8% positive predictive value and 10.21 positive likelihood ratio. These values were higher than those of CRP, ESR, and PMN proportion. The results of joint test analysis for the diagnosis of RA-PJI were as follows. The specificity of the series test was 100%, and the sensitivity of the parallel test was 100%; the specificity of the joint index diagnostic test was 100%, AUC was 0.926 (95% CI: 0.848, 1.000), the difference between AUC and AUC=0.5 was statistically significant ( P<0.05). Conclusion:The optimum cut-off values of CRP, ESR, synovial fluid WBC and PMN proportion for the diagnosis of PJI in patients with RA are all higher than those of patients with OA. Their optimal cut-off values can be used as important auxiliary indexes for a clear diagnosis of PJI in patients with RA. Compared with other indexes, the synovial fluid WBC has strong predicting power and lower misdiagnosis rate, which could be the best detection index for identifying PJI in patients with RA. The joint test could improve the sensitivity or specificity of PJI diagnosis in patients with RA. The combination with multiple detection indexes could provide a reference for the early and accurate diagnosis of PJI in patients with RA.
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OBJECTIVE：To provide referen ce for promoting innovation cooperation of pharmaceutical manufacturing industry among regions and building a more perfect and close pharmaceutical innovation cooperation network. METHODS ：Based on China ’s pharmaceutical manufacturing cooperation patent data published by the State Intellectual Property Office ，the main cross-region cooperation patents among 31 provinces，autonomous regions and municipalities in China in 2016 were extracted ；based on literature review ，some hypotheses were put forward about the factors that may affect the cross regional innovation cooperation of Chinese pharmaceutical manufacturing industry. Taking the provincial R&D cooperation intensity as the dependent variable and the above influencing factors as the independent variables ，QAP analysis method was used to establish the model for data analysis. RESULTS & CONCLUSIONS ：Differences in regional economic GDP ，geographic distance ，economic distance ，technical distance，and whether Beijing or Shanghai are involved in the cooperation area all have an impact on cross-regional innovation cooperation in the pharmaceutical manufacturing industry. Large regional economic GDP difference is conducive to promoting cooperation. Developed regions represented by Beijing and Shanghai have strong radiating effects and can significantly promote cooperation. Geographical distance and economic distance have a negative effect on cross-regional innovation cooperation in pharmaceutical manufacturing ，while technological distance has positive effect.
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Objective:To evaluate the effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy.Methods:Sixty healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 240-270 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis-associated encephalopathy group (group SAE), low-dose tetramethylpyrazine group (group L-TMP), and high-dose tetramethylpyrazine group (group H-TMP). Sepsis-associated encephalopathy was induced by cecal ligation and puncture (CLP) in anesthetized rats.Tetramethylpyrazine 5 and 20 mg/kg were intraperitoneally injected once a day in L-TMP and H-TMP groups, respectively, at 5 days prior to CLP.Morris water maze test was performed at 1-5 days after CLP to assess the cognitive function, and the escape latency and ratio of time spent in the target quadrant were recorded.Five rats were sacrificed at 1 day after CLP, the brains were removed, and the hippocampi were isolated for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 by enzyme-linked immunosorbent assay.Rats were sacrificed after the end of Morris water maze test, and hippocampi were removed for detection of the expression of Toll-like receptor 1 (TLR1), activated caspase-3, Bax and Bcl-2 by using Western blot. Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the expression of TLR1, activated caspase-3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in group SAE, group L-TMP and group H-TMP, and the contents of IL-1β, TNF-α and IL-6 were significantly increased in group SAE and group L-TMP ( P<0.05). Compared with group SAE, the escape latency was significantly shortened, the ratio of time spent in the target quadrant was increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the expression of TLR1, activated caspase-3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in group L-TMP and group H-TMP ( P<0.05). Conclusion:The mechanism by which tetramethylpyrazine reduces sepsis-associated encephalopathy may be related to inhibiting hippocampal inflammatory responses in rats.
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OBJECTIVE@#To determine the maximum dose of continuously infused mivacurium for intraoperative neuromonitoring and observe its adverse effects in thyroid surgery.@*METHODS@#Twenty-eight patients undergoing thyroid surgery with intraoperative neuromonitoring received continuous infusion of mivacurium at the initial rate of 5.43 μg?kg?min, and the infusion rate for the next patient was adjusted based on the response of the previous patient according to the results of neurological monitoring. The depth of anesthesia was maintained with sevoflurane and remifentanil during the surgery. The LD50 and 95% of mivacurium were calculated using Brownlee's up-and-down sequential method.@*RESULTS@#The LD50 of continuously infused mivacurium was 8.94 μg?kg?min (95% : 8.89- 8.99 μg?kg?min) during thyroid surgery, which did not affect neurological function monitoring. Transient chest skin redness occurred after induction in 9 patients (32.1%). None of the patients experienced intubation difficulties or showed intraoperative body motions during the surgery.@*CONCLUSIONS@#In patients undergoing thyroid surgery under anesthesia maintained by inhalation and intravenous infusion, the LD50 of mivacurium was 8.94 μg?kg?min (95% : 8.89-8.99 μg?kg?min) for continuous infusion, which does not cause serious adverse effects during the operation.
Subject(s)
Humans , Anesthesia , Anesthetics, Inhalation , Anesthetics, Intravenous , Intraoperative Neurophysiological Monitoring , Methods , Lethal Dose 50 , Mivacurium , Neuromuscular Nondepolarizing Agents , Remifentanil , Sevoflurane , Thyroid Gland , General SurgeryABSTRACT
This study was aimed to develop in-line monitoring of extraction process of Lonicerajaponica in the extraction process trajectory of Re-Du-Ning (RDN) injection.Several batches of near-infrared (NIR) spectrum dates were collected and multivariate statistical process control (MSPC) method was in conjunction with.The results showed that using score,Hotelling T2 and DModX control chart,various normal and abnormal behaviors of the test batches were detected in time by comparison with the extraction process trajectory.It was concluded that the process trajectory for in-line quality control based on NIR spectrum dates and MSPC could indicate the changes of process.It was a feasible technology tool of the total process quality control during traditional Chinese medicine (TCM) manufacturing process.
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Long-term spaceflight affects numerous organ systems in the body, including metabolic dysfunction. Recently, ample evidence has demonstrated that the liver is a vulnerable organ during spaceflight. However, the changes in hepatocyte proliferation and cell cycle control under microgravity remain largely unexplored. In the present study, we first confirmed that the serum levels of aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase, biochemical markers of liver function, were altered in rats under tail suspension (TS) conditions to simulate microgravity, as shown in previous reports. Next, we demonstrated that the cell proliferation activity, determined by Ki67, PCNA and PH3, was significantly decreased at the different TS time points (TS for 14, 28 and 42 days) compared with that in the control group. Consistently, the positive cell cycle regulators Ccna2, Ccnd1, Cdk1, Cdk2 and cyclin D3 were also significantly decreased in the TS groups as shown by quantitative real-time PCR and western blotting analysis. Subsequent analysis revealed that the aberrant hepatocyte proliferation inhibition under simulated microgravity was associated with the upregulation of miR-223 in the liver. We further found that miR-223 inhibited the proliferation of Hepa1-6 cells and identified CDK2 and CUL1 as its direct targets. In addition, the decreased expression of CDK2 and CUL1 was negatively correlated with the level of p27 in vitro and in vivo, which may have been responsible for retarding hepatocyte proliferation. Collectively, these data indicate that upregulation of miR-223 was associated with the inhibition of liver cell growth and reveal the role of miR-223 in rat hepatocyte proliferation disorders and the pathophysiological process under simulated microgravity.
Subject(s)
Animals , Rats , Alanine Transaminase , Alkaline Phosphatase , Aspartate Aminotransferases , Biomarkers , Blotting, Western , Cell Cycle , Cell Cycle Checkpoints , Cell Proliferation , Cyclin D3 , Hepatocytes , Hindlimb Suspension , In Vitro Techniques , Liver , Proliferating Cell Nuclear Antigen , Real-Time Polymerase Chain Reaction , Space Flight , Up-Regulation , WeightlessnessABSTRACT
Aim To observe the effects of 17?-estradiol(E2)and exercise on the protein expression of peroxisome proliferators activated receptor ?(PPAR?)in bone tissues and bone marrow adipocytes in ovariectomized rats.Methods Forty female Sprague-Dawley rats,aged three months,were randomly divided into the following four groups:sham-operation(Sham),ovariectomized(OVX),ovariectomized plus moderate-intensity treadmill exercise(EX,18 m?minute-1,45 min?day-1,5 uphill,4 times?week-1)and ovariectomized treated with E2(25 ?g?kg-1,3 times?week-1)group.At the end of experiment,the morphological changes of femur and tibia were observed decalcifiedly by HE staining and the protein expression of bone PPAR? was detected by Western blot.Results The number of fat vacuoles and PPAR? protein expression in OVX group was significantly higher than that of other three groups.Conclusion E2 and exercise can benefit the bone morphological structure and these effects might be partly related to the inhibition of both PPAR? protein expression in bone tissues and adipogenic differentiation of bone marrow in OVX rats.