Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.

Objective To investigate the mechanism of action of circ-0058063 regulating ERK/MAPK signaling pathway on ferroptosis in esophageal cancer cells.Methods EC9706 cells were randomly divided into the Control group,the si-NC group,the si-circ-0058063 group,and the si-circ-0058063+ISO group.qRT-PCR was used to detect the expression of circ-0058063 in esophageal cancer tissues and cells;CCK-8 and clone formation assay were used to detect the cell proliferation ability.The levels of Fe2+,malondialdehyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in cells were detected.Western blot was used to detect the ERK/MAPK signaling pathway and the expression of ferroptosis-related protein in cells.Results The expression level of circ-0058063 in esophageal cancer tissue was significantly higher than that in adjacent tissues(P<0.05);the expression level of circ-0058063 in human esophageal cancer cell EC9706 was significantly higher than that in human normal esophageal epithelial cell HEEC(P<0.05).Compared with the Control group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063 group were significantly reduced(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly increased(P<0.05).Compared with the si-circ-0058063 group,the expression level of circ-0058063 in cells,cell survival rate,number of cloned cells,GSH level,ratios of p-ERK1/2/ERK1/2 and p-p38MAPK/p38MAPK,as well as the expression levels of SLC7A11 and GPX4 protein in the si-circ-0058063+ISO group were significantly increased(P<0.05),while the levels of Fe2+,MDA,and ROS in cells were significantly decreased(P<0.05).Conclusion Knockdown of circ-0058063 can inhibit the proliferation of esophageal cancer cells and induce ferroptosis,and its mechanism of action may be related to the inhibition of ERK/MAPK signaling pathway activation.

Objective To investigate the protective effect and mechanism of heat acclimation(HA)on electromagnetic field(EMF)induced hippocampus neuron injury in mice.Methods Forty healthy BALB/c male mice(18～22 g,7 weeks old)were randomly divided into 4 groups(n=10):Control group(Con),HA group(34℃,30 d),EMF group(2 450 MHz,20 min/d,4 weeks)and HA+EMF group(HA preconditioning+EMF).Sucrose preference test was performed to evaluate sucrose preference levels of mice in each group.Tail suspension test and forced swimming test were utilized to observe the immobility time.Morris water maze test was conducted to determine the learning and memory capabilities.Pathological changes in the hippocampus were observed with HE staining.Immunohistochemical assay for Iba1(marker of microglia),CD68(marker of pro-inflammatory phenotype)and CD206(marker of anti-inflammatory phenotype)were used to detect the number and activation phenotype of microglia in the hippocampus.ELISA was applied to measure the levels of TNF-α,IL-1β,TGF-β and IL-10 in the hippocampus of each group.Western blotting was performed to determine the protein levels of HSP70 in the hippocampus.Results As compared with the Con group,the EMF group showed a decreased preference for sucrose(P<0.05),prolonged immobile time in the tail suspension test(P<0.01)as well as in the forced swimming test(P<0.01),extented escape latency on the 7th day(P<0.01),and a decreased time of crossing the platform(P<0.05).EMF exposure resulted in that the hippocampal neurons were in disordered arrangement,loose structure and irregular morphology,with swollen cytoplasm and condensed nuclei,swollen and more microglial cells in the hippocampus(P<0.01),and enhanced relative fluorescence intensity of CD68(P<0.01),but not in CD206 fluorescence intensity(P=0.885).All these findings suggested that activated microglia predominantly exhibited a pro-inflammatory M1 phenotype during this phase.In the hippocampus,the levels of TNF-α and IL-1β were significantly increased,while the levels of IL-10 and TGF-β were significantly decreased(P<0.01).HA treatment reversed the conditions induced by EMF exposure,including better preference for sucrose(P<0.01),shorten immobile time in tail suspension test(P<0.05)and forced swimming test(P<0.01),less escape latency on the 7th day(P<0.01),and improved hippocampal cell injuries.Compared with the Con group,there were more microglial cells in the hippocampus in the HA+EMF group,with increased relative fluorescence intensity of M2 phenotype marker CD206(P<0.01)and decreased CD68 fluorescence intensity(P<0.01).HA treatment also significantly decreased the expression of TNF-α and IL-1β levels(P<0.01),increased the expression of IL-10 and TGF-β(P<0.01),and elevated the protein level of HSP70(P<0.01)when compared with the EMF group.Conclusion HA may ameliorate EMF-induced hippocampus neurons injury in mice by altering the phenotype of activated microglia and inhibiting inflammatory responses.

Patients suffering from nerve injury often experience exacerbated pain responses and complain of memory deficits. The dorsal hippocampus (dHPC), a well-defined region responsible for learning and memory, displays maladaptive plasticity upon injury, which is assumed to underlie pain hypersensitivity and cognitive deficits. However, much attention has thus far been paid to intracellular mechanisms of plasticity rather than extracellular alterations that might trigger and facilitate intracellular changes. Emerging evidence has shown that nerve injury alters the microarchitecture of the extracellular matrix (ECM) and decreases ECM rigidity in the dHPC. Despite this, it remains elusive which element of the ECM in the dHPC is affected and how it contributes to neuropathic pain and comorbid cognitive deficits. Laminin, a key element of the ECM, consists of α-, β-, and γ-chains and has been implicated in several pathophysiological processes. Here, we showed that peripheral nerve injury downregulates laminin β1 (LAMB1) in the dHPC. Silencing of hippocampal LAMB1 exacerbates pain sensitivity and induces cognitive dysfunction. Further mechanistic analysis revealed that loss of hippocampal LAMB1 causes dysregulated Src/NR2A signaling cascades via interaction with integrin β1, leading to decreased Ca²⁺ levels in pyramidal neurons, which in turn orchestrates structural and functional plasticity and eventually results in exaggerated pain responses and cognitive deficits. In this study, we shed new light on the functional capability of hippocampal ECM LAMB1 in the modulation of neuropathic pain and comorbid cognitive deficits, and reveal a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified hippocampal LAMB1/integrin β1 signaling as a potential therapeutic target for the treatment of neuropathic pain and related memory loss.
Animals ; Laminin/genetics* ; Hippocampus/metabolism* ; Neuralgia/metabolism* ; Cognitive Dysfunction/etiology* ; Male ; Peripheral Nerve Injuries/metabolism* ; Extracellular Matrix/metabolism* ; Integrin beta1/metabolism* ; Pyramidal Cells/metabolism* ; Signal Transduction

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Isoflavones which mainly distributed in leguminous plants have plenty of health benefits.Isoflavone synthase(IFS)is a membrane-associated cytochrome P450 enzyme(CYP450)which carries out the unique aryl-ring migration and hydroxylation.So far,few crystal structures of plant P450s have been obtained.We determined the crystal structure of IFS from Medicago truncatula at 1.9 ? by MAD method using a selenomethionine substituted crystal and conducted molecular docking and mutagenesis study.The structure of IFS complexed with imidazole exhibits the helix Ⅰa-loop-helix Ⅰβ motif which cor-responds to helix Ⅰ of other P450s.Compared with structures of common P450s,IFS/imidazole structure contains an extra domain,i.e.,the γ-domain.The structure reveals a homodimer in which the γ-domain of one molecule interacts with the β-domain of another.The plane of heme group makes an angle of ap-proximately 40° with the helix Ⅰa-loop-helix Ⅰβ motif.Molecular docking combined with mutagenesis study suggested that Trp-128 and Asp-300 might play important roles in substrate binding and recogni-tion.Phe-301,Ser-303 and Gly-305 from the helix Ⅰa-loop-helix Ⅰβ motif may play important roles in the aryl-ring migration.These novel structural features reveal insights into the unique reaction mechanism of IFS and provide a basis for engineering IFS in leguminous crops for health purpose.

Objective To elucidate the pharmacokinetic characteristics and primary metabolic pathways of anthocyanins in vivo,as well as the endogenous metabolites exhibiting sensitive responses to bilberry extract intervention in rats by LC-MS/MS technology,following oral administration of bilberry extract.Methods Multi-component pharmacokinetic technology was employed to study the systemic exposure characteristics of anthocyanins in blood,the metabolic product profile,and the dynamic concentration changes of anthocyanins and their metabolites in plasma after oral administration of bilberry extract to rats.Metabolomics technology was used to analyze changes in endogenous metabolites at the time point when most anthocyanins reached their peak plasma concentration.Results After administration of European cranberry extract,a total of 18 anthocyanin parent compounds and 14 metabolites were detected in rat plasma.Glucuronidation was identified as the primary metabolic pathway.The time to reach peak concentration(Tmax)for most parent compounds ranged from 15 to 60 minutes.Moreover,30 minutes after oral dosing with the cranberry extract,the levels of various endogenous acyl-carnitines,fatty acids,and lysophosphatidylcholines in the blood decreased.The plasma exposure of most anthocyanin components and their metabolites showed a highly linear correlation with the administered dose(R2>0.9).Conclusion This study clarified the main pharmacokinetic characteristics and metabolic pathways of anthocyanins from bilberry extract in rats,as well as the potential impact on various endogenous metabolites.It provides data support for effectively exploring the pharmacodynamic material basis and mechanism of action of bilberry extract.