Background: Inflammatory bowel disease (IBD) is frequently complicated by secondary bone loss driven by chronic inflammation and gut-bone axis dysregulation. Although dried ginger has pharmacological activities relevant to intestinal inflammation, the effects of dried ginger milk extract (DGME), a lipophilic constituent-enriched preparation, on IBD-associated bone loss (IBD-BL) remain unknown. This study evaluated the preventive and therapeutic effects of DGME on IBD-BL and explored the underlying mechanisms. Methods: Mice with DSS-induced IBD-BL were treated with DGME (250, 125, or 62.5 mg/kg) or sulfasalazine. Colitis severity, bone microarchitecture, osteoclast activity and Th17 cells were assessed by histology, micro-computed tomography, histomorphometry and flow cytometric analysis. UHPLC-Q-TOF MS, network pharmacology, 16S rRNA sequencing, fecal metabolomics, and in vitro assays were used for mechanistic investigation. Results: DGME ameliorated colitis, improved trabecular bone microarchitecture, and reduced osteoclast-related bone destruction. These effects were associated with selective suppression of pathogenic bone marrow TNF-α+ Th17 cells and downregulation of Il17a, Rorc, Tnfα, Ccr2, Ccr6, Cxcr4, Csf1, and Tnfsf11. Compared with aqueous extract, DGME was enriched in 19 lipophilic constituents. Multi-omics analyses showed that DGME remodeled gut microbiota and metabolite profiles, characterized by enrichment of Lactobacillus, Anaerotruncus, vanillin, and spermidine. Both vanillin and spermidine suppressed Th17 effector genes and inhibited MEK/ERK signaling in vitro. Conclusions: DGME alleviated IBD-BL by suppressing pathogenic TNF-α+ Th17 responses and remodeling the gut microbiota-metabolite axis. This study not only extends the therapeutic application of dried ginger from intestinal inflammation to IBD-BL, but also identifies vanillin and spermidine as candidate functional mediators linked to MEK/ERK inhibition.

BACKGROUND:Ma-Xing-Shi-Gan decoction (MXSG) shows clinical efficacy in asthma, yet how it shapes gut-lung immunity-particularly type 2 innate lymphoid responses-remains poorly defined. PURPOSE:To investigate whether MXSG mitigates asthma by restraining group 2 innate lymphoid cells (ILC2s) via a gut microbiota-tryptophan metabolic pathway, and to identify microbiota-dependent active compounds. METHODS:An asthma mouse model was used. ILC2 in the lung and intestinal lamina propria were assessed by flow cytometry. Rag1⁻/⁻ mice were used to assess T and B cell-independent effects. Untargeted fecal metabolomics and antibiotic-mediated microbiota depletion were conducted to evaluate metabolic and microbial contributions. Microbiota-dependent MXSG constituents were traced using anaerobic fecal fermentation coupled with LC-MS/MS profiling, followed by in vivo validation. RESULTS:MXSG significantly alleviated pulmonary inflammation, reduced bronchoalveolar lavage eosinophils and improved histopathology. It decreased ILC2s populations in lung and gut. These effects were preserved in Rag1⁻/⁻ mice but abolished with antibiotics pretreatment, indicating microbiota dependence. Metabolomics revealed that MXSG reprogrammed tryptophan metabolism, restoring tryptamine and rebalancing kynurenine, indole, and serotonin-related branches. Anaerobic fermentation and LC-MS/MS profiling identified microbiota-dependent flavonoids, and isorhamnetin partially reproduced the anti-inflammatory and ILC2-modulating effects in vivo. CONCLUSION:MXSG exerts its anti-asthmatic effects via the gut microbiota-tryptophan metabolism-ILC2 axis. These findings reveal a novel gut-lung mechanism centered on type 2 innate immunity and microbiota-derived indole metabolism.

BACKGROUND:Traditional Chinese medicines, as a burgeoning field of medication, significantly alleviate ulcerative colitis (UC) by improving intestinal microbiota-metabolism. Our previous studies demonstrated the significant efficacy of Hudi Enteric-coated capsules (HDEC), Qingchang Wenzhong decoction (QCWZ), and Modified Wumei pill (MWMP) using a mouse model of colitis. However, the mechanism of these therapies through the modulation of microbiota-metabolism remains uncertain. OBJECTIVE:Three multicenter randomized controlled trials were designed to explore the effects of three therapies on the microbiota-metabolism of UC patients with different severity. METHODS:A total of 143 patients with different severities of UC were recruited from 10 hospitals. The clinical efficacy of HDEC for mild UC, QCWZ for moderate UC, and MWMP for severe UC (SUCs) was evaluated by colorectal Mayo scores and systemic inflammatory indicators. The 16S rRNA sequencing and metabolomics were used to analyze intestinal microbiota and metabolite profiles. RESULTS:Three therapies used alone or combined with mesalazine (MS) were comparable to MS alone in improving Mayo scores and hematic inflammatory parameters. Microbial diversities and architectures of SUCs showed the greatest response to MWMP+MS than other medications, as reflected by the enriched Ruminococcus and Anaerostipes together with the reduced Enterococcus, Streptococcus, and Streptococcus anginosus. Furthermore, MWMP+MS boosted the production of the microbiota-derived short-chain fatty acids (SCFAs) of SUCs. These differential microbes and metabolites further displayed significant statistical relationships with clinical parameters. CONCLUSION:Herbal therapies, especially MWMP+MS, effectively improve microbiota composition and SCFA metabolism, which correlates with the improvements of serum inflammatory markers and endoscopic findings in patients.

Many studies have shown that the development of allergic asthma is associated with intestinal microbiota dysbiosis. Based on the gut-lung axis theory, probiotic intervention may be a potential strategy for respiratory diseases. Lacticaseibacillus paracasei K56 was reported to regulate gut microbiota in mice. However, its effect on allergic asthma has not been reported. In this study, we investigated the effect of the K56 on ovalbumin-induced asthma and its possible mechanisms. Our results showed that K56 reduced asthma symptoms and inflammatory cell infiltration in the lung of asthmatic mice. And K56 regulated the differentiation of helper T cells in the lung and intestine. Results from 16S rRNA gene sequencing showed that K56 prophylaxis significantly elevated the richness of Akkermansia and Burkholderia. Meanwhile, K56 abrogated the decrease in the levels of short-chain fatty acids (SCFAs) in the feces. In addition, a rebound in the mRNA expression of the SCFA receptors was observed after K56 prophylaxis. Notably, the regulatory T cell (Treg) frequencies and the FFAR3 levels were positively correlated. These results suggest that K56 could attenuate asthma, possibly by modulating the intestinal microbiota and regulating Treg differentiation through SCFA metabolized. Our study showed that K56 may be used as a probiotic to prevent pulmonary inflammation and dysbiosis of the intestinal microbiota in allergic asthma.

BACKGROUND:cGAS-STING-induced cellular senescence is a key driver of age-related chronic obstructive pulmonary disease (COPD). Bu-fei decoction (BFD) is a traditional Chinese medicine formula with significant clinical efficacy for COPD. However, the specific mechanism by which BFD modulates the cGAS-STING pathway to impact age-related COPD remains unclear. PURPOSE:To evaluate the therapeutic efficacy of BFD in age-related COPD and elucidate the underlying mechanisms. STUDY DESIGN AND METHODS:Flow cytometry and RT-qPCR were conducted to assess the phenotypes and transcriptional profiles of peripheral CD4+ naïve T cells from aged COPD patients and healthy controls. Young and aged COPD mouse models were established using cigarette smoke extract and lipopolysaccharide to investigate age-dependent mechanisms and BFD-related effects. C1qbp-knockdown Jurkat T cells were used to validate BFD's mechanisms in vitro. Network pharmacology and molecular docking predicted BFD-derived bioactive compounds targeting the cGAS-STING pathway. RESULTS:C1qbp downregulation in CD4+ Tnaive cells of aged COPD patients and mice significantly correlated with activated cGAS-STING signaling and elevated senescence markers. C1qbp knockdown in Jurkat T cells recapitulated these findings, triggering spontaneous cGAS-STING activation and senescence-related gene upregulation. BFD exhibited multi-therapeutic effects in aged COPD mice, improving lung function, reducing pulmonary inflammation, and restoring CD4+ Tnaive populations while suppressing cGAS-STING signaling and cellular senescence. The therapeutic benefits were substantially diminished when C1qbp was silenced. Twelve potential cGAS-STING-targeting bioactive compounds were predicted from BFD, mainly including formononetin, β-sitosterol, quercetin, etc. CONCLUSION: BFD mitigates CD4+ Tnaive cell senescence and attenuates age-related COPD, primarily by inhibiting the cGAS-STING pathway in a C1qbp-dependent manner.

Objective: Tuo-Min-Ding-Chuan decoction (TMDC), a traditional Chinese prescription, has demonstrated significant clinical efficacy in treating allergic asthma. This study aimed to investigate the mechanism of TMDC in treating asthma from the perspective of Treg cells and gut microbiota across distinct gut segments (jejunum, ileum, cecum, and colon). Methods: An ovalbumin (OVA)-induced asthma model was established in mice, followed by oral administration of TMDC at high, medium, and low dose. Immune cells and lung inflammation were examined to assess asthma severity. Microbial composition was determined by 16S rRNA sequencing. Antibiotic cocktail and Lactobacillus rhamnosus GG (LGG) were administrated to confirm the key role of specific bacteria. Results: TMDC attenuated lung inflammation (p < 0.01) and eosinophilic infiltration (p < 0.01) as well as IL-4 and IL-5 secretion (p < 0.01); it was also associated with an increase in Treg cells in the lung, small intestine (SI), and colon (p < 0.05). Meanwhile, TMDC restored the number of microbiota species and the Shannon index in the hindgut and reinstated beneficial bacteria, such as Allobaculum and Turicibacter, which were diminished in asthmatic mice. Notably, TMDC significantly enriched Bifidobacterium and Lactobacillus, particularly in the hindgut. Lactobacillus abundance was significantly correlated (p < 0.05) with Treg cells, IL-4, IL-5, and eosinophils. Furthermore, LGG supplementation restored elevated lung inflammation (p < 0.05) and decreased Treg cells (p < 0.01) due to antibiotic-induced microbiota depletion. Conclusion: TMDC alleviated asthma by promoting Treg cell expansion in a Lactobacillus-dependent manner across different gut segments, providing new insights into its therapeutic mechanisms.

BACKGROUND:Gut microbiota imbalance is well-known as one important trigger of allergic asthma. Ma-Xing-Shi-Gan decoction (MXSG) is a traditional Chinese medicine prescription with ideal clinical efficacy on asthma. However, whether and how MXSG exerts its efficacy on asthma through gut microbiota remains unclear. PURPOSE:To investigate the underlying mechanism of MXSG against asthma using multi-omics technologies. METHODS:An asthma model was established using 8-week-old C57BL/6 J mice, after which they were daily administrated with high-, medium- and low-dose MXSG for 7 days. Histopathological examinations and flow cytometry were performed to evaluate the effects of MXSG on lung immune injury. Key regulatory pathways were predicted via network pharmacology and verified using 16S rRNA sequencing, metagenomics, metabolomics, and in vivo experiments including the knockout of the targeting gene. RESULTS:MXSG alleviated asthma symptoms, elevated intestinal microbial diversities, and enriched potential beneficial microbes such as Lactococcus, Lactobacillus, and Limosilactobacillus. Network pharmacology and experimental validation highlighted the IL-17/Treg signaling as crucial for asthma treatment. IL-17 knockout experiments revealed its necessity for Treg differentiation during asthma. Moreover, IL-17-deficient asthmatic mice exhibited lower levels of Lactobacillus and significant changes in microbial genes involving histone deacetylases (HDAC) and short-chain fatty acids (SCFAs). Finally, MXSG significantly boosted SCFA production and reduced HDAC9 expression, which were correlated with Treg cell ratios. CONCLUSION:Our study delineates a novel mechanism where MXSG synergizes with the IL-17 family to enrich intestinal beneficial microbes (e.g. Lactobacillus) and SCFAs. This inhibits the expression of SCFA-downstream HDAC9 to promote Treg differentiation, and thus potentially alleviates asthma.

Critical thinking has been regarded as an essential skill for college students, which is especially imperative for medical students to possess the ability to have in-depth insight into complex clinical situations. Medical Immunology is an overarching principle connecting multiple medical subjects, which emphasizes that immunity is both beneficial and harmful to the host, thus putting higher demands on students’ critical thinking. The utilization of Nobel Prize stories has been cited as a thematic framework for classroom teaching of other courses, showing numerous educational benefits. Therefore, this study rejuvenated a case-based teaching approach by creating and introducing a vibrant material library centered on numerous iconic Nobel Prize cases in Medical Immunology and evaluating its effects on the critical thinking of medical students. A total of 70 second-year medical undergraduates from the Beijing University of Chinese Medicine were divided into a control group and an experimental group of 35 cases each. Throughout the semester, the control received the traditional teaching method, and the experimental group adopted case-based teaching based on the Nobel prize-centered material library. The process of teaching design and practice was described using “Antitoxin and immunoserum therapy” as a classical example. A unified assessment of the critical thinking dispositions of participants was conducted at the beginning and end of the semester using the Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV). Intra-group longitudinal comparisons and inter-group parallel evaluations indicated that, compared with the conventional teaching approach, Nobel Prize case-based learning induced a statistically significant increase in the overall score of the CTDI-CV, as well as the scores within the subdimensions of truth-seeking, analyticity, and maturity in judgment (p < 0.05). Pearson correlation analysis further indicated a positive correlation between the total score of the CTDI-CV and the final grade (p < 0.05), which emphasized the crucial role of critical thinking dispositions in academic achievement. The case-based classroom teaching centered on Nobel Prize cases for Medical Immunology can effectively improve the critical thinking dispositions of medical undergraduates, which contributes to cultivating high-level medical and healthcare talents with excellent comprehensive quality in the new era.

Chronic inflammation can promote cancer development as observed in inflammation‐induced colorectal cancer (CRC). However, the poor treatment outcomes emphasize the need for effective treatment. Astragalus polysaccharide (APS), a vital component of the natural drug Astragalus, has anti-tumor effects by inhibiting cancer cell proliferation and enhancing immune function. In this study, we found that APS effectively suppressed CRC development through activating CD8+ T cells and reversing its inhibitory state in the tumor microenvironment (TME) of AOM/DSS inflammation‐induced CRC mice. Network pharmacology and clinical databases suggested that the STAT3/ Galectin-3(Gal-3)/LAG3 pathway might be APS's potential target for treating CRC and associated with CD8+ T cell dysfunction. In vivo experiments showed that APS significantly reduced phosphorylated STAT3 and Gal-3 levels in tumor cells, as well as LAG3 in CD8+ T cells. Co-culture experiments with MC38 and CD8+ T cells demonstrated that APS decreased the expression of co-inhibitory receptor LAG3 in CD8+ T cells by targeting STAT3/Gal-3 in MC38 cells. Mechanism investigations revealed that APS specifically improved CD8+ T cell function through modulation of the STAT3/Gal-3/LAG3 pathway to inhibit CRC development, providing insights for future clinical development of natural anti-tumor drugs and immunotherapies as a novel strategy combined with immune checkpoint inhibitors (ICIs).

Idiopathic pulmonary fibrosis (IPF), as the most common idiopathic interstitial pneumonia, is caused by a complex interaction of pathological mechanisms. Interestingly, IPF frequently occurs in the middle‐aged and elderly populations but rarely affects young people. Salvianolic acid B (SAB) exerts antioxidant, antiinflammatory, and antifibrotic bioactivities and is considered a promising drug for pulmonary disease treatment. However, the pharmacological effects and mechanisms of SAB on cellular senescence of lung cells and IPF development remain unclear. We used bleomycin (BLM)‐induced pulmonary fibrosis mice and different lung cells to investigate the antisenescence impact of SAB and explain its underlying mechanism by network pharmacology and the Human Protein Atlas database. Here, we found that SAB significantly prevented pulmonary fibrosis and cellular senescence in mice, and reversed the senescence trend and typical senescence‐associated secretory phenotype (SASP) factors released from lung macrophages and alveolar type II (AT2) epithelial cells, which further reduced lung fibroblasts activation. Additionally, SAB alleviated the epithelial–mesenchymal transition process of AT2 cells induced by transforming growth factor beta. By predicting potential targets of SAB that were then confirmed by chromatin immunoprecipitation‐qPCR technology, we determined that SAB directly hampered the binding of transcription factor stimulating protein 1 to the promoters of SASPs (P21 and P16), thus halting lung cell senescence. We demonstrated that SAB reduced BLM‐induced AT2 and macrophage senescence, and the subsequent release of SASP factors that activated lung fibroblasts, thereby dual‐relieving IPF. This study provides a new scientific foundation and perspective for pulmonary fibrosis therapy.

Background and aim: Dachengqi Decoction (DCQD) as a classic traditional Chinese medicine has been reported to be effective in treating asthma, but its mechanism remains unknown. This study aimed to reveal the mechanisms of DCQD on the intestinal complications of asthma mediated by group 2 innate lymphoid cells (ILC2) and intestinal microbiota.Experimental procedure: Ovalbumin (OVA) was used to construct asthmatic murine models. IgE, cyto-kines (e.g., IL-4, IL-5), fecal water content, colonic length, histopathologic appearance, and gut microbiota were evaluated in asthmatic mice treated with DCQD. Finally, we administered DCQD to antibiotic -treated asthmatic mice to measure the ILC2 in the small intestine and colon.Results and conclusion: DCQD decreased pulmonary IgE, IL-4, and IL-5 levels in asthmatic mice. The fecal water content, the colonic length weight loss, and the epithelial damage of jejunum, ileum, and colon of asthmatic mice were ameliorated by DCQD. Meanwhile, DCQD greatly improved intestinal dysbiosis by enriching Allobaculum, Romboutsia and Turicibacter in the whole intestine, and Lactobacillus gasseri only in the colon. However, DCQD caused less abundant Faecalibaculum and Lactobacillus vaginalis in the small intestine of asthmatic mice. A higher ILC2 proportion in different gut segments of asthmatic mice was reversed by DCQD. Finally, significant correlations appeared between DCQD-mediated specific bacteria and cytokines (e.g., IL-4, IL-5) or ILC2. These findings indicate that DCQD alleviated the concurrent in-testinal inflammation in OVA-induced asthma by decreasing the excessive accumulation of intestinal ILC2 in a microbiota-dependent manner across different gut locations.(c) 2023 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).

Intestinal microbiota dysbiosis and metabolic disruption are well-known as the primary triggers of ulcerative colitis (UC). However, their role in regulating the group 3 innate lymphoid cells (ILC3s), which are essential for intestinal health, remains unexplored during the development of disease severity. Here, our results showed that the microbiota structure of patients with severe UC (SUCs) differed from those with mild UC (MiUCs), moderate UC (MoUCs), and healthy controls (HCs). Microbes producing secondary bile acids (SBAs) and SBAs decreased with the aggravation of UC, and a strong positive correlation existed between them. Next, fecal microbiota transfer was used to reproduce the human-derived microbiota in mice and decipher the microbiota-mediated inflammatory modulation during an increase in disease severity. Mice receiving SUC-derived microbiota exhibited enhancive inflammation, a lowered percentage of ILC3s, and the down-regulated expressions of bile acid receptors, including vitamin D receptor (VDR) and pregnane X receptor (PXR), in the colon. Similar to clinical results, SBA-producing microbes, deoxycholic acids (DCA), and 12-ketolithocholic acids (12-KLCA) were diminished in the intestine of these recipients. Finally, we compared the therapeutic potential of DCA and 12-KLCA in preventing colitis and the regulatory mechanisms mediated by ILC3s. 12-KLCA but not DCA represented a strong anti-inflammatory effect associated with the higher expression of VDR and the lower secretion of IL-17A from colonic ILC3s. Collectively, these findings provide new signatures for monitoring the acute deterioration of UC by targeting gut microbiota and bile acid metabolism and demonstrate the therapeutic and preventive potential of a novel microbiota-derived metabolite, 12-KLCA.

目的 基于"肺与大肠相表里"理论探讨鼠李糖乳杆菌对过敏性哮喘小鼠细胞外信号调节蛋白激酶1/2(ERK1/2)和p38丝裂原激活蛋白激酶(p38 MAPK)通路及相关免疫细胞的影响.方法 将18只雌性C57 BL/6小鼠随机分为对照组、模型组、鼠李糖乳杆菌组,每组6只.采用卵白蛋白(OVA)致敏加激发方法构建小鼠过敏性哮喘模型,鼠李糖乳杆菌组于雾化激发前给予鼠李糖乳杆菌灌胃,连续7 d,对照组和模型组给予等量生理盐水灌胃.末次灌胃后取各组小鼠肺组织和结肠组织,HE染色进行组织病理观察;ELISA法检测血清OVA特异性IgE含量,流式细胞术检测肺组织中2型固有淋巴样细胞(ILC2)比例,Western blot法检测肺组织中p-ERK1/2和p-p38 MAPK表达情况.结果 与对照组比较,模型组小鼠支气管及血管周围存在明显炎症细胞浸润,部分肺泡结构消失;结肠腺体排列紊乱,隐窝和杯状细胞明显减少,黏膜及黏膜下层炎性细胞浸润;血清OVA特异性IgE含量、肺组织中ILC2比例、肺组织中p-ERK1/2及p-p38 MAPK相对表达量均明显升高(P均<0.05).与模型组比较,鼠李糖乳杆菌组小鼠支气管炎性细胞浸润明显改善;结肠腺体、杯状细胞增多,排列较为整齐,炎细胞浸润明显减少;血清OVA特异性IgE含量、肺组织中ILC2比例、肺组织中p-ERK1/2及p-p38 MAPK相对表达量均明显降低(P均<0.05).结论 鼠李糖乳杆菌可能通过抑制ERK1/2及p38 MAPK磷酸化,减少肺部ILC2,从而减轻过敏性哮喘的肺部炎症.

在新医科教育背景下,越来越多新的教学理念被应用于中医学专业课程教学.医学免疫学与微生物学是联系基础医学和临床实践的重要学科,也是中医药传承创新和中西医结合研究的重要切入点.因此,做好本课程的教学设计对于增强学生学习兴趣及提高教学效果起到至关重要的作用.建构主义理论认为学习是学习者依据原有经验,在互动情境中主动地建构新知识,从而完成教学目标的过程.本课程组基于医学免疫学和微生物学课程特点及中医类专业学生特点,将建构主义学习理论应用于教学实践,对课程的教学内容和教学方法进行了改革.文章从课程教学内容整体设计、教材建设及分析、学情分析、教学目标、重点难点及解决策略、教法学法的多元化应用、教学过程实施、教学效果评价等方面,以"免疫预防"内容为例,详细介绍了课程的教学设计和实践过程.尤其是在教学实施的过程中,应用多元化教学方法循序渐进地引入教学内容,使学生在讨论分析中获取、运用并建构新知识,同时进行能力培养和思政教育,完成了多项教学目标.该课程教学模式能够为教学工作提供参考,也可应用于其他中医专业课程的教学设计中,以服务于高等院校及医院培养中医类及医药类专业人才.

Pulmonary inflammation as one of the extraintestinal manifestations of ulcerative colitis (UC) has attracted extensive attention, and its pathogenesis is closely related to gut dysbiosis. Bifidobacterium animalis subsp. lactis BL-99 (BL-99) can alleviate osteoporosis caused by UC, but less research has been done on other extraintestinal manifestations (EIM) caused by UC. This study aimed to explore the role and potential mechanisms of BL-99 on DSS-induced pulmonary complications in colitis mice. The results showed that BL-99 decreased weight loss, disease activity index score, colonic pathology score, and the production of pro-inflammatory cytokines (e.g., TNF-α, IL-1β, and IL-6) in colitis mice. BL-99 also alleviated DSS-induced lung pathological damage by suppressing the infiltration of pro-inflammatory cytokines, inflammatory monocytes, and macrophages. Furthermore, 16S rRNA gene sequencing showed lower abundances of several potentially pathogenic bacteria (e.g., Burkholderia, Shigella, and Clostridium perfringens) and enrichment in specific beneficial bacteria (e.g., Adlercreutzia and Bifidobacterium animalis) in colitis mice with BL-99 treatment. Targeted metabolomics suggested that BL-99 intervention promoted the production of intestinal acetate and butyrate. Finally, we observed that the pulmonary expression of primary acetate and butyrate receptors, including FFAR2, FFAR3, and, GPR109a, was up-regulated in BL-99-treated mice, which negatively correlated with inflammatory monocytes and macrophages. Altogether, these results suggest that BL-99 might be utilized as a probiotic intervention to prevent the incidence of colitis-related lung injury owing to its ability to shape the intestinal microbiota and suppress inflammation.

Sensitivity analysis: We will consider running sensitivity analysis to identify the robustness and stability of merged results by excluding studies with high risk of bias.

With the concept of the gut-lung axis reinforced in recent years, emerging evidence has shown that intestinal homeostasis is vital for lung health. Nevertheless, the impacts of lung homeostasis on intestinal tracts and their mechanism are rarely studied. Our results showed that papain-induced asthmatic mice exhibited apparent colonic injuries compared with controls, including increased intestinal permeability, neutrophil and Th17 infiltration in the colonic lamina propria. Moreover, the intranasal administration of papain aggravated such colonic injuries in mice with dextran sulfate sodium-induced colitis, as evidenced by increased occult blood scores, shortened colon length, and accumulated neutrophils. The level of IL-17A was also higher in the serum of asthmatic mice than wild-type mice. Interestingly, the pathologic scores, the proportion of Th17 cells, and neutrophil infiltration in the colon were markedly reduced after IL-17A blocking. Similarly, longer length, lower pathologic scores, and fewer neutrophils were also observed in the colon of IL-17-deficient asthmatic mice. More importantly, we demonstrated that severe gastrointestinal symptoms could accompany clinical asthmatics. The frequencies of Th17 cells and the mRNA expression of IL-17A in the peripheral blood of these patients were significantly enhanced. Besides, the gastrointestinal symptom rating scale scores positively correlated with the frequencies of Th17 in asthmatics. These findings enlighten that IL-17A aggravates asthma-induced intestinal immune injury by promoting neutrophil trafficking, which facilitates the exploration of new potential biomarkers to treat asthma.

The hepatic protective role of Sagittaria sagittifolia polysaccharide (SSP) and its possible mechanism were discussed in mice and L02 hepatocytes injured by heavy metals mixture of Cd + Cr (VI) + Pb + Mn + Zn + Cu. After 30-day intervention, blood and liver samples were collected for the relevant assessments. Methyl thiazolyl tetrazolium (MTT) assay showed 24 h was the best protecting point and the SSP protection at 1 mg/mL was strongest in L02 hepatocytes. SSP can alleviated hepatic injury, as evidenced by significantly decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and the malondialdehyde (MDA) content, also increased the superoxide dismutase (SOD) activity and glutathione (GSH), total sulphydryl (T-SH) contents. SSP effectively reduced pathological damage of mice and accumulation of heavy metals in liver, as well as decreased the level of reactive oxygen species (ROS) in L02 hepatocytes. After SSP treatment, the protein expressions or gene transcription of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 (NQO1) and heme oxygenase1 (HO-1) decreased in L02. The protein expression of Nrf2 and NQO1 were increased while HO-1 was decreased in liver. Besides, SSP can attenuates apoptosis through reducing the protein expression of Bcl-2-associated X protein (Bax) and caspase-3, and increasing B-cell lymphoma gene 2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl). SSP protects against six-heavy-metal-induced hepatic injury in mice and L02 hepatocytes. Supported by Nrf2 gene silencing, the mechanisms may correlate with activating Nrf2 pathway to mitigate oxidative stress and apoptosis.

目的 研究芍药甘草汤对支气管哮喘小鼠肠道菌群结构的调节作用.方法 将50只SPF级BALB/c雌性小鼠随机分为正常组、模型组、醋酸地塞米松组、芍药甘草汤1:1组、芍药甘草汤2:1组.通过卵白蛋白致敏、雾化激发建立肠道菌群紊乱模型.从实验第15天开始,雾化前30 min灌胃,连续灌胃14 d.正常组、模型组给予等量蒸馏水,醋酸地塞米松组(0.676 mg/kg)、芍药甘草汤1:1组(6.01 g/kg)、芍药甘草汤2:1组(6.01 g/kg)给予相应的药物灌胃.实验第29天采集各组结肠组织及粪便样本,观察分析小鼠的一般状态、哮喘典型症状和结肠组织病理改变,各组随机选取6只小鼠进行16S rRNA测序分析肠道菌群多样性和物种丰富度的变化.结果 醋酸地塞米松组、芍药甘草汤1:1组、芍药甘草汤2:1组小鼠的一般状态和哮喘典型症状得到明显改善.病理组织检测显示:正常组结肠组织清晰,结构完整,模型组结肠黏膜及黏膜下层有大量炎性细胞和肿大淋巴结,醋酸地塞米松组充血水肿情况改善,芍药甘草汤1:1组仍可见炎性细胞浸润,芍药甘草汤2:1组结构较完整,黏膜及黏膜下层偶见散在炎性细胞.16S rRNA测序结果显示:与正常组比较,模型组Chao1指数、PD指数降低(P<0.01),observed species指数降低(P<0.05);与模型组比较,醋酸地塞米松组、芍药甘草汤2:1组PD指数升高(P<0.01),Chao1指数、observed species指数升高(P<0.05).肠道菌群菌属水平显示:与正常组相比,模型组毛螺菌属丰度增加(P<0.05),罗斯氏菌属丰度增加(P<0.01),拟普雷沃菌属丰度减少(P<0.05);与模型组相比,芍药甘草汤1:1组毛螺菌属丰度降低(P<0.05);与醋酸地塞米松组相比,芍药甘草汤1:1组拟普雷沃菌属、拟杆菌属、乳杆菌属、罗斯氏菌属丰度增加(P<0.01),芍药甘草汤2:1组罗斯氏菌属丰度降低(P<0.01);与芍药甘草汤1:1组相比,芍药甘草汤2:1组乳杆菌属、罗斯氏菌属丰度降低(P<0.01).结论 芍药甘草汤可改善哮喘小鼠的典型症状、结肠组织病理情况等,其作用机制可能与其恢复肠道菌群的多样性、丰富度及调节菌群结构有关.

分析医学免疫学与微生物学课程当前教学中存在的问题,并结合教研室教学提出教学改革措施,旨在优化课程体系和评价方法,提高课程教学质量,增强非医专业学生对免疫学与微生物学的学习兴趣,为学生更好地从事与医学相关工作积淀丰富的知识储备.