Digital and intelligent technologies serve as the core engine driving the inheritance of the essence and the innovation while upholding the fundamentals of traditional Chinese medicine（TCM）. Currently， the digital and intelligent transformation of TCM has undergone four developmental stages， exhibiting inherent characteristics such as long-term inevitability， objective standardization， and ecological evolution. By introducing quantitative metrics， digital and intelligent technologies have achieved breakthroughs in TCM knowledge inheritance and innovation， clinical diagnosis and treatment， and herbal medicine supply. The practical applicability of methodological innovations has been empirically validated， though significant disparities exist in technological adaptability and application depth across different fields. Overall， the digital and intelligent transformation of TCM remains in its nascent stage， grappling with multiple structural challenges：weak data foundations， inadequate technological adaptability， incomplete institutional frameworks， shortages of multidisciplinary talent， lagging policies and regulations， and urban-rural digital divide. In order to foster sustainable development and modernization of TCM， this paper establishes a six-dimensional collaborative governance framework of encompassing data， technology， organization， institutions， environment and ethics， which is rooted in data governance and digital governance theories. Future efforts should center on standardization， integration， and ecosystem development to build a data and technology foundation. Focus should be placed on deepening innovation and application of key TCM-specific technologies， while simultaneously strengthening interdisciplinary talent cultivation， improving institutional mechanisms and policy frameworks， and increasing support for rural areas. By adopting a people-centered and technology-empowered approach， we can overcome developmental constraints and unleash the powerful driving force of digital and intelligent technologies for the inheritance of TCM.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objective To construct mice hepatocellular carcinoma models with different tumor immune microenvironments(TIME)and explore the differences.Methods H22 and hepa1-6 were used to construct subcutaneous transplantation tumor model of C57 mice as homologous hepatocellular carcinoma cell lines(denoted as H22 group and hepal-6 group,each n=8),and the differences of TIME were evaluated.Immunohistochemistry was used to detect and quantify the infiltration of T cells,CD4+T cells,CD8+T cells,regulatory T cells and B cells in TIME.Flow cytometry was performed to detect the differences of composition of immune cell subpopulations in peripheral blood and tumor parenchyma.Gene expression profile characteristics of tumor tissue were analyzed based on high-throughput transcriptome sequencing technology,and enrichment analyses of immune-related signaling pathways were evaluated combined with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG).Results H22 group showed cold and hepa1-6 group showed hot TIME characteristics.The number of T cells,CD4+T cells and CD8+T cells in tumor tissue of H22 group were all lower,while the proportion of T cells,CD4+T cells and CD8+T cells in peripheral blood were all higher than those of hepa1-6 group(all P＜0.05).Compared with H22 group,up-regulated genes of tumor tissue in hepa1-6 group expressed significantly enriched in tumor immune activation-related signaling pathways.Conclusion H22 and hepa1-6 hepatocellular carcinoma models showed distinct TIME characteristics of cold and hot tumors,respectively,and the amount of immune cells in tumor tissue of the former were significantly lower than those in the latter.

Chronic pain has emerged as a prevalent medical challenge in contemporary society.Patients suffering from chronic pain frequently develop comorbid psychological disorders,including anxiety,depression,post-traumatic stress disorder,and various psychiatric syndromes.These psychological complications not only affect patients' pain perception and responses,but may also constitute critical obstacles during pain management interventions.Acupuncture is a long-established clinical practice that has demonstrated remarkable efficacy in alleviating diverse pain types and has shown favorable therapeutic outcomes in ameliorating emotional disturbances such as anxiety and depression.The precise mechanisms underlying acupuncture-induced analgesia and anxiolytic effects,however,remain to be fully elucidated.In this context,it is essential to establish suitable and stable animal models to allow in-depth investigations into the pathogenesis of pain-related emotional disorders and the mechanistic foundations of acupuncture.This article presents a comprehensive review of recent literature regarding the selection of experimental animals,model-establishment method ologies,and behavioral-assessment paradigms pertaining to animal model platforms of chronic pain with comorbid anxiety.We also provide an in-depth discussion of research advancements regarding acupuncture intervention parameters,including needling techniques,acupoint selection,treatment duration,and efficacy evaluation within these animal models.This review proposes comprehensive and reference strategies for constructing preclinical animal models to investigate the mechanisms of acupuncture in managing chronic pain with comorbid anxiety,thus supporting scientific advancements in related research fields.

Objectives:To explore the predictive value of residual Murray's law-based quantitative flow ratio(μQFR)on long-term vessel-oriented composite endpoints(VoCE).Methods:This retrospective study included 3 510 patients from the FAVOR Ⅲ China trial.Offline residual μQFR analysis was performed on all vessels(diameter≥2.5 mm)with 50%-90%stenotic lesions.Patients were stratified into high-,intermediate-,and low-risk groups based on residual μQFR tertiles.The primary endpoint was 3-year VoCE,defined as a composite of cardiac death related to the target vessel,target vessel-related spontaneous myocardial infarction,and ischemia-driven target vessel revascularization.Results:Offline analysis was performed on 5 256 vessels from 3 510 patients.The mean residual μQFR was 0.92±0.75.The high-risk group(residual μQFR≤0.91)with 1 554 patients(1 958 vessels);the intermediate-risk group(residual μQFR 0.92-0.96)with 1 211 patients(1 906 vessels);and the low-risk group(residual μQFR>0.96)with 745 patients(1 392 vessels).Over 3-year follow-up,VoCE occurred in 227 vessels(4.3%).The 3-year VoCE incidence was significantly higher in the high-risk group compared to the intermediate-and low-risk groups(6.2%vs.4.1%vs.2.5%,log-rank P<0.001),primarily driven by ischemia-driven target vessel revascularization(5.0%vs.3.0%vs.1.6%,log-rank P<0.001).Hypertension(OR=0.83,95%CI:0.72-0.96),hypercholesterolemia(OR=0.84,95%CI:0.73-0.97),bifurcation lesions(OR=0.72,95%CI:0.63-0.83),moderate/severe calcification(OR=0.70,95%CI:0.57-0.84),and tandem lesions(OR=0.59,95%CI:0.47-0.75)were independent predictors of lower residual μQFR values.Conclusions:Lower residual μQFR is significantly associated with increased VoCE risk during the 3-year follow up period.

Objective To construct mice hepatocellular carcinoma models with different tumor immune microenvironments(TIME)and explore the differences.Methods H22 and hepa1-6 were used to construct subcutaneous transplantation tumor model of C57 mice as homologous hepatocellular carcinoma cell lines(denoted as H22 group and hepal-6 group,each n=8),and the differences of TIME were evaluated.Immunohistochemistry was used to detect and quantify the infiltration of T cells,CD4+T cells,CD8+T cells,regulatory T cells and B cells in TIME.Flow cytometry was performed to detect the differences of composition of immune cell subpopulations in peripheral blood and tumor parenchyma.Gene expression profile characteristics of tumor tissue were analyzed based on high-throughput transcriptome sequencing technology,and enrichment analyses of immune-related signaling pathways were evaluated combined with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG).Results H22 group showed cold and hepa1-6 group showed hot TIME characteristics.The number of T cells,CD4+T cells and CD8+T cells in tumor tissue of H22 group were all lower,while the proportion of T cells,CD4+T cells and CD8+T cells in peripheral blood were all higher than those of hepa1-6 group(all P＜0.05).Compared with H22 group,up-regulated genes of tumor tissue in hepa1-6 group expressed significantly enriched in tumor immune activation-related signaling pathways.Conclusion H22 and hepa1-6 hepatocellular carcinoma models showed distinct TIME characteristics of cold and hot tumors,respectively,and the amount of immune cells in tumor tissue of the former were significantly lower than those in the latter.

AIM:This study investigated the potential mechanism of acupuncture regulating adenosine A1 re-ceptor(ADORA1)in the mouse caudate putamen(CPu)to improve neuroplasticity and alleviate inflammatory pain.METHODS:Male C57BL/6 mice were randomly divided into five groups,namely,saline,complete Freund's adjuvant(CFA),acupuncture(MA),acupuncture+ADORA1 shRNA(MA+shRNA),and acupuncture+negative shRNA(MA+NCshRNA)groups.Twenty-one days before modeling,the mice in the MA+shRNA and MA+NCshRNA groups were in-jected with ADORA1 shRNA and control virus into the CPu.Modeling was performed 21 d later by injection of CFA into the right plantar skin of mice in the model and acupuncture groups to induce adjuvant-mediated arthritis.On day 2 after modeling,mice in the acupuncture groups received acupuncture at bilateral"Zusanli"points,30 min per session,once a day,for a total of 7 days.The paw thermal radiation pain threshold was used as an indicator of the effects on pain in the mice.Changes in the protein levels of ADORA1,synaptophysin(SYP),synapsin(SYN)I,SYN II,and brain-derived neurotrophic factor(BDNF)in the CPu were assessed by Western blot,and transmission electron microscopy was used to examine the dendritic structure and synaptic ultrastructure of neurons within the CPu.RESULTS:(1)Compared with the saline group,CFA modeling significantly reduced the thermal radiation pain threshold in mice(P<0.01),as well as the protein levels of ADORA1(P<0.01).Compared with the CFA group,the thermal pain threshold in the MA group in-creased between days 1 and 7 of acupuncture(P<0.05 or P<0.01),and ADORA1 protein levels increased(P<0.01).(2)Compared with the saline group,SYN I,SYN II,and BDNF protein levels were increased in the CFA group(P<0.05 or P<0.01),while relative to the CFA group,the levels of SYN I,SYN II,and BDNF were reduced in the acupuncture group(P<0.05 or P<0.01).No significant changes in SYP protein levels were observed in any of the groups.(3)Golgi staining and Sholl analysis showed that compared with the saline group,there were reductions in the total dendritic length and number of intersection points in the CFA group,while the dendritic spine density increased(P<0.05).Relative to the CFA group,the total dendritic length and the number of intersection points were increased in the MA group,while the dendritic spine density decreased(P<0.05).(4)Transmission electron microscopy revealed that compared with the Sa-line group,the synaptic clefts were narrower in the CFA group,while the density of synaptic vesicles in the presynaptic membrane was increased.Compared with the CFA group,synaptic clefts in the MA group were wider,and synaptic vesi-cle densities in the presynaptic membrane were reduced.(5)Twenty-one days after viral transfection,the thermal pain threshold in the MA and MA+NCshRNA groups increased from day 1 to day 7 of acupuncture relative to the CFA and MA+shRNA groups(P<0.05 or P<0.01),while the expression of ADORA1 was increased in both the MA and MA+NCshRNA groups(P<0.05 or P<0.01).(6)Compared with the CFA and MA+shRNA groups,the protein expression of SYN II and BDNF in the MA and MA+NCshRNA groups was reduced(P<0.05 or P<0.01).No significant changes in SYN I protein were observed in any of the groups.CONCLUSION:Acupuncture on Zusanli point can alleviate chronic pain in CFA-treated mice,potentially mediated by up-regulation of ADORA1 expression in the CPu brain region,thereby improving neuroplasticity.

Chronic pain has emerged as a prevalent medical challenge in contemporary society.Patients suffering from chronic pain frequently develop comorbid psychological disorders,including anxiety,depression,post-traumatic stress disorder,and various psychiatric syndromes.These psychological complications not only affect patients' pain perception and responses,but may also constitute critical obstacles during pain management interventions.Acupuncture is a long-established clinical practice that has demonstrated remarkable efficacy in alleviating diverse pain types and has shown favorable therapeutic outcomes in ameliorating emotional disturbances such as anxiety and depression.The precise mechanisms underlying acupuncture-induced analgesia and anxiolytic effects,however,remain to be fully elucidated.In this context,it is essential to establish suitable and stable animal models to allow in-depth investigations into the pathogenesis of pain-related emotional disorders and the mechanistic foundations of acupuncture.This article presents a comprehensive review of recent literature regarding the selection of experimental animals,model-establishment method ologies,and behavioral-assessment paradigms pertaining to animal model platforms of chronic pain with comorbid anxiety.We also provide an in-depth discussion of research advancements regarding acupuncture intervention parameters,including needling techniques,acupoint selection,treatment duration,and efficacy evaluation within these animal models.This review proposes comprehensive and reference strategies for constructing preclinical animal models to investigate the mechanisms of acupuncture in managing chronic pain with comorbid anxiety,thus supporting scientific advancements in related research fields.

AIM:This study investigated the potential mechanism of acupuncture regulating adenosine A1 re-ceptor(ADORA1)in the mouse caudate putamen(CPu)to improve neuroplasticity and alleviate inflammatory pain.METHODS:Male C57BL/6 mice were randomly divided into five groups,namely,saline,complete Freund's adjuvant(CFA),acupuncture(MA),acupuncture+ADORA1 shRNA(MA+shRNA),and acupuncture+negative shRNA(MA+NCshRNA)groups.Twenty-one days before modeling,the mice in the MA+shRNA and MA+NCshRNA groups were in-jected with ADORA1 shRNA and control virus into the CPu.Modeling was performed 21 d later by injection of CFA into the right plantar skin of mice in the model and acupuncture groups to induce adjuvant-mediated arthritis.On day 2 after modeling,mice in the acupuncture groups received acupuncture at bilateral"Zusanli"points,30 min per session,once a day,for a total of 7 days.The paw thermal radiation pain threshold was used as an indicator of the effects on pain in the mice.Changes in the protein levels of ADORA1,synaptophysin(SYP),synapsin(SYN)I,SYN II,and brain-derived neurotrophic factor(BDNF)in the CPu were assessed by Western blot,and transmission electron microscopy was used to examine the dendritic structure and synaptic ultrastructure of neurons within the CPu.RESULTS:(1)Compared with the saline group,CFA modeling significantly reduced the thermal radiation pain threshold in mice(P<0.01),as well as the protein levels of ADORA1(P<0.01).Compared with the CFA group,the thermal pain threshold in the MA group in-creased between days 1 and 7 of acupuncture(P<0.05 or P<0.01),and ADORA1 protein levels increased(P<0.01).(2)Compared with the saline group,SYN I,SYN II,and BDNF protein levels were increased in the CFA group(P<0.05 or P<0.01),while relative to the CFA group,the levels of SYN I,SYN II,and BDNF were reduced in the acupuncture group(P<0.05 or P<0.01).No significant changes in SYP protein levels were observed in any of the groups.(3)Golgi staining and Sholl analysis showed that compared with the saline group,there were reductions in the total dendritic length and number of intersection points in the CFA group,while the dendritic spine density increased(P<0.05).Relative to the CFA group,the total dendritic length and the number of intersection points were increased in the MA group,while the dendritic spine density decreased(P<0.05).(4)Transmission electron microscopy revealed that compared with the Sa-line group,the synaptic clefts were narrower in the CFA group,while the density of synaptic vesicles in the presynaptic membrane was increased.Compared with the CFA group,synaptic clefts in the MA group were wider,and synaptic vesi-cle densities in the presynaptic membrane were reduced.(5)Twenty-one days after viral transfection,the thermal pain threshold in the MA and MA+NCshRNA groups increased from day 1 to day 7 of acupuncture relative to the CFA and MA+shRNA groups(P<0.05 or P<0.01),while the expression of ADORA1 was increased in both the MA and MA+NCshRNA groups(P<0.05 or P<0.01).(6)Compared with the CFA and MA+shRNA groups,the protein expression of SYN II and BDNF in the MA and MA+NCshRNA groups was reduced(P<0.05 or P<0.01).No significant changes in SYN I protein were observed in any of the groups.CONCLUSION:Acupuncture on Zusanli point can alleviate chronic pain in CFA-treated mice,potentially mediated by up-regulation of ADORA1 expression in the CPu brain region,thereby improving neuroplasticity.

Acute pancreatitis (AP) is a severe inflammatory disease characterized by self-digestion of pancreatic tissue and inflammatory responses. Recent studies have revealed a close connection between gut microbiota and AP. The gut microbiota community, a complex ecosystem composed of trillions of microorganisms, is closely associated with various physiological activities of the host, including metabolic processes, immune system regulation, and intestinal structure maintenance. However, in patients with AP, dysbiosis of the gut microbiota are believed to play a key role in the occurrence and progression of the disease. This dysbiosis not only impairs the integrity of the intestinal barrier, but may also exacerbate inflammatory responses through multiple mechanisms, thereby affecting the severity of the disease and patient' clinical prognosis. This article reviews the mechanisms of action of gut microbiota in AP, explores how gut microbiota dysbiosis affects disease progression, and evaluates current clinical treatment methods to regulate intestinal flora, including probiotic supplementation, fecal microbiota transplantation, antibiotic therapy, and early enteral nutrition. In addition, this article discusses the efficacy and safety of the aforementioned therapeutic approaches, and outlines future research directions, aiming to provide novel perspectives and strategies for the diagnosis, treatment and prognostic evaluation of AP. Through in-depth understanding the interaction between gut microbiota and AP, it is expected that more precise and personalized therapeutic regimens will be developed to improve patients' quality of life and clinical outcomes.
Humans ; Gastrointestinal Microbiome ; Dysbiosis ; Pancreatitis/microbiology* ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use* ; Acute Disease ; Anti-Bacterial Agents/therapeutic use* ; Enteral Nutrition