ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang （BXT） inhibits epithelial-mesenchymal transition （EMT） in chronic atrophic gastritis （CAG） rats by regulating the interleukin-17（IL-17）/extracellular regulated protein kinases（ERK）/CCAAT enhancer binding protein β（C/EBPβ）signaling pathway， thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling， the rats were randomly divided into the model group， low-， medium-， and high-dose groups （0.549， 1.098， 2.196 g·kg^-1， respectively） of BXT， and the positive drug group （vitacoenzyme， 0.3 g·kg^-1）. A normal control group was also set up. After 8 weeks of intervention， the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of IL-17， tumor necrosis factor-α （TNF-α）， cyclooxygenase-2 （COX-2）， and C/EBPβ in serum， as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin， N-cadherin， and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17， p-ERK， and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ， ERK， and its phosphorylated form （p）-ERK in gastric mucosa. Real-time polymerase chain reaction （Real-time PCR） was applied to measure the mRNA expression levels of ERK， COX-2， and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group， the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly increased （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBPβ in serum were significantly increased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased， while the content of E-cadherin was significantly decreased （P<0.01）. Compared with the model group， after intervention with different doses of BXT， the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ， ERK， and p-ERK in gastric mucosa were significantly reduced （P<0.05，P<0.01）. The levels of IL-17， TNF-α， COX-2， and C/EBP β in serum were significantly decreased （P<0.01）. The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased， while the content of E-cadherin was increased （P<0.05，P<0.01）. ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum， regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.

Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

Objective: To develop a comprehensive health economics evaluation model for HIV blood screening using Markov modeling, so as to evaluate the quality-of-life adjustment years (QALYs) gained by transfusion recipients after implementation of blood HIV screening. Methods: Shenzhen Blood Center was selected as the validation case for model development. Based on historical HIV screening data of Shenzhen Blood Center and published literature, the health economics evaluation of donor HIV screening was performed using cost-utility analysis. The single factor sensitivity analysis was performed on parameters in the model. Results: 3.09 QALYs were gained for each transfusion recipient prevented from HIV infection. During 2020-2023, donor HIV screening at Shenzhen Blood Center saved 506.76 QALYs, and each QALY saved 182 900 yuan. Conclusion: From the perspective of long-term benefit of transfusion recipients, HIV screening of blood donors demonstrates high health and economic value.

BACKGROUND: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance. METHODS: An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo . We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo . RESULTS: AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis. CONCLUSION AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.
Animals ; Glaucoma/metabolism* ; Neuroprotective Agents/pharmacology* ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Artificial Intelligence ; Retinal Ganglion Cells/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Male

Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.

Background and aims:Early and accurate diagnosis of the coexistence of Wilson's disease(WD)and chronic hepatitis B(CHB)presents a significant challenge for clinicians.The objective of this study was to retrospectively analyse the characteristics of such patients to improve clinical practice and provide a reference for clinical management.Methods:From January 2011 to December 2022,35 patients with concurrent CHB and WD(CHB+WD group)were identified.A total of 127 patients with CHB(CHB group)and 168 patients with WD(WD group)were included in the control group between January 2016 and December 2021.Propensity score matching(PSM)was performed to balance the baseline values between groups.The Kaplan-Meier(K-M)survival analysis and log-rank test were performed to compare the prognoses.Results:In the cohort of 35 patients with concurrent CHB and WD,74.3％of patients(26 patients)faced a substantial delay of up to 10 years(range:0-40 years)in WD diagnosis following their CHB diagnosis.Twenty-three(65.7％)patients had cirrhosis at the time of WD diagnosis,and 26(74.3％)patients experienced liver failure.The levels of serum copper and uric acid were lower in patients in the CHB+WD group than in those in the CHB group.Patients in the CHB+WD group presented higher alanine transaminase and total bile acid levels compared to those in the WD group.K-M survival analysis indicated that patients with CHB and WD had poorer outcomes than those with CHB alone;however,the outcomes were similar to those of individuals with WD alone.The optimal cut-point of serum ceruloplasmin(CP)in identifying WD in CHB patients was 0.10 g/L before PSM and after PSM.Conclusions:The present study emphasizes the importance of clinicians being vigilant for concurrent CHB and WD diagnoses,as delays in WD diagnosis may adversely affect patient outcomes.CHB patients with serum CP below 0.10 g/L are highly recommended to screen for WD.

T cell response plays an important role in anti-viral infection and anti-tumor immunity,and antigen-specific T cell detection is essential for study of T cell response.This article reviews progress of antigen-specific T cell detection technology,including enzyme-linked immunospot(ELISPOT)assay,intracellular cytokine staining(ICS)assay and activation-induced labeling(AIM)assay,which based on detection of cytokine secretion or activation phenotypes of specific T cells after stimulation and reactivation with antigen in vitro.Another class of methods include Tetramer technology based on known epitopes-human leukocyte antigen(HLA)restriction and recently developed single-cell transcriptomes and T-cell antigen receptor(TCR)sequencing technology.Application of the above methods has advanced our understanding of antigen specific T cell response:Strength and duration of the response,subpop-ulation information,epitopes and their associated HLA-restriction,TCR cloning information and transcriptome characteristic.

Currently,a wide range of oral antibacterial materials are clinically used,including metal element antibacterial materials(such as silver,zinc,copper,titanium),and non-metal element antibacterial materials(such as fluorine).In recent years,cerium ox-ide nanoparticles have attracted great interest in the field of oral medicine due to their unique antibacterial,anti-inflammatory,antioxi-dant,redox capabilities.At the same time,they also have the characteristics of promoting tissue regeneration,inhibiting biofilm forma-tion and good biocompatibility.To enhance the performance of oral materials,nanoparticles have been integrated into products such as composite resins,adhesives,and denture systems.Additionally,they have shown potential for modifying oral ceramic materials and an-ti-tumor effects.This review focuses on the latest research progress in various fields of oral medicine,including endodontics,periodon-tology,implantology,prosthodontics,and orthodontics,based on the biological characteristics of nano-cerium oxide.Our goal is to re-veal the potential of cerium oxide in the diagnosis and treatment of oral diseases and to provide ideas and references for the expansion of clinical applications in oral medicine.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

T cell response plays an important role in anti-viral infection and anti-tumor immunity,and antigen-specific T cell detection is essential for study of T cell response.This article reviews progress of antigen-specific T cell detection technology,including enzyme-linked immunospot(ELISPOT)assay,intracellular cytokine staining(ICS)assay and activation-induced labeling(AIM)assay,which based on detection of cytokine secretion or activation phenotypes of specific T cells after stimulation and reactivation with antigen in vitro.Another class of methods include Tetramer technology based on known epitopes-human leukocyte antigen(HLA)restriction and recently developed single-cell transcriptomes and T-cell antigen receptor(TCR)sequencing technology.Application of the above methods has advanced our understanding of antigen specific T cell response:Strength and duration of the response,subpop-ulation information,epitopes and their associated HLA-restriction,TCR cloning information and transcriptome characteristic.