Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. Methods Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. Results NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. Conclusions There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Research progress on invasive cervical resorption / 口腔疾病防治

@#Tooth absorption can be divided into physiological absorption and pathological absorption. Root absorption of mature deciduous teeth is physiological absorption. Pathological absorption includes internal absorption and external absorption. Internal absorption, also known as intramedullary absorption, includes inflammatory absorption and alternative absorption. External tooth absorption originates from the outer surface of the root or the neck of the tooth and can be divided into inflammatory absorption, alternative absorption, pressure resorption and invasive cervical resorption. Invasive cervical resorption (ICR) is pathological damage caused by many factors, which usually begins in the cemento-enamel junction and extends peripherally or horizontally in the dentin. It hardly invades the pulp. Orthodontic devices, trauma, bleaching, systemic diseases, and the use of certain medications can all lead to invasive cervical resorption. The clinical manifestations of ICR are usually asymptomatic or not obvious, and most of which are found in imaging examinations. Because caries and internal absorption are often misdiagnosed through plain apical radiography, cone beam computed tomography (CBCT) can help to better understand the situation of invasive cervical resorption. Because the pathogenesis and etiology of invasive cervical resorption are not fully understood, clinical negligence and inadequate treatment of invasive cervical resorption can even cause unnecessary tooth loss. This article reviews the latest research progress on the histopathologic features, pathogenic mechanism, susceptibility factors, diagnosis and treatment of ICR, with special emphasis on susceptibility factors and their mechanisms.

Preliminary study on the mechanism of dexmedetomidine regulating lncRNA HOTAIR to improve lung injury in septic mice / 中华急诊医学杂志

Objective:To investigate the mechanism of dexmetomidine (DEX) in improving lung injury in septic mice.Methods:Male C57BL/6 mice were randomly assigned to the blank group (NC), sham operation group (sham), cecal ligation and puncture group (CLP), and Dex treatment group (CLP+DEX), 36 mice per group. Mice in the CLP group were intraperitoneally injected with 1 mL sterile saline 15 min before CLP, and mice in the CLP + DEX group were intraperitoneally injected with 50 μg/kg DEX 15 min before CLP. The survival rate was recorded within 24 h after CLP. The mice were sacrificed at 0, 3, 6, 12, and 24 h after CLP, and lung tissues were collected. The expression levels of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in the lung of mice were detected by qPCR. RAW264.7 cell were cultured in vitro, LPS (100 ng/mL) and DEX (1 μ mol/L) were used to establish a cell model for studying the mechanism of Dex, and the expression of cytokines (IL-6, IL-1β, TNF-α) and lncRNA-HOTAIR in RAW264.7 cell model were detected by qPCR. In addition, the effect of lncRNA-HOTAIR on sepsis was explored in vivo and in vitro by knockdown or overexpression of HOTAIR.Results:The survival rate of the CLP+DEX group was higher than that of the CLP group within 24 h after surgery, and the levels of IL-6, IL-1β, and TNF-α in the lungs were significantly lower than those in the CLP group at 6, 12, and 24 h after surgery ( P<0.05). In addition, the level of lncRNA HOTAIR showed that the expression level of lncRNA HOTAIR in the lungs of mice were decreased after Dex treatment, and were decreased 1.1 times ( P<0.05), 4.0 times ( P<0.01) and 3.8 times ( P<0.01) at 6, 12, and 24 h, respectively. Compared with the NC group, knockdown of HOTAIR significantly decreased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.05), and overexpression of HOTAIR significantly increased the levels of IL-1β, IL-6, and TNF-α in septic mice ( P<0.01). Conclusions:DEX can reduce the production of inflammatory factors in the lungs of septic mice and improve the survival rate of septic mice. The mechanism may be related to the inhibition of HOTAIR expression.

Induced pluripotent stem cell-derived exosome attenuates the inflammatory response in microglia / 中华急诊医学杂志

Objective:To investigate the effects of induced pluripotent stem cell-derived exosome (iPSC-Exo) on releasing inflammatory factors from microglia induced by lipopolysaccharide (LPS).Methods:iPSC derived from the tubular epithelial cells of sepsis encephalopathy patients were resuscitated and cultured. The iPSC-Exo was isolated by low-temperature ultracentrifugation and analyzed by transmission electron microscopy, Western blot and high sensitivity flow cytometry (HSFCM). Based on the concentration of iPSC-Exo, human microglia line HMO6 cells activated by LPS (100 ng/mL) were divided into four groups randomly: LPS+ phosphate buffer solution (PBS) group, LPS+iPSC-Exo 10 5 group, LPS+iPSC-Exo 10 6 group and LPS+iPSC-Exo 10 7 group. The control group was added equal PBS but not LPS. After culture for 24 h, the concentrations of malondialdehyde in cells were detected. Quantitative RT-PCR was used to measure the mRNA expression levels of macrophage inflammatory protein 2 (MIP2), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in the cells and enzyme-linked immunosorbent assay (ELISA) was used to assess the concentration of these cytokines in the supernatant. Under the same concentration of iPSC-Exo, one-way ANOVA and SNK- q test were used for comparison between groups. Results:The extracts showed spherical membrane structure by transmission electron microscopy. HSFCM showed the mean diameter of the extracts was (74.66±15.60) nm and the concentration around 2.98×10 10/mL. Western blot analysis showed high expression of exosome markers CD63, Alix and TSG101, but not GM130. Intracellular MDA concentration and mRNA expression levels and protein concentration of MIP2, TNF-α, IL-1β and IL-6 in the LPS+PBS group were significantly higher than those in the control group (all P<0.01). With the increase of iPSC-Exo concentration, the intracellular MDA concentration decreased gradually ( P<0.01), the mRNA expression levels of inflammatory factors showed a gradual downward trend (all P<0.05). Each inflammatory cytokine in the supernatant declined in a manner that was almost consistent with mRNA. Concentrations of MDA remained constant in the control group. Conclusions:iPSC-Exo derived from the tubular epithelial cells of sepsis encephalopathy patients alleviate oxidative stress and inflammation effect of microglia induced by LPS, and the modulatory effect is dose-dependent.

Clinical study of self-made Xingqi Jiedu Decoction combined with goserelin in the treatment of endometriosis / 国际中医中药杂志

Objective:To evaluate the curative effect of self-made Xingqi Jiedu Decoction combined with goserelin for endometriosis (EMT).Methods:Randomized controlled trial. A total of 84 patients with EMT in the hospital were enrolled as observation objects between July 2019 and July 2021. According to random number table method, they were divided into the control group (subcutaneous injection of goserelin) and the observation group (self-made Xingqi Jiedu Decoction on basis of control group), 42 in each group. All were treated for 6 months. TCM syndromes were scored before and after treatment. The severity of pelvic pain was evaluated by VAS. The levels of FSH, LH and estradiol (E 2) were detected by full-automatic chemiluminescence immunoassay and corresponding reagents, and levels of serum IL-1β, IL-8 and TNF-α were detected by ELISA. The adverse events were recorded, and clinical curative effect was evaluated. Results:The differences in total response rate between observation group and control group was statistically significant [95.24% (40/42) vs. 80.95% (34/42); χ2=4.09, P=0.043]. After treatment, scores of TCM syndromes and VAS in observation group were significantly lower than those in the control group ( t=14.30, 7.32, P<0.01). After treatment, FSH [(5.36±1.03) U/L vs. (6.20±1.35) U/L, t=3.21], E 2[(230.57±36.84) pmol/L vs. (265.28±37.53) pmol/L, t=4.28] and LH [(8.15±1.18) U/L vs. (9.24±2.01) U/L, t=3.03] in the observation group were significantly lower than those in the control group ( P<0.01). The levels of IL-1β, IL-8 and TNF-α in the observation group were significantly lower than those in the control group ( t=5.05, 5.07, 3.82, P<0.01). During treatment, differences in incidence of adverse reactions between observation group and control group was statistically significant [19.05% (8/42) vs. 4.76% (2/42); χ2=4.09, P=0.043]. Conclusion:The self-made Xingqi Jiedu Decoction combined with goserelin can improve hormone level, inhibit inflammatory response and improve clinical curative effect in EMT patients.

Research progress on mechanism of epithelial mesenchymal transition induced by chrysotile exposure / 环境与职业医学

As a mineral material widely used in life, chrysotile is a public health concern for its fibrogenicity and carcinogenicity. Currently, more than 50 countries have completely banned the import and use of chrysotile, but China is still the world's largest consumer and second largest producer of chrysotile, with a large occupationally exposed population. Investigations have shown that chrysotile miners are significantly more likely to develop pulmonary fibrosis, lung cancer, and mesothelioma than workers in other occupations. Chrysotile-induced cancers generally have a decades-long latency period and are difficult to diagnose and treat in a timely manner. Therefore, the cancer fatality due to chrysotile exposure is significant and is a leading contributor to occupational cancer death. Epithelial mesenchymal transition is a key step in the biological processes of chronic inflammation, fibrosis, carcinogenesis, and cancer metastasis in tissues and organs, also plays an important role in pulmonary fibrosis, lung cancer, and other diseases due to chrysotile exposure. This paper summarized the mechanisms of chrysotile inducing epithelial interstitial transition from dynamics of inflammatory factors, mitogen-activated protein kinase pathways, oxidative stress, and other biological pathways, and proposed possible research directions for further study on chrysotile-induced epithelial mesenchymal transition, aiming to provide a reliable basis and reference for in-depth research on pulmonary fibrosis, lung cancer, and other diseases due to chrysotile exposure.

Protective effects and mechanism of Dachengqi decoction on intestinal septic mice / 中国药房

OBJECTIVE To study the protective effects of Dachengqi decoction （DCQD） on intestinal septic mice， and to explore the possible mechanisms from the Toll-like receptor 4（TLR4）/myeloid differentiation factor 88（MyD88） signaling pathway. METHODS The SPF male C57BL/6J mice were randomly divided into Sham group， Sham+DCQD-H group， model （CLP） group， DCQD-L group， DCQD-H group and Positive group. The model of intestinal sepsis was established by cecal ligation and puncture in CLP group， DCQD-L group， DCQD-H group and Positive group. Three days before the operation and seven days after the operation， DCQD-L group and DCQD-H group were given DCQD intragastrically at 4， 8 g/kg （calculated by crude drug）， respectively. Positive group was given ulinastatin intraperitoneally 2 h before operation and 7 d after the operation （at 50 000 U/kg）. In Sham group and Sham+DCQD-H group， only cecum of mice was exposed without ligation and puncture. Sham+DCQD- H group was given DCQD intragastrically （8 g/kg，calculated by crude drug） 3 days before the operation and 7 days after the operation. Both the Sham group and CLP group were given normal saline 0.2 mL intragstrically and intraperitoneally each day， for 10 consecutive days. After the operation， the severity of sepsis was assessed， and the 7 d survival rate of mice was assessed. One hour after the last medication， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in serum and ileum of mice were determined； the pathological and morphological changes of mice’s liver， lung， kidney and ileum were observed； mRNA expressions of the TLR4 and MyD88 in ileum were tested. RESULTS Compared with CLP group， sepsis score， the levels of TNF-α and IL-6 in serum and ileum （except for IL-6 in ileum of DCQD-L group）， damage score of the liver， lung， kidney and ileum， mRNA expressions of TLR4 and MyD88 in ileum were all decreased significantly in DCQD-L group and DCQD-H group （P＜0.05 or P＜0.01）， while 7 d survival rate （except for DCQD-L group） was increased significantly （P＜0.05）. The damage to liver tissue in mice was significantly improved， and inflammation infiltration and apoptosis were reduced； lung tissue damage had been alleviated， with varying degrees of improvement in alveolar atrophy， bleeding and edema； the renal tissue damage was improved and weakened dilation of renal tubular lumen was weakened； the damage and edema of ileal tissue were significantly improved. CONCLUSIONS DCQD may exert a protective role on intestinal septic model mice. The mechanism may be related to the inhibition of systemic inflammation， the reduction of multiple organ damage， and down-regulation of TLR4/MyD88 signaling pathway.

Clinical Effect of Guanxin Shutong Capsules in Treating Coronary Heart Failure with Heart Blood Stasis / 中国实验方剂学杂志

ObjectiveTo investigate the clinical effect of Guanxin Shutong capsules （GXSTC） on coronary heart failure with heart blood stasis. MethodA total of 98 coronary heart failure patients with heart blood stasis who visited the expert clinics of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from June 2020 to August 2022 were selected. They were randomized into a control group and an observation group， with 49 in each group. The two groups were given standardized treatment according to the guidelines for coronary heart failure. On this basis， the observation group was treated with Chinese patent medicine GXSTC. The cardiac structural and functional indicators， total effective rate of symptoms， exercise tolerance， heart rate variability （HRV）， quality of life and inflammatory factor levels of the two groups before and after treatment were compared. ResultBefore treatment， there was no notable difference in high-sensitivity C-reactive protein （hs-CRP）， six minute walk test （6MWT）， minnesota living with heart failure questionnaire （MLHFQ） score， left ventricular ejection fraction （LVEF）， tumor necrosis factor-α （TNF-α）， left ventricular end-diastolic diameter （LVEDD）， N-terminal pro-brain natriuretic peptide （NT-proBNP） and HRV between the two groups， and thus the data were comparable. After treatment， the observation group had higher effective rates of traditional Chinese medicine （TCM） symptoms （Z=-2.362， P<0.05） and New York heart association class （NYHA） functional classes （Z=-2.175， P<0.05） than the control group. The two groups presented decreased LVEDD， TNF-α， NT-proBNP and hs-CRP （P<0.05， P<0.01） while increased MLHFQ， 6MWT and HRV（P<0.05，P<0.01） after treatment as compared with those before treatment， and the observation group had more decrease or increase than the control group （P<0.05， P<0.01）. ConclusionGXSTC combined with standardized treatment relieves the physical symptoms of coronary heart failure patients with heart blood stasis， improves exercise tolerance and quality of life， reduces inflammatory reaction， increases HRV， and improves cardiac structure and function.

Qiju Dihuangtang Combined with Chinese Medicine Fumigation in Treatment of Dry Eye and Its Effect on Levels of Tear IL-6 and MMP-9 / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Qiju Dihuangtang combined with Chinese medicine fumigation in the treatment of dry eye and its effect on the levels of interleukin-6 （IL-6） and matrix metalloproteinase-9 （MMP-9） in tears. MethodA total of 120 patients with dry eye of liver-kidney Yin deficiency syndrome who were treated in the Department of Ophthalmology， The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine（TCM） from october 2019 to october 2021 were randomized into the observation group and control group. The control group was given sodium hyaluronate eye drops， and the observation group was treated with sodium hyaluronate eye drops， Qiju Dihuangtang， and Chinese medicine fumigation. The treatment lasted 30 days for both groups. The changes of ocular surface disease index （OSDI）， TCM syndrome score， tear secretion （SIT）， tear film breaking up time （BUT）， corneal fluorescein staining （FL）， and tear interleukin-6 （IL-6） and matrix metalloproteinase-9 （MMP-9） were observed. ResultAfter the treatment， the total effective rate was 90.0% （54/60） in the observation group and 75.0% （45/60） in the control group （χ2=4.675， P<0.05）. After treatment， the OSDI score and TCM syndrome score were lower than those before treatment in both groups （P<0.05）， and lower in the observation group than in the control group （P<0.05）. After treatment， the SIT and BUT were higher （P<0.05） and FL score was lower （P<0.05） than those before treatment in both groups. After treatment， the improvement of the above indicators in the observation group was better than that in the control group （P<0.05）. After treatment， the levels of IL-6 and MMP-9 were lower than those before treatment in both groups （P<0.05）， and lower in the observation group than in the control group （P<0.05）. ConclusionQiju Dihuangtang combined with Chinese medicine fumigation can effectively improve subjective symptoms， promote tear secretion， prolong BUT， enhance corneal epithelial repair， and reduce the levels of tear IL-6 and MMP-9 in the treatment of dry eye.

Effect of Bufeitang on Lung-gut Axis in Rats with Lung Qi-deficiency Syndrome of Chronic Obstructive Pulmonary Disease / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Bufeitang on intestinal flora of rats with lung Qi-deficiency syndrome of chronic obstructive pulmonary disease（COPD）， and to explore the mechanism of traditional Chinese medicine in regulating intestinal flora and thus restoring the balance of lung-gut axis. MethodA total of 84 rats were randomly divided into 7 groups， including blank group， model group， fecal bacterial transplantation（FMT） group， dexamethasone group and low， medium and high dose groups of Bufeitang， 12 rats in each group. Except for the blank group， cigarette and sawdust fumigation combined with intratracheal instillation of lipopolysaccharide（LPS） were used to establish the COPD rat model with lung Qi-deficiency syndrome in all other groups. The low， medium and high dose groups of Bufeitang were intragastric administrated with Bufeitang（3.645， 7.29， 14.58 g·kg-1）， the FMT group was given fecal bacteria liquid enema（10 mL·kg-1）， dexamethasone group was given dexamethasone acetate tablet suspension by gavage（0.135 mg·kg-1）， the blank group and model group were given equal amount of distilled water. Fresh feces were collected after 28 d of continuous intervention for 16S rRNA gene sequencing. Lung and colon tissues were stained with hematoxylin-eosin（HE） for pathomorphological observation， and enzyme-linked immunosorbent assay （ELISA） was performed to detect the contents of tumor necrosis factor-α（TNF-α） and interleukin-8（IL-8） in lung tissues. ResultCompared with the blank group， the model group showed severe abnormal lung tissue structure with alveolar atrophy and collapse accompanied by severe inflammatory cell infiltration. Compared with the model group， the extent of injury was significantly improved， and inflammatory cell infiltration was reduced with basically normal alveolar structure in the high dose group of Bufeitang. Compared with the blank group， the model group had severely abnormal colonic tissue structure， the epithelial cells in the mucosal layer were eroded and shed， the number of inflammatory cells increased， the submucosal layer was edematous and the gap was enlarged. Compared with the model group， the extent of damage was significantly improved in the medium and high dose groups of Bufeitang， the epithelial cells in the mucosal layer were neatly and closely arranged， with only a small amount of inflammatory cell infiltration and no significant degeneration. Compared with the blank group， the TNF-α and IL-8 levels of lung tissue in the model group were significantly increased（P<0.01）. Compared with the model group， the TNF-α and IL-8 levels of lung tissues in the low， medium and high dose groups of Bufeitang were significantly decreased（P<0.01）. Bufeitang significantly modulated the number of bacteria species as well as alpha and beta diversity of model rats， corrected the return of intestinal flora to normal abundance and diversity， and positively regulated 4 differential phyla（such as Firmicutes， Proteobacteria） and 13 differential genera（such as Turicibacter， Lactobacillus， Anaerobiospirillum， Intestinimonas） in COPD model rats with lung Qi-deficiency syndrome， and down-regulated 2 carbohydrate metabolic pathway functions， including the pentose phosphate pathway（non-oxidative branch） Ⅰ and the Calvin-Benson-Bassham cycle. ConclusionBufeitang can modulate the abundance and diversity of intestinal flora species， affect the function of metabolic pathways， repair the structure of lung and colon tissues， regulate the level of inflammatory factors， and thus improve COPD with lung Qi-deficiency syndrome. The mechanism may be related to its regulation of inflammation-related intestinal flora to restore the balance of lung-gut axis in COPD with lung Qi-deficiency syndrome.

Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells / 中国结合医学杂志

OBJECTIVE@#To examine the anti-inflammatory effect of grape seed extract (GSE) in animal and cellular models and explore its mechanism of action.@*METHODS@#This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis (MS)-experimental autoimmune encephalomyelitis (EAE) mice model were further explored. The C57BL/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17 and the inflammatory factors such as tumor necrosis factor- α (TNF- α), interleukin-1 β (IL-1 β), IL-6, IL-12, IL-17 and interferon-γ (IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay (ELISA), immunofluorescence staining and Western blot, respectively.@*RESULTS@#GSE reduced the secretion of TNF-α, IL-1 β and IL-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide (P<0.01), inhibited the secretion of TNF-α, IL-1 β, IL-6, IL-12, IL-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days (P<0.05 or P<0.01), and reduced the differentiation of Th1 and Th17 mediated by CD3 and CD28 factors (P<0.01). GSE significantly improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4 (TLR4) and Rho-associated kinase (ROCKII, P<0.05 or P<0.01), and inhibited the secretion of inflammatory factors (P<0.01 or P<0.05). In the central nervous system, GSE inhibited the infiltration of CD45+CD11b+ and CD45+CD4+ cells, and weakened the differentiation of Th1 and Th17 (P<0.05). Moreover, it reduced the secretion of inflammatory factors (P<0.01), and prevented the activation of microglia (P<0.05).@*CONCLUSION@#GSE had a beneficial effect on the pathogenesis and progression of EAE by inhibiting inflammatory response as a potential drug and strategy for the treatment of MS.

Inhibitory Effect of Cinobufotalin on Macrophage Inflammatory Factor Storm and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism.@*METHODS@#THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot.@*RESULTS@#1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway.@*CONCLUSION@#Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.

Asiatic acid improves insulin secretion of β cells in type 2 diabetes through TNF- α/Mfn2 pathway / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg－1·d－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.

Clinical effect of Kangfuxin solution combined with lidocaine and gentamicin in the treatment of oral ulcer / 药学实践杂志

Objective To investigate the clinical efficacy of Kangfuxin solution combined with lidocaine and gentamicin in the treatment of oral ulcers. Method A total of 120 patients with oral ulcer admitted to Tongzhou District Maternity and Child Health Care Hospital of Beijing from May 2019 to July 2021 were selected and divided into observation group and control group randomly. 58 patients were treated with lidocaine as a control group and 62 patients in the observation group were treated with Kangfuxin solution combined with lidocaine and gentamicin. The clinical efficacy, including oral ulcer condition, visual analogue scale (VAS score) after 3d and 5d of treatment, inflammatory factor levels and adverse reactions were observed and compared between the two groups before and after treatment. Results The overall effective rate of the treatment group (95.12%) was higher than that of the control group (74.36%) and the difference was statistically significant (P<0.05). The ulcer area, ulcer healing time, and chewing improvement period were remarkably reduced compared with those in the control group (P<0.05). The VAS scores after 3d and 5d of treatment, the levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups were statistically significant (P<0.05). There was no significant difference in the incidence of adverse reactions (3.22%) between the observation group and the control group (6.90%) (P>0.05). Conclusion Kangfuxin solution combined with lidocaine and gentamicin showed better curative effect on oral ulcer. This treatment regimen could effectively ameliorate various clinical symptoms of patients with oral ulcer, reduce patient pain and downregulate the levels of inflammatory factors, and help patients recover with high safety profile.

Effects of oxycodone hydrochloride and dezocine on hemodynamics and levels of inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia

Abstract We aimed to compare the effects of oxycodone hydrochloride and dezocine on hemodynamics and inflammatory factors in patients receiving gynecological laparoscopic surgery under general anesthesia. A total of 246 patients were divided into group A and B (n=123). Hemorheology indices were recorded 5 min after anesthesia (T0), 1 min after pneumoperitoneum (T1), when position was changed 5 min after pneumoperitoneum (T2), 15 min after pneumoperitoneum (T3), 1 min (T4) and 5 min (T5) after position was restored. Visual analogue scale scores 1, 2, 6, 12, 24 and 48 h after operation were recorded. Postoperative adverse reactions and visceral pain were observed. The expression levels of inflammatory factors were detected by enzyme-linked immunosorbent assay 12 h after operation. Compared with group A, group B had higher heart rate and mean arterial pressure at T2, lower central venous pressure and cardiac output at T1-T3, and higher systemic vascular resistance at T1-T5 (P<0.05). The incidence rate of pain syndrome in group A was lower (P<0.05). Group A had lower tumor necrosis factor-alpha and interleukin-6 expression levels and higher interleukin-10 level than those of group B (P<0.05). For gynecological laparoscopic surgery, oxycodone preemptive analgesia has superior outcomes to those of dezocine

Effects of acupuncture on neurologic function and serum inflammatory factors after thrombolysis in acute ischemic stroke / 中国针灸

OBJECTIVE@#To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS).@*METHODS@#A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups.@*RESULTS@#After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05).@*CONCLUSION@#Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.

Intense pulsed light combined with meibomian gland massage and diquafosol sodium eye drops in the treatment of lipid deficiency / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the efficacy of intense pulsed light combined with meibomian gland massage and diquafosol eye drops in lipid deficiency dry eye disease and related cytokines.METHODS: A total of 511 patients(1 022 eyes)with lipid deficiency dry eye diagnosed in the ophthalmology clinic of our hospital from January to December 2021 were selected as the research objects. They were divided into two groups according to the patient's wishes: 294 cases(588 eyes)in the study group were treated with diquafosol sodium eye drops combined with intense pulsed light and meibomian gland massage, while 217 cases(434 eyes)in the control group were treated with artificial tears combined with intense pulsed light and meibomian gland massage. The levels of tear tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)and lactoferrin(LF)before and after treatment were detected, the corneal fluorescein staining(CFS)score, tear film break-up time(BUT), and Schirmer Ⅰ(SⅠt)under no surface anesthesia, ocular surface disease index(OSDI)were compared, the correlation between TNF-α, IL-1β, LF levels and CFS, BUT, SⅠt, OSDI before treatment was analyzed, and the occurrence of adverse reactions was observed.RESULTS: There was no significant difference in preoperative OSDI, SⅠt, BUT, CFS and levels of TNF-α, IL-1β and LF between the two groups(P&#x003E;0.05). The SⅠt, BUT, CFS and levels of TNF-α, IL-1β and LF in the study group at 3, 6 and 9wk after treatment were better than those of control group(P&#x003C;0.05). There were no differences in OSDI score of both groups at 9wk after treatment(P&#x003E;0.05). The TNF-α and IL-1β were negatively correlated with SⅠt and BUT, while they were positively correlated with CFS and OSDI; LF and SⅠt were positively correlated with SⅠt and BUT, while they were negatively correlated with CFS and OSDI(all P&#x003C;0.01); The adverse reaction rate of the study group(5.78%)was significantly lower than that of the control group(11.52%; P&#x003C;0.05).CONCLUSION: Intense pulsed light combined with meibomian gland massage and diquafosol sodium eye drops is effective and well tolerated in the treatment of lipid deficiency dry eye.

The preventive effect and mechanism of Dayuanyin in hypoxic pulmonary hypertension through NF-κB signaling pathway / 药学学报

Dayuanyin (DYY) has been shown to reduce lung inflammation in both coronavirus disease 2019 (COVID-19) and lung injury. This experiment was designed to investigate the efficacy and mechanism of action of DYY against hypoxic pulmonary hypertension (HPH) and to evaluate the effect of DYY on the protection of lung function. Animal welfare and experimental procedures are approved and in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Science. Male C57/BL6J mice were randomly divided into 4 groups: control group, model group, DYY group (800 mg·kg-1), and positive control sildenafil group (100 mg·kg-1). The animals were given control solvents or drugs by gavage three days in advance. On day 4, the animals in the model group, DYY group and sildenafil group were kept in a hypoxic chamber containing 10% ± 0.5% oxygen, and the animals in the control group were kept in a normal environment, and the control solvent or drugs continued to be given continuously for 14 days. The right ventricular systolic pressure, right ventricular hypertrophy index, organ indices and other metrics were measured in the experimental endpoints. Meantime, the expression levels of the inflammatory factors in mice lung tissues were measured. The potential therapeutic targets of DYY on pulmonary hypertension were predicted using network pharmacology, the expression of nuclear factor kappa B (NF-κB) signaling pathway-related proteins were measured by Western blot assay. It was found that DYY significantly reduced the right ventricular systolic pressure, attenuated lung injury and decreased the expression of inflammatory factors in mice. It can also inhibit hypoxia-induced activation of NF-κB signaling pathway. DYY has a protective effect on lung function, as demonstrated by DYY has good efficacy in HPH, and preventive administration can slow down the disease progression, and its mechanism may be related to inhibit the activation of NF-κB and signal transducer and activator of transcription 3 (STAT3) by DYY.

Preoperative intravitreal injection of Conbercept combined with pars plana vitrectomy in the treatment of proliferative diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of pars plana vitrectomy(PPV)combined with preoperative intravitreal injection of conbercept in the treatment of proliferative diabetic retinopathy(PDR)and its effect on aqueous humor inflammatory factors.METHODS: A non-randomized controlled clinical trial was designed. The clinical data of 100 patients(100 eyes)with PDR who were admitted to the hospital from March 2019 to January 2022 were collected(the heavier eye was selected when both eyes had PDR, while the right eye was selected when the PDR degree was the same)and divided into control group and combined group according to their treatment wishes. The 48 eyes in the control group received PPV alone, and 52 eyes in the combined group received intravitreal injection of conbercept combined with PPV. Follow-up period was 12mo. The operative time, pre-and post-operative best corrected visual acuity(BCVA LogMAR), central retinal thickness(CRT)and postoperative complications in the two groups were statistically analyzed. And the levels of inflammatory factors(IL-6, IL-10, IFN-γ and TNF-α)in aqueous humor were compared between the two groups.RESULTS: Compared with the control group, the levels of inflammatory factors IL-6, IL-10, IFN-γ and TNF-α in aqueous humor in combination group were significantly decreased. The operation time of the combined group was significantly shorter than that of the control group, and the number of electrocoagulation, iatrogenic retinal hole and silicone oil filling were less in the combined group than those in the control group(all P&#x003C;0.05). There was no significant difference in preoperative BCVA and CRT between the two groups(all P&#x003E;0.05). The BCVA and CRT improved at 1, 6 and 12mo after surgery in both groups, but the improvement was more significant in the combined group(all P&#x003C;0.05). The postoperative incidence of complications in the combined group were lower than that in the control group(11.5% vs. 35.4%, P&#x003C;0.05). There was no significant difference in the recurrence rate of PDR between the two groups(P&#x003E;0.05).CONCLUSIONS: Intravitreal injection of conbercept combined with PPV in the treatment of PDR has a significant effect, which can shorten the operation time, inhibit the inflammatory effect, reduce postoperative complications, and contribute to the improvement of patients' vision.

Effect of hypothermic machine perfusion on expression levels of inflammatory cytokines in rat kidney / 器官移植

Objective To evaluate the effect of hypothermic machine perfusion (HMP) on the expression levels of inflammatory cytokines in rat kidney. Methods Thirty male rats were randomly divided into the control (Control group), static cold storage group (SCS group) and HMP group, with 10 rats in each group. The velocity, intrarenal resistance and pH value of perfusion effluent were recorded during HMP. The expression levels of CXC chemokine ligand (CXCL)1, CXCL2, interferon (IFN)-β1, IFN-α4, CC chemokine ligand (CCL)2, CCL20, interleukin (IL)-17α, IL-17C and tumor necrosis factor (TNF)-α messenger RNA (mRNA) in renal tissues were evaluated by reverse transcription polymerase chain reaction (RT-PCR). Pathological changes of the kidney were observed by hematoxylin-eosin (HE) staining. Results During HMP, the velocity and intrarenal resistance remained stable, and the pH value of perfusion effluent was decreased slowly. RT-PCR showed that the relative expression levels of CXCL1, CXCL2, CCL2, CCL20, IL-17α, IL-17C and TNF-α mRNA in the SCS and HMP groups were higher compared with those in the Control group. Compared with the SCS group, the relative expression levels of CXCL1, CXCL2, CCL2, CCL20, IL-17α and TNF-α mRNA were up-regulated in the HMP group (all P<0.05). HE staining revealed that the morphology of renal cells was normal in the Control group, whereas evident epithelial necrosis, cytoplasmic vacuolation, brush border loss and epithelial shedding were observed in the SCS group. Compared with the SCS group, pathological changes in the HMP group were alleviated. Conclusions HMP may activate renal inflammation, and inhibiting the activation of inflammation during HMP is expected to further improve the effect of allograft preservation.