This paper systematically reviews the core concepts and lines of theoretical inheritance of major spleen-stomach theories in traditional Chinese medicine （TCM）， including spleen deficiency theory， spleen-stomach damp-heat theory， and liver-spleen disharmony theory. It is found that these theories have all undergone a developmental trajectory characterized by classical foundation， refinement of therapeutic methods， systematization of pathogenesis， and modern innovation. The evolution of spleen-stomach theory has achieved a shift from a singular focus on tonifying the spleen to regulating dynamic middle-jiao （焦） balance， and from localized spleen-stomach regulation to the circular movement of qi involving all five zang organs. In terms of modern disease-syndrome integrative research， spleen deficiency syndrome is shown to be closely associated with impairment of the gastrointestinal mucosal barrier， metabolic disorders， and gene polymorphisms related to Helicobacter pylori-associated gastric diseases. Spleen-stomach damp-heat syndrome is closely linked to hyperactive energy metabolism， inflammatory cytokines， and abnormal expression of aquaporins. Liver-spleen disharmony syndrome is mainly associated with dysregulation of the brain-gut axis and microbiota-related metabolic disorders. It is proposed that future research on spleen-stomach diseases and syndromes should further elucidate their potential multidimensional differential biological characteristics， thereby promoting the modernization of the TCM discipline of spleen-stomach studies.

This article systematically reviews the current research status as well as diagnosis and treatment strategies of traditional Chinese medicine （TCM） for gastroesophageal reflux disease （GERD）. Studies demonstrate that TCM， based on the "disease-syndrome combination" approach， exhibits multi-target advantages in alleviating symptoms of various GERD subtypes， promoting mucosal repair， regulating emotions， and facilitating the reduction of western medication. To address clinical challenges such as symptom overlap and limited therapeutic efficacy， strategies have been proposed including "treating different diseases with the same method" and integrated regulation based on viscera correlation. Future efforts should focus on elucidating the mechanisms of compound prescriptions， promoting TCM drug development under the "three-combination" evaluation framework that integrates TCM theory， human experience and clinical trial evidence， and optimizing integrated traditional and western medicine models to enhance GERD management.

Animal model research on spleen and stomach diseases in traditional Chinese medicine （TCM） is of great significance for elucidating the nature of diseases and syndromes and for revealing the mechanisms of action of Chinese herbal medicinals. At present， studies on classical TCM syndrome models of spleen and stomach diseases mainly focus on spleen deficiency syndrome， liver constraint syndrome， and damp-heat syndrome. Model construction is mostly based on the etiological and pathophysiological characteristics of syndrome， and model evaluation primarily involves macroscopic manifestations and physicochemical indicators. This paper summarizes the current research status of animal models integrating disease and syndrome for seven common spleen and stomach diseases， including chronic gastritis and gastric precancerous lesions， gastroesophageal reflux disease， functional dyspepsia， inflammatory bowel disease， irritable bowel syndrome， functional constipation， and functional diarrhea. The modeling methods and characteristics of disease-syndrome combined animal models for each disease are analyzed. It is proposed that future research on disease-syndrome integration in spleen and stomach diseases should move toward syste-matic， precise， and integrative development， and that interdisciplinary and cross-disciplinary research approaches should be adopted to enhance the predictive value and application efficiency of disease-syndrome combined animal models.

Based on the theoretical framework of "grease-turbidity-heat toxin"， this paper elucidates the patholo-gical evolution pattern underlying the alternation between active and remission phases of inflammatory bowel disease （IBD）. It is proposed that the active phase of IBD represents a progressive and explosive process characterized by internal accumulation of grease turbidity， constraint transforming into heat， and exuberant heat generating toxin. During the remission phase， the pathogenic process manifests as subsidence of heat toxin， depletion of qi and yin， latent retention of residual turbidity， and a state of coexistence between deficiency of healthy qi and lingering pathogenic factors. Accordingly， a staged therapeutic strategy with dynamic intervention and targeted modulation has been established. During the active phase， treatment follows the sequential principle of unblocking， clearing， and resolving pathogenic factors. In the early stage， the therapeutic approach focuses on regulating qi movement， fortifying the spleen， and resolving turbidity， using Tongxie Essential Formula （痛泻要方） and Shenling Baizhu Powder （参苓白术散） to regulate qi and fortify spleen. In the middle stage， the strategy emphasizes clearing heat， eliminating dampness， and dispersing pathogenic accumulation through downward and outward pathways， and Gegen Qinlian Decoction （葛根芩连汤） combined with Banxia Xiexin Decoction （半夏泻心汤） is used to clear and resolve damp-heat. In the late stage， treatment aims to resolve toxin， restrain sore， cool blood， and stabilize collaterals， using Baitouweng Decoction （白头翁汤）， Shaoyao Decoction （芍药汤）， and Xijiao Dihuang Decoction （犀角地黄汤） to eliminate toxins and cool blood. During the remission phase， the principle of reinforcing， consolidating， and penetrating is adopted to restore internal balance and clear the source， using Sishen Pills （四神丸） and Sijunzi Decoction （四君子汤） to reinforce healthy qi and venting pathogens.

Based on the theory of Zi Wu Liu Zhu （子午流注， the ebb and flow of midnight and midday） and the clinical characteristics of diarrhea-predominant irritable bowel syndrome （IBS-D） that its symptoms mainly occur during chou （丑） period （01：00—03：00）， mao （卯） period （5：00—7：00）， and si （巳） period （9：00—11：00）， this paper proposes a temporal pathogenesis chain of "liver constraint during chou period， intestinal stagnation during mao period， and spleen deficiency during si period". Within this chain， liver constraint serves as the initiating factor， and intestinal stagnation manifests as the branch， while spleen deficiency constitutes the root of the disease. Accordingly， a chronotherapeutic principle of "soothing the liver， regulating the intestines， and fortifying the spleen" is proposed， establishing a corresponding time-based syndrome differentiation and treatment system. During chou period， the treatment should focus on soothing the liver to relieve constraint and calming the mind to tranquilize the spirit， thereby blocking the mechanism of liver constraint overacting on the spleen. During mao period， the focus is regulating qi to resolve dampness and harmonizing the intestine to alleviate the branch symptoms of morning abdominal pain and diarrhea. During si period， the suggested method is fortifying the spleen and supplementing qi to drain dampness and stop diarrhea， thereby restoring the pivot of spleen-stomach transportation and transformation. These methods are complemented by strategies to optimize medication compliance， thereby providing a new chronotherapeutic approach for clinical diagnosis and treatment of IBS-D.

Based on the theoretical framework of "grease-turbidity-heat toxin"， this paper elucidates the patholo-gical evolution pattern underlying the alternation between active and remission phases of inflammatory bowel disease （IBD）. It is proposed that the active phase of IBD represents a progressive and explosive process characterized by internal accumulation of grease turbidity， constraint transforming into heat， and exuberant heat generating toxin. During the remission phase， the pathogenic process manifests as subsidence of heat toxin， depletion of qi and yin， latent retention of residual turbidity， and a state of coexistence between deficiency of healthy qi and lingering pathogenic factors. Accordingly， a staged therapeutic strategy with dynamic intervention and targeted modulation has been established. During the active phase， treatment follows the sequential principle of unblocking， clearing， and resolving pathogenic factors. In the early stage， the therapeutic approach focuses on regulating qi movement， fortifying the spleen， and resolving turbidity， using Tongxie Essential Formula （痛泻要方） and Shenling Baizhu Powder （参苓白术散） to regulate qi and fortify spleen. In the middle stage， the strategy emphasizes clearing heat， eliminating dampness， and dispersing pathogenic accumulation through downward and outward pathways， and Gegen Qinlian Decoction （葛根芩连汤） combined with Banxia Xiexin Decoction （半夏泻心汤） is used to clear and resolve damp-heat. In the late stage， treatment aims to resolve toxin， restrain sore， cool blood， and stabilize collaterals， using Baitouweng Decoction （白头翁汤）， Shaoyao Decoction （芍药汤）， and Xijiao Dihuang Decoction （犀角地黄汤） to eliminate toxins and cool blood. During the remission phase， the principle of reinforcing， consolidating， and penetrating is adopted to restore internal balance and clear the source， using Sishen Pills （四神丸） and Sijunzi Decoction （四君子汤） to reinforce healthy qi and venting pathogens.

ObjectiveTo construct a risk prediction model for chronic atrophic gastritis （CAG） that combines disease and syndrome by integrating spleen deficiency and blood stasis syndrome scores， gastric stem cell marker analysis， and network pharmacology and to elucidate the mechanism link between spleen deficiency， blood stasis， and gastric stem cell dysregulation. MethodsA total of 60 patients were stratified into high-risk CAG， low-risk CAG， and non-atrophic groups based on the operative link for gastritis assessment （OLGA）/operative link for gastric intestinal metaplasia assessment （OLGIM） stages. General data and syndrome scores of the patients were collected. Immunohistochemistry was employed to measure the protein levels of leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， trefoil factor 2 （TFF2）， and β-catenin in gastric mucosa across groups. Transcriptomic data （GSE130823） from the Gene Expression Omnibus （GEO） database were analyzed to validate the expression of these molecular markers at the gene level. A Firth penalized maximum likelihood logistic regression model was employed to integrate clinical， molecular， and TCM syndrome data to develop a CAG risk prediction model. Finally， network pharmacology analysis was conducted on spleen-invigorating herbs （Astragali Radix， Atractylodis Macrocephalae Rhizoma， and Dioscorea Rhizoma） and blood-activating herbs （Hedyotis diffusa， Salviae Miltiorrhizae Radix et Rhizoma， and Curcumae Rhizoma） to identify overlapping targets between these herbs and differentially expressed genes between low-grade intraepithelial neoplasia （LGIN） and gastritis， thereby clarifying the role of spleen deficiency and blood stasis in CAG progression from a pharmacological perspective. ResultsHigh-risk CAG patients exhibited higher blood stasis scores （4.60±1.50，2.62±1.32， P<0.01）， progressive nuclear accumulation of β-catenin （A 0.28-0.53， P<0.01）， and an increased LGR5⁺/TFF2⁺ ratio （A 1.02-1.92， P<0.01）. Blood stasis scores were correlated with LGR5/TFF2 imbalance （P=0.03） and activation of the Wnt/β-catenin signaling pathway （CTNNB1 increase， log₂=0.78）. The integrated prediction model （blood stasis score≥5 + β-catenin>0.38 + LGR5/TFF2>1.5） outperformed a pure biomarker approach ［Area Under the Curve （AUC） 0.92，0.89， ΔAUC=0.03， P=0.02］. Moreover， network pharmacology revealed 66 overlapping targets between spleen-invigorating/blood-activating herbs and LGIN， which were functionally enriched in mucosal repair and anti-oxidative stress， and negatively correlated with the Wnt/β-catenin signaling pathway （P<0.01）. ConclusionThis study developed an integrated risk prediction model for CAG by combining TCM spleen deficiency and blood stasis syndromes with gastric stem cell molecular markers. Furthermore， it proposed for the first time the "blood stasis-Wnt/β-catenin-stem cell axis" hypothesis， preliminarily elucidating that spleen deficiency and blood stasis may exacerbate gastric stem cell dysregulation and promote malignant transformation of CAG through hypoxia-induced Wnt activation. This provides a theoretical foundation and a translational tool for risk stratification and multi-target TCM intervention in CAG.

ObjectiveTo construct a risk prediction model for chronic atrophic gastritis （CAG） that combines disease and syndrome by integrating spleen deficiency and blood stasis syndrome scores， gastric stem cell marker analysis， and network pharmacology and to elucidate the mechanism link between spleen deficiency， blood stasis， and gastric stem cell dysregulation. MethodsA total of 60 patients were stratified into high-risk CAG， low-risk CAG， and non-atrophic groups based on the operative link for gastritis assessment （OLGA）/operative link for gastric intestinal metaplasia assessment （OLGIM） stages. General data and syndrome scores of the patients were collected. Immunohistochemistry was employed to measure the protein levels of leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5）， trefoil factor 2 （TFF2）， and β-catenin in gastric mucosa across groups. Transcriptomic data （GSE130823） from the Gene Expression Omnibus （GEO） database were analyzed to validate the expression of these molecular markers at the gene level. A Firth penalized maximum likelihood logistic regression model was employed to integrate clinical， molecular， and TCM syndrome data to develop a CAG risk prediction model. Finally， network pharmacology analysis was conducted on spleen-invigorating herbs （Astragali Radix， Atractylodis Macrocephalae Rhizoma， and Dioscorea Rhizoma） and blood-activating herbs （Hedyotis diffusa， Salviae Miltiorrhizae Radix et Rhizoma， and Curcumae Rhizoma） to identify overlapping targets between these herbs and differentially expressed genes between low-grade intraepithelial neoplasia （LGIN） and gastritis， thereby clarifying the role of spleen deficiency and blood stasis in CAG progression from a pharmacological perspective. ResultsHigh-risk CAG patients exhibited higher blood stasis scores （4.60±1.50，2.62±1.32， P<0.01）， progressive nuclear accumulation of β-catenin （A 0.28-0.53， P<0.01）， and an increased LGR5⁺/TFF2⁺ ratio （A 1.02-1.92， P<0.01）. Blood stasis scores were correlated with LGR5/TFF2 imbalance （P=0.03） and activation of the Wnt/β-catenin signaling pathway （CTNNB1 increase， log₂=0.78）. The integrated prediction model （blood stasis score≥5 + β-catenin>0.38 + LGR5/TFF2>1.5） outperformed a pure biomarker approach ［Area Under the Curve （AUC） 0.92，0.89， ΔAUC=0.03， P=0.02］. Moreover， network pharmacology revealed 66 overlapping targets between spleen-invigorating/blood-activating herbs and LGIN， which were functionally enriched in mucosal repair and anti-oxidative stress， and negatively correlated with the Wnt/β-catenin signaling pathway （P<0.01）. ConclusionThis study developed an integrated risk prediction model for CAG by combining TCM spleen deficiency and blood stasis syndromes with gastric stem cell molecular markers. Furthermore， it proposed for the first time the "blood stasis-Wnt/β-catenin-stem cell axis" hypothesis， preliminarily elucidating that spleen deficiency and blood stasis may exacerbate gastric stem cell dysregulation and promote malignant transformation of CAG through hypoxia-induced Wnt activation. This provides a theoretical foundation and a translational tool for risk stratification and multi-target TCM intervention in CAG.

ObjectiveTo investigate the current status and related factors of maternal influenza vaccination willingness among pregnant and postpartum women in Shanghai and Liaoning Province, China, and to explore the facilitators and barriers affecting vaccination uptake, so as to provide references for future practices in promoting maternal influenza immunization in China. MethodsA convergent mixed-methods research was conducted. From January to March 2024, a questionnaire survey was conducted among women attending prenatal and postnatal care at 7 medical institutions in Shanghai and Dalian, Liaoning Province, which aimed to assess pregnant women’s knowledge about influenza vaccine and their willingness to vaccination during pregnancy, as well as to identify the related factors. In addition, purposive sampling method was used to conduct in-depth interviews with pregnant women and perinatal healthcare service providers to explore their perspectives on influenza vaccination during pregnancy, including the reasons for their willingness or unwillingness to receive ( or recommend) the vaccine, and the relevant facilitators and barriers to vaccination. ResultsA total of 366 pregnant and postpartum women participated in the questionnaire survey, and 9.56% (35/366) of them were willing to receive the influenza vaccine during pregnancy. The results of multivariate logistic stepwise regression analyses showed that primipara (aOR=0.158, 95%CI: 0.037‒0.671, P=0.012), family members’ support for influenza vaccination during pregnancy (aOR=0.015, 95%CI: 0.003‒0.082, P<0.001) were associated with higher willingness to receive influenza vaccine during pregnancy. Absence of influenza infection during pregnancy (aOR=5.383, 95%CI: 1.801‒16.092, P<0.001), and lack of knowledge regarding influenza vaccination during pregnancy (aOR=11.294, 95%CI: 3.593‒35.496, P<0.01) were associated with lower willingness to receive influenza vaccine during pregnancy. Qualitative findings indicated that the facilitators to vaccination willingness among pregnant and postpartum women included the recommendation of healthcare service providers, adequate knowledge of influenza vaccine information and family members’ support for vaccination. Conversely, the barriers to vaccination willingness included low recommendation from the healthcare service providers, lack of knowledge about the safety of influenza vaccine during pregnancy and inadequate attention to influenza and influenza vaccine. ConclusionThe willingness to receive influenza vaccination among pregnant and postpartum women in Shanghai and Liaoning Province is relatively low. It is recommended that China should promptly improve the evidence-based system for the safety and efficacy of influenza vaccines for pregnant and postpartum women, along with an establishment of the mechanism for addressing adverse reactions. Furthermore, it is essential to enhance educational outreach to pregnant and postpartum women, their families, and healthcare service providers, thereby increasing the accessibility of information regarding influenza vaccination, which are expected to enhance the willingness of pregnant and postpartum women to receive the vaccine.

The theory of "holism of five organs" highly encapsulates the understanding of TCM on the integrity, connectivity, and unity of the internal life functions and morphological structures of the human body. Functional gastrointestinal disorders (FGIDs) frequently overlap, and TCM has significant advantages in their prevention and treatment based on the theory of the holistic view and syndrome differentiation and treatment. Exosomes are extracellular vesicles whose secretory form and biological functions fully reflect the "holism of five organs", and they are of great value in the pathogenesis, diagnosis and treatment of overlap of symptoms of FGIDs. This article interpreted the relationship between exosomes and overlap of symptoms of FGIDs with the "holism of five organs", aiming to provide new ideas and methods for the prevention and treatment of overlap of symptoms of FGIDs, as well as partly explain the scientific connotation of the theory of "holism of five organs".