Effect of Fangji Fulingtang on Macrophage Polarization and Oxidative Stress in Mouse Model of Myocardial Fibrosis / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Fangji Fulingtang on macrophage polarization and oxidative stress in the mouse model of myocardial fibrosis. MethodThe mouse model of myocardial fibrosis was established by subcutaneous injection of isoproterenol （ISO， 5 mg·kg-1·d-1）. Fifty C57BL/6J mice were randomly assigned into control （0.9% NaCl）， model （0.9% NaCl）， low- and high-dose （3.315 g·kg-1·d-1 and 13.26 g·kg-1·d-1， respectively） Fangji Fulingtang （FFD-L and FFD-H， respectively）， and metoprolol tartrate （Meto， 15 mg·kg-1·d-1） groups， with 10 mice each group. After 2 weeks of treatment， the heart appearance， cardiac weight index （CWI）， heart weight （HW）/tibia length （TL） ratio， and myocardial histopathological alterations were observed. Meanwhile， the serum levels of creatine kinase-MB （CK-MB）， transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， IL-6， IL-10， malondialdehyde （MDA）， superoxide dismutase （SOD）， and glutathione （GSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The expression levels of CD86 and CD206 were observed by immunohistochemical staining. ResultCompared with the model group， the FFD-L， FFD-H， and Meto groups showed improved heart appearance， decreased CWI and HW/TL ratio （P<0.01）， lowered serum levels of CK-MB， TGF-β1， TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， and elevated IL-10 level （P<0.05）. Furthermore， the three groups showed reduced infiltration of inflammatory cells， myocardial injury， collagen deposition， and myocardial fibrosis， decreased CD86， SOD， and GSH （P<0.01）， and increased CD206 and MDA （P<0.01）. ConclusionFangji Fulingtang can mitigate ISO-induced myocardial fibrosis by regulating macrophage polarization and oxidative stress.

Dendrobium Polysaccharides Mitigate CSE-induced Inflammatory Damage of Human Bronchial Epithelial Cells via TLR4/NF-κB Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effects of Dendrobium polysaccharides on the secretion of inflammatory cytokines and Toll-like receptor 4 （TLR4）/nuclear factor （NF）-κB pathway in 16HBE cells exposed to cigarette smoke extract （CSE）. MethodThe 16HBE cells were classified into the control， CSE， and CSE+ Dendrobium polysaccharides （100， 200， 400 mg·L-1） groups. The cell-counting kit-8 （CCK-8） assay was employed to measure the cell viability， and a microscope was used to observe the cell morphology. The enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-8， IL-1β， IL-4， IL-13， and transforming growth factor （TGF）-β in cell culture supernatants. Real-time PCR was carried out to determine the mRNA levels of Toll-like receptor 4 （TLR4）， nuclear factor-κB （NF-κB）， and IL-4. Western blot was employed to determine the protein levels of interleukin-4 receptor （IL-4R）， TLR4， myeloid differentiation primary response protein 88 （MyD88）， NF-κB， phosphorylated nuclear factor-κB （p-NF-κB）， and nucleoproteins nuclear factor-κB （NEs-NF-κB）. The immunofluorescence assay was employed to measure the nuclear translocation of NF-κB. ResultCompared with the control group， the CSE group showed elevated levels of IL-8， IL-1β， IL-4， IL-13， and TGF-β in the cell culture supernatants （P<0.05， P<0.01）， up-regulated expression levels of TLR4， MyD88， NF-κB， p-NF-κB， NEs-NF-κB， and IL-4 （P<0.01）， and significant nuclear translocation of NF-κB. Compared with the CSE group， Dendrobium polysaccharides increased the cell survival rate， recovered the cell activity， lowered the levels of IL-8， IL-1β， IL-4， IL-13， and TGF-β， down-regulated the expression of TLR4， MyD88， NF-κB， p-NF-κB， NEs-NF-κB， and IL-4 （P<0.05， P<0.01）， and reduced the nuclear translocation of NF-κB. ConclusionDendrobium polysaccharides showed significant protective effects on the 16HBE cells exposed to CSE by inhibiting the TLR4/NF-κB signaling pathway.

Research advance on the role of pro-inflammatory cytokines in sepsis / 中华危重病急救医学

Sepsis, a series of pathophysiological abnormalities caused by infection, is also one of the most important factors of death and disability in infected patients all over the world, so it has always been the focus of the medical community. Cytokines are small molecule proteins secreted by cells with biological activity, involved in the immune and inflammatory regulation of sepsis. Many studies using cytokine targeting to treat sepsis have achieved beneficial effects, and the level of cytokines is also believed to be related to the development, severity of sepsis, so they are reliable biomarkers of sepsis. Among them, pro-inflammatory cytokines such as interferon-β (IFN-β) and interleukins (IL-1β, IL-3, IL-6, and IL-7) are the focus of the discussion in this review. IFN-β and IL-1β are double-sided in the treatment of sepsis, namely early low-dose treatment can reduce sepsis by restoring the function of immune cells and play a protective effect, but they are also related to severe inflammatory response of sepsis and can aggravate the mortality of sepsis patients. IL-3 and IL-6 focus more on enhancing inflammatory factors and play a damage role. IL-7 mainly participates in immune regulation, promoting lymphocyte activation and protecting sepsis.

Cardioprotective of Saffron (Crocus sativus L.) treatment in patients with type 2 diabetes mellitus: a systematic review and meta-analysis / 数字中医药（英文）

Objective@#To investigate the cardioprotective effect of Saffron (Crocus sativus L.) treatment as a potential supplement on patients with type 2 diabetes mellitus (T2DM).@*Methods@#Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to analyze articles retrieved from PubMed, ScienceDirect, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and China Biology Medicine (CBM) with a publication time span from January 15, 2015 to March 20, 2023. The articles were published in English only, including randomized controlled trials (RCTs) on adult patients who were diagnosed with T2DM, and received either Saffron or placebo treatment. Meta-analysis was performed using Review Manager 5.4 software. The present study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) with a registration number as CRD42023443180.@*Results@#Seven RCTs with 455 patients were included in the study. The data revealed that Saffron treatment significantly reduced tumor necrosis factor (TNF)-α (P = 0.008) and fasting blood glucose (FBG) (P = 0.04) levels compared with what placebo did in T2DM patients. No significant differences were shown in the levels of interleukin (IL)-6, malondialdehyde (MDA), high serum C-reactive protein (hs-CRP), lipid profile, blood pressure, and body mass index (BMI) between Saffron and placebo ( P > 0.05) .@*Conclusion@#Saffron treatment has a cardioprotective effect in T2DM patients by reducing TNF-α and FBG levels. However, the potential anti-oxidant, anti-hypertensive, and anti-dyslipidaemia effects of the phytochemical need to be further investigated.

Efficacy and mechanism of scalp acupuncture for spastic cerebral palsy / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of scalp acupuncture for spastic cerebral palsy (CP), and to explore its possible mechanism based on brain white matter fiber bundles, nerve growth related proteins and inflammatory cytokines.@*METHODS@#A total of 90 children with spastic CP were randomly divided into a scalp acupuncture group and a sham scalp acupuncture group, 45 cases in each group. The children in the two groups were treated with conventional comprehensive rehabilitation treatment. The children in the scalp acupuncture group were treated with scalp acupuncture at the parietal temporal anterior oblique line, parietal temporal posterior oblique line on the affected side, and parietal midline. The children in the sham scalp acupuncture group were treated with scalp acupuncture at 1 cun next to the above point lines. The needles were kept for 30 min, once a day, 5 days a week, for 12 weeks. Before and after treatment, the diffusion tensor imaging (DTI) indexes of magnetic resonance (FA values of corticospinal tract [CST], anterior limb of internal capsule [ICAL], posterior limb of internal capsule [ICPL], genu of internal capsule [ICGL], genu of corpus callosum [GCC], body of corpus callosum [BCC] and splenium of corpus callosum [SCC]), serum levels of nerve growth related proteins (neuron-specific enolase [NSE], glial fibrillary acidic protein [GFAP], myelin basic protein [MBP], ubiquitin carboxy terminal hydrolase-L1 [UCH-L1]) and inflammatory cytokines (interleukin 33 [IL-33], tumor necrosis factor α [TNF-α]), cerebral hemodynamic indexes (mean blood flow velocity [Vm], systolic peak flow velocity [Vs] and resistance index [RI], pulsatility index [PI] of cerebral artery), surface electromyography (SEMG) signal indexes (root mean square [RMS] values of rectus femoris, hamstring muscles, gastrocnemius muscles, tibialis anterior muscles), gross motor function measure-88 (GMFM-88) score, modified Ashworth scale (MAS) score, ability of daily living (ADL) score were observed in the two groups. The clinical effect of the two groups was compared.@*RESULTS@#After treatment, the FA value of each fiber bundle, Vm, Vs, GMFM-88 scores and ADL scores in the two groups were higher than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were higher than those in the sham scalp acupuncture group (P<0.05). After treatment, the serum levels of NSE, GFAP, MBP, UCH-L1, IL-33, TNF-α as well as RI, PI, MAS scores and RMS values of each muscle were lower than those before treatment (P<0.05), and the above indexes in the scalp acupuncture group were lower than those in the sham scalp acupuncture group (P<0.05). The total effective rate was 95.6% (43/45) in the scalp acupuncture group, which was higher than 82.2% (37/45) in the sham scalp acupuncture group (P<0.05).@*CONCLUSION@#Scalp acupuncture could effectively treat spastic CP, improve the cerebral hemodynamics and gross motor function, reduce muscle tension and spasticity, and improve the ability of daily life. The mechanism may be related to repairing the white matter fiber bundles and regulating the levels of nerve growth related proteins and inflammatory cytokines.

Analysis of key genes and targeted protection methods affecting the survival of human islets / 器官移植

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.

Effect of Maxing Shigantang and Supplemented Guominjian Decoction on Symptoms and Inflammatory Cytokine Levels in Induced Sputum of Children with Cough Variant Asthma / 中国实验方剂学杂志

ObjectiveTo investigate effect of Maxing Shigantang and supplemented Guominjian decoction on symptoms and levels of inflammatory cytokines in induced sputum of children with cough variant asthma （CVA）. MethodA total of 118 CVA children who were treated in our hospital from January 2020 to January 2021 were enrolled and randomized into the control group and the observation group with the random number table method. Control group received routine western medicine and the observation group was treated by routine western medicine， Maxing Shigantang， and supplemented Guominjian decoction. In the one-month follow-up， the scores of cough and accompanying symptoms， levels of inflammatory cytokines ［interleukin-10 （IL-10）， interleukin-5 （IL-5）， tumor necrosis factor-α （TNF-α）， neutrophil， eosinophil］ in induced sputum， pulmonary function parameters ［forced vital capacity （FVC）， forced expiratory volume in one second （FEV1）， FEV1/FVC］， and treatment outcomes were compared between the two groups. Moreover， the frequency of acute asthma attacks during the three-month follow-up was also compared. ResultNo cases dropped out from this study. After treatment， the scores of cough and accompanying symptoms were decreased in both groups （P<0.05） and were lower in observation group than in control group （P<0.05）. After treatment， FVC， FEV1， and FEV1/FVC were raised in both groups and were higher in observation group than in control group （P<0.05）. The increase in the level of IL-10 along with the decrease in levels of IL-5， TNF-α， neutrophil， and eosinophil in induced sputum was found in both groups after treatment （P<0.05）， and observation group had higher level of IL-10 and lower levels of IL-5， TNF-α， neutrophil， and eosinophil than the control group （P<0.05）. The effective rate was 86.44% （51/59） in observation group， which was higher than the 69.49% （41/59） in control group （χ2=4.933， P<0.05）. No serious adverse reaction occurred in either group. The frequency of acute asthma attacks during the three-month follow-up was （1.09±0.18） in observation group， which was lower than the （2.83±049） in the control group （P<0.05）. ConclusionRoutine western medicine combined with Maxing Shigantang and supplemented Guominjian decoction can effectively and safely alleviate the airway inflammatory responses， control the clinical symptoms， improve pulmonary function， and reduce the frequency of acute recurrence in the treatment of CVA children.

Effect of electroacupuncture on myocardial fibrosis in spontaneously hypertensive rats based on cholinergic anti-inflammatory pathway / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Neiguan" (PC 6) on myocardial fibrosis in spontaneously hypertensive rats (SHR), and explore preliminarily the mediating role of cholinergic anti-inflammatory pathway (CAP) and its downstream nuclear factor κB (NF-κB) signaling pathway.@*METHODS@#Six 12-week-old WKY male rats were employed as the normal group. Eighteen 12-week-old SHR were randomly divided into 3 groups, i.e. a model group, an EA group and a blocking group (EA after blocking α7 nicotinic acetylcholine receptor [α7nAchR]), with 6 rats in each one. In the EA group, EA was delivered at "Neiguan"(PC 6) and the site 0.5 cm from its left side, with disperse-dense wave, 2 Hz/15 Hz in frequency and 1 mA in current intensity. One intervention took 30 min and was given once every 2 days, lasting 8 weeks. In the blocking group, prior to each EA, the α7nAchR specific blocker, α-bungartoxin was injected intravenously in the tails of the rats. After EA intervention, the systolic blood pressure (SBP), the diastolic blood pressure (DBP) and the mean arterial pressure (MAP) were measured with non-invasive blood pressure monitor. Using echocardiogram, the left ventricular (LV) anterior wall end-diastolic thickness (LVAWd) , LV posterior wall end-diastolic thickness (LVPWd) and the LV end-diastolic internal diameter (LVIDd) were measured. The level of hydroxyproline (Hyp) in the myocardial tissue was determined by using alkaline hydrolysis, and that of acetylcholine (Ach) was detected by ELISA. With the real-time PCR adopted, the mRNA expression of NF-κB p65, tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 were determined.@*RESULTS@#Compared with the normal group, SBP, DBP, MAP, LVAWd and LVPWd were increased (P<0.01), and LVIDd was decreased (P<0.01) in the rats of the model group. SBP, DBP, MAP and LVAWd were dropped (P<0.01, P<0.05), and LVIDd rose (P<0.01) in the EA group when compared with those in the model group. The differences in the above indexes were not statistically significant between the blocking group and the model group (P>0.05). Compared with the normal group, Hyp level and the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue increased (P<0.01, P<0.05) and Ach level decreased (P<0.01) in the model group. Hyp level, the mRNA expression of NF-κB p65, TNF-α, IL-1β and IL-6 in the myocardial tissue were reduced (P<0.05, P<0.01) and Ach level rose (P<0.01) in the EA group when compared with those in the model group. These indexes were not different statistically between the blocking group and the model group (P>0.05).@*CONCLUSION@#CAP may be involved in ameliorating the pathological damage of myocardial fibrosis during EA at "Neiguan"(PC 6). The underlying effect mechanism is associated with up-regulating the neurotransmitter, Ach and down-regulating mRNA expression of NF-κB p65 and pro-inflammatory factors such as TNF-α, IL-1β and IL-6 in myocardial tissue.

Epidemiological characteristics of SARS-CoV-2 pneumonia in kidney transplant recipients : a single-center retrospective study / 器官移植

Objective To investigate the epidemiological characteristics of SARS-CoV-2 pneumonia in kidney transplant recipients and analyze the risk and protective factors of severe/critical infection with SARS-CoV-2. Methods Clinical data of 468 kidney transplant recipients infected with SARS-CoV-2 were retrospectively analyzed. According to the severity of infection, they were divided into mild SARS-CoV-2 infection recipients (n=439) and SARS-CoV-2 pneumonia group (n=29). Among the 439 mild SARS-CoV-2 infection recipients, 87 recipients who were randomly matched with their counterparts in the SARS-CoV-2 pneumonia group according to sex, age and transplantation time at a ratio of 3∶1 were allocated into the mild SARS-CoV-2 infection group. Twenty-nine recipients in the SARS-CoV-2 pneumonia group were divided into the moderate SARS-CoV-2 pneumonia group (n=21) and severe/critical SARS-CoV-2 pneumonia group (n=8). Baseline data of all recipients were collected. The risk and protective factors of SARS-CoV-2 infection in kidney transplant recipients were identified. Results The proportion of recipients complicated with 2-3 types of complications in the SARS-CoV-2 pneumonia group was higher than that in the mild SARS-CoV-2 infection group, and the proportion of recipients treated with tacrolimus(Tac)+mizoribine+glucocorticoid immunosuppression regimen in the SARS-CoV-2 pneumonia group was lower than that in the mild SARS-CoV-2 infection group, and significant differences were observed (both P<0.05). In 29 kidney transplant recipients with SARS-CoV-2 pneumonia in the SARS-CoV-2 pneumonia group, white blood cells, the absolute values of lymphocytes, eosinophils, total T cells, CD4+T cells and CD8+T cells, and serum uric acid levels were significantly lower, whereas ferritin levels were significantly higher than the values prior to SARS-CoV-2 pneumonia, and significant differences were observed (all P<0.05). Compared with the moderate SARS-CoV-2 pneumonia group, the proportion of recipients with hypoxemia was higher, the proportion of recipients treated with Tac/ciclosporin (CsA)+mycophenolate mofetil+glucocorticoid immunosuppression regimen was higher, and the proportion of recipients administered with 2-3 doses of SARS-CoV-2 vaccine was lower in the severe/critical SARS-CoV-2 pneumonia group, and significant differences were observed (all P<0.05). Conclusions More complications and immunosuppression regimen containing mycophenolate mofetil are the risk factor for SARS-CoV-2 infection in kidney transplant recipients. Vaccination with SARS-CoV-2 vaccine and immunosuppression regimen containing mizoribine are probably the protective factors for lowering the risk of SARS-CoV-2 infection. The levels of inflammatory cytokines are associated with the severity of SARS-CoV-2 pneumonia.

Chemokine receptor CX3CR1 promotes local remodeling of monocyte-derived Langerhans cell subsets to maintain chronic skin inflammation / 中华微生物学和免疫学杂志

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

Caprylic Acid Improves Lipid Metabolism, Suppresses the Inflammatory Response and Activates the ABCA1/p-JAK2/p-STAT3 Signaling Pathway in C57BL/6J Mice and RAW264.7 Cells / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the effects of caprylic acid (C8:0) on lipid metabolism and inflammation, and examine the mechanisms underlying these effects in mice and cells.@*METHODS@#Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a high-fat diet (HFD) without or with 2% C8:0, palmitic acid (C16:0) or eicosapentaenoic acid (EPA). RAW246.7 cells were randomly divided into five groups: normal, lipopolysaccharide (LPS), LPS+C8:0, LPS+EPA and LPS+cAMP. The serum lipid profiles, inflammatory biomolecules, and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.@*RESULTS@#C8:0 decreased TC and LDL-C, and increased the HDL-C/LDL-C ratio after injection of LPS. Without LPS, it decreased TC in mice ( P < 0.05). Moreover, C8:0 decreased the inflammatory response after LPS treatment in both mice and cells ( P < 0.05). Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD, C16:0 and EPA, and resulted in lower TNF-α, NF-κB mRNA expression than that with HFD ( P < 0.05). In RAW 264.7 cells, C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group, and higher protein expression of ABCA1, p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups ( P < 0.05).@*CONCLUSION@#Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response, and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.

Research progress of inflammatory cytokines in rheumatoid arthritis / 中国药理学通报

Rheumatoid arthritis (RA) is the most common eause of autoimmune arthritis in the world.In RA patients serum or plasma cytokine levels may indicate the severity of the disease.Cytokine gene polymorphism can be used as a marker of RA susceptibility and severity.Rheumatoid arthritis is a systemic connective tissue disease.Not only joints, but other organs (lungs.lymph nodes, spleen, skin, heart or eyes) may also he involved.'Hie main goal of treatment for rheumatoid arthritis is to avoid joint destruction through early and aggressive anti-inflammatory treatment.In the past few decades, various therapies were used for patients when methotrexate was ineffective or intolerant to alter the joint and systemic prognosis and the patients' disability.Among them, cytokine targeted therapy have long been identified to be the most promising therapy.This article re- views the effector functions of different inflammatory factors and their role in the RA pathogenesis and the targeted inhibitors targeting inflammatory factors that can currently be used for the treatment of RA.

Value of autotaxin in predicting refractory Mycoplasma pneumoniae pneumonia in children and its correlation with inflammatory cytokines / 中国当代儿科杂志

OBJECTIVES@#To study the value of autotaxin (an autocrine motility factor) level in serum and bronchoalveolar lavage fluid (BALF) in predicting refractory Mycoplasma pneumoniae pneumonia (RMPP) in children and its correlation with interleukin-6 (IL-6), interleukin-8 (IL-8), and C-reactive protein (CRP).@*METHODS@#A retrospective analysis was performed on 238 children with Mycoplasma pneumoniae pneumonia who were admitted from January 2019 to December 2021. According to disease severity, they were divided into two groups: RMPP (n=82) and general Mycoplasma pneumoniae pneumonia (GMPP; n=156). The two groups were compared in terms of the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF to study the value of autotaxin level in serum and BALF in predicting RMPP in children, as well as the correlation of autotaxin level with IL-6, IL-8, and CRP in children with RMPP.@*RESULTS@#Compared with the GMPP group, the RMPP group had significantly higher levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF (P<0.05). For the children with RMPP, the levels of autotaxin, IL-6, IL-8, and CRP in serum and BALF in the acute stage were significantly higher than those in the convalescent stage (P<0.05). The receiver operating characteristic (ROC) curve showed that the level of autotaxin in serum and BALF had a good value in predicting RMPP in children, with an area under the curve of 0.874 (95%CI: 0.816-0.935) and 0.862 (95%CI: 0.802-0.924), respectively. The correlation analysis showed that the level of autotaxin in serum and BALF was positively correlated with IL-6, IL-8, and CRP levels (P<0.001).@*CONCLUSIONS@#The level of autotaxin in serum and BALF increases and is correlated with the degree of disease recovery and inflammatory cytokines in children with RMPP. Autotaxin can be used as a predictive indicator for RMPP in children.

Effect of Buyang Huanwutang on Platelet Function and Inflammatory Cytokine in Rat Model of Acute Blood Stasis Induced by Multiple Factors / 中国实验方剂学杂志

ObjectiveTo explore the effect of Buyang Huanwutang （BYHWT） on platelet function and inflammatory cytokines in the rat model of acute blood stasis. MethodThe model of acute blood stasis was established with SD rats by ice water bath combined with injection of epinephrine. Rats were randomly assigned into four groups： normal group， model group， BYHWT （3.2 g·kg-1） group， and aspirin （60 mg·kg-1） group. The rats were injected with epinephrine hydrochloride on day 8 after 7 days of modeling. The macroscopic indexes of triditional Chinese medicine （TCM） syndrome including tongue manifestation and pulse manifestation were observed， while hemorheological indexes， blood coagulation， and platelet aggregation were detected. The serum levels of the inflammatory cytokine matrix metalloprotein-9 （MMP-9） and the adhesion factor intercellular adhesion molecule-1 （ICAM-1） and were determined by enzyme-linked immunosorbent assay （ELISA）. ResultThe pulse distention of rats in the model group was lower than that in the normal group （P<0.01）， while BYHWT improved the pulse distention of the rats with the syndrome of blood stasis （P<0.01）. In the model group， the tongue showed the characteristics of blood stasis syndrome， with dark purple veins at the tongue bottom and lower values of R， G， B on the tongue surface than those in the normal group （P<0.01）， which， however， can be recovered by BYHWT （P<0.01）. The blood viscosity at high， medium， and low shear stress and the plasma viscosity in the model group were higher than those in the normal group （P<0.01， P<0.05）. Compared with the model group， BYHWT restored the whole blood viscosity under high， medium and low shear stress and plasma viscosity （P<0.05，P<0.01）. The model group had shorter prothrombin time （PT）， shorter thrombin time （TT）， and higher fibrinogen （FIB） than the normal group （P<0.05， P<0.01）. BYHWT improved the TT and reduced the FIB in the rats with blood stasis syndrome （P<0.01）. The platelet aggregation rate induced by arachidonic acid （AA） and adenosine diphosphate （ADP） in the model group was higher than that in normal group （P<0.01） and BYHWT decreased the platelet aggregation rate of the rats with blood stasis syndrome （P<0.01）. The results of scanning electron microscopy showed that the model group exhibited excessive platelet activation， obvious pseudopodia， and increased aggregation of platelets compared with the normal group， while platelet activation and aggregation were rare in the BYHWT group. The serum levels of MMP-9 and ICAM-1 in the model group were higher than those in the normal group （P<0.01）， which were decreased in the BYHWT group （P<0.05， P<0.01）. ConclusionThe SD rats with the syndrome of acute blood stasis induced by ice water bath combined with injection of epinephrine demonstrate obvious changes in platelet function and morphology， inflammation， and abnormal cell adhesion. In the treatment of acute blood stasis in rats， BYHWT may reduce thrombosis and improve blood consistency and cohesion by mitigating inflammation， down-regulating cell adhesion factor overexpression， and improving platelet shape and function.

Analysis of clinical features of 16 cases with Chlamydia psittaci pneumonia / 中华危重病急救医学

Objective:To analyze the clinical characteristics of Chlamydia psittaci pneumonia and to investigate the correlation between serum inflammatory biomarkers and severity of the disease. Methods:Sixteen patients with Chlamydia psittaci pneumonia admitted to the Huizhou Municipal Central Hospital from January 2020 to July 2021 were selected as the study subjects, including 10 severe cases and 6 mild cases. Clinical data were collected and analyzed, such as baseline characteristics, clinical symptoms, laboratory inspection and chest imaging manifestations. Results:① Thirteen Chlamydia psittaci pneumonia were associated with a definite bird or poultry contact history. Common symptoms included high fever, chill, cough, fatigue, and anorexia (16 cases), dyspnoea (12 cases), and other systemic symptoms. ② Laboratory test results showed normal white blood cell count (WBC, 10 cases), decreased lymphocyte count (LYM, 13 cases), increased high sensitive C-reactive protein (hs-CRP, 16 cases), D-dimer (15 cases), lactate dehydrogenase (LDH, 13 cases), aspartate aminotransferase (AST, 16 cases) and alanine aminotransferase (ALT, 12 cases) levels, however, the albumin (Alb, 15 cases) lever was decreased. The numbers of CD3 + T cells and CD4 + T cells decreased in 10 patients. ③ The levels of D-dimer, interleukins (IL-2, IL-6, IL-10) in severe Chlamydia psittaci pneumonia were significantly higher than those in mild Chlamydia psittaci pneumonia [D-dimer (μg/L): 10 257±4 203 vs. 1 085±642, IL-2 (ng/L): 1.1 (0.8, 1.7) vs. 0.3 (0.1, 0.7), IL-6 (ng/L): 315 (182, 505) vs. 75 (18, 131), IL-10 (ng/L): 7.0±4.1 vs. 2.3±0.7], but the LYM was lower (×10 9/L: 0.4±0.1 vs. 1.1±0.4), with significant differences (all P < 0.05). ④ Chest imaging manifestations were exudative lesions and large consolidation of lungs. Large consolidation of both lungs can occur in some critically ill patients. Conclusions:Chlamydia psittaci pneumonia is mainly associated with a bird or poultry contact history. The clinical manifestations usually present high fever, dyspnea, normal or slightly increased leucocytes, and lung consolidation. The levels of LYM, D-dimer, IL-2, IL-6 and IL-10 in serum are expected to predict the severity of the Chlamydia psittaci pneumonia.

The pathogenetic role of macrophage polarization in the necrotizing enterocolitis / 中国小儿急救医学

Objective:To investigate the effect of macrophage polarization in the pathogenesis of necrotizing enterocolitis(NEC).Methods:C57BL/6 mice were chose to construct the NEC model.The preterm pups were randomly assigned into the control group( n=10) and the NEC group( n=19). The pups in the control group were breastfed by mothers while the NEC group were treated with hypoxia, hypothermia, hypertonic feeding and lipopolysaccharide treatment.The intestinal tissues from the lower part of duodenum to the colon were collected after the pups were born after 96 hours.HE staining was used to observe the intestinal histological structure.Intestinal mucosal permeability was detected by the measurement of concentration of FD70 in plasma after gastric gavage.The expression of Pan-keratin of intestinal epithelium was detected by immunofluorescence histochemistry.Enterocyte apoptosis was detected by TUNEL staining.The expression of CD86 and CD206 protein were determined by western blotting and the percentage of M1 and M2 macrophages was calculated by flow cytometry.RT-PCR was used to detect the expression of mRNA levels of granulocyte-macrophage colony stimulating factor, interleukin(IL)-6, IL-10 and IL-12. Results:Compared with the control group, the pups in the NEC group had low survival rate(100.0% vs.36.8%), different level of intestinal injury, incomplete integrity of intestinal epithelium, increased mucosal permeability(1.53±0.80 vs.14.32±1.27, P<0.05)and enterocyte apoptosis(1.9%±1.1% vs.7.6%±2.6%, P<0.05). Western blotting showed that the expression of CD86 protein(1.00±0.01 vs.1.50±0.10, P<0.05) increased while CD206 protein decreased(1.00±0.01 vs.0.60±0.05, P<0.05) in the NEC group.Flow cytometry showed that the percentage of CD68 + CD86 + M1 macrophages increased(1.90%±0.19% vs.10.20%±0.38%, P<0.05) while the CD68 + CD206 + M2 macrophages decreased(5.8%±0.33% vs.3.7%±0.56%, P<0.05) in the NEC group.The expression of the mRNA levels of pro-inflammatory cytokines, granulocyte-macrophage colony stimulating factor(1.00±0.05 vs.1.83±0.17, P<0.05), IL-6 (1.00±0.13 vs.2.00±0.58, P<0.05) and IL-12(1.00±0.05 vs.1.49±0.22, P<0.05) increased and the anti-inflammatory cytokine IL-10(1.00±0.22 vs.0.09±0.01, P<0.05) decreased. Conclusion:Polarization of macrophages towards the pro-inflammatory M1 subtype plays an important role in the pathogenesis of NEC.

Clinical observation on deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle for trigeminal neuralgia of wind and heat / 中国针灸

OBJECTIVE@#To compare the clinical therapeutic effect between deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle and conventional acupuncture in patients with trigeminal neuralgia (TN) of wind and heat, and explore its mechanism.@*METHODS@#A total of 60 patients with TN of wind and heat were randomized into an observation group (30 cases) and a control group (30 cases). In the observation group, deep needling with round sharp needle was applied at Xiaguan (ST 7), and tapping with plum-blossom needle was applied at Yangbai (GB 14), Quanliao (SI 18), Dicang (ST 4), Sibai (ST 2), etc. of affected side. In the control group, conventional acupuncture was applied at the same acupoints selected in the observation group. The treatment was given once a day, 5 times a week for 4 weeks in the both groups. Before and after treatment, the scores of short-form McGill pain questionnaire (SF-MPQ), TCM syndrome, patient global impression of change (PGIC) and comprehensive symptom were observed, the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vasoactive intestinal peptide (VIP) and β-endorphin (β-EP) were detected, and the adverse reaction was observed in the both groups.@*RESULTS@#After treatment, the scores of PRI, PPI, VAS, TCM syndrome, PGIC and comprehensive symptom and the serum levels of IL-6, TNF-α and VIP were decreased compared before treatment in the both groups (@*CONCLUSION@#Deep needling at Xiaguan (ST 7) with round sharp needle combined with plum-blossom needle can effectively treat the trigeminal neuralgia of wind and heat and relieve pain, its therapeutic effect is superior to conventional acupuncture. The mechanism may be related to the regulation of serum IL-6, TNF-α, VIP and β-EP.

Study on the modeling method and pathological parameters of chronic atrophic gastritis / 中华消化杂志

Objective:To explore an ideal method for establishing a mouse model of chronic atrophic gastritis (CAG).Methods:CAG mouse models were established with five different modeling methods ( N-methyl- N′-nitro- N-nitrosoguanide (MNNG), sodium salicylate, sodium deoxycholate, Helicobacter pylori infection, and combinations of them) in BALB/c and C57 mice. The effect of each modeling method was evaluated by histological observation of gastric mucosa, plasma biochemical parameters, inflammatory response score, and the expression of anti-inflammatory factors. Results:The results of histological observation of gastric mucosa showed that all of the 5 methods could successfully establish CAG mouse models. In BALB/c mice, compared with the healthy control group, significant features of CAG accompanied with intestinal metaplasia was found in the model group established by combination of MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate. From the results of serological detection, compared with the normal control group, the mRNA expression levels of related anti-inflammatory factors interleukin-2, interleukin-10, interleukin-13 and growth differentiation factor-15 of each model group decreased, which indicated that the mice of each CAG model group had different degrees of inflammation. The results of plasma biochemical parameters indicated that plasma gastrin of each group decreased and the ratio of pepsinogen Ⅰ and pepsinogen Ⅱ significantly dropped. The above results demonstrated that in BLAB/c mice, MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate was better than other four modeling methods. For C57 mice, it was also found that simple chemical drug mutagenesis and Helicobacter pylori replication method both could successfully establish CAG models. No matter from pathological observation, relative expression of anti-inflammatory factors and analysis of plasma biochemical parameters, the effects of combination of the two methods was better. Conclusion:The CAG mouse model established by MNNG-free drinking, 2% sodium salicylate and 20 mmol sodium deoxycholate can provide a certain reference for the establishment and application of mouse model in CAG experiments in the future for pharmacological research.

TLR8 in the Trigeminal Ganglion Contributes to the Maintenance of Trigeminal Neuropathic Pain in Mice / 神经科学通报·英文版

Trigeminal neuropathic pain (TNP) is a significant health problem but the involved mechanism has not been completely elucidated. Toll-like receptors (TLRs) have recently been demonstrated to be expressed in the dorsal root ganglion and involved in chronic pain. Here, we show that TLR8 was persistently increased in the trigeminal ganglion (TG) neurons in model of TNP induced by partial infraorbital nerve ligation (pIONL). In addition, deletion or knockdown of Tlr8 in the TG attenuated pIONL-induced mechanical allodynia, reduced the activation of ERK and p38-MAPK, and decreased the expression of pro-inflammatory cytokines in the TG. Furthermore, intra-TG injection of the TLR8 agonist VTX-2337 induced pain hypersensitivity. VTX-2337 also increased the intracellular Ca

Therapeutic effect of chondroitin sulfate combined with triptolide liposome on arthritic rats / 中国药理学通报

Aim To compare the therapeutic effects of free triptolide (TP), free triptolide-chondroitin sulfate ( TP-CS-Lips ) , triptolide liposome ( TP-Lips ) and triptolide combined with chondroitin sulfate liposome (TP-CS-Lips) on collagen-induced arthritis (CIA) rats. Methods A total of 48 SD SPF rats were select ed in the study, 8 of which were randomly treated as controls and the remained 40 rats were injected with complete Frederik's adjuvant -chicken type II collagen to establish CIA. The 48 rats successfully modeled were randomly divided into five groups; model group, TP group, TP-CS group, TP-Lips group and TP-CS-Lips group. The treatment groups were intraperitoneally injected with corresponding drugs (TP:30 jig • kg"1, CS:100 mg • kg"1) every day, while the control group and model group were intraperitoneally injected with an equal volume of 0. 9% sodium chloride solution once a day, with a treatment cycle of 28 days. Before administration (0 d) and at 7 d, 14 d, 21 d and 28 d , the body mass index and arthritis index of rats were evaluated; thymus index and splenic index of each group were analyzed. HE staining was used to observe the pathological changes of cartilage. The expressions of inflammatory cytokines IL-1, TNF- and 1L-6 in serum were detected by ELISA. Results Compared with model group, TP-CS-Lips significantly increased the body mass of arthritic rats (P <0. 05) , and the arthri-tis index score was also significantly induced ( P < 0. 05) ; thymus and spleen indexes of rats significantly decreased (P<0. 05) ; pathological injury of cartilage of knee joint was significantly reduced; the IL-l, TNF- and IL-6 levels of serum also significantly decreased (P <0.05). Furthermore, the therapeutic effect of TP-CS-Lips was superior to that of TP, TP-CS and TP- Lips in arthritic rats. Conclusions TP-CS-Lips could significantly enhance the therapeutic effect of CIA, which provides experimental basis for the development of nano-agents for the treatment of arthritis.