ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes （T2DM）. MethodsA 12-week randomized， placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group （40 cases） was administered with Astragali Radix Granules， while the control group （40 cases） received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 （GLP-1） levels were measured using enzyme-linked immunosorbent assay （ELISA）. Glucose metabolism indicators including fasting blood glucose （FPG）， 2-hour postprandial blood glucose （2 h PG），glycated albumin（GA）， and glycated hemoglobin （HbA1c） were evaluated. Pancreatic function was evaluated using fasting C-peptide （FCP）， 2-hour postprandial C-peptide （2 h CP）， and C-peptide area under the curve （AUC_cp）. Traditional Chinese medicine （TCM） syndrome scores， clinical efficacy， and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators， compared with the baseline， both groups exhibited significantly lower FPG， 2 h PG， GA and HbA1C （P<0.01），while FCP， 2 h CP and AUC_cp were significantly higher （P<0.01）. Compared with the control group after the treatment， the observation group showed significantly lower FPG， 2 h PG， GA and HbA1C（P<0.05， P<0.01），and significantly higher FCP， 2 h CP and AUC_cp （P<0.05， P<0.01）， indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota， no significant differences were detected in the Chao1， Shannon and Simpson indexes of the two groups compared with their respective baselines. However， compared with the post-treatment control group， the observation group demonstrated significant increases in the Chao1， Shannon and Simpson indexes （P<0.05， P<0.01）. The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups， indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level， compared with the baseline， both groups showed a significant increase in the relative abundance of Bacteroidota（P<0.01）. The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment （P<0.01）. Compared with the post-treatment control group， the observation group had a significantly higher relative abundance of Bacteroidota（P<0.01）. No significant difference was found in Firmicutes/Bacteroidota （F/B） ratio between the two groups after treatment， and other phyla showed no significant differences. At the genus level， compared with the baseline， the observation group exhibited a significant increase in Bacteroides （P<0.01） and a significant decrease in Escherichia-Shigella （P<0.01）， whereas no significant difference was seen in the control group . Compared with the control group after treatment， the observation group after treatment had a significantly higher relative abundance of Bacteroides （P<0.01）. No significant differences were seen in other genera. Linear discriminant analysis （LDA） identified potential characteristics taxa： in the observation group， Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level， in the control group， Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes， F/B ratio and Fusobacterium， and negatively correlated with Bacteroidota， Proteobacteria， Bacteroides and Escherichia-Shigella. In terms of clinical efficacy， compared with the control group， the total effective rate of the observation group was significantly higher （P<0.05）. Compared with the baseline， the scores for shortness of breath， fatigue， weakness， spontaneous sweating and reluctance to speak significantly decreased in both groups （P<0.01）. Compared with the control group after treatment， the score for weakness was significantly lower in the observation group （P<0.01），indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety， compared with the baseline， alanine aminotransferase （ALT） levels significantly decreased in both groups （P<0.05，P<0.01），indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control， possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.

Cerium oxide nanoparticles (CeO₂ NPs), as the oxides of the most abundant elements in rare earths, have been widely used in biomedical and industrial production and other fields that are closely related to human life. China is a large country in resources and production of rare earth, and the impact of CeO₂ NPs on human health has been increasingly concerned. In response to the possible health risks of CeO₂ NPs, researchers begin to focus on their toxic effects on living organisms, especially on the reproductive system. The male reproductive system is not only responsible for producing sperm and regulating the secretion of testosterone, but also plays a key role in maintaining male sexual characters and function. Any adverse effects on the male reproductive system may lead to reduced fertility and reproductive dysfunction. Some studies have shown that long-term exposure to CeO₂ NPs may lead to gonadal damage, sex hormone disorders, and other problems in male animals. Therefore, an in-depth study of the potential effects of CeO₂ NPs on the male reproductive system is of great scientific significance and practical value. In this study, we reviewed the male reproductive toxicity of CeO₂ NPs in terms of spermatogenic cells, spermatozoa structure, blood-testis barrier, hypothalamic-pituitary-gonadal axis, and functional changes in epididymis, and analyzed the effects of the size and shape of physicochemical parameters of CeO₂ NPs on the toxicity to male reproductive system. The findings will provide a theoretical basis and scientific evidence for the rational use of CeO₂ NPs.

ObjectiveTo explore the effect of Ganoderma leucocontextum ethanol extract (GLE) on silicosis and its potential molecular mechanism using network pharmacology, molecular docking technology and animal experiments. Methods i) The components of GLE were analyzed using ultra-performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS) method. The active components, potential molecular pathways and targets of GLE in the intervention of inflammation process of silicosis was explored using network pharmacology and molecular docking technology. ii) Specific pathogen free male C57BL6/J mice were divided into four groups with 10 mice in each group. The mice in the silicosis model group and GLE intervention group were given a dose of 80 μL silica suspension with a mass concentration of 50 g/L once by non-exposed tracheal instillation, and the mice in the blank control group and GLE control group were given an equal volume of sterile 0.9% sodium chloride solution. From the second day after modeling, GLE control group and GLE intervention group were given GLE at a dose of 200 mg/(kg•d) by gavage, while blank control group and silicosis model group were given the same volume of 0.9% sodium chloride solution by gavage, once per day for 35 days. After that, the histopathological changes of lung tissues of mice were observed, the lung mass coefficient, inflammation score and the ratio of collagen deposition area were calculated, and the levels of tumor necrosis factor (TNF) -α, interleukin (IL) -1β and IL-6 in the lung tissues of mice were detected by enzyme-linked immunosorbent assay. Results i) A total of 76 active components of GLE were detected by UPLC-QE-MS. Among them, 36 ingredients met the screening criteria of the five principles of drug-like components. A total of 67 potential targets of the 36 GLE active ingredients to improve the inflammatory response of silicosis were screened based on the network pharmacology theory. The result of Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Ontology functional analysis showed that IL signaling and cytokine signaling of immune cells played a key role in the process of anti-silicosis of GLE. The results of molecular docking showed that the top 10 targets based on the 67 intersection targets were TNF, IL6, B-cell lymphoma 2, cellular tumor antigen p53, Caspase-3 subunit p12, JUN, epidermal growth factor receptor, IL1B, 67 kDa matrix metalloproteinase-9 and prostaglandin G/H synthase 2. The result of protein-protein interaction analysis showed that glycyrrhetinic acid had the strongest affinity with the key targets TNF-α, IL-1β and IL-6, followed by ganoderma acid DM, alismatol C, ganoderma acid β and red sapogenin. ii) The results of histopathological examination showed that the inflammatory response and collagen deposition were alleviated in the lungs of mice with silicosis. The lung mass coefficient, inflammation score, ratio of collagen deposition area and IL-6 expression in lung were lower in mice of the GLE intervention group (all P<0.05), compared with the silicosis model group. However, there was no significant difference in the levels of TNF-α and IL-1β in lung tissues between the two groups (all P>0.05). Conclusion GLE may reduce silica-induced lung inflammation and fibrosis by inhibiting the IL-6 level in lung tissues of mice. Its mechanism is associated with the synergistic action of multi-components, multi-targets and multi-pathways.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Rosacea is a chronic recurrent inflammatory skin disease, and correct assessment of clinical symptoms and severity may facilitate treatment options. This review summarizes a range of subjective, semi-subjective and objective methods currently used in the assessment of rosacea severity, in order to provide useful tools for clinical assessment of rosacea severity and give guidance on treatment modification according to the therapeutic effect.

Objective:To investigate the clinicopathological characteristics of spiradenocarcinoma, cylindrocarcinoma, and spiradenocylindrocarcinoma, and to understand the correlations between their morphological patterns and clinical behaviors.Methods:Seven cases of spiradenocarcinoma, cylindrocarcinoma, and spiradenocylindrocarcinoma diagnosed at Fudan University Shanghai Cancer Center, Shanghai, China from 2015 to 2021 were collected. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out.Results:There were four men and three women in the cohort, with ages ranging from 46 to 75 years (mean, 61 years). The tumors were located on the head and neck (four cases), extremities (two cases), and trunk (one case). Histologically, the residuum of a benign neoplasm was present in all cases. One case presented salivary gland-type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG). Another case showed salivary gland-type basal cell adenocarcinoma-like pattern, high-grade (BCAC-HG). The remaining five cases were invasive adenocarcinoma, not otherwise specified (IAC-NOS). One of IAC-NOS contained a mucinous adenocarcinoma component. Immunohistochemically, BCAC-LG and BCAC-HG predominantly expressed basal cell markers such as p63 and p40, whereas IAC-NOS primarily exhibited positivity for CK7, a glandular epithelial marker. Follow-up was available for six patients, ranging from 1 to 9 years (mean, 4.5 years). Among the four patients of IAC-NOS with follow-up, three showed recurrences, two had regional lymph node metastases, and one died.Conclusions:The malignant components of spiradenocarcinomas, cylindrocarcinomas, and spiradenocylindrocarcinomas in this cohort contain BCAC-LG, BCAC-HG and IAC-NOS. This study also shows the presence of mucinous adenocarcinoma components in IAC-NOS. The tumors with IAC-NOS have a relatively poorer prognosis than those without.

In recent years, immune checkpoint inhibitors (ICIs) have been widely used in malignant solid tumors with remarkable efficacy. However, in colorectal cancer (CRC), ICIs have shown significant therapeutic effects only in patients with highly microsatellite unstable/mismatch repair-deficient metastatic CRC and these patients are only a minority of all CRC patients. In contrast, the majority of patients, those with microsatellite stable (MSS)/mismatch repair-complete (pMMR)-type metastatic CRC, could hardly benefit from ICI monotherapies, and immune combination therapies have become the key to solveing this clinical challenge. This article introduces the common patterns and possible mechanisms of immune-combination therapies for MSS/pMMR-type CRC, the exploration and progress made in the application of immune-combination therapies, as well as the possible predictive markers of efficacy of immune therapies. The prospects and directions of ICIs in the treatment of MSS/pMMR-type CRC are also discussed.

Purpose/Significance To explore the changes,challenges,key application scenarios and future development directions of generative artificial intelligence(AI)represented by ChatGPT in the field of hospital management,and to provide references for the ap-plication of AI natural language processing(NLP)technology in the field of hospital management in China.Method/Process Through literature review and analysis,the changes and challenges brought about by the rapid development of generative AI in the field of hospital management are sorted out,its key application scenarios and future development directions in the field of hospital management are empha-sized and explored.Result/Conclusion AI has broad application prospects in the field of hospital management,and it should focus on exploring its practical application scenarios and strategic directions to provide reference and guidance for promoting the high-quality de-velopment of public hospitals.

Bluetongue virus is an arbovirus that seriously harms ruminants such as sheep,this study aims to investigate the molecular mechanism of bluetongue virus infection and host cell interferon antiviral immune response.The study was conducted to characterize the mRNA expression of inter-feron pathway genes by real-time fluorescence quantitative PCR,as well as Western blot analysis of MDA5,TRAF3,RIG-Ⅰ,and TBK1 protein expression in BHK-21 cells induced by BTV with a multiplicity of infections(MOI)of 1 for 18,24,and 36 h.The results showed that the most pro-nounced changes in the expression of interferon signaling pathway genes were observed at 24 h of induction,the gene mRNA expression levels of the IFN-α,IFN-β,RIG-Ⅰ,TBK1,MDA5,VISA,and TRAF3 genes were upregulated.However,the mRNA expression levels of IKKε and TRAF6 genes were downregulated.At the protein level,MDA5 and TBK1 proteins were upregulated while RIG-1 and TRAF3 proteins were downregulated,which showed that BTV infection induces a typeⅠ interferon immune response in BHK-21 cells.This study lays the foundation for further exploring the antiviral immunity mechanism of IFN-Ⅰ signaling pathway regulatory genes in host cells infected with BTV infection.

Objective To systematically evaluate the measurement properties and methodological quality of the palliative quality assessment tools based on the cancer patient experiences,and to provide an evidence-based basis for the selection of a high-quality assessment tool for healthcare professionals.Methods Systematic search of PubMed,Embase,Web of Science,CINAHL,CNKI,Wanfang database,VIP database,and China Biomedical Literature database for studies related to the evaluation of the measurement properties of the self-report palliative care quality assessment tools for cancer patients.The search period from the date of creation to December 10,2023.There are 2 researchers who independently conducted literature screening and data extraction according to the COSMIN selection criteria,and used the COSMIN Risk of Bias Inventory and Quality Criteria Scale to measure the academic characteristics and form the final recommendations.Results A total of 19 studies involving 8 assessment tools for cancer patients were included.The final 6 assessment tools were recommended at level B.2 assessment tools are recommended at level A.Conclusion The SF-QCQ-PC and the Self-Report Palliative Care Quality Assessment Tool for Terminal Cancer Patients can be provisionally recommended.However,further validation of its measurement properties is still needed.