AIM:To automatically identify and quantitatively assess myopia-related fundus structural changes by combining non-mydriatic color fundus photography with an artificial intelligence(AI)-powered quantitative fundus analysis system and to further analyze the correlations between these fundus parameters and spherical equivalent(SE), axial length(AL), and age, providing the objective basis for monitoring myopia progression and supporting the formulation of personalized myopia prevention and control strategies. METHODS:A cross-sectional study was conducted enrolling myopic patients aged 18-50 y who underwent myopia screening from March 2023 to December 2023. Patients were stratified into three groups based on SE: the -3.00 D

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

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.

Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.

To summarize the clinical experience of Professor LIU Shangyi in treating pruritus vulvae. It is believed that women have the physiological characteristics of liver and kidney as the root， and their pubic area is easily attacked by wind-dampness pathogenic qi， so the core mechanism of pruritus vulvae is proposed as wind-dampness accumulation and deficiency of liver and kidney. The core treatment method is to dispel wind-dampness and nourish the liver and kidneys， and modify the Danggui Decoction （当归饮子） to form a self-prescribed Yinyang Formula （阴痒方） as the basic prescription to treat pruritus vulvaen.

Objective:To investigate the dynamic changes of cytokine levels in patients with sepsis and to identify potential biomarkers for evaluating the prognosis of the disease.Methods:A total of 195 patients with sepsis hospitalized at the Department of Infectious Diseases and the Department of Critical Care Medicine of the First Affiliated Hospital of Soochow University from August 2022 to October 2024 were recruited, and 70 healthy individuals undergoing physical examinations were recruited as the healthy control group. The levels of 11 cytokines, including interferon γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were compared between the sepsis patients and the healthy controls. Spearman correlation analysis was used to assess the correlation between cytokine levels and sequential organ failure assessment (SOFA) scores in sepsis patients. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic value of cytokines for sepsis. Delong test was used to compare AUC. Based on the 28-day survival outcomes, the sepsis patients were categorized into non-survival group and survival group. The levels of the 11 cytokines in patients on the 1st, 3rd, 7th, 14th, 21st and 28th days after confirmed sepsis were dynamically monitored, and their change characteristics were analyzed. Mann-Whitney U test was used for statistical comparison. Results:The age of the 195 patients with sepsis was 68.0 (55.0, 76.0) years old, including 124 males (63.6%), 64 died and 131 survived.The levels of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, TNF-α, CRP in the sepsis group were all higher than those in the healthy control group ( Z=-2.99, -5.42, -4.95, -4.09, -5.05, -11.30, -8.66, -8.23, -5.64, -4.75, -2.12 and -10.75, respectively, all P<0.05). The differences were statistical significance. The levels of IL-2 ( r=0.149, P=0.037), IL-6 ( r=0.223, P=0.002), IL-8 ( r=0.159, P=0.026), and IL-10 ( r=0.188, P=0.009) in patients with sepsis were positively correlated with SOFA scores. The AUC of CRP in diagnosing sepsis was 0.989 with the sensitivity of 97.4% and the specificity of 100.0%. The AUC of IL-6 in diagnosing sepsis was 0.953, with the sensitivity of 93.3% and the specificity of 97.1%, and the AUC of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12P70, IL-17A, and TNF-α were 0.620, 0.718, 0.699, 0.665, 0.703, 0.850, 0.836, 0.727, 0.691, and 0.574, respectively.The AUC of the 11 cytokines were all lower than that of CRP, and the differences were all statistically significant ( Z=2.34, 10.24, 8.03, 8.08, 10.64, 8.70, 5.91, 5.17, 8.91, 9.25 and 4.10, respectively, all P<0.05).During the dynamic monitoring, the IFN-γ and IL-1β levels in the non-survival group increased gradually. The IFN-γ levels on the 14th and 21st day in the non-survival group were higher than those in the survival group ( Z=0.53 and 0.08, respectively, both P<0.05), and IL-1β levels on the 14th, 21st, and 28th days were also higher than those in the survival group ( Z=0.03, 0.26 and 0.31, respectively, all P<0.05). IL-6 and IL-8 levels reached their peaks on the 14th day, which were significantly higher than those in the survival group ( Z=0.01 and 0.02, respectively, both P<0.05), and then decreased, and the differences were all statistically significant. Conclusions:The levels of IFN-γ and IL-1β in the non-survival sepsis patients show a gradually increasing trend. The dynamic changes of IL-6 have certain significance for the prediction of disease severity and prognosis evaluation in sepsis.

Objective To explore the effects and mechanisms of Changpu Yujin Tang(CPYJT)on the NOD-like receptor thermal protein domain associated protein 3/cysteinyl aspartate specific proteinase-1/Gasdermin D(NLRP3/Caspase-1/GSDMD)signaling pathway-mediated neuroinflammation in rats with Tourette syndrome(TS).Methods SPF-grade male SD rats were randomly divided into the Control and TS groups.After successful modeling in the TS group,the rats were randomly divided into the Model,Tiapride,and CPYJT groups,and were treated with the corresponding drugs for 4 weeks.After the treatment,the rats' behavior was scored,H & E staining was used to observe pathological changes in the striatum,ELISA was used to measure the content of IL-1β and IL-18,RT-qPCR was used to detect the expression of NLRP3 and ASC mRNA,and Western blot was used to detect the expression of NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins.Results Compared with the Control group,the Model group showed increased scores of stereotyped and motor behaviors(P＜0.01),pathological changes in the striatal tissue,increased content of IL-1β and IL-18(P＜0.01),and upregulated expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Compared with the Model group,the Tiapride group and the CPYJT group showed decreased scores of stereotyped and motor behaviors(P＜0.01),improved pathological damage in the striatal tissue,reduced content of IL-1β and IL-18(P＜0.01),and inhibited expression of NLRP3,ASC mRNA,and NLRP3,ASC,Caspase-1,Cleaved-Caspase-1,GSDMD,and GSDMD-NT proteins(P＜0.01).Conclusion The therapeutic effect of CPYJT on TS is related to the inhibition of the neuroinflammatory response mediated by the NLRP3/Caspase-1/GSDMD signaling pathway.