To gain an in-depth understanding of the clinical application of Rehmanniae Radix during the Qing Dynasty and to clarify its specifications and corresponding therapeutic effects， this study took Rehmanniae Radix in the prescriptions documented in Research on Medical Cases of the Qing Imperial Court as the research subject. According to historical medical literature， a comprehensive investigation was conducted on the specifications， therapeutic efficacy， frequency of use， dosage， and seasonal patterns of Rehmanniae Radix employed by imperial physicians. The findings revealed that Rehmanniae Radix in the medical cases of the Qing court was primarily classified into three categories： Xiaoshengdi， Zhongshengdi， and Dashengdi. Xiaoshengdi was also referred to as Xishengdi or Cishengdi， all denoting dried Rehmanniae Radix. The term Xishengdi was inconsistently defined in the literature. It should refer to the slender variant of dried Rehmanniae Radix and was utilized as a specific specification in the medical cases of the Qing court. In contrast， the wild fresh roots of Rehmanniae Radix， described as "as slender as fingers"， were commonly documented as fresh Rehmanniae Radix in these medical cases. There were variations in Rehmanniae Radix size and grading between historical and contemporary standards. Furthermore， therapeutic differences were observed among Rehmanniae Radix specifications in the medical cases of the Qing court. Xiaoshengdi and Zhongshengdi exhibited slightly stronger blood-cooling and heat-clearing effects while maintaining a non-cloying Yin-nourishing property. In contrast， Dashengdi demonstrated a greater emphasis on Yin supplementation with relatively milder heat-clearing activity. In the medical cases of the Qing court， the dosage of Rehmanniae Radix in different specifications was usually 11.2-18.7 g per dose， typically administered twice daily. Rehmanniae Radix in different specifications exhibits variations in efficacy， which can provide evidence-based insights for precise clinical application.

To gain an in-depth understanding of the clinical application of Rehmanniae Radix during the Qing Dynasty and to clarify its specifications and corresponding therapeutic effects， this study took Rehmanniae Radix in the prescriptions documented in Research on Medical Cases of the Qing Imperial Court as the research subject. According to historical medical literature， a comprehensive investigation was conducted on the specifications， therapeutic efficacy， frequency of use， dosage， and seasonal patterns of Rehmanniae Radix employed by imperial physicians. The findings revealed that Rehmanniae Radix in the medical cases of the Qing court was primarily classified into three categories： Xiaoshengdi， Zhongshengdi， and Dashengdi. Xiaoshengdi was also referred to as Xishengdi or Cishengdi， all denoting dried Rehmanniae Radix. The term Xishengdi was inconsistently defined in the literature. It should refer to the slender variant of dried Rehmanniae Radix and was utilized as a specific specification in the medical cases of the Qing court. In contrast， the wild fresh roots of Rehmanniae Radix， described as "as slender as fingers"， were commonly documented as fresh Rehmanniae Radix in these medical cases. There were variations in Rehmanniae Radix size and grading between historical and contemporary standards. Furthermore， therapeutic differences were observed among Rehmanniae Radix specifications in the medical cases of the Qing court. Xiaoshengdi and Zhongshengdi exhibited slightly stronger blood-cooling and heat-clearing effects while maintaining a non-cloying Yin-nourishing property. In contrast， Dashengdi demonstrated a greater emphasis on Yin supplementation with relatively milder heat-clearing activity. In the medical cases of the Qing court， the dosage of Rehmanniae Radix in different specifications was usually 11.2-18.7 g per dose， typically administered twice daily. Rehmanniae Radix in different specifications exhibits variations in efficacy， which can provide evidence-based insights for precise clinical application.

BACKGROUND:The formation of postoperative abdominal adhesions is a complicated process,and the prevention of postoperative adhesions is an urgent problem in clinic. OBJECTIVE:To analyze the mechanism of adhesion at cellular and molecular levels,and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes. METHODS:"Abdominal adhesion,pelvic adhesion,postoperative adhesion,epithelial mesenchymal transformation,mesenchymal stem cells,stem cell exosomes,mesenchymal stem cell exosomes"were selected as Chinese and English search terms.We searched PubMed,CNKI,and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023.After systematic analysis,54 articles were finally included for the review. RESULTS AND CONCLUSION:(1)Any pathological factors such as peritoneal inflammation,mechanical injury,tissue ischemia,and foreign body implantation cause peritoneal surface injury,resulting in postoperative abdominal adhesion.The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair,inflammatory response,fibrinolytic system,coagulation pathway and other processes,involving a variety of cytokines and signaling pathways.Wnt/β-catenin pathway can induce fibrosis and angiogenesis,and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis.Meanwhile,nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors,promotes fibroblast proliferation,and plays a key role in the process of tissue fibrosis.(2)The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine.It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions.(3)Compared with traditional methods for treating abdominal adhesions,mesenchymal stem cell exosome has biological activity and is safe to use.Mesenchymal stem cell exosomes without special culture and expansion have lower immunogenicity,longer stability and other advantages,can guide a normal repair and healing through a variety of ways.(4)Mesenchymal stem cell exosome has been proven to be involved in regulating the above processes of adhesion formation in previous studies,showing potential application prospects in clinical studies.However,further clinical studies are needed to explore appropriate treatment options for mesenchymal stem cell exosomes to address the problem of clinical translation.

When prostate cancer （PCa） progresses to the metastatic castration-resistant stage， significant challenges arise in clinical treatment. Microtubulin inhibitors have become first-line drugs for the treatment of metastatic castration-resistant PCa due to their unique mechanism of action. Among them， taxanes （e.g. docetaxel and cabazitaxel） remain standard care with proven survival benefits， while other microtubule inhibitors （e.g. vincristine， colchicine） show limited clinical utility due to toxicity. Currently， the clinical approach primarily employs docetaxel-based triple therapy and combined with immune checkpoint inhibitors to improve the prognosis of PCa patients， reverse the immunosuppressive state of the tumor microenvironment， and enhance therapeutic efficacy. Despite the remarkable clinical efficacy of microtubule inhibitors in the treatment of PCa， the emergence of drug resistance has limited their long-term application. To address this issue， researchers have explored new solutions， including the development of novel microtubule inhibitors in combination with ATP-binding cassette subfamily B member 1 inhibitors， the concurrent use of fatty acid synthase inhibitors with microtubule inhibitors， and the development of degraders based on proteolysis-targeting chimeras technology. Future research should focus on target discovery， drug formulation optimization， and personalized approaches to overcome current therapeutic limitations.

Brain organoids are three-dimensional (3D) neural cultures that self-organize from pluripotent stem cells (PSCs) cultured in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.

Based on the discussion of "eight weak areas" in The Inner Canon of Yellow Emperor （《黄帝内经》）， combined with the typical rash manifestations of atopic dermatitis， it is believed that atopic dermatitis is mostly deficiency-excess complex， and that pathogens intruding eight weak areas are the core of its pathogenesis. The external cause is exterior deficiencies， with heat， wind， dampness and other pathogenic qi attacking. The heart， lungs， kidneys out of balance， and excess pathogen are the internal cause， in which fire constraint and excessive heat are the basis of the disease， the wind invading leads to the progress of the changes， dampness obstructing channels and colla-terals make the condition persistent. Internal and external pathogens combination and retention result to the course of the disease lingering and difficult to cure. The internal treatment is to regulate zang-fu organs， and the formula could use self-prescribed modified Qingrun Tongluo Decoction （清润通络汤）， clearing heart and reducing fire in order to clear the heat and cool the blood， moistening lungs and generating metal to consolidate the exterior and dispel the wind， and nourishing kidneys and draining water to dispel the dampness and activate the collaterals. The external treatment applies maceration， fire acupuncture， wrapping to dredge the eight weak areas and regulate qi and blood in channel， so as to expel pathogens.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

Rheumatoid arthritis （RA） is an autoimmune disease characterized primarily by erosive arthritis， with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years， challenges such as suboptimal efficacy， drug resistance， severe side effects， and high costs of long-term treatment remain， especially for patients in the early stages of RA， as well as those with RA complications， comorbidities， and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine， the 27^th session of the Clinical Dominant Disease Series （Rheumatoid Arthritis） Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine （TCM）， western medicine， and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA， especially during the early stage， periods of low to moderate disease activity， remission phase， and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA， refractory cases， and stages with severe complications， by rapidly controlling disease progression， alleviating symptoms， enhancing the quality of life， and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA， TCM shows potential in regulating immunity， alleviating symptoms， and improving physical constitution， which provides new insights into the comprehensive treatment of RA with comorbidities. However， high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future， individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.

ObjectiveTo explore the effect of gypenosides （GPs） on liver lipid deposition in metabolism-associated fatty liver disease （MAFLD） mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout （ApoE^-/-） mice were randomly divided into a model group， a low-dose GPs （GPs-L） group， a high-dose GPs （GPs-H） group， and a simvastatin （SV） group. Starting from the second week， mice in the blank group were given a maintenance diet， and the other four groups were fed a high-fat diet daily. After eight weeks of feeding， mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg^-1·d^-1 and 2.973 mg·kg^-1·d^-1， respectively， and mice in the SV group were given simvastatin of 2.275 mg·kg^-1·d^-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid （NEFA） and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin （HE） and oil red O staining. The levels of coenzyme Q₁₀ （CoQ₁₀）， glutathione （GSH）， malondialdehyde （MDA）， and Fe²⁺ in serum， as well as nicotinamide adenine dinucleotide phosphate ［NAD（P）H］ in the liver were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of ferroptosis suppressor protein 1 （FSP1） in the liver of mice was observed by the immunohistochemical （IHC） method， and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction （Real-time PCR） and Wes automated protein expression analysis system. ResultsCompared with those in the blank group， the levels of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver in the model group were significantly increased， and the level of HDL-C in serum was significantly decreased （P<0.01）. The liver tissue structure changed， and there were fat vacuoles of different sizes and a large number of red lipid droplets， with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased， while the level of MDA and Fe²⁺ in serum was significantly increased （P<0.01）. The mRNA and protein expressions of cystine/glutamate transporter （xCT/SLC7A11）， glutathione peroxidase （GPX4）， p62， nuclear factor E₂-related factor 2 （Nrf2）， and FSP1 were significantly decreased， and the mRNA and protein expressions of tumor antigen （p53）， spermidine/spermine N1-acetyltransferase 1 （SAT1）， arachidonate 15-lipoxygenase （ALOX15）， and Kelch-like epichlorohydrin-associated protein-1 （Keap1） were significantly increased （P<0.01）. Compared with those in the model group， the level of TC， TG， LDL-C， ALT， and AST in serum and TG and NEFA in the liver of mice in the GPs-L， GPs-H， and SV groups were decreased， while the level of HDL-C in serum was significantly increased （P<0.05， P<0.01）. The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased， while the levels of MDA and Fe²⁺ in serum were significantly decreased （P<0.05， P<0.01）. The mRNA and protein expressions of xCT， GPX4， p62， Nrf2， and FSP1 were significantly increased， while the mRNA and protein expressions of p53， SAT1， ALOX15， and Keap1 were significantly decreased （P<0.05， P<0.01）. ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.

Rheumatoid arthritis （RA） is an autoimmune disease characterized primarily by erosive arthritis， with a high prevalence and disability rate. Although significant progress has been made in the treatment of RA in recent years， challenges such as suboptimal efficacy， drug resistance， severe side effects， and high costs of long-term treatment remain， especially for patients in the early stages of RA， as well as those with RA complications， comorbidities， and severe conditions. Hosted by the China-Japan Friendship Hospital and organized by the Youth Committee of the China Association of Chinese Medicine， the 27^th session of the Clinical Dominant Disease Series （Rheumatoid Arthritis） Youth Salon invited nearly 20 experts and scholars from traditional Chinese medicine （TCM）， western medicine， and interdisciplinary fields to actively discuss the clinical needs of modern medicine and the advantageous stages and aspects of TCM in RA. Experts at the salon agreed that TCM has unique advantages in the treatment of RA， especially during the early stage， periods of low to moderate disease activity， remission phase， and in addressing complications and comorbidities. TCM can achieve both prevention and treatment by regulating the immune system and restoring immune homeostasis. The integrated approach of traditional Chinese and western medicine demonstrates significant advantages in active RA， refractory cases， and stages with severe complications， by rapidly controlling disease progression， alleviating symptoms， enhancing the quality of life， and facilitating recovery. Given the frequent occurrence of multiple comorbidities in RA， TCM shows potential in regulating immunity， alleviating symptoms， and improving physical constitution， which provides new insights into the comprehensive treatment of RA with comorbidities. However， high-quality clinical studies on integrated traditional Chinese and western medicine in RA are still lacking. It is necessary to establish large-scale clinical cohorts and biological databases to provide a scientific basis for the development of precision-targeted therapies and clinical treatment protocols. In the future， individualized treatment strategies integrating traditional Chinese and western medicine are expected to become an important direction for improving the quality of life in RA patients.