AIM: To investigate the diagnostic and prognostic value of differential expression of Cyclin D1 and p53 in eyelid tumors.METHODS: This retrospective study enrolled patients who underwent surgical resection for eyelid tumors at our hospital between March 2018 and March 2023. Participants were categorized into benign and malignant groups based on tumor characteristics. Clinical data were collected. Genetic data for eyelid tumors were obtained from the GEO database, and differential gene analysis, including volcano plot visualization and KEGG pathway enrichment analysis, was performed using the Sangerbox 3.0 platform. Immunohistochemistry was used to detect the expression levels of Cyclin D1, p53, and BAX in tissue samples. Correlations with clinical features were analyzed using Spearman analysis, and prognostic factors were identified via Logistic regression analysis.RESULTS: This study included 69 patients with eyelid tumors(78 eyes), categorized into a benign group(37 patients, 41 eyes)and a malignant group(32 patients, 37 eyes)based on tumor characteristics. There were significant differences between the two groups in histological subtype, TNM staging, vascular invasion, differentiation status, and local infiltration(all P<0.05). Among benign tumors: pigmented nevi in 11 eyes(27%), hemangiomas in 9 eyes(22%), squamous cell papillomas in 5 eyes(12%), epidermoid cysts in 5 eyes(12%), seborrheic keratoses in 4 eyes(10%), neurofibromas in 3 eyes(7%), and both calcifying epithelioma and xanthelasma in 2 eyes each(5%); among malignant tumors: basal cell carcinoma in 18 eyes(49%), meibomian gland carcinoma in 8 eyes(22%), squamous cell carcinoma in 5 eyes(14%), sebaceous gland carcinoma in 4 eyes(11%), lymphoma and malignant melanoma each in 1 eye(3%). At the follow-up cutoff date of March 2025, the 2-year survival rate in the benign group(95%)was significantly higher than that in the malignant group(78%; P<0.05). Bioinformatics analysis identified 4 103 differentially expressed genes, including Cyclin D1, p53, and BAX, which were predominantly involved in pathways such as the p53 signaling pathway and calcium-related signaling. Spearman analysis revealed that local invasion(rs=0.71, P<0.05)and TNM stage(rs=0.73, P<0.05)correlated with Cyclin D1 expression; local invasion(rs=0.76, P<0.05)and histological subtype(rs=0.65, P<0.05)correlated with p53 expression. Logistic regression results indicated that Cyclin D1, p53, TNM staging, and local invasion were prognostic risk factors. ROC curve analysis demonstrated that the combined detection of these four indicators had the highest predictive value for prognosis(AUC=0.83).CONCLUSION: High expression of cyclin D1 and p53 serves as molecular markers for distinguishing benign from malignant eyelid tumors and assessing prognosis. Combined detection of these markers with TNM staging and local invasion demonstrates high predictive value for prognosis.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Corneal alkali burns are a common form of corneal trauma, and their treatment has been a challenge in ophthalmology. Traditional treatments include anti-inflammatory, immunosuppressive, and corneal transplantation, with limited results. This review focuses on the research progress of mesenchymal stem cells(MSCs)and their derived extracellular vesicles(MSCs-EVs)in the treatment of corneal alkali burns. MSCs have the ability of self-renewal, multidirectional differentiation, and immunomodulation, and the MSCs-EVs inherit its function from MSCs. MSCs-EVs inherit the functions of MSCs and has lower immunogenicity and better biocompatibility, which provides a new avenue for ophthalmic treatment. In addition, bioscaffolds are used as scaffolds or drug delivery systems in tissue engineering to promote tissue regeneration due to their excellent biocompatibility and degradability. This article reviews the mechanism of action and research progress of MSCs-EVs and combined bioscaffolds in the treatment of corneal alkali burns, and explores their potential in promoting the repair of corneal alkali burns and improving vision. These findings provide new strategies for the treatment of corneal alkali burns and are expected to improve the prognosis of patients.

Corneal alkali burns are a common form of corneal trauma, and their treatment has been a challenge in ophthalmology. Traditional treatments include anti-inflammatory, immunosuppressive, and corneal transplantation, with limited results. This review focuses on the research progress of mesenchymal stem cells(MSCs)and their derived extracellular vesicles(MSCs-EVs)in the treatment of corneal alkali burns. MSCs have the ability of self-renewal, multidirectional differentiation, and immunomodulation, and the MSCs-EVs inherit its function from MSCs. MSCs-EVs inherit the functions of MSCs and has lower immunogenicity and better biocompatibility, which provides a new avenue for ophthalmic treatment. In addition, bioscaffolds are used as scaffolds or drug delivery systems in tissue engineering to promote tissue regeneration due to their excellent biocompatibility and degradability. This article reviews the mechanism of action and research progress of MSCs-EVs and combined bioscaffolds in the treatment of corneal alkali burns, and explores their potential in promoting the repair of corneal alkali burns and improving vision. These findings provide new strategies for the treatment of corneal alkali burns and are expected to improve the prognosis of patients.

The transcription factor HOXB13 plays crucial roles in cancer development. HOXB13 is abnormally expressed in most cancers, which makes it a valuable therapeutic target for cancer therapy. The level of HOXB13 differs significantly between healthy and cancer tissues, which indicates that the level of HOXB13 is closely related to carcinogenesis. The regulatory network mediated by HOXB13 in cancer proliferation, metastasis, and invasion has been systematically investigated. Moreover, HOXB13 variants play distinct roles in different cancers and populations. By understanding the molecular mechanisms and mutation features of HOXB13, we provide a comprehensive overview of carcinogenesis networks dependent on HOXB13. Finally, we discuss advancements in anticancer therapy targeting HOXB13 and the roles of HOXB13 in drug resistance to molecular-targeted therapies, which serves as a foundation for developing HOXB13-targeted drugs for clinical diagnosis and cancer therapies.
Humans ; Neoplasms/metabolism* ; Homeodomain Proteins/metabolism* ; Carcinogenesis/genetics* ; Mutation ; Gene Expression Regulation, Neoplastic ; Molecular Targeted Therapy ; Drug Resistance, Neoplasm/genetics*

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*

Objective : To investigate the effect and mechanism of sex-determining region Y-box transcription factor 4(SOX4) on autophagy in small cell lung cancer(SCLC) cells. Methods : Human SCLC cell line NCI-H446 was transfected with small interfering RNA(siRNA) to knockdown SOX4. RT-qPCR and Western blot were used to verify the transfection efficiency. NCI-H446 cells were divided into control group, si-SOX4 group, si-SOX4+oe-Beclin1 group and oe-Beclin1 group. Western blot analysis was performed to detect the ratio of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ expression and the expression of Beclin1 and p62 in different groups of cells. The transcriptional regulation of Beclin1 by SOX4 was detected by dual luciferase reporter assay and chromatin immunoprecipitation PCR(ChIP-PCR) assay. CCK-8 assay was used to detect the proliferation ability of NCI-H446 cells in different groups. Flow cytometry was used to detect the apoptosis rate of NCI-H446 cells in different groups. Transwell assay was performed to determine the cell migration and invasion ability in different groups. Results: Compared with the control group or the si-NC group, the relative mRNA and protein expression level of SOX4 in si-SOX4 group were down-regulated(P<0.05), and the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression level of Beclin1 in si-SOX4 group decreased(P<0.05), the relative protein expression of p62 increased(P<0.05). The relative luciferase activity of Beclin1 WT in the si-SOX4 group was lower than that in the si-NC group(P<0.05); the relative enrichment of Beclin1 promoter in the Anti-SOX4 group was higher than that in the Anti-Ig G group( P<0. 05). Compared with control group,cell proliferation activity decreased,cell apoptosis rate increased,migration number and invasion number decreased in si-SOX4 group( P<0. 05). Compared with the si-SOX4 group,the ratio of LC3-Ⅱ/LC3-Ⅰ protein expression and the relative protein expression of Beclin1 increased in si-SOX4 + oe-Beclin1 group,while the relative protein expression of p62 decreased,cell proliferation activity increased,apoptosis rate decreased,migration number and invasion number increased( P<0. 05). Conclusion Down-regulation of SOX4 can inhibit autophagy,decrease proliferation activity of NCI-H446 cells,and inhibit cell migration and invasion by inhibiting Beclin1 expression.

OBJECTIVE To explore the efficacy and influencing factors of intravitreal injection of ranibizumab in the treatment of macular edema （ME） secondary to retinal vein obstruction （RVO） with different optical coherence tomography （OCT） subtypes. METHODS A retrospective study was conducted on 150 patients with ME secondary to RVO treated at Dept. of Ocular Trauma of Tianjin Eye Hospital between January 1， 2021 and January 1， 2024. According to OCT findings， patients were classified into the diffuse retinal thickening （DRT） group （48 cases）， cystoid macular edema （CME） group （83 cases）， and serous retinal detachment （SRD） group （19 cases）. The best corrected visual acuity （BCVA） and central macular thickness （CMT） were compared before and at 1， 3 and 6 months after treatment. Clinical efficacies of 3 groups were compared based on CMT and fluorescein fundus angiography （FFA） findings before and after treatment. Adverse events and the number of additional injections of ranibizumab during treatment were compared among 3 groups. Using “ineffectiveness” in clinical outcomes at 6 months post- treatment as the dependent variable and patients’ baseline data as the independent variables， a multivariate Logistic regression analysis was conducted to identify risk factors influencing the clinical efficacy of ranibizumab. RESULTS The proportion of branch RVO was significantly higher in the CME and SRD groups than in the DRT group （P＜0.05）， while central RVO （CRVO） was more frequent in the DRT group than in the CME and SRD groups （P＜0.05）. The proportion of patients with ischemia was highest in the SRD group， followed by the CME and DRT groups （P＜0.05）， while the proportion of patients with ischemia in the CME group was significantly higher than that in the DRT group （P＜0.05）. Before treatment， the BCVA and CMT showed no significant differences among the 3 groups （P＞0.05）. After treatment， BCVA and CMT in all 3 groups were significantly reduced compared to those before treatment （P＜0.05）. At different treatment time points， patients in the CME group and SRD group consistently showed significantly higher BCVA and CMT values compared to those in the DRT group （P＜0.05）. Six months after treatment， the differences in clinical efficacy among the 3 groups were statistically significant （P＜0.05）， with the proportion of non-responders in the SRD group being significantly higher than that in the DRT group and the CME group （P＜0.05）. The number of additional injections of ranibizumab in patients from the CME group and the SRD group was significantly more than that in the DRT group （P＜0.05）. The incidence of adverse reactions did not differ significantly among 3 groups （P＞0.05）. Multivariate Logistic regression revealed that CRVO and ischemic type were common risk factors affecting the clinical efficacy of ranibizumab in all 3 groups， while longer disease duration was an independent risk factor for the clinical efficacy of ranibizumab in patients from the DRT group. CONCLUSIONS The therapeutic efficacy of ranibizumab varies among different OCT phenotypes of ME secondary to RVO. DRT patients achieve the best visual improvement， SRD patients have the highest non-response rate， and CME/SRD patients require more additional injections of ranibizumab. CRVO and ischemia are shared adverse prognostic factors for poor prognosis in various subtypes of ME secondary to RVO. Individualized treatment and follow-up strategies should be developed based on OCT patterns and risk factors.

Based on ultra-performance liquid chromatography-quadrupole-electrostatic field Orbitrap high-resolution mass spectrometry(UPLC-Q-Orbitrap HRMS) technology and molecular docking, the bitter-tasting substances(hereafter referred to as "bitter substances") in Cistanche deserticola extract were investigated, and the bitter taste and efficacy relationship was explored to lay the foundation for future research on de-bittering and taste correction. Firstly, UPLC-Q-Orbitrap HRMS was used for the qualitative analysis of the constituents of C. deserticola, and 69 chemical components were identified. These chemical components were then subjected to molecular docking with the bitter taste receptor, leading to the screening of 20 bitter substances, including 6 phenylethanol glycosides, 5 flavonoids, 3 phenolic acids, 2 cycloalkenyl ether terpenes, 2 alkaloids, and 2 other components. Nine batches of fresh C. deserticola samples were collected from the same origin but harvested at different months. These samples were divided into groups based on harvest month and plant part. The bitterness was quantified using an electronic tongue, and the content of six potential bitter-active compounds(pineconotyloside, trichothecene glycoside, tubulin A, iso-trichothecene glycoside, jinshihuaoside, and jingnipinoside) was determined by high-performance liquid chromatography(HPLC). The total content of phenylethanol glycosides, polysaccharides, alkaloids, flavonoids, and phenolic acids was determined using UV-visible spectrophotometry. Chemometric analyses were then conducted, including Pearson's correlation analysis, gray correlation analysis, and orthogonal partial least squares discriminant analysis(OPLS-DA), to identify the bitter components in C. deserticola. The results were consistent with the molecular docking findings, and the two methods mutually supported each other. Finally, network pharmacological predictions and analyses were performed to explore the relationship between the targets of bitter substances and their efficacy. The results indicated that key targets of the bitter substances included EGFR, PIK3CB, and PTK2. These substances may exert their bitter effects by acting on relevant disease targets, confirming that the bitter substances in C. deserticola are the material basis of its bitter taste efficacy. In conclusion, this study suggests that the phenylethanol glycosides, primarily pineconotyloside, mauritiana glycoside, and gibberellin, are the material basis for the "bitter taste" of C. deserticola. The molecular docking technique plays a guiding role in the screening of bitter substances in traditional Chinese medicine(TCM). The bitter substances in C. deserticola not only contribute to its bitter taste but also support the concept of the "taste-efficacy" relationship in TCM, providing valuable insights and references for future research in this area.
Molecular Docking Simulation ; Taste ; Chromatography, High Pressure Liquid ; Cistanche/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Humans ; Mass Spectrometry

Objective This study investigated the regulatory effect of high mobility group protein B1 (HMGB1) in the peripheral blood of patients with primary immune thrombocytopenia (ITP) on myeloid dendritic cells (mDC) and Th17/regulatory T cells (Treg) balance. Methods The study enrolled 30 newly diagnosed ITP patients and 30 healthy controls.Flow cytometry was used to measure the proportion of mDC, Th17, and Treg cells in the peripheral blood of ITP patients and healthy controls. ELISA was conducted to quantify the serum levels of HMGB1, interleukin 6 (IL-6), IL-23, IL-17, and transforming growth factor β(TGF-β). The mRNA levels of retinoic acid-related orphan receptor γt(RORγt) and forehead box P3(FOXP3) were detected by real-time PCR. The correlation between the abovementioned cells, cytokines, and platelet count was assessed using Pearson linear correlation analysis. Results The proportion of Th17 cells and the expression levels of HMGB1, IL-6, IL-23, IL-17 and the level of RORγt mRNA in the peripheral blood of ITP patients were higher than those in healthy controls. However, the Treg cell proportion and TGF-β level were lower in ITP patients than those in healthy controls. In patients with ITP, the proportion of mDC and the level of FOXP3 mRNA did not show significant changes. The proportion of mDC cells was significantly correlated with the expression of IL-6 and IL-23. Moreover, the expression of HMGB1 showed a significant correlation with the expression of mDC, IL-6, IL-23, RORγt mRNA, and IL-17. Notably, both the proportion of mDC cells and the expression of HMGB1 were negatively correlated with platelet count. Conclusion The high expression of HMGB1 in peripheral blood of ITP patients may induce Th17/Treg imbalance by promoting the maturation of mDC and affecting the secretion of cytokines, thereby potentially playing a role in the immunological mechanism of ITP.
Humans ; Th17 Cells/cytology* ; HMGB1 Protein/genetics* ; T-Lymphocytes, Regulatory/cytology* ; Female ; Male ; Dendritic Cells/metabolism* ; Adult ; Middle Aged ; Purpura, Thrombocytopenic, Idiopathic/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics* ; Young Adult ; Interleukin-23/blood* ; Interleukin-17/blood* ; Interleukin-6/blood* ; Forkhead Transcription Factors/genetics* ; Myeloid Cells/cytology* ; Aged