BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

italic>Candida albicans (C. albicans) stands as the primary opportunistic fungal pathogen responsible for fungal infections. The formation of biofilms constitutes a key virulence trait of C. albicans and a pivotal factor in drug resistance. Consequently, the development of antifungal drugs possessing biofilm inhibitory properties holds importance in the treatment of fungal infectious diseases. This study conducted in-depth research of the novel biofilm inhibitor named 1-(cyclopentylamino)-3-(4-(2,4,4-trimethylpentan-2-yl)phenoxy)propan-2-ol (IMB-H12). IMB-H12 showed good inhibitory activity on the formation of biofilms and a certain scavenging effect on mature biofilms. Preliminary research on the mechanism of action has found that IMB-H12 can inhibit the transformation from yeast to hyphal phase, inhibit the formation of mycelium, and reduce the adhesion activity and hydrophobicity of Candida albicans. IMB-H12 could also induce changes in the content of cell wall components, downregulate the expression of multiple genes related to adhesion and hyphal formation. Therefore, further research on this compound is expected to discover new lead compounds with antifungal activity.

Objective To study the diagnostic value of miR-571 for liver fibrosis by detecting miR-571 expression in the peripheral blood of patients with liver fibrosis.Methods From December 2022 to September 2023,40 patients with liver fibrosis,40 patients with chronic hepatitis,and 40 healthy controls were chosen as research subjects.The expression level of miR-571 in peripheral blood was detected using a real-time quantitative polymerase chain reaction,and the relative expression of miR-571 in each group was evaluated.The Spearman correlation method was utilized to examine the relationship between miR-571 and clinical detection indices.To assess the capacity of miR-571 and the multivariate diagnostic model to identify liver fibrosis,binary logistic regression was used to create a multivariate diagnostic model,and ROC curves were generated.Results The expression of miR-571 was significantly higher in the liver fibrosis group than in the healthy control and hepatitis groups,and the difference was statistically significant(P<0.001).The expression level of miR-571 was positively connected with ALT,APRI score,and FIB-4 index(r = 0.23,0.30,0.22,P<0.05)and negatively correlated with PLT(r =-0.19,P<0.05)according to Spearman correlation analysis.Logistic regression research revealed that miR-571 and the FIB-4 index were independent risk factors for liver fibrosis.The AUC for miR-571 to diagnose fibrosis was 0.91(95%CI:0.85～0.96),while the AUC for miR-571 paired with the FIB-4 index was 0.94(95%CI:0.90～0.98).Conclusion MiR-571 expression was shown to be considerably higher in the peripheral blood of hepatic fibrosis patients,and the combined FIB-4 index offers some clinical diagnostic value for hepatic fibrosis.

Objective:Chronic urticaria presents a chronic process of recurrent attacks,and its first-line treatment is second-generation antihistamine with limited treatment options.The efficacy of antihistamine varies among individuals and cannot meet the needs of all patients.This study aims to explore the clinical efficacy and safety of Zhiyang Xiaozhen granules combined with antihistamine in the treatment of chronic urticaria patients. Methods:We retrospectively analyzed the clinical data of patients with chronic urticaria who visited the Xiangya Hospital of Central South University from April 2020 to March 2021.The patients who received conventional second-generation antihistamine treatment were selected as a control group,while the patients who received combined treatment with Zhiyang Xiaozhen granules on the basis of conventional second-generation antihistamine treatment were selected as an observation group.The differences in the Weekly Urticaria Activity Score(UAS7)and Dermatology Life Quality Index(DLQI)between the 2 groups before and 4 weeks after treatment were compared.The Symptom Score Reduce Index(SSRI)was used to evaluate and compare the efficacy of the 2 treatment regimens. Results:After 4 weeks of treatment,the UAS7 levels in both groups were significantly reduced(P=0.001 and P<0.001,respectively).The effective rates of the control group and the observation group were 61.11%and 59.38%,respectively when converting UAS7 to SSRI for efficacy evaluation,and there was no statistically significant difference in efficacy between the 2 groups(P>0.05);however,when converting DLQI to SSRI for efficacy evaluation,the effective rates of the control group and the observation group were 33.33%and 46.88%,respectively,and the difference in efficacy between the 2 groups was statistically significant(P<0.001).There were 3 patients with adverse drug reactions related to drowsiness in both groups. Conclusion:The combination of Zhiyang Xiaozhen granules and second-generation antihistamine can effectively improve disease activity in patients with chronic urticaria,and the improvement in quality of life is better than that with the second-generation antihistamine alone.

Objectives:To assess the efficacy of cord blood-assisted haploid peripheral blood stem cell transplantation (haplo-cord-PBSCT) versus unrelated donor peripheral blood stem cell transplantation (UD-PBSCT) in the treatment of malignant hematological diseases.Methods:A retrospective analysis was performed on one hundred and four patients with malignant hematological diseases who underwent haplo-cord-PBSCT and fifty-two patients who underwent UD-PBSCT at Xiangya Hospital of Central South University between January 2016 and December 2021.Results:①The median implantation time for neutrophils in the haplo-cord-PBSCT and UD-PBSCT groups was 13 (9–22) days and 13 (10–24) days, respectively ( P=0.834), whereas the median implantation time for platelets was 15 (7–103) days and 14 (8-38) days, respectively ( P=0.816). The cumulative implantation rate of neutrophils at 30 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group was 100% ( P=0.314), and the cumulative platelet implantation rate at 100 days after transplantation was 95.2% (95% CI 88.3% - 98.1% ) and 100% ( P=0.927), respectively. 30 days after transplantation, both groups of patients achieved complete donor chimerism, and no umbilical cord blood stem cells were implanted. ②The cumulative incidence rates of grade Ⅱ-Ⅳ acute GVHD within 100 days after transplantation in the haplo-cord-PBSCT group and the UD-PBSCT group were 29.1% (95% CI 20.1% –38.1% ) and 28.8% (95% CI 17.2% –41.6% ( P=0.965), respectively. The cumulative incidence rates of grade Ⅲ/Ⅳ acute GVHD were 7.8% (95% CI 3.6% –14.0% ) and 9.6% (95% CI 3.5% –19.5% ) ( P=0.725). The cumulative incidence rates of 2-year chronic GVHD in the haplo-cord-PBSCT group and the UD-PBSCT group were 45.3% (95% CI 36.1% -56.1% ) and 35.1% (95% CI 21.6% –44.1% ), respectively ( P=0.237). The cumulative incidence rates of severe chronic GVHD at 2 years after transplantation were 13.6% (95% CI 7.6% -21.3% ) and 12.9% (95% CI 5.1% -24.3% ), respectively ( P=0.840). ③The 2-year CIR after transplantation in the haplo-cord-PBSCT group and UD-PBSCT group were 12.8% (95% CI 7.0% –20.5% ) and 10.0% (95% CI 3.6% –20.2% ), respectively ( P=0.341), and the NRM were 14.7% (95% CI 8.4% –22.6% ) and 16.2% (95% CI 7.4% –28.0% ), respectively ( P=0.681). ④The 2-year OS rates in the haplo-cord-PBSCT and UD-PBSCT groups after transplantation were 82.2% (95% CI 74.8% –90.3% ) and 75.5% (95% CI 64.2% -88.7% ), respectively ( P=0.276). The 2-year DFS rates were 69.9% (95% CI 61.2% –79.8% ) and 73.8% (95% CI 62.4% -87.3% ), respectively ( P=0.551). The 2-year rates of GVHD-free/recurrence-free survival (GRFS) were 55.3% (95% CI 44.8% -64.8% ) and 64.7% (95% CI 52.8% –79.3% ), respectively ( P=0.284) . Conclusion:The findings of this study indicate that haplo-cord-PBSCT and UD-PBSCT have comparable efficacy and safety in the treatment of malignant hematological diseases and can be used as an alternative treatment options.

Objective:To investigate the effect of lipopolysaccharide(LPS)on the crawling ability of fibroblasts derived from the scrotal skin under hypoxic conditions,its impact on vascular regeneration during wound healing,and the potential mechanism un-derlying chronic non-healing scrotal wound caused by gram-negative bacterial infection.Methods:We extracted peripheral blood buffy coats from healthy donors after venous blood centrifugation,divided them into four groups(normoxia,normoxia+LPS,hypoxia,and hypoxia+LPS)for pretreatment,and isolated the corresponding cultured supernatant.Then we measured the levels of VEGF-A,FGF and IL-8 secreted using enzyme-linked immunosorbent assay(ELISA),determined the cytotoxicity of different pretreated superna-tants by lactate dehydrogenase(LDH)release assay,and detected the cell migration ability and vascular formation in human-umbical vein endothelial cells(HUVEC).Results:Under hypoxic conditions,the expression of HIF-1 α was significantly lower in the fibro-blasts from the chronic scrotal wound than in the normal fibroblasts(0.09±0.00 vs 0.48±0.01,P＜0.05),the viability of the cells showed no statistically significant difference from that under normoxic conditions(P＞0.05),and the proliferation and migration abilities of the cells were markedly improved([83.09±2.56]％vs[17.84±1.12]％,P＜0.05).The viability of the scrotal fibroblasts was significantly lower in the normoxia+LPS than in the hypoxia+LPS group([20.15±1.19]％vs[32.54±1.57]％,P＜0.05).The cells treated with LPS,compared with those in the non-LPS groups,exhibited remarkably decreased endo-thelial cell tubes formed(5.20±0.15 va 55.30±1.15,P＜0.05),down-regulated expression of VEGF(OD value:0.59±0.07 vs 1.25±0.11,P＜0.05)and up-regulated expression of IL-8(OD value:2.42±0.07 vs 0.87±0.11,P＜0.05).Conclusion:The supernatant derived from the peripheral blood buffy coats treated with LPS has a stronger cytotoxicity and weaker an-giogenesis than that untreated under hypoxic or normoxic conditions,which may be one of the critical factors for difficult healing of scrotal wound.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

AIM: To investigate the changes in retinal nerve fiber layer(RNFL)and macular retinal thickness(MRT)in children with refractive abnormalities and amblyopia, and their predictive value of outcome.METHODS: A total of 168 children with myopic refractive abnormalities and monocular amblyopia admitted to our hospital from January 2020 to October 2022 were selected as the observation group, with 118 cases of mild to moderate amblyopia and 50 cases of severe amblyopia, and 168 children with normal vision were included as the control group in a 1:1 ratio during the same period. The changes of RNFL and MRT in two groups of children were statistically counted, and the correlation between the severity of refractive abnormalities and RNFL and MRT in children with amblyopia was analyzed. Additionally, the observation group was divided into effective subgroup and ineffective subgroup based on the therapeutic effect. The general information, as well as RNFL and MRT of the effective subgroup and the ineffective subgroups before and after treatment were compared. Logistic was used to analyze the factors influencing efficacy, and ROC curves was plotted to analyze the predictive value of RNFL and MRT alone or in combination for efficacy.RESULTS: RNFL and MRT of cases of severe amblyopia were higher than those of the mild to moderate amblyopia and the control groups(all P<0.05); the severity of amblyopia in children with refractive abnormalities is positively correlated with RNFL and MRT(rs=0.745 and0.724, both P<0.001); among patients of mild to moderate and severe, there were statistically significant differences between the effective and ineffective subgroups in terms of initial treatment age, fixation form, treatment compliance, as well as RNFL, MRT, and their differences before and 1mo postoperatively(all P<0.05). Logistic analysis showed that initial treatment age, fixation nature, treatment compliance, RNFL and MRT before and 1mo postoperatively were all factors influencing the therapeutic effect of amblyopia with refractive abnormalities in children(all P<0.05); after 1mo of treatment, the combined prediction of RNFL and MRT was significantly better than that of single prediction in children with mild to severe amblyopia.CONCLUSION:There are differences in RNFL and MRT in children with abnormal refractive amblyopia, and they are closely related to the different degrees and curative effects of children. The combination of RNFL and MRT after 1mo of treatment has certain value in predicting children with different degrees of abnormal refractive amblyopia.