Dimethyl fumarate inhibits NLRP3/AIM2 inflammasomes to prevent spleen radiation injury ZHANG / 中国药理学通报

Aim To investigate the protective effect of dimethyl fumarate on spleen injury induced by gamma radiation in mice and the related mechanism. Methods C57BL/6 mice were randomly divided into the blank control group, radiation model group and DMF administration group, which were administered once at 12 h before irradiation and once at 0. 5 h, 12 h, 24 h and 48 h after irradiation. The 30-day survival rate, body weight and pathological injury of spleen were measured after a one-time total body irradiation of Co 7 rays (8 Gy). TUNEL staining was used to detect apoptosis of spleen cells. Enzyme-linked immunoassay ( ELISA) was applied to detect the contents of TNF-a, IL-1 p, IL-6, IL-18, NLRP3 and AIM2 in spleen. Western blot test and immunofluorescence staining test was employed to verify the changes of NLRP3 and AIM2 contents in spleen tissue after irradiation. Results DMF could obviously improve the survival rate of irradiated mice, improve the weight loss of irradiated mice, re-duce the pathological injury of spleen, and inhibit the apoptosis of spleen cells after irradiation. ELISA results showed that DMF could significantly inhibit the increase of spleen inflammatory cytokines TNF-a, IL-lp, IL-6, IL-18 and inflammasome components NL-RP3 and AIM2 induced by irradiation. Western blot and tissue immunofluorescence staining also confirmed that DMF could inhibit the increase of NLRP3 and AIM2 inflammasome protein levels caused by irradiation. Meanwhile, NLRP3 agonist and AIM2 agonist could antagonize the radiation protection effect of DMF on spleen cells. Conclusion DMF can ameliorate spleen injury of Co 7-ray injured mice, and its mechanism is closely related to NLRP3/AIM2 inflamma-somes, which can be used as a potential protective drug for radiation injury.

Effect of safflower yellow on learning and memory ability of APP/PS1 at different months based on TLR4/NF-KB signaling pathway / 中国药理学通报

Aim To investigate the effect of safflower yellow (SY) on learning and memory ability of APP/ PS1 mice at different disease stages, and to explore the mechanism of SY anti- Alzheimer's disease by using 3-,6- and 9-month-old APP/PS 1 transgenic mice as experimental animal models. Methods Behavioral experiments were conducted to observe the effects of SY on learning and memory of APP/PS1 mice of different months. ELISA was used to detect the effect of SY on the expression of inflammatory factors in cortex of mice of different months. Western blot was used to detect the microglia activation marker protein, and its mechanism of action was further analyzed. Results SY could enhance the learning and memory ability of mice aged 3, 6 and 9 months, reduce the content of IL-6 and increase the content of TGF-β1 in brain tissue, up-regulate the expression levels of arginase-1 (arg-1) and triggering receptor expressed on myeloid cells 2 (tREM2) in brain tissue of mice of different months, and down-regulate the expression levels of inducible nitric oxide synthase (iNOS), Toll-like receptors 4 (tlr4) and nuclear factor-kappa B (nf-KB). Conclusions Compared with 3- and 9-month-old mice, SY is the most effective in improving learning memory in 6-month-old APP/PS1 mice. SY inhibits TLR4/NF-KB pathway activation by inducing TREM2 expression in brain tissue of APP/PS 1 transgenic mice, promotes microglia phenotype shift to anti-inflammatory phenotype, reduces chronic neuroinflammatory response, and improves learning memory in APP/PS1 mice at all months of age.

Protective effect and mechanism of Longshengzhi capsules on cerebral ischemia-reperfusion injury in rats / 中国药房

OBJECTIVE To explore the protective effect and mechanism of Longshengzhi capsules on cerebral ischemia- reperfusion injury in rats. METHODS The model of middle cerebral artery occlusion （MCAO） was established by using the improved thread occlusion method. The experiment was divided into six groups： sham surgery group （only separating blood vessels without inserting thread plugs， given the same volume of normal saline）， model group （modeling， given the same volume of normal saline）， nimodipine group （positive control， modeling， dose of 20 mg/kg）， and low-dose， medium-dose， and high-dose groups of Longshengzhi capsules （modeling， doses of 0.72， 1.44 and 2.88 g/kg， respectively）， with 10 mice in each group. Each group was given corresponding medication solution/normal saline by gavage， once a day， for 7 consecutive days. One hour after the last administration， the Zea Longa scoring method was used to score the neurological deficits in each group of rats， and the ABC enzyme-linked immunosorbent assay was used to detect the serum levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rats； TTC staining was used to observe the volume of cerebral infarction in rats and calculate the cerebral infarction volume ratio. Hematoxylin eosin staining was used to observe the pathological changes in the brain tissue of rats. Immunohistochemical staining was used to detect the positive expression of NLRP3 protein in the brain tissue of rats. Real-time fluorescence quantitative PCR was used to detect mRNA relative expressions of Toll-like receptor 4 （TLR4） and nuclear factor-κB （NF-κB） in the brain tissue of rats. Western blot assay was adopted to detect the relative expressions of TLR4， NLRP3 and phosphorylated NF-κB （p-NF-κB） protein in the brain tissue of rats and its intracellular NF-κB protein. RESULTS Compared with the sham surgery group， the neural dysfunction score， serum levels of TNF-α and IL-6， cerebral infarction volume ratio， relative expression levels of NF-κB and TLR4 mRNA， as well as protein relative expressions of TLR4， NLRP3 and p-NF-κB in the brain tissue， and relative protein expression of intracellular NF-κB were increased significantly in the model group （P＜0.01）； the enlarged gap and significant edema were observed in cortical nerve cells of brain tissue in rats， with a large amount of inflammatory cell infiltration； the positive expression of NLRP3 protein in brain tissue of rats obviously increased. Compared with the model group， the levels of the above indicators in the medium-dose and high-dose groups of Longshengzhi capsules， as well as the Nimodipine group， were reversed to varying degrees， and most differences were statistically significant （P＜0.05 or P＜0.01）； the pathological morphology observation showed a significant improvement， and the positive expression of NLRP3 protein in the brain tissue of rats was obviously reduced. CONCLUSIONS Longshengzhi capsules may inhibit TLR4/NF-κB/NLRP3 signaling pathway and neuroinflammatory response， thereby achieving a protective effect against cerebral ischemia-reperfusion injury in rats.

Improvement of Skin Barrier and Anti-inflammatory Mechanism of Huangliansan on Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect of Huangliansan on atopic dermatitis （AD） model mice induced by 2， 4-dinitrochlorobenzene （DNCB）. MethodA total of 42 male BALB/c mice were randomly divided into normal group， model group， hydrocortisone group， low， medium， and high-dose groups （0.3， 0.6， 1.2 g·kg-1） of Huangliansan oil， and water extract group （0.6 g·kg-1） of Huangliansan. In addition to the normal group， DNCB was applied on the back of mice in other groups to establish the AD model. On the 15th day after DNCB stimulation， each group was given the corresponding drug or solvent， and the changes in skin lesions， dermatitis score， and frequency of scratching were observed and recorded. Hematoxylin-eosin （HE） staining was used to observe the histopathological changes in the skin and spleen. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA levels of filaggrin （FLG）， lorophane （LOR）， and involucrin （IVL） in skin， as well as immunoglobulin E （lgE）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interferon-γ （IFN-γ） in spleen. ResultCompared with the normal group， the model group showed symptoms of skin swelling and scab， and the score of dermatitis， the frequency of scratching， and the spleen index were increased （P<0.05）. The expression levels of FLG， LOR， and IVL in skin tissue were significantly decreased （P<0.01）， and the mRNA expressions of IgE， IL-4， IL-6， IL-1β， and TNF-α in the spleen were significantly increased， while the expression level of IFN-γ was significantly decreased （P<0.01）. Compared with the model group， the symptoms of skin erythema， scaly， and scab of mice in each drug group were alleviated to varying degrees， and the score of dermatitis， the frequency of scratching， and the spleen index were decreased （P<0.05， P<0.01）. In addition， the expression levels of FLG， LOR， and IVL in the skin of mice in the drug group were increased （P<0.05， P<0.01）， and the mRNA expression of IgE， IL-4， IL-6， IL-1β， and TNF-α in spleen were decreased. IFN-γ was increased （P<0.05， P<0.01）， and the lesions of the skin and spleen were improved to varying degrees. The medium-dose group of Huangliansan oil and hydrocortisone group had the most obvious manifestations （P<0.05， P<0.01）. The indexes in the medium-dose group of Huangliansan oil were better than those in the water extract group of Huangliansan. ConclusionHuangliansan may improve the expression level of skin barrier protein， inhibit the expression of helper T cell 2 （Th2）-related inflammatory factors， increase the expression of helper T cell 1 （Th1） inflammatory factors， restore the skin barrier function and Th1/Th2 balance in the spleen， regulate the inflammatory response in the spleen of AD mice， and thus relieve AD. Huangliansan oil is more effective than water extract.

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.

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.

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.

Melatonin promotes osteogenesis of bone marrow mesenchymal stem cells by improving the inflammatory state in ovariectomized rats / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effects of melatonin (MT) on bone mass and serum inflammatory factors in rats received ovariectomy (OVX) and to investigate the effects of MT on the levels of inflammatory factors in culture medium and osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) stimulated by lipopolysaccharide.@*METHODS@#Fifteen 12-week-old Sprague Dawley (SD) rats were randomly divided into 3 groups. The rats in Sham group only received bilateral lateral abdominal incision and suture, the rats in OVX group received bilateral OVX, and the rats in OVX+MT group received 100 mg/(kg·d) MT oral intervention after bilateral OVX. After 8 weeks, the levels of serum inflammatory factors [interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)] were detected using ELISA assay. Besides, the distal femurs were detected by Micro-CT to observe changes in bone mass and microstructure, and quantitatively measured bone volume fraction, trabecular thickness, and trabecular number. The BMSCs were extracted from the femurs of three 3-week-old SD rats using whole bone marrow culture method and passaged. The 3rd-5th passage BMSCs were cultured with different concentrations of MT (0, 1, 10, 100, 1 000 µmol/L), and the cell viability was then detected using cell counting kit 8 (CCK-8) to select the optimal concentration of MT for subsequent experiments. Cells were devided into osteogenic induction group (group A) and osteogenic induction+1/5/10 μg/mL lipopolysaccharide group (group B-D). The levels of inflammatory factors (IL-1β, IL-6 and TNF-α) in cell culture medium were detected using ELISA assay after corresponding intervention. According to the results of CCK-8 method and ELISA detection, the cells were intervened with the most significant concentration of lipopolysaccharide for stimulating inflammation and the optimal concentration of MT with osteogenic induction, defining as group E, and the cell culture medium was collected to detect the levels of inflammatory factors by ELISA assay. After that, alkaline phosphatase (ALP) staining and alizarin red staining were performed respectively in groups A, D, and E, and the expression levels of osteogenic related genes [collagen type Ⅰ alpha 1 chain (Col1a1) and RUNX family transcription factor 2 (Runx2)] were also detected by real time fluorescence quantitative PCR (RT-qPCR).@*RESULTS@#ELISA and Micro-CT assays showed that compared with Sham group, the bone mass of the rats in the OVX group significantly decreased, and the expression levels of serum inflammatory factors (IL-1β, IL-6, and TNF-α) in OVX group significantly increased (P<0.05). Significantly, the above indicators in OVX+MT group were all improved (P<0.05). Rat BMSCs were successfully extracted, and CCK-8 assay showed that 100 µmol/L was the maximum concentration of MT that did not cause a decrease in cell viability, and it was used in subsequent experiments. ELISA assays showed that compared with group A, the expression levels of inflammatory factors (IL-1β, IL-6, and TNF-α) in the cell culture medium of groups B-D were significantly increased after lipopolysaccharide stimulation (P<0.05), and in a concentration-dependent manner. Moreover, the expression levels of inflammatory factors in group D were significantly higher than those in groups B and C (P<0.05). After MT intervention, the expression levels of inflammatory factors in group E were significantly lower than those in group D (P<0.05). ALP staining, alizarin red staining, and RT-qPCR assays showed that compared with group A, the percentage of positive area of ALP and alizarin red and the relative mRNA expressions of Col1a1 and Runx2 in group D significantly decreased, while the above indicators in group E significantly improved after MT intervention (P<0.05).@*CONCLUSION@#MT may affect the bone mass of postmenopausal osteoporosis by reducing inflammation in rats; MT can reduce the inflammation of BMSCs stimulated by lipopolysaccharide and weaken its inhibition of osteogenic differentiation of BMSCs.

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.

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.

Exploring on Mechanism of Gegen Qinliantang in Interventing Antibiotic-associated Diarrhea Based on 16S rRNA Sequencing and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Gegen Qinliantang（GQT） on the intestinal flora of antibiotic-associated diarrhea（AAD） by 16S rRNA sequencing and network pharmacology. MethodSixty SD rats were randomly divided into six groups（n=10）， including blank group， model group， GQT high-， medium- and low-dose groups（10.08， 5.04， 2.52 g·kg-1） as well as Lizhu Changle group（0.15 g·kg-1）， except for the blank group， each group was given clindamycin（250 mg·kg-1） by gavage once a day for 7 consecutive days. After successful modeling， the blank group and the model group were given equal volumes of normal saline by gavage. The other groups were given corresponding doses of drugs by gavage for 14 days. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to screen the active components and targets of GQT， GeneCards， Online Mendelian Inheritance in Man（OMIM） database， Pharmacogenetics and Pharmacogenomics Knowledge Base（PharmGKB）， DrugBank and DisGeNET were used to search for AAD disease targets. The drug-disease common targets were obtained by R software. STRING was applied to analyze the target protein-protein interaction， and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis was performed. Then hematoxylin-eosin（HE） staining was used to observe the pathological changes of the colon， and 16S rRNA sequencing of AAD colon content flora structure further verified the results of network pharmacology. ResultThrough network pharmacology， it was found that 238 active components were screened from GQT and acted on 276 component targets， among which quercetin， puerarin， wogonin and apigenin were the main core components of GQT， 1 097 AAD disease targets and 127 drug-disease intersection targets. The protein-protein interaction network mainly included core targets such as protein kinase B1（Akt1）， interleukin（IL）-6 and IL-1β， which were mainly enriched in the IL-17 signaling pathway. It was verified through animal experiments that compared with the blank group， the colon structure of the model group was seriously abnormal， the intestinal epithelial columnar cells were damaged， the goblet cells were reduced， and a large number of inflammatory cells were infiltrated. Compared with the model group， the colon structure of the GQT high-dose group improved， but there were still abnormalities， the colon structure of GQT medium- and low- dose groups and Lizhu Changle group improved significantly and reached the normal level. GQT could improve the structural diversity of AAD intestinal flora. At the phylum level， the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased. At the genus level， the abundance of Lactobacillus was increased， and the abundances of Prevotella and Bacteroides were decreased. Among them， Lactococcus could be used as a biomarker for AAD treatment with GQT， and the prediction of functional metabolism of intestinal flora revealed that GQT could promote acetate and lactate metabolic pathways in the intestine. ConclusionGQT may activate IL-17 signaling pathway by acting on the targets of Akt1 and IL-6 through key components such as quercetin and wogonin， and improve the abundance of Lactococcus in the intestinal tract as well as acetate and lactate metabolic pathways， so as to play a role in repairing the intestinal barrier for the treatment of AAD.

Protective effects of ginsenosides on macrophages subjected to simulated weightlessness / 数字中医药（英文）

@#[Objective] To investigate the evolution of inflammation under conditions and the effects of ginsenosides on macrophages subjected to the simulated weightlessness, with the aim of mitigating the inflammation. [Methods] Initially, genes related to weightlessness, inflammation, and immunity were identified in the GeneCards database. Then, Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) protein network analysis was conducted to determine the core targets involved in the weightlessness-induced inflammation. Subsequently, Label-Free Quantitative (LFQ) proteomics was carried out to discern the distinctive genes within ginsenoside-treated Tohoku Hospital Pediatrics-1 (THP-1) cells. Next, utilizing the outcomes of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the biological processes and signaling pathways in which ginsenosides predominately engaged were scrutinized, and the primary targets of ginsenosides in combating weightlessness-induced inflammation were examined. Finally, enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α from lipopolysaccharide (LPS)-induced THP-1 cells under simulated weightlessness conditions, as well as during the weightlessness recovery period following treatment with ginsenosides. [Results] A total of 2 933 genes associated with inflammation, 425 genes linked to weightlessness, and 4 564 genes connected to immunity were retrieved from the GeneCards database. Protein-protein interaction (PPI) networks were generated to identify pivotal targets associated with weightlessness-induced inflammation such as IL-1β, IL-6, TNF, and albumin (ALB). It was found that ginsenosides primarily participated in the regulation of various inflammationrelated signaling pathways and pathways related to pathogenic microorganism infections. Moreover, it has a significant impact on the expression of proteins such as cluster of differentiation 40 (CD40), IL-1β, and poly ADP-ribose polymerase 1 (PARP1). As revealed in the simulated weightlessness cell test, ginsenosides exhibited a remarkable capacity to attenuate the secretion of inflammatory factors, specifically IL-6 and TNF-α (P < 0.000 1), in THP-1 macrophages following induction by LPS under simulated weightlessness conditions. In addition, it reduced the secretion of IL-1β, IL-6, IL-8, and TNF-α (P < 0.000 1) during the weightlessness recovery phase [Conclusion] Weightlessness can disrupt several inflammation-related signaling pathways, but ginsenosides were shown to mitigate the release of various inflammatory factors in macrophages subjected to simulated weightlessness, thereby exerting a protective role against inflammation. This study has laid a theoretical groundwork for further exploring the potential application of ginsenosides in safeguarding against LPS induced inflammation in a weightlessness environment.

Effects of recombinant human interferon α2a suppository on levels of inflammatory factors in cervical mucus of HPV-infected patients / 中国生物制品学杂志

@#Objective To investigate the effects of recombinant human interferon α2a(rhIFNα2a) suppository on the levels of inflammatory factors in the cervical mucus of patients infected with human papillomavirus(HPV).Methods A total of60 HPV-positive patients admitted to the Second Affiliated Hospital of Xi'an Jiaotong University from March to August in 2022 were selected as study objects,and then divided into observation and control groups,30 cases for each group,according to the random number table method.The observation group was given rhIFNα2a suppository therapy by vaginal medication,once every other day,continuous 10 times a month as a course of treatment,and 3 consecutive courses of treatment.The control group did not use drugs.The cervical secretions were collected and the levels of IL-1β,IL-2R,IL-6,IL-8,IL-10 and tumor necrosis factor-α(TNF-α) were measured by chemiluminescence assay.Results After 3 months of treatment,the levels inflammatory factors IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group were significantly lower than those in the control group(t=-2.717,-2.686,-3.178 and-3.25,respectively,each P <0.05).Compared with before treatment,the levels of IL-1β,IL-6,IL-8 and TNF-α in cervical mucus of patients in the observation group also decreased significantly(t=5.934,4.092,6.495 and 3.287,respectively,each P <0.01),while in the control group,only the level of IL-8 in cervical mucus was significantly different(t=2.345,P=0.024).Conclusion rhIFNα2a suppository can reduce the level of inflammatory factors in cervical mucus,attenuate the inflammatory response and accelerate the clearance of HPV.

Functional study of Zinc in regulating M1 polarization of tumor associated macrophages during radical resection of lung cancer / 中华胸心血管外科杂志

Objective:To explore the molecular mechanism of zinc donor regulating macrophage polarization, and to explore the correlation between serum zinc content and the clinical index during radical resection of lung cancer.Methods:One hundred and thirty-two patients who undergoing radical resection of lung cancer were enrolled in this study. The serum zinc content was detected by atomic absorption spectrophotometry before operation. The patients were allocated into high-Zn group and low-Zn group. The blood samples of the included subjects were collected before operation (before), immediately after operation (POP1) and 6 hours after operation (POP2), and the plasma high-sensitivity C-reactive protein (hs-CRP) and catalase were detected. The correlation between serum zinc content and clinical features were analyzed. Metrological statistics was performed by using t test or Mann- Whitney test, and counting statistics was performed by χ2 test. Results:The POP1-hs-CRP[(1.69±0.66)mg/L vs. (1.99±0.43)mg/L, POP2-hs-CRP[(3.51±1.01)mg/L vs. (4.59±0.78)mg/L] and other indicators of high-Zn group were significantly lower than those of low-Zn group.Conclusion:There is a negative correlation between serum zinc content and the inflammation during radical resection of lung cancer, suggesting that appropriate zinc supplementation has a protective effect on radical resection of lung cancer patients.

Construction and evaluation of a prognostic model for severe acute pancreatitis based on CT scores and inflammatory factors / 中华危重病急救医学

Objective:To construct a prognostic model for severe acute pancreatitis (SAP) based on CT scores and inflammatory factors, and to evaluate its efficacy.Methods:128 patients with SAP diagnosed admitted to the First Hospital Affiliated to Hebei North College from March 2019 to December 2021 were enrolled and given Ulinastatin combined with continuous blood purification therapy. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8), tumor necrosis factor-α (TNF-α), and D-dimer were measured before and on the third day of treatment. An abdominal CT was performed on the third day of treatment to assess the modified CT severity index (MCTSI) and extra-pancreatic inflammatory CT score (EPIC). Patients were divided into the survival group ( n = 94) and the death group ( n = 34) according to the 28-day survival prognosis after admission. The risk factors for the SAP prognosis were analyzed using Logistic regression, which was then used to build nomogram regression models. The value of the model was evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA). Results:Before treatment, the levels of CRP, PCT, IL-6, IL-8 and D-dimer in the death group were higher than those in the survival group. After treatment, the levels of IL-6, IL-8 and TNF-α in the death group were higher than those in the survival group. MCTSI and EPIC scores in the survival group were lower than those in the death group. Logistic regression analysis shows that, pre-treatment CRP > 140.70 mg/L, D-dimer > 2.00 mg/L, and post-treatment IL-6 > 31.28 ng/L, IL-8 > 31.04 ng/L, TNF-α > 31.04 ng/L, and MCTSI > 8 points were all independent risk factors for SAP prognosis [odds ratios ( OR) and 95% confidence intervals (95% CI) were 8.939 (1.792-44.575), 6.369 (1.368-29.640), 8.546 (1.664-43.896), 5.239 (1.108-24.769), 4.808 (1.126-20.525), 18.569 (3.931-87.725), all P < 0.05]. Model 1 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α) had a lower C-index than that model 2 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI; 0.988 vs. 0.995). The mean absolute error (MAE) and mean square error (MSE) of model 1 (0.034, 0.003) were higher than those of model 2 (0.017, 0.001). When the threshold probability was in the range of 0-0.66 or 0.72-1.00, the net benefit of model 1 was lower than that of model 2. When the threshold probability was in the range of 0.66-0.72, the net benefit of model 1 was higher than that of model 2. In addition, model 2 had a higher C-index than acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) and bedside index of acute pancreatitis severity (BISAP, 0.995 vs. 0.833, 0.751). Model 2 had a lower MAE (0.017) and MSE (0.001) than APACHEⅡ (0.041, 0.002). Model 2 had a lower MAE than BISAP (0.025). Model 2 had a higher net benefit than both APACHEⅡ and BISAP. Conclusion:The prognostic assessment model of SAP consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI has high discrimination, precision and clinical application value, and is superior to APACHEⅡ and BISAP.

Effect of Compound Duzhong Jiangu Granules on joint function, quality of life and inflammatory factors in patients with Kashin-Beck disease / 中华地方病学杂志

Objective:To study the effect of Compound Duzhong Jiangu Granules on joint function, quality of life and inflammatory factors in patients with Kashin-Beck disease.Methods:By group design, 135 patients with Kashin-Beck disease in Chongxin County, Pingliang City, Gansu Province, were selected and divided into intervention group (100 cases treated with Compound Duzhong Jiangu Granules, 12 g/bag, 1 bag/time, 3 times/day, treatment for 1 month) and control group (35 cases treated with ibuprofen, 0.3 g/capsule, 1 capsule/time, 2 times/day, treatment for 2 weeks) according to the randomized, single-blind principle. The changes of joint dysfunction index score, joint function improvement rate, total scores of Kashin-Beck disease quality of life (KBDQOL) and scores of each dimension were analyzed before treatment, 1 month and 3 months after treatment. The serum levels of interleukin-6 (IL-6), nuclear factor κB (NFκB)-p65, inducible nitric oxide synthase (NOS2), nitric oxide (NO), and prostaglandin E2 (PGE2) were detected by enzyme-linked immunosorbent assay before treatment and 1 month after treatment.Results:The total scores of joint dysfunction index of the intervention group and the control group 1 month after treatment and 3 months after treatment were lower than those before treatment, but 3 months after treatment was higher than 1 month after treatment ( P < 0.001). One month after treatment, the total effective rates of joint function improvement in the intervention group and the control group were 68.00% (68/100) and 54.55% (18/33), respectively; 3 months after treatment, the total effective rates of the intervention group and the control group were 36.00% (36/100) and 39.39%(13/33), respectively. The total scores and scores of each dimension of KBDQOL were not significant for the main effect of the group ( P > 0.05), but significant for the main effect at the time point ( P < 0.05), and there was no interactive effect ( P > 0.05). There were significant differences in the scores of social support and mental status dimensions in the intervention group at different time points ( P < 0.001). And in the intervention group, the total score, the scores of physical function, activity limitation, economy and overall health dimensions were statistically significant between before treatment and 1 month after treatment, 1 month after treatment and 3 months after treatment( P < 0.05); however, there was no significant difference between before treatment and 3 months after treatment ( P > 0.05). One month after treatment, the serum PGE2 levels of both groups were decreased ( P < 0.05), and there was no difference in other inflammatory factors at different groups and time points ( P > 0.05). Conclusion:Compound Duzhong Jiangu Granules can effectively inhibit the inflammatory reaction of patients with Kashin-Beck disease, promote the improvement of joint function and improve the quality of life in various aspects.

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.