BACKGROUND:Traditional treatments for corneal alkali burns are limited,especially in controlling inflammation,preventing neovascularization,and inhibiting corneal scarring.Natural,synthetic,or composite materials provide a wide range of treatment options.However,the mechanism by which biomaterials promote corneal alkali burn repair has not yet been systematically understood. OBJECTIVE:To summarize the current research on biomaterials in promoting corneal alkali burn repair in and outside China,and review the mechanism and application of biomaterials in repairing corneal alkali burn. METHODS:The first author searched"cornea,alkali burn,amniotic membrane,hyaluronic acid,collagen,chitosan,polymer materials"as Chinese keywords and"amniotic membrane,hyaluronic acid,collagen,chitosan,polymer,cornea,alkali burn"as English keywords in PubMed,Web of Science,CNKI,and WanFang databases.According to inclusion and exclusion criteria,76 eligible articles were finally included for review. RESULTS AND CONCLUSION:(1)In the field of corneal alkali burn repair,biomaterials such as amniotic membrane,hyaluronic acid,collagen,chitosan,and degradable polymer materials have been widely studied and applied.Each of these biomaterials has its own characteristics,advantages,and disadvantages,and stands out in different aspects.(2)First and foremost,amniotic membranes are considered one of the most promising biomaterials due to their abundance of bioactive factors.They are biocompatible and can regulate the corneal inflammatory response.However,there are issues with donor shortages and susceptibility to infectious diseases.(3)Hyaluronic acid has good moisturizing properties and biocompatibility,and is able to improve the survival rate of corneal cells and increase corneal transparency.(4)The good biocompatibility and scaffold structure of collagen enable the promotion of corneal cell adhesion and proliferation,as well as the reconstruction of corneal tissue structure.(5)Chitosan is recognized for its good biocompatibility and degradability,making it suitable as a carrier for drug delivery and cell transplantation.(6)Degradable polymer materials have good controllability over degradation and can provide a good support and delivery platform for the repair of corneal alkali burns,but further research is needed on their stability and biocompatibility.(7)Overall,there is currently no single biomaterial that can completely address the repair problem of corneal alkali burns,and each biomaterial has its own specific application scenarios and limitations.(8)Future research directions should focus on further improving the properties and structure of biomaterials,exploring more effective combination applications,and deeply understanding the interaction mechanism between biomaterials and corneal tissue,in order to enhance the therapeutic effect of corneal alkali burns and the quality of life of patients.

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

Cervical spine health issues not only seriously affect patients' quality of life but also impose a heavy burden on the social healthcare system. Existing guidelines lack sufficient clinical guidance on lifestyle and work habits, such as exercise, posture, daily routine, and diet, making it difficult to meet practical needs. To address this, relying on the China Association of Chinese Medicine, Wangjing Hospital of China Academy of Chinese Medical Sciences took the lead and joined hands with more than ten institutions to form a multidisciplinary guideline development group. For the first time, the group developed the Guidelines for Cervical Spine Health Intervention based on evidence-based medicine methods, strictly following the standardized procedures outlined in the World Health Organization Handbook for Guideline Development and the Guiding Principles for the Formulation/Revision of Clinical Practice Guidelines in China (2022 Edition). This proposal systematically explains the methods and steps for developing the guideline, aiming to make the guideline development process scientific, standardized, and transparent.
Humans ; Practice Guidelines as Topic/standards* ; Cervical Vertebrae ; China

OBJECTIVE: To assess the efficacy and safety of a new conditioning regimen with chidamide and BEAM for autologous hematopoietic stem cell transplantation (AHSCT) in patients with lymphoma. METHODS: Medical records and further follow-up data from 85 patients with lymphoma from May 2015 to September 2020 in our hospital were retrospectively collected and analyzed. RESULTS: Among 85 patients, 52 cases accepted BEAM regimen and 33 cases accepted CBEAM followed by AHSCT. In CBEAM group, 18 patients (54.5%) received AHSCT as salvage therapy, while only 26.9% (14 cases) for salvage in BEAM group ( P < 0.01). CBEAM conditioning resulted in shorter neutrophil engraftment of 2 days, while no significant difference was found in platelet engraftment. Although the incidence of liver impairment was higher in CBEAM group (12.1%), the grade of impairment was only Ⅰ to Ⅱ. The two conditioning regimens both achieved good complete remission rate of over 90%, and no transplant-related death occurred. The median follow-up time in the CBEAM group was 18(12, 22) months, and 39(20, 59) months in the BEAM group. There were no significantly differences in 2-year progression-free survival (PFS) and overall survival (OS) rate between the two groups (P >0.05). In patients with refractory or relapsed non-Hodgkin lymphoma, the 2-year PFS rate after transplantation in BEAM group and CBEAM group was 74.1% and 92.9%, respectively (P >0.05), indicating that chidamide may have certain advantages in prolonging PFS. CONCLUSION CBEAM conditioning regimen has a good efficacy and safety in lymphoma patients before AHSCT, especially in refractory and relapsed non-Hodgkin lymphoma patients, suggesting that it could serve as an alternative conditioning regimen prior to AHSCT for lymphoma.
Humans ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning/methods* ; Transplantation, Autologous ; Retrospective Studies ; Aminopyridines/therapeutic use* ; Lymphoma/therapy* ; Benzamides/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Male ; Female ; Cytarabine/therapeutic use* ; Melphalan/therapeutic use* ; Adult ; Middle Aged ; Podophyllotoxin/therapeutic use* ; Carmustine ; Etoposide

OBJECTIVES: Patients with connective tissue diseases (CTD) have a high incidence of cardiac involvement, which often presents insidiously and can progress rapidly, making it one of the leading causes of death. Multiparametric cardiovascular magnetic resonance (CMR) provides a comprehensive quantitative evaluation of myocardial injury and is emerging as a valuable tool for detecting cardiac involvement in CTD. This study aims to investigate the correlations between CMR features and serological biomarkers in CTD patients, assess their potential clinical value, and further explore the impact of pre-CMR immunotherapy intensity on CMR-specific parameters, thereby evaluating the role of CMR in the early diagnosis of CTD-related cardiac involvement. METHODS: A retrospective analysis was conducted on 72 consecutive CTD patients who underwent CMR at Xiangya Hospital of Central South University between September 2019 and March 2024. Clinical data, serological markers, and CMR parameters were collected. Differences in CMR parameters were compared between CTD patients with positive and negative serological markers. Correlations between serological biomarkers and CMR parameters were analyzed, with subgroup analyses performed for different CTD subtypes. Logistic regression (univariate and multivariate) was applied to explore the effects of pre-CMR immunotherapy intensity on CMR parameters, and receiver operating characteristic (ROC) curve analysis was used to determine cutoff values. RESULTS: In differential analyses, CTD patients with elevated interleukin (IL)-1β and IL-6 levels exhibited significantly higher myocardial T₂ values compared with those with normal levels (P=0.014, P=0.012). Elevated IL-10 was associated with a higher prevalence of microvascular lesions on CMR (P=0.038). Correlation analysis revealed a significant positive association between high-sensitivity cardiac troponin T (hs-cTnT) and T₂ values (r=0.371, P=0.009). ROC analysis indicated that when the hs-cTnT threshold was 0.01 ng/mL, the sensitivity and specificity for predicting elevated left ventricular T₂ values were 85.71% and 61.11%, respectively [area under the curve (AUC)=0.767, P=0.001]. hs-cTnT and creatine kinase (CK) were also positively correlated with native T₁ values (r=0.371, P=0.009; r=0.364, P=0.032). Erythrocyte sedimentation rate (ESR) showed a positive correlation with the percentage of the late gadolinium enhancement (LGE) (r=0.236, P=0.047). Conversely, hs-cTnT correlated negatively with global radial strain (GRS) (r=-0.297, P=0.034), while CK correlated negatively with both GRS and global circumferential strain (GCS) (r=-0.292, P=0.022; r=-0.282, P=0.027). Among patients with elevated hs-cTnT, the cumulative glucocorticoid dose prior to CMR was negatively associated with elevated T₂ values (OR=0.997, P=0.018), and this correlation remained significant after adjusting for duration of steroid use (OR=0.997, P=0.044). ROC analysis showed that when the cumulative glucocorticoid dose did not exceed 613 mg/mL (prednisone equivalent), the sensitivity and specificity for predicting elevated T₂ values were 90.48% and 77.78%, respectively (AUC=0.862, P<0.001). CONCLUSIONS Several inflammatory biomarkers demonstrate correlations with specific CMR parameters, with hs-cTnT showing the strongest associations across multiple indices. Elevated hs-cTnT suggests a high likelihood of cardiac involvement in CTD patients. Furthermore, pre-CMR immunotherapy intensity significantly influences the specificity of T₂ mapping, indicating its importance in interpreting CMR results. These findings provide critical insights for clinicians in the early recognition, timely intervention, and disease evaluation. Future research should further explore the role of CMR in the assessment of CTD-related cardiac assessment of CTD-related cardiac involvement. Future studies should further explore the role of CMR in evaluating CTD cardiac manifestations and its integration with other clinical data to optimize patient management.
Humans ; Retrospective Studies ; Male ; Female ; Connective Tissue Diseases/blood* ; Middle Aged ; Adult ; Biomarkers/blood* ; Magnetic Resonance Imaging/methods* ; ROC Curve ; Interleukin-6/blood* ; Troponin T/blood*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Objective:To analyze the clinical characteristics,treatment,and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma(ETP-ALL/LBL).Methods:Clinical data of 113 T lymphoblastic leukemia/lymphoma(T-ALL/LBL)patients from January 2006 to January 2019 were collected from three hematology research centers,including Peking University Third Hospital,the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital,Chinese Medical University.The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients.Results:In 113 T-ALL/LBL patients,13 cases(11.5％)were diagnosed as ETP-ALL/LBL,including 11 males,with a median age of 28(18-53)years.Compared with non-ETP-ALL/LBL patients,there were no significant differences in age,sex,incidence of large mediastinal mass,clinical stage,international prognostic index(IPI)score,white blood cell(WBC)count and lactate dehydrogenase(LDH)level among ETP-ALL/LBL patients.Among 13 ETP-ALL/LBL patients,9 cases(69.2％)achieved complete remission(CR),and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients.Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation(allo-HSCT),ETP-ALL/LBL group had a worse 5-year overall survival(OS)rate compared with non-ETP-ALL/LBL group(0 vs 7.1％,P=0.008),while in patients with allo-HSCT,there was no significant difference for 5-year OS rate between the two group(37.5％vs 40.2％,P＞0.05).Multivariate Cox regression analysis showed that CR after induction therapy,allo-HSCT,and LDH level were independent prognostic factors affecting T-ALL/LBL patients.Conclusion:No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients.Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.

Objective:To summarize the clinical characteristics,therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma(HL).Methods:A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled,and their clinical data,including sex,age,pathological type,Ann Arbor stage,ECOG score,blood test,β2-microglobulin,lactate dehydrogenase level,albumin level were collected.The clinical characteristics,therapeutic effect and long-term prognosis of the patients were summarized and analyzed.Results:In classical HL,nodular sclerosis HL accounted for the highest proportion of 51.6％,followed by mixed cellularity HL(36.5％),lymphocyte-rich classical HL(3.2％),and lymphocyte depletion HL(0.7％),while nodular lymphocyte predominant HL accounted for 4.8％.The 3-year overall survival(OS)rate of HL patients was 89.8％,and 5-year OS was 85.0％.The 3-year progression-free survival(PFS)rate was 73.4％,and 5-year PFS was 63.1％.Multivariate regression analysis indicated that IPI score was an independent negative factor,while hemoglobin(Hb)level was an independent positive factor for OS in HL patients.When the mediastinal mass size was 9.2 cm,it was most significant to judge the survival status of HL patients.5-year OS and 5-year PFS were 97.4％and 76.0％in early-stage HL patients without large mass,respectively,while in patients with advanced-stage HL was 83.4％and 55.9％(both P＜0.05).After 2-4 courses of treatment,the overall response rate(ORR)of patients who received chemotherapy combined with radiotherapy was 95.0％,while that was 89.6％in those with chemotherapy alone.Conclusions:The overall prognosis of patients with HL is satisfactory,especially those in early-stage without large mass.IPI score and Hb level are independent risk factors for the prognosis of HL patients.A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.

Objective:To investigate the anti-chronic myelogenous leukemia(CML)activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression,and explore the potential role of its signaling pathway.Methods:Firstly,CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B,imatinib,and their combination on the proliferation and migration of K562 cells.Furthermore,the apoptosis rate of K562 cells treated with Csn-B,imatinib,and their combination was detected by flow cytometry.The expression levels of Nur77,Pim-1,Drp1,p-Drp1 S616,Bcl-2 and Bax in K562 cells were detected by Western blot.Finally,the expression levels of reactive oxygen species(ROS)in K562 cells treated with Csn-B,imatinib and their combination were detected by immunofluorescence assay.Results:The level of Nur77 in CML patients decreased significantly compared with normal population in dataset of GSE43754(P＜0.001).Csn-B combined with imatinib could significantly inhibit the proliferation and migration of K562 cells(both P＜0.001),and induce apoptosis(P＜0.001).Csn-B promoted Nur77 expression in K562 cells,and synergistically enhanced imatinib sensitivity when combined with imatinib.Csn-B combined with imatinib could significantly enhanced ROS levels in K562 cells and mitochondria compared with single-drug treatment(both P＜0.001).Conclusion:Csn-B combined with imatinib can enhance ROS expression and induce apoptosis of K562 cells through Nur77/Pim-1/Drp1 pathway.