Innovation and application of metabolomics technology for research in the biomedical field / 药学学报

Metabolomics technology played an important role in the field of biomedical research, such as disease diagnosis, pathogenesis analysis, drug target exploration, formulation of treatment guidelines, etc. Due to the systematic and holistic characteristics of metabolomics research, it has shown certain advantages in the analysis of the basis of pharmacodynamic substances of traditional Chinese medicines and the development of new medicines from traditional Chinese medicines. With the continuous innovation of metabolomics research, many advanced technologies have been developed, which make up for the shortcomings of conventional metabolomics studies in searching for disease targets, identifying functional compounds and interpreting biological significance. Furthermore, the rapid development of metabolomics technology has created new opportunities for the diagnosis of diseases and the development of new drugs in traditional Chinese medicine. Herein, different from conventional metabolomics techniques and methods, nine new metabolomics technologies with wide application prospects in the past 10 years were reviewed from the perspective of new tools, new ideas and new samples, with a view to providing new insights on relevant metabolomics research in the biomedical field and providing new motivation for innovation and development of metabolomics technologies.

Analysis of metabolites of rocuronium bromide in human bile and the study of transmembrane transport mechanism / 药学学报

Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).

Effects of Transcranial Direct Current Stimulation over Vagus Nerve on Dysphagia after Stroke / 中国康复理论与实践

Objective:To study the effect of transcranial direct current stimulation (tDCS) regulating excitability of the vagus nerve on dysphagia after stroke. Methods:From September, 2020 to February, 2021, 28 patients with dysphagia after stroke were randomly divided into control group (n = 14) and tDCS group (n = 14). Both groups accepted swallowing function training, and tDCS group received anodal tDCS over vagus nerve, while the control group received sham tDCS. They were assessed with modified Mann Assessment of Swallowing Ability (MMASA) and Australian Therapy Outcome Measures (AusTOMs)-swallowing scale before and after treatment. Results:The scores of MMASA (|t| > 5.593, P < 0.001) and AusTOMs swallowing scale (|Z| > 2.121, P < 0.05) increased in both groups after treatment, and were higher in tDCS group than in the control group (|t| = 2.439, |Z| = 2.079, P < 0.05). Conclusion:Anodal tDCS over vagus nerve may further release dysphagia after stroke.

Advances in the pathogenesis of depression based on purinergic system and purine metabolism / 药学学报

Depression was a complex and difficult to regulate disease, which was closely related to purinergic system and purine metabolism disorder. Although there had been studies to improve depression by regulating purinergic system, the mechanism of action was complex and needed to be sorted out. Recently, a large number of studies had found that the addition of exogenous purine metabolites adenosine, inosine and guanosine had a significant antidepressant effect, indicating that regulating the level of purine substances in purine metabolism could also improve depression, which was of great significance to the further study of the pathogenesis and treatment of depression. In view of this, this study reviewed the relationship between purinergic system or purine metabolism and depression, in order to provide a reference for the further study of the pathogenesis of depression.

Effect of Porphyromonas gingivalis lipopolysacchearide on the expression of CC chemokine receptor 2 in monocytes / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Porphyromonas gingivalis lipopolysacchearide (Pg-LPS) on the expression of CC chemokine receptor 2 (CCR2) in THP-1 monocyte and to explore the relationship between periodontitis and cardiovascular disease in molecular level.</p><p><b>METHODS</b>THP-1 monocytes were incubated with different concentrations of Pg-LPS (10, 100, 1000 µg/L) for 1, 4 and 24 h respectively, then flow cytometry and reverse transcription-PCR were adopted to determine cell surface protein levels and mRNA levels of CCR2.</p><p><b>RESULTS</b>The protein levels and mRNA levels of CCR2 were higher in all experiment groups of 1 h and 4 h than that in the control group (P < 0.05) , except the protein expression of CCR2 in T1 group of 1 h (55.74 ± 0.96) . The protein expression (52.56 ± 0.61, 40.98 ± 0.86, 26.50 ± 0.67) and mRNA levels (0.095 ± 0.006,0.070 ± 0.004,0.046 ± 0.004) of CCR2 were lower in all experiment groups than that in the control group (56.99 ± 0.44,0.104 ± 0.003) at 24 h (P < 0.05) . The protein levels and mRNA levels of CCR2 were increased in all experiment groups at 4 h and reduced at 24 h (P < 0.05).</p><p><b>CONCLUSIONS</b>Pg-LPS can upregulate CCR2 expression on THP-1 monocyte surface in concentration dependent manner in early stage, promoting the monocyte chemoattractant. Periodontitis may promote atherosclerosis by enhancing monocyte chemoattractant through periodontal pathogens.</p>

Analysis on the clinical characteristics and related risk factors of patients with hemorrhagic transformation after cerebral infarction / 中华流行病学杂志

Objective To analyze and summarize the clinical characteristics and risk factors for patients with hemorrhagic transformation (HT) after cerebral infarction to provide guidance for its clinical treatment and prevention.Methods In this study,data from 49 hospitalized patients with HT in the First Department of Neurology,China-Japan Union Hospital of Jilin University from October 2009 to March 2012,were reviewed retrospectively and 106 cases with acute cerebral infarction only during the same period,were chosen randomly as controls.Gender and age of the patients were comparable.Relevant information was collected.SPSS 17.0 statistical package was applied for data processing.Qualitative data were processed with x2 test,and measurable data was processed with t-test.Each index was analyzed with uni-variate analysis while statistically significant risk factors were included in the logistic review model to conduct the multivariate regression analysis.Results (1) Clinical symptoms deteriorating after hemorrhage in 21 cases accounted for 42.9％ of the HT group,among which the cases on degree of disturbance to consciousness had an aggravation in 8 cases and hemiplegia increase in another 7 cases.Headaches and dizziness were found in 5 cases.(2)Number of infarction within 15 days after the occurrence of HT accounted for 87.0％.(3)HT-related factors increased the risk of HT in cerebral infarction such as cortical infarction,large area of infarction,atrial fibrillation,cerebral embolism,diabetes and high level of low-density lipoprotein cholesterol (P＜0.05).The most important factors were atrial fibrillation and cerebral embolism.(4)PH-2 seemed more unlikely to link with clinical symptoms than other subtypes of HT.Conclusion Cerebral infarction after occlusion of the main artery trunk was prone to HT,especially when it appeared within 15 days.Short-term prognosis seemed to be related to the subtypes of HT,with risk factors as cortical infarct,massive cerebral infarction,atrial fibrillation,cerebral embolism,diabetes,high low-density lipoprotein cholesterol etc.on HT.

Pretreatment of donor dendritic cells with NBD-peptide prolongs mouse cardiac allograft survival / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effects of NBD-peptide pretreatment of the donor dendritic cells in immune tolerance induction in mouse allograft recipients and investigate the mechanisms.</p><p><b>METHODS</b>BALB/c mouse DCs pretreated with NBD-peptide (NBD-Peptide-DC) were injected into the recipient C57BL/6 mice 7 days before transplantation. Cervical heterotopic heart transplantation model was established using the cuff technique and the cardiac allograft survival time was observed. Pathological analysis were performed to examine the graft injection and the responsiveness of the recipient spleen T cell to the donor alloantigen was determined by mixed lymphocyte reaction (MLR). The serum levels of cytokines were determined using ELISA.</p><p><b>RESULTS</b>The cardiac allograft survival time in the NBD-Peptide-DC-treated group (21.83-/+3.54 days) was significantly longer than that in the Day9-DC group (13.33-/+2.58 days) and PBS-treated group (6.66-/+1.21 days) (P<0.01), with also significantly lower pathological grade for graft rejection (P<0.01). The donor-derived NBD-Peptide-DCs induced alloantigen-specific T-cell hyporesponsiveness. In the NBD-Peptide-DC-treated group, the serum levels of IL-12 and IFN-gamma decreased significantly (P<0.01), but the levels of IL-4 and IL-10 increased significantly (P<0.01).</p><p><b>CONCLUSION</b>Injection of donor-derived NBD-Peptide-DCs can leads to donor-specific tolerance in the transplant recipients, and the induction of recipient T-cell hyporesponsiveness and polarization of Th2 response may play important roles in immune tolerance to cardiac allografts.</p>

Experimental study on mechanical properties of decellularized porcine aortic valve and effects of precoating methods of biological scaffold on histocompatibility / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the mechanical properties of decellularized porcine aortic valve, and to explore the effects of precoating methods of biological scaffold on histocompatibility.</p><p><b>METHODS</b>Fresh porcine aortic valves were decellularized using trypsin, TritonX-100 and nuclease. Treated valves were evaluated by light microscopy, scanning electron microscopy (SEM) and mechanical test. Three groups of scaffold were precoated with phosphate buffered saline (PBS), poly-L-lysine (PLL) and fetal bovine serum (FBS) respectively. Myofibroblasts were seeded onto each scaffold. Light and electron microscopic observation was performed and MTT test was used to examine efficiency of cell attachment.</p><p><b>RESULTS</b>HE stain and SEM showed that cells were almost absent in the treated leaflet. The wave-like collagen together with the whole three-dimensional structure was maintained. Compared with normal valves, the Max-load, Max-stress and elastic modulus decreased while the Max-strain increased (P<0.05). The result of MTT test showed more cells were attached on the valves treated with FBS compared to the other two groups. Histological investigations also confirm that the high degree of cell attachment on the valves precoated with FBS (F=129.26, P=0.000).</p><p><b>CONCLUSIONS</b>Enzyme combined with detergent and nucleases can remove cells from porcine aortic valves. Meanwhile the mechanical properties of these valves may be altered. Precoating porcine aortic valve with FBS is an effective method to improve cell attachment, growth and increasing.</p>

Origin of neointimal cells in autologous vein graft in rat model / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the potential cell sources of neointimal cells in autologous vein graft in rat model.</p><p><b>METHODS</b>Vein graft neointimal cell origins were investigated using a model of vein-to-artery interposition modal. Slides were stained with hematoxylin and eosin, immunohistochemical staining was also performed with primary antibodies alpha-smooth actin or CD34.</p><p><b>RESULTS</b>Neointimal thickening was greater at the proximal ends (65.2 +/- 4.6) microm and, to a lesser extent, distal ends (64.7 +/- 5.3) microm, in comparison to the middle of the graft (63.5 +/- 5.6) microm. Vein-originating cells survived and make a contribution to neointimal formation within the vein graft, mostly adjacent to the lumen, suggesting an intimate association with endothelial cells, donor arterial smooth muscle cells or circulating progenitor cells.</p><p><b>CONCLUSIONS</b>Vein graft neointimal cells arise predominantly from vein-derived endothelial cells, donor arteria smooth muscle cells or circulating progenitor cells. It suggests clinical relevance of stenosis-inhibiting therapies directed at the vein graft or early system pharmacologic administration.</p>