OBJECTIVE To analyze the prototype components absorbed into blood and brain of Lithocarpus litseifolius leaves， so as to provide a reference for clarifying the pharmacological material basis of its prevention and treatment of central nervous system dis eases. METHODS The ethanol extract of L. litseifolius leaves， as well as the gastric lavage fluid and perfusion solution were prepared. Using rats as subjects， plasma samples of intestinal wall metabolism， intestinal flora metabolism and hepatic metabolism were prepared via in situ intestinal perfusion and closed intestinal loop method； while comprehensive metabolic plasma samples， brain tissue samples， and cerebrospinal fluid samples were collected after intragastric administration. UPLC-HRMS technology was utilized to analyze and identify chemical components and prototype components absorbed into blood and brain of L. litseifolius leaves. RESULTS A total of 66 chemical constituents were identified in L. litseifolius leaves， primarily consisting of flavonoids， organic acids， and others. A total of 16， 13， 11， and 5 prototype components were identified in intestinal wall metabolism， intestinal flora metabolism， hepatic metabolism， and comprehensive metabolic plasma samples， respectively. Additionally， 4 prototype components were detected in brain tissue and 9 in cerebrospinal fluid. Phloridzin， trilobatin， phloretin-2- O -malonyl hexoside， and phloretin were identified as common components across all sample types. CONCLUSIONS Prototype components absorbed into blood and brain of L. litseifolius leaves， such as phloridzin， trilobatin， phloretin， and other components may serve as the pharmacological material basis for their therapeutic effects on central nervous system diseases.

Objective:To analyze the causal relationship between type 2 diabetes and lumbar bone mineral density and spinal fractures and to further explore the impact of central obesity on the diabetic bone paradox.Methods:A Mendelian randomization (MR) study was implemented. Single nucleotide polymorphisms (SNPs) associated with type 2 diabetes were selected from the data of genome-wide association studies as instrumental variables, with lumbar bone density and spinal fractures as the outcome variables. The inverse variance weighting method, weighted median method, and MR-Egger regression were applied to identify a causal relationship between type 2 diabetes and osteoporosis at the genetic level. Additionally, to analyze the impact of central obesity in the diabetic bone paradox, the waist-to-hip ratio was introduced as a new exposure variable, with type 2 diabetes and lumbar bone density as outcome variables, and the MR method was applied again to uncover the influencing factors.Results:The screening criteria were based on the three main assumptions of MR. Finally, 62 SNPs for type 2 diabetes and 241 SNPs for waist-to-hip ratio were included in the MR analysis. Using inverse variance weighting as the primary analysis, the causal association effect analysis indicated a causal relationship between type 2 diabetes and increased lumbar bone density ( OR=1.047 6, P=0.007) and spinal fractures ( OR=1.000 9, P=0.014). A causal relationship between waist-to-hip ratio and type 2 diabetes ( OR=1.638 6, P<0.001) was identified, indicating that the waist-to-hip ratio was a risk factor for type 2 diabetes and may have a causal association with increased lumbar bone density ( OR=1.096 3, P=0.044). This suggests that the waist-to-hip ratio may indirectly affect the relationship between diabetes and osteoporosis. The MR-Egger intercept test showed no horizontal pleiotropy in this study. The leave-one-out analysis indicated that no single SNP had a significant impact on the overall results. Furthermore, the MR-pleiotropy residual sum and outlier (MR-PRESSO) test results did not detect any outlier SNPs. Conclusion:MR analysis identified a causal relationship between type 2 diabetes and increased lumbar bone density as well as a higher risk of spinal fractures, a paradox that may be related to central obesity.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.

Objective To investigate the effects of periodontitis induced by Prevotella nigrescens(Pn)combined with ligation on cognitive functions in mice.Methods Twenty-four C57BL/6J mice were randomly divided into control group,ligation group,and ligation+Pn treatment(P+Pn)group.Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks.After modeling,alveolar bone resorption was assessed using micro-CT and histological analysis.Learning and memory abilities of the mice were evaluated using open field test(OFT),novel object recognition test(NORT),and Morris water maze test(MWM).Seven weeks after the start of modeling,the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.Results After 6 weeks of molar ligation,micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice,and histological analysis showed apical migration of the junctional epithelium,epithelial ridge hyperplasia,and lymphocyte infiltration,and these changes were obviously worsened in P+Pn group.Alveolar bone height decreased significantly in both ligation groups compared to the control group.Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT,showed reduced novel object preference in NORT,and exhibited longer escape latencies in MWM,and the mice in P+Pn group had significantly poorer performances in the tests.Histologically,obvious neuronal cytoplasmic degeneration,necrosis,nuclear pyknosis,vacuolation,and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.Conclusion Pn infection aggravates alveolar bone destruction,accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.

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.

Consensus method is not only a common technical approach to the formulation of the acupuncture-moxibustion guidelines, but also an important way to form the recommended treatment protocols of acupuncture-moxibustion guidelines. Based on the theory of implementation science, the paper explores the influencing factors of consensus-reaching to acupuncture-moxibustion guidelines, and puts forward methodological suggestions on the consensus method performed in the formulation of acupuncture-moxibustion guidelines, so as to advance the rational application of consensus method and enhance the scientificity and transparency of acupuncture-moxibustion guidelines.
Moxibustion/standards* ; Humans ; Acupuncture Therapy/standards* ; Consensus ; Practice Guidelines as Topic

From the perspective of evidence integration and utilization in guidelines, based on the carrier variety, medical experience is composed of the literature on the practical experience of medical scholars recorded in the ancient and modern time, and the individual opinions in the expert consensus. These two types of carrier for medical experience play the different roles in the key steps during formulating the acupuncture-moxibustion guidelines. Three values are summarized, named being conductive to centering the key clinical questions and strongly representing these questions; being used as a basis to judge the clinical applicability of the recommended regimens; and facilitating the recommendation.
Humans ; Moxibustion/standards* ; Acupuncture Therapy/standards* ; Practice Guidelines as Topic

Acupuncture-moxibustion technical specifications are a crucial component of the acupuncture-moxibustion standardization system. This study reviews the current development status of acupuncture-moxibustion technical specifications in China, and analyzes their classifications and characteristics. It is found that the scope and classification of acupuncture technical specifications remain unclear in academic circles, and the development process faces numerous difficulties and challenges. Therefore, this study proposes the need for a systematic approach to the planning and management of acupuncture technical specifications based on a clear definition of acupuncture techniques and categories. Additionally, it suggests conducting methodological research on the development of acupuncture technical specifications and promoting the rational application of the consensus method in this process.
China ; Moxibustion/methods* ; Acupuncture Therapy/instrumentation* ; Humans ; Acupuncture/standards*

This paper analyzes the main issues exposed in the current demand investigations on developing acupuncture and moxibustion technical standards, including the lack of survey methods, insufficient data support, and inadequate demand analysis. It proposes the targeted improvement strategies by examining technical and clinical standard cases. It suggests that the demand investigations on developing acupuncture and moxibustion standards should be designed differently based on the categories and levels of standards, with a focus on multi-integration of market demand, clinical evidence, and policy background. This paper provides the research ideas and methodological suggestions for developing acupuncture and moxibustion standards, which is valuable for enhancing the applicability and practicability of standards.
Moxibustion/standards* ; Humans ; Acupuncture Therapy/standards*

The expert consensus on the clinical treatment of herpes zoster with fire needling was developed, and the commonly used fire needling treatment scheme verified by clinical research was selected to form a standardized diagnosis and treatment scheme for acute herpes zoster and postherpetic neuralgia (PHN), so as to answer the core problems in clinical application. The consensus focuses on patients with herpes zoster, and forms recommendations for 9 key clinical issues, covering simple fire needling and TCM comprehensive therapy based on fire needling, including fire needling combined with cupping, fire needling combined with Chinese herb, fire needling combined with cupping and Chinese herb, fire needling combined with filiform needling, fire needling combined with moxibustion, and provides specific recommendations and operational guidelines for various therapies.
Humans ; Herpes Zoster/therapy* ; Acupuncture Therapy/instrumentation* ; Consensus ; Clinical Protocols