Objective: To investigate the mechanism of in alleviating colonic mucosal inflammation in ten-eleven translocation (TET) protein 2 gene knockout (TET2-/-) mice with ulcerative colitis (UC) by regulating DNA methyltransferase (DNMT) and DNA hydroxymethylase. Methods: Male specific pathogen-free (SPF) grade C57BL/6J wild-type (WT) mice (n = 8) and TET2-/- mice (n = 20) were used to establish UC models by freely drinking 3% dextran sulfate sodium solution for 7 d. After UC model validation through histopathological examination in two mice from each type, the remaining mice were divided into four groups (n = 6 in each group): WT model (WT + UC), TET2-/- model (TET2-/- + UC), TET2-/- mild moxibustion (TET2-/- + MM), and TET2-/- electroacupuncture (TET2-/- + EA) groups. TET2-/- + MM group received mild moxibustion on Tianshu (ST25) and Qihai (CV6) for 10 min daily for 7 d. The TET2-/- + EA group also applied electroacupuncture (1 mA, 2/100 Hz) at the same acupoints for 10 min daily for 7 d. The disease activity index (DAI) scores of each group of mice were accessed daily. The colon lengths of mice in groups were measured following intervention. The pathological changes in the colon tissues were observed with hematoxylin and eosin (HE) staining. The concentrations of interleukin (IL)-6, C-C motif chemokine 17 (CCL17), and C-X-C motif chemokine ligand 10 (CXCL10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of DNMT proteins (DNMT1, DNMT3A, and DNMT3B) in the colon tissues was detected by immunohistochemistry. The expression of 5-methylcytosine (5-mC), 5-hydroxymethylcytosine (5-hmC), histone deacetylase 2 (HDAC2), and DNA hydroxymethylase family proteins (TET 1 and TET3) was detected using immunofluorescence, which also determined the co-localization of TET1 and IL-6 protein. Results: Compared with WT + UC group, TET2-/- + UC group exhibited significantly higher DAI scores and shorter colon lengths (P < 0.01). Both mild moxibustion and electroacupuncture significantly decreased DAI scores and ameliorated colon shortening in TET2-/- mice (P < 0.001). Histopathological scores of TET2-/- + UC mice were significantly higher than those of WT + UC group (P < 0.001) and were significantly reduced after both mild moxibustion and electroacupuncture interventions (P < 0.001). Serum levels of IL-6, CCL17, and CXCL10 were significantly elevated in TET2-/- + UC group compared with WT + UC group (P < 0.001). Mild moxibustion significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.001, P < 0.001, and P < 0.01, respectively), while electroacupuncture also significantly reduced IL-6, CCL17, and CXCL10 levels (P < 0.05, P < 0.01, and P < 0.01, respectively). TET2-/- + UC mice showed increased expression levels of DNMT1, DNMT3A , DNMT3B, and 5-mC (P < 0.05, P < 0.01 and P < 0.001, respectively), with decreased expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001). Mild moxibustion significantly reduced DNMT1, DNMT3B, and 5-mC levels (P < 0.05, P < 0.01, and P < 0.001, respectively), while increasing expression levels of TET1, TET3, 5-hmC, and HDAC2 (P < 0.001, P < 0.001, P < 0.05, and P < 0.001, respectively). Electroacupuncture significantly decreased 5-mC and DNMT3B levels (P < 0.001 and P < 0.01, respectively) and increased 5-hmC and HDAC2 levels (P < 0.05 and P < 0.001, respectively), but did not significantly affect TET1 and TET3 expression (P > 0.05). Compared with TET2-/- + MM group, TET2-/- + EA group showed significantly higher 5-mC expression (P < 0.001). TET2-/- + UC group exhibited markedly increased IL-6 expression and higher co-localization of TET1 and IL-6 in mucosal epithelium, whereas minimal IL-6 expression was observed in the other groups. Conclusion Mild moxibustion and electroacupuncture significantly ameliorate colonic inflammation exacerbated by TET2 deficiency in UC mice via epigenetic modulation. Distinct mechanisms exist between the two interventions: mild moxibustion regulates both DNMT and hydroxymethylase, whereas electroacupuncture primarily affects DNMT.

Traditional Chinese Medicine (TCM), as a treasure of the Chinese nation, plays a significant role in maintaining public health. In 2019, the Central Committee of the Communist Party of China and the State Council proposed for the first time the establishment of a TCM registration and evaluation evidence system that integrates TCM theory, "personal experience" and clinical trials (referred to as the "Three-in-One" System) to promote the inheritance and innovation of TCM. Subsequently, the National Medical Products Administration issued several guiding principles to advance the improvement and implementation of this system. Owing to the complexity of its implementation, there are still differing understandings within the TCM industry regarding the positioning of the "Three-in-One" Registration and Evaluation Evidence System, as well as the connotation and value orientation of the "personal experience." To address this, Academician WANG Qi, President of the TCM Association, China International Exchange and Promotion Association for Medical and Healthcare and TCM master, led a group of academicians, TCM masters, TCM pharmacology experts and clinical TCM experts to convene a "Seminar on Promoting the Implementation of the ′Three-in-One′ Registration and Evaluation Evidence System for Chinese Medicinals." Through extensive discussions, an expert consensus was formed, clarifying the different roles of the TCM theory, "personal experience" and clinical trials within the system. It was further emphasized that the "personal experience" is the core of this system, and its data should be derived from clinical practice scenarios. In the future, the improvement of this system will require collaborative efforts across multiple fields to promote the high-quality development of the Chinese medicinal industry.

Objective Summarizes the current research status of defensive medicine in China and provides references for future research.Methods The search period spans from the inception of the database to March 2024.CNKI,Wan-fang Data,Web of Science,PubMed databases were queried,followed by literature screening based on predeter-mined inclusion and exclusion criteria.The current landscape of defensive medicine research in China was synthe-sized and categorized based on fundamental research characteristics,measurement methodologies,influencing fac-tors,and other relevant aspects.Results A total of 24 Chinese literature sources and 4 foreign literature sources were incorporated,indicating a prevalent occurrence of defensive medicine in China.Measurement tools for defen-sive medicine exhibit variability across different studies.Key influencing factors encompass doctor's demographic vari-ables such as gender,age,and professional status,institutional factors like legal frameworks and medical in-surance,and sociol-cultural factors such as doctor-patient relationships and adverse public perceptions.Conclusion Defensive medicine is relatively widespread and influenced by various factors in China.It's urgent to explore the for-mation mechanism of defensive medicine from multiple perspectives and provide evidence for passive defen-sive medicine governance.

Objective:To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study.Methods:Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters.Results:A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 ( β=0.74%, P=1.51×10 -7, OR=1.06, 95% CI: 1.03-1.09) and ch.17.49619327- SPOP ( β=0.23%, P=7.54×10 -7, OR=1.17, 95% CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated ( β=-0.39%, P<0.001) and hypermethylated ( β=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions:IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

ObjectiveTo provide more basic information of comparative medicine for the study of biological changes and pathogenesis of COVID-19 by systematical sorting and analyzing the transcriptome data.MethodsFollowing a retrieval strategy, using COVID-19 and SARS-CoV-2 as key words, transcriptome datasets related to COVID-19 from January 2020 to May 2023 were collected from GEO, ArrayExpress and GEN Transcriptome databases. The composition, distribution, and research application of COVID-19 transcriptome data resources were analyzed. Data distribution was visually displayed and correlation analysis was performed. The research applications and limitations of existing COVID-19 transcriptome data were analyzed from the perspectives of clinical medicine and comparative medicine, focusing on clinical-related molecular mechanisms, biomarkers and related immune responses, treatment intervention strategies, etc. The research value and application prospects were discussed.Results A total of 975 sets of COVID-19 transcriptome data were included. Among three databases, datasets from humans accounted for the highest proportion, namely 71.9%, 77.9%, and 90%, respectively. Species other than humans, such as mice, were the main sources of data, with the respiratory and nervous systems having the highest distribution of data. Twenty-seven datasets were associated with clinical significance. Analysis revealed that respiratory tract injury and other related molecular mechanisms were obtained through transcriptome data mining. Biomarkers such as cfDNA could be used as therapeutic targets. The severity of COVID-19 infection was associated with cell changes and disorders represented by M1 macrophages. Comparative medical analysis showed that mice, hamsters, and other animals were susceptible to SARS-CoV-2. Rhesus monkeys and cynomolgus monkeys exhibited infection characteristics highly similar to human. Apart from respiratory symptoms, hamsters also exhibited digestive system symptoms. SARS-CoV-2 can replicate in the respiratory organs of various susceptible animals, the intestines of ferrets and the ears of minks, resulting in interstitial pneumonia, diffuse lung injury and other pathological changes of varying degrees. Based on the differences in immune responses, hamsters can be used for neutralizing antibody reaction research.Conclusion Currently there is a wealth of COVID-19 transcriptome data, but there is a lack of comparative transcriptome research. Transcriptomics can be combined with comparative medicine to further explore the differences in comparative medicine of COVID-19.

Objective This study analyzes the omics data resources in human-infecting coronavirus animal models collected from various public databases,focusing on data distribution,dataset quantity,data types,species,strains,and research content.It aims to enhance our understanding of biological characteristics and pathogenic mechanisms of coronaviruses,thereby providing a solid foundation for devising effective therapeutic strategies and preventive measures.Methods Query strategies,including specific virus names,time ranges,and inclusion and exclusion criteria,were defined to retrieve data from major public omics databases such as GEO and ArrayExpress.Secondary filtering was performed based on different field types to obtain a more accurate data list.An omics data text database was established for bibliometric analysis.Co-occurrence networks were constructed for the analysis of the correlation strengths between different research themes,technical methods,and involved species.The cell types,organs,and biological pathways involved in studies were examined to further elucidate the pathogenic interplay between pathogens and hosts.Results About twenty public databases containing coronavirus-related omics data were identified,with a primary focus on novel coronavirus infection.Commonly used species include humans,mice,hamsters,and monkeys,while the commonly used virus strains are Wuhan-Hu-1 and USA-WA1/2020.Lung tissues are primarily used in animal models such as mice,macaques,and ferrets,while airway epithelial cells and Calu-3 cells are predominantly employed in human-related studies.Expression profiling data indicate that gene pathways involved in inflammation,cytokine response,complement pathway,cell damage,proliferation,and differentiation are significantly upregulated after infection.Proteomics studies reveal significant changes in phosphoproteome,ubiquitinome,and total proteome of patient samples at different infection stages.Specific protein categories,including viral receptors and proteases,transcription factors,cytokines,proteins associated with coagulation system,angiogenesis-related proteins,and fibrosis markers,show alterations after coronavirus infection.In addition,metabolomics data suggest that phosphocholine,phosphoethanolamine,arachidonic acid,and oleic acid could serve as potential metabolic markers.Epigenomics research indicates m6A methylation plays a role in SARS-CoV-2 replication,infection,and transmission,affecting host cell-virus interactions.Among these,N,S,and non-structural proteins 2 and 3 exhibit the most significant ubiquitination.Trends in microbiomics research suggest that microbial communities in the gut and wastewater are emerging as new research focuses.Conclusion The data types of coronavirus omics are diverse,with a wide variety of models and cell types used.The selection of species and technical methods for modelling varies based on the characteristics of different viruses.Multi-omics data from animal models of coronavirus infection can reveal key interactions between hosts and pathogens,identifying biomarkers and potential therapeutic targets,and provide valuable information for a deeper understanding of biological characteristics and infection mechanisms of coronaviruses.

Jinqi Jiangtang Capsule (JQJTC) is clinically used for the prevention and treatment of type 2 diabetes, but the contents of its main chemical components are not yet clear. In this study, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was established for the determination of 15 components in JQJTC, including new chlorogenic acid, chlorogenic acid, cryptochlorogenic acid, formononetin, ononin, calycosin, calycosin-7-glucoside, astragaloside IV, berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine. The method was used to determine the contents of 15 components in the capsule and then to investigate the influence of excipients on the contents of the components in JQJTC. The separation was performed on a ACQUITY UPLC BEH C₁₈ column (100 mm × 2.1 mm, 1.7 μm) with a mobile phase consisting of 0.1% acetic acid and 5 mmol·L^-1 ammonium acetate (A) and acetonitrile (B) with gradient elution at a flow rate of 0.3 mL·min^-1 and a column temperature at 40 ℃. Electron spray ionization was used for mass spectrometry in positive ion mode. The established method meets the requirements of methodology of content determination in Chinese pharmacopoeia. The contents of 15 components in JQJTC varied from high to low. The top 5 contents were berberine, chlorogenic acid, magnoflorine, coptisine, and cryptochlorogenic acid, accounting for 87.31% of the total content. The contents of 10 components, including the alkaloids of coptidis rhizoma (berberine, epiberberine, berberrubine, coptisine, jatrorrhizine, palmatine and magnoflorine) and the organic acids of honeysuckle (new chlorogenic acid, chlorogenic acid, and cryptochlorogenic acid) in the whole formula extract without excipients was significantly lower than that in the capsule. These components accounted for 99.20% of the determined component contents. In this experiment, an accurate, sensitive and efficient UHPLC-MS/MS method for the determination of multi-components in JQJTC was established, which stably and reliably detected the contents of 15 components in the capsule and could provide the basis for more comprehensive quality analysis. It was also found that excipients had an increasing effect on the contents of detected alkaloid and organic acid components, which may be beneficial to the effectiveness of the capsules.

Objective:To study the expressions of C-C class chemokine 17 (CCL17), C-C class chemokine 22 (CCL22), and C-C chemokine receptor 4 (CCR4) in newly diagnosed multiple myeloma (NDMM) for analyzing their correlations with clinical features and to preliminarily explore their roles in the development of NDMM.Methods:The study included 40 patients with NDMM and 20 healthy volunteers from the Department of Hematology of the Affiliated Hospital of Zunyi Medical University from July 2020 to December 2022. Peripheral blood, bone marrow, and bone marrow biopsy tissue samples were collected from the two groups. The expression levels of CCL17, CCL22, and CCR4 in patients with NDMM were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction (RQ-PCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The mRNA expression levels of CCL17, CCL22, and CCR4 in the bone marrow mononuclear cell (BMMNC) of patients with NDMM were analyzed to assess their correlations with clinical indicators.Results:The mRNA expression levels of CCL17, CCL22, and CCR4 in BMMNC were higher in patients with NDMM than in controls (all P<0.05). The protein expression levels of CCL17 and CCL22 in peripheral blood supernatants and bone marrow supernatants were higher in patients with NDMM than in controls (all P<0.05). The expression levels of CCL17, CCL22, and CCR4 in bone marrow biopsy tissues were higher in patients with NDMM than in controls (all P<0.05). The mRNA expression level of CCL17 was increased in NDMM patients with combined anemia, bone damage, renal damage, and M protein level ≥30 g/L (all P<0.05). The mRNA expression level of CCL22 was increased in NDMM patients with combined anemia, bone damage, and renal damage (all P<0.05). The mRNA expression level of CCR4 was increased in NDMM patients with combined anemia and renal damage (all P<0.05) . Conclusion:CCL17, CCL22, and CCR4 were highly expressed in clinical samples from patients with NDMM compared to those from controls, and they may be involved in the occurrence and development of NDMM.

The concept of'harmony'is the soul of traditional Chinese culture,which has a profound impact on the formation and development of traditional Chinese medicine(TCM).TCM is rooted in traditional Chinese culture,and the mode of thinking in TCM is in line with traditional Chinese culture.Based on the harmony culture,TCM has developed a unique view of health,disease and therapeutics.From the view of the harmony culture and by combining with years of clinical experience in treating dermatosis,Chinese medical master XUAN Guo-Wei has applied the concept of'harmony'in the TCM syndrome differentiation and treatment system in clinic,and has developed the academic thoughts of harmonizing therapy for removing toxins for the diagnosis and treatment of dermatosis.The thoughts of harmonizing therapy for removing toxins includes four aspects,namely harmonizing yin and yang,harmonizing healthy qi and pathogenic qi,harmonizing water and fire(i.e.,clod and hot),and harmonizing the administration of formula and drugs,aiming to remove toxins and expel pathogens and value the harmony.The thoughts of harmonizing therapy for removing toxins will beneficial to the comprehensive understanding of the unique health-disease-therapeutics concept in TCM,and will be helpful for managing the doctor-patient relationship,which is of enlightening significance to the modern clinical practice with TCM.