Sangjuyin， as a pungent and cooling agent with precise therapeutic effect， is a classic pungent formula for cooling relief of the epidermis， which is highly respected by medical practitioners. This formula is from the Wenbing Tiaobian written by WU Jutong in the Qing dynasty， on the basis of which subsequent medical practitioners have made additions and subtractions to apply it. The authors used the bibliometric method to systematically organize the medical books from the Qing dynasty and the Republic of China and modern literature to analyze the composition， concoction， decoction， efficacy， and previous and modern application of Sangjuyin. After examination， the drug base of this formula is basically clear. Armeniacae Semen Amarum is the dried mature seeds of Armeniaca vulgaris， family Rosaceae. Forsythiae Fructus is the dried fruit of Forsythia suspensa， family Mulleinaceae. Menthae Haplocalycis Herba is the dried above-ground part of Mentha haplocalyx， family Labiatae. Mori Folium is the dried leaves of Morus alba， family Moraceae. Chrysanthemi Flos is the dried head of Chrysanthemum morifolium， family Asteraceae. Platycodonis Radix is the dried root of Eryngium grandiflorum， family Eryngium. Glycyrrhizae Radix et Rhizoma is the dried root and rhizome of Glycyrrhiza uralensis of the Leguminosae family， and Phragmitis Rhizoma is the fresh or dried rhizome of Phragmites communis of the Gramineae family. It is recommended that the eight drugs be used in raw form as medicine. The dosage and method of decoction were converted into a modern single dosage of 7.46 g Armeniacae Semen Amarum， 5.60 g Forsythiae Fructus， 2.98 g Menthae Haplocalycis Herba， 9.33 g Mori Folium， 3.73 g Chrysanthemi Flos， 7.46 g Platycodonis Radix， 2.98 g Glycyrrhizae Radix et Rhizoma， and 11.19 g Phragmitis Rhizoma， with 400 mL water added， and the solution was boiled to obtain 200 mL， taken twice a day. Sangjuyin has the efficacy of dispersing wind and clearing heat， promoting lung and relieving cough， and it is used for treating the initial onset of wind-warmth and the evidence of evil spirits in the lungs and collaterals. Modern research has shown that Sangjuyin is often used in the treatment of cough， pneumonia， rhinitis， and other respiratory diseases， and the results of this study provide a reference for the later development of Sangjuyin.

OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

BackgroundAnxiety disorder is a common mental disorder， with its prevalence showing a continuous upward trend， significantly affecting the quality of life and social function of patients. Due to the lack of objective and reliable biomarkers in clinical practice， the early identification and treatment of anxiety disorder have been somewhat limited. Plasma proteins have the potential to serve as biomarkers for mental diseases， however， the causal relationship between them and anxiety disorder remains unclear. ObjectiveTo identify the plasma proteins that have a causal relationship with anxiety disorders， and to elucidate the associated biological pathways， in order to provide references for the search for biomarkers of anxiety disorders and the exploration of potential therapeutic targets. MethodsBased on the protein quantitative trait locus （pQTL） data of 4 907 plasma proteins covering 35 559 Icelandic individuals from the deCODE database， and the genome-wide association studies （GWAS） data of 50 486 patients with anxiety disorders and 330 460 healthy controls， the inverse-variance weighted （IVW） method was used as the main analysis method， supplemented by MR-Egger method， weighted median method， simple model method， and weighted model method for bidirectional Mendelian randomization analysis. Enrichment analysis of gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways was conducted for the related proteins. Sensitivity analysis was performed using Cochran's Q test， MR-Egger intercept test， MR-PRESSO test， and leave-one-out analysis to evaluate the robustness of the results. ResultsA total of 10 plasma proteins were identified as significantly associated with anxiety disorders. Among these， SPATA9 （OR=0.856， 95% CI： 0.784–0.934， P<0.01） and PDE5A （OR=0.911， 95% CI： 0.864–0.961， P<0.01） were identified as protective factors， while CRYGD （OR=1.209， 95% CI： 1.095–1.334， P<0.01）， BTN3A3 （OR=1.045， 95% CI： 1.018–1.073， P<0.01）， SERPINB13 （OR=1.102， 95% CI： 1.040–1.168， P<0.01）， ERBB4 （OR=1.283， 95% CI： 1.109–1.484， P<0.01）， LSAMP （OR=1.096， 95% CI： 1.037–1.158， P<0.01）， ICOSLG （OR=1.283， 95% CI： 1.104–1.490， P<0.01）， DNAJB11 （OR=1.172， 95% CI： 1.076–1.277， P<0.01）， and TREML1 （OR=1.115， 95% CI： 1.054–1.179， P<0.01） were identified as risk factors. The sensitivity analysis showed that the results were robust， with no heterogeneity （Cochran's Q test P>0.05） or pleiotropy （MR-Egger intercept test P>0.05）. Enrichment analysis indicated that these plasma proteins were enriched in biological processes such as T-cell signal transduction， lymphocyte proliferation， cell membrane structure and synaptic function， as well as the intestinal immune network that produces IgA and the ErbB signaling pathway. ConclusionThis study identified 10 plasma proteins associated with anxiety disorders. The functions of these plasma proteins involve multiple biological processes such as neural development and immune regulation.

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.

Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Objective: To investigate the role of butyric acid-producing bacteria in long bone homeostasis in mice with periodontitis under a high-fat/high-sugar diet and to provide new insights for the prevention and treatment of periodontitis and related bone metabolic diseases. Methods: This study has been approved by the Animal Welfare and Ethics Committee of the Experimental Animal Center. Initially, 14 mice were randomly divided into the CON group (the control group) and the LIG group (the periodontitis group). Mice in the LIG group had experimental periodontitis induced by ligating the second maxillary molars bilaterally and were fed a high-fat and high-sugar diet. After 8 weeks, samples were collected. Micro-computed tomography (Micro-CT) was used to analyze alveolar bone resorption and various parameters of the proximal tibia trabecular bone, including bone mineral density (BMD), bone volume per tissue volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), and trabecular separation (Tb.Sp). After decalcification, hematoxylin and eosin (HE) staining was performed on maxillary bone sections to assess periodontal tissue inflammation and connective tissue destruction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect related genes in the distal femur and proximal tibia bone tissues, including osteocalcin (OCN), osteogenic transcription factor (Osterix), osteoprotegerin (OPG), tartrate resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), receptor activator of nuclear factor kappa-B (RANK), and receptor activator of nuclear factor kappa-B ligand (RANK-L). Subsequently, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + butyric acid-producing bacteria (BP) group, and LIG + BP group. The breeding, sampling, and sample detection methods remained the same. Finally, the other 28 mice were randomly divided into the CON group (the control group), LIG group (the periodontitis group), CON + sodium butyrate (SB) group, and LIG + SB group. The breeding, sampling, and sample detection methods remained the same. Results: ①Periodontitis modeling was successful. Compared with the CON group, the LIG group exhibited significant alveolar bone resorption of the maxillary second molar, aggravated periodontal tissue inflammation, and connective tissue destruction. ②Periodontitis exacerbated long bone resorption in mice fed a high-fat high-sugar diet. Compared with the CON group, the LIG group had significantly lower BMD, BV/TV, Tb.N, and Tb.Th (P<0.05), and significantly higher Tb.Sp (P<0.05). HE staining of the proximal tibia showed that the trabeculae in the LIG group were sparse and disordered, with some areas showing fractures or dissolution. The expression of osteoblast markers (OCN, Osterix, OPG) was significantly lower in the LIG group (P<0.05), while the expression of the osteoclast marker TRAP showed an increasing trend (P>0.05). The ratio of RANK-L/OPG was significantly higher in the LIG group compared with the CON group (P<0.05). ③ Supplementation with butyric acid-producing bacteria alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BMD and Tb.Th were significantly higher in the LIG + BP group. HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + BP group compared with the LIG group. The expression of OCN and Osterix was significantly higher in the LIG + BP group, while the expression of osteoclast-specific genes (OSCAR, RANK, RANK-L) was significantly lower (P<0.05). ④ Supplementation with butyrate alleviates periodontitis-induced disruption of long bone homeostasis in mice fed a high-fat/high-sugar diet. Compared with the LIG group, BV/TV and Tb.N were significantly higher in the LIG + SB group, and Tb.Sp was significantly lower (P<0.05). HE staining of the proximal tibia showed that bone resorption was mitigated in the LIG + SB group compared with the LIG group. The expression of Osterix, OPG, OSCAR, TRAP, and RANK was significantly lower in the LIG + SB group compared with the LIG group (P<0.05). Conclusion Periodontitis disrupts the long bone homeostasis of mice fed a high-fat high-sugar diet, aggravating long bone resorption. Supplementation with butyric acid-producing bacteria or butyrate can effectively alleviate the disruption of long bone homeostasis caused by periodontitis.

OBJECTIVE To explore the effect and mechanism of embryonic intervention with Zuogui pill on the glucose tolerance in offsprings of pregnant rats with gestational diabetes mellitus. METHODS Pregnant rats were randomly divided into blank group， model group， positive control group （insulin glargine）， Zuogui pill low-， medium- and high-dose groups （4.725， 9.45， 18.9 g/kg）. In addition to the blank group， streptozotocin was injected intraperitoneally to establish a gestational diabetes mellitus rat model. From day 6 to day 18 of pregnancy， each group was given relevant medicine and distilled water intragastrically， once a day. After 21 days of birth， the body weight and body length of offsprings were recorded， and the area under the curve （AUC） was calculated through a glucose tolerance test. After 22 days of birth， fasting blood glucose （FBG）， fasting insulin （FINS） levels in serum， insulin sensitivity index （ISI）， and homeostasis model assessment of insulin resistance （HOMA-IR） were measured， and the morphological structure of pancreatic tissue was observed. The protein spectrum of pancreatic tissue was analyzed by tandem mass tag-based proteomics， and protein and mRNA expression levels of apolipoprotein A1（ApoA1）， solute carrier family 27 member 1 （Slc27a1）， kininogen 1（Kng1） and sodium/potassium-transporting ATPase subunit alpha 2 （Atp1a2）， solute carrier family 7 member 5 （Slc7a5）， solute carrier family 3 member 2 （Slc3a2）， bile acid-coenzyme A： amino acid N- acyltransferase （Baat）， eukaryotic translation initiation factor 2 subunit gamma （Eif2s3） were detected. RESULTS Compared with the model group， the body weight， body length and ISI of offsprings in the positive control group and Zuogui pill medium-dose group were significantly increased （P＜0.05）， while the glucose tolerance and islet cell proliferation were significantly improved， and the AUC， FBG， FINS and HOMA-IR were significantly decreased （P＜0.05）. There were 88 potential target proteins for the embryonic intervention of Zuogui pill in offsprings of pregnant rats with gestational diabetes mellitus，involving multiple pathways such as peroxisome proliferator-activated receptor （PPAR）， cyclic guanosine monophosphate-protein kinase G （cGMP-PKG）， fat digestion and absorption， and bile secretion. The proteins closely related to glucose metabolism and insulin resistance mainly included ApoA1， Slc27a1， Kng1， Atp1a2， Slc7a5， Slc3a2， Baat， and Eif2s3. Among them， compared with the model group， protein and mRNA expressions of Slc7a5， Slc3a2， and Baat in the pancreatic tissues of pregnant rat offsprings in the Zuogui pill medium-dose group were significantly up-regulated （P＜0.05）； protein and mRNA expressions of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 were all significantly down-regulated （P＜0.05）. CONCLUSIONS The intervention of Zuogui pill in the embryonic period on offsprings of pregnant rats with gestational diabetes mellitus can improve their blood glucose levels and pancreatic pathological morphology. The mechanism may be related to the upregulation of the expressions of Slc7a5， Slc3a2， and Baat and the down-regulation of ApoA1， Slc27a1， Kng1， Atp1a2 and Eif2s3 expressions in the PPAR， cGMP-PKG， fat digestion and absorption， and bile secretion pathways.

Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.