Apigenin and baicalein ameliorate thoracic aortic structural deterioration and cognitive deficit via inhibiting AGEs/RAGE/NF-κB pathway in D-galactose-induced aging rats.

Apigenin and baicalein are structurally related flavonoids that have been reported to have multiple pharmacological activities. The aim of this study was to investigate the protective effects and potential mechanisms of apigenin and baicalein in D-galactose-induced aging rats. First, apigenin and baicalein showed remarkable antioxidant activity and anti-glycation activity in vitro. Secondly, the protective effects of apigenin and baicalein on aging rats were investigated. We found that apigenin and baicalein supplementation significantly ameliorated aging-related changes such as declines in the spatial learning and memory and histopathological damage of the hippocampus and thoracic aorta. In addition, our data showed that apigenin and baicalein alleviated oxidative stress as illustrated by decreasing MDA level, increasing SOD activity and GSH level. Further data showed that they significantly reduced the accumulation of advanced glycation end products (AGEs), inhibited the expression of RAGE, down-regulated phosphorylated nuclear factor (p-NF-κB (p65)). Our results suggested that the protective effects of apigenin and baicalein on aging rats were at least partially related to the inhibition of AGEs/RAGE/NF-κB pathway and the improvement of oxidative damage. Overall, apigenin and baicalein showed almost equal anti-aging efficacy. Our results provided an experimental basis for the application of apigenin and baicalein to delay the aging process.

Susceptibility to e-cigarette adoption among tobacco-naïve youths: a cross-sectional study in Shenzhen, China.

Background: The rise in e-cigarette use among youth is a significant global public health issue. It is important to identify those at increased risk and implement effective strategies to reduce e-cigarette popularity among the youth. Objective: This study aims to identify predictors of e-cigarette uptake in youths with no prior tobacco use, considering individual, familial and the broader societal environmental factors. Methods: For this investigation, a group of 2,487 tobacco-free youths was selected from 15 high schools in Shenzhen, China. Susceptibility to e-cigarettes was determined by assessing the possibility of future use and the openness to trying e-cigarettes if presented by friends. Both chi-square tests and logistic regression were applied to identify factors linked to susceptibility to e-cigarette use. Results: Among the respondents, 5.5% (n = 136) were found to be susceptible to e-cigarette use. The analysis revealed factors tied to this risk: perceptions of e-cigarettes, the impact of vaping peers, paternal parenting styles, the extent of social support, exposure to messages both for and against e-cigarettes use, and secondhand smoke (SHS) exposure. Youths who downplayed the addictive nature of e-cigarettes (aOR = 2.01; 95% CI: 1.14-3.55; p = 0.016), those with friends who engaged in vaping (aOR = 3.43-7.64; 95%CI: 2.36-20.42; p < 0.001), those experiencing over-protective or rejective maternal parenting (aOR = 1.68-3.01; 95%CI: 1.11-5.77; p = 0.001-0.014) or rejective paternal parenting (aOR = 3.63; 95%CI: 1.99-6.59; p < 0.001), those aware of e-cigarette advertisements (aOR = 1.82; 95%CI: 1.28-2.60; p = 0.001), and those exposed to SHS at home (aOR = 1.68; 95%CI: 1.17-2.41; p = 0.005) or at public places (aOR = 1.72-1.79; 95%CI: 1.21-2.57; p = 0.002-0.003) were more prone to e-cigarettes. In contrast, youths who believed using e-cigarettes reduces one's attractiveness (aOR = 0.34; 95%CI: 0.16-0.72; p = 0.005) or perceived that vaping made social interactions less enjoyable (aOR = 0.26; 95%CI: 0.12-0.58; p = 0.001), those who benefited from high social support (aOR = 0.30-0.60; 95%CI: 0.17-0.97; p < 0.001), and those who noticed message about e-cigarettes' adverse consequence (aOR = 0.54; 95%CI: 0.38-0.77; p = 0.001) were less likely to be inclined toward e-cigarette use. Conclusion: The propensity of the youth to e-cigarette usage is shaped by a multiple element. An all-encompassing strategy that addresses the individual, familial, and the broader societal aspects is imperative for the effective prevention of e-cigarette initiation among youth.

KLF4 inhibited the senescence-associated secretory phenotype in ox-LDL-treated endothelial cells via PDGFRA/NAMPT/mitochondrial ROS.

BACKGROUND: Inflammation is one of the significant consequences of ox-LDL-induced endothelial cell (EC) dysfunction. The senescence-associated secretory phenotype (SASP) is a critical source of inflammation factors. However, the molecular mechanism by which the SASP is regulated in ECs under ox-LDL conditions remains unknown. RESULTS: The level of SASP was increased in ox-LDL-treated ECs, which could be augmented by KLF4 knockdown whereas restored by KLF4 knock-in. Furthermore, we found that KLF4 directly promoted PDGFRA transcription and confirmed the central role of the NAPMT/mitochondrial ROS pathway in KLF4/PDGFRA-mediated inhibition of SASP. Animal experiments showed a higher SASP HFD-fed mice, compared with normal feed (ND)-fed mice, and the endothelium of EC-specific KLF4-/- mice exhibited a higher proportion of SA-ß-gal-positive cells and lower PDGFRA/NAMPT expression. CONCLUSIONS: Our results revealed that KLF4 inhibits the SASP of endothelial cells under ox-LDL conditions through the PDGFRA/NAMPT/mitochondrial ROS. METHODS: Ox-LDL-treated ECs and HFD-fed mice were used as endothelial senescence models in vitro and in vivo. SA-ß-gal stain, detection of SAHF and the expression of inflammatory factors determined SASP and senescence of ECs. The direct interaction of KLF4 and PDGFRA promotor was analyzed by EMSA and fluorescent dual luciferase reporting analysis.

Design, synthesis, and biological evaluation of novel chrysin derivatives as poly(ADP-ribose) polymerase 1 (PARP1) inhibitors for the treatment of breast cancer.

In this study, we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly (ADP-ribose) polymerase 1 (PARP1). Among these derivatives, compound 5d emerged as the most effective chrysin-based inhibitor of PARP1, with an IC50 value of 108 nmol·L-1. This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA damage. Furthermore, 5d induced apoptosis and caused an extended G1/S-phase in these cell lines. Molecular docking studies revealed that 5d possesses a strong binding affinity toward PARP1. In vivo, in a xenograft model, 5d effectively reduced tumor growth by downregulating PARP1 expression. Overall, compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

[Determination of 21 organophosphate esters and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish a method for simultaneous determination of 21 organophosphate esters(OPEs) and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry. METHODS: The drinking water was purified by automatic solid phase extraction with HLB column, eluted by methanol, determined by liquid chromatography tandem mass spectrometry with ACQUITY UPLC BEH(100 mm×2.1mm, 1.7 µm) column, and quantified by internal standard method. RESULTS: The optimized method could simultaneously detect 21 organophosphate esters and their metabolites in drinking water. The detection limit was 0.01-0.24 ng/L, the quantitation limit was 0.03-0.77 ng/L. The recovery range was 57.6%-121.2% and the relative standard deviation is 1.2%-11.1% when the concentration was 0.8-20 ng/L. Senventeen tap water and 30 packaged drinking water collected by the supermarket were measured. The ΣOPEs range was 16.8-177 ng/L, and the Σdi-OPEs range was 0.328-16.3ng/L, indicating the exposure risk of organophosphates and their metabolites in water. CONCLUSION: The pretreatment of the method is simple, automatic and sensitive, and is suitable for simultaneous high-throughput determination of organophosphate esters and their metabolites in large quantities of drinking water.

Causal Relationship between Parkinson's Disease with Heart and Vascular Disease: A Two-Sample Mendelian Randomization Study.

INTRODUCTION: The aim of this study was to investigate the causal relationship between Parkinson's disease (PD) and myocardial infarction (MI), atrial fibrillation and flutter (AF), and venous thromboembolism (VTE) by Mendelian randomization (MR) analysis. METHODS: By using data from publicly available genome-wide association studies from databases, single nucleotide polymorphisms were screened as instrumental variables, and the MR analysis was finished by inverse-variance weighted (IVW), MR-egger, weighted median methods. RESULTS: The primary IVW method showed a negative association between genetically predicted PD and risk of MI (OR = 0.9989; 95% CI: 0.9980-0.9998; p = 0.02). However, PD was not significantly associated with AF or VTE. CONCLUSION: This study suggests a negative association between PD with MI, which implies that PD has a protective effect on MI.

Effects of pressure-controlled ventilation targeting end-inspiratory flow rate on pulmonary complications and inflammation levels in patients undergoing spinal surgery in the prone position: a randomized clinical trial.

BACKGROUND: This study assessed the impact of pressure-controlled ventilation (PCV) focusing on end-inspiratory flow rate on the incidence of postoperative pulmonary complications (PPCs) and inflammation levels in patients undergoing spinal surgery in the prone position. METHODS: A total of 187 patients who underwent posterior spinal surgery were enrolled and randomly divided into 3 groups: 61 in the volume-controlled ventilation (VCV) group (group V), 62 in the PCV-volume-guaranteed (VG) group (group P1), and 64 in the PCV-VG end-expiratory zero flow rate group (group P2). Indicators including tidal volume (VT), peak airway pressure (Ppeak), and dynamic lung compliance (Cdyn) were recorded. The Ppeak, Cdyn, PETCO2, and oxygenation index (PaO2/FiO2) after intubation (T0), after prone position (T1), 60 min after prone position (T2), and after supine position at the end of surgery (T3) of the three groups were collected. RESULTS: In the within-group comparison, compared with T0, Ppeak increased at T1 - 2 in groups V and P1 (P < 0.01), whereas it decreased at T1 - 3 in group P2 (P < 0.01). Cdyn decreased at T1 - 2 and PaO2/FiO2 increased at T1 - 3 in all three groups (P < 0.01), and PaO2/FiO2 increased at T1 - 3 (P < 0.01). Compared with group V, Ppeak decreased at T0 - 3 in group P1 (P < 0.01) and at T1 - 3 in group P2 (P < 0.01), while Cdyn increased at T0 - 3 in groups P1 and P2 (P < 0.01). Compared with group P1, Ppeak was elevated at T0 (P < 0.01) and decreased at T1 - 3 (P < 0.05), and Cdyn was elevated at T0 - 3 in group P2 (P < 0.01). The total incidence of PPCs in group P2 was lower than that in group V (P < 0.01). Compared with the preoperative period, serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels were increased at 24 and 72 h after surgery in group V (P < 0.01), whereas that was increased at 24 h after surgery in group P1 and group P2 (P < 0.01). Compared with group V, serum IL-6 and CRP levels were reduced at 24 h after surgery in groups P1 and P2 (P < 0.01 or < 0.05). CONCLUSION: In patients undergoing spinal surgery in the prone position, PCV-VG targeting an end-inspiratory zero flow rate lowers the incidence of PPCs and inflammation levels.

The role of education attainment on 24-hour movement behavior in emerging adults: evidence from a population-based study.

Purpose: The purpose of this study was to explore the relationship between education level and health behavior including sleep, work activity, exercise activity, and sedentary behavior among emerging adults. Methods: This study utilized data from the National Health and Nutrition Examination Survey (NHANES) collected between 2007 and 2018. The study sample included 4,484 emerging adults aged 18-25 years and the weighted participants were 30,057,813. Weighted multivariable regression analysis was performed to investigate the association between education level and the aforementioned health behavior, adjusting for age, gender, race/ethnicity, marital status, poverty-income ratio, BMI, smoking, and alcohol drinking status. Results: This study revealed that higher education level was associated with shorter sleep duration [Fully adjusted model, ß (95% CI): -0.588 (-0.929, -0.246), p < 0.001]. Additionally, those with higher education levels were more likely to allocate time in sedentary behavior [ß (95% CI): 90.162 (41.087, 139.238), p < 0.001]. Moreover, higher education level was related to less work activity [ß (95% CI): -806.991 (-1,500.280, -113.703), p = 0.023] and more exercise activity time [ß (95% CI): 118.196 (-21.992, 258.385), p = 0.097]. Subgroup analysis further verified this trend and detected that males with higher education level tended to participate in less work activity [ß (95% CI): -1,139.972 (-2,136.707, -143.237), p = 0.026] while females with higher education level tended to engage in more exercise activity [Fully adjusted model, ß (95% CI): 141.709 (45.468, 237.950), p = 0.004]. Conclusion: This study highlighted the importance of education level as a significant factor in promoting healthy behavior among emerging adults. The findings underscored the need for the Ministry of Education to prioritize educating this demographic about the significance of maintaining adequate sleep patterns and reducing sedentary habits. Encouraging them to allocate more time for work and physical activities can significantly contribute to their overall wellbeing and success, ultimately fostering a healthier next generation.

Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production / 药学学报

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Apigenin analogs as α-glucosidase inhibitors with antidiabetic activity.

This study investigated the inhibitory potential of a series of synthesized compounds (L1-L27) on α-glucosidase. Among them, compound L22 showed significant inhibitory effect. Through enzymatic kinetics studies, we demonstrated that L22 acts via a non-competitive inhibition mode with a Ki value of 2.61 µM, highlighting its high affinity for the enzyme. Molecular docking studies revealed the formation of hydrogen bonds between L22 and α-glucosidase and diverse interactions with neighboring amino acid residues. Furthermore, molecular dynamics simulations confirmed the stability of the L22-α-glucosidase complex. In a mouse model of type 2 diabetes, treatment with L22 significantly lowered fasting blood glucose levels, and reduced insulin resistance, suggesting its potential as a therapeutic agent for type 2 diabetes. Furthermore, L22 showed a protective effect against oxidative stress in the liver and alleviated liver and pancreatic abnormalities. These results provide valuable insights into the mechanism of action of L22 and its potential applications to treat type 2 diabetes, and improve liver health.

Progress in the clinical treatment of keloids.

Keloid is a pathological scar that is higher than the skin surface following skin damage. Its lesion range often extends beyond the original damage boundary and does not naturally subside over time. Its pathogenesis is very complex, currently the main causes include fibroblast excessive proliferation, collagen and extracellular matrix (Extracellular matrix, ECM) excessive deposition, excessive angiogenesis, and so on. The traditional treatment method primarily involves surgical intervention, but it is associated with a high recurrence rate post-surgery. Consequently, many treatment methods are derived according to the different clinical characteristics of keloid. This paper will review the therapeutic progress in recent years from surgical treatment, physiotherapy, drug therapy, and biological therapy, with the goal of offering valuable insights for the clinical treatment of keloids.

Impact of percutaneous coronary intervention on renal function in patients with coronary heart disease.

The relationship between cardiac and renal function is complicated. The impact of percutaneous coronary intervention (PCI) on renal function in patients with coronary artery disease is still unclear. The current study sought to assess renal function change, including the time course of renal function, after elective PCI in patients with improved renal function and to identify renal function predictors of major adverse cardiovascular events. We examined data from 1572 CHD patients who had coronary angiography (CAG) or PCI in this retrospective cohort study. Patients receiving elective PCI (n=1240) and CAG (n=332) between January 2013 and December 2018 were included. Pre-PCI and procedural variables associated with post-PCI eGFR, change in renal function after post-PCI follow-up, and post-PCI eGFR association with major adverse cardiovascular events were investigated. Following the procedure, 88.7 percent of PCI group patients had unchanged or improved renal function. The treatment of PCI was found to independently correlate with IRF following coronary angiography in an analysis of patients undergoing PCI [OR 4.561 (95% CI:2 .556-8.139); p<0.001]. The area under the receiver operating characteristic (ROC) curve is 0.763 (model with the treatment of PCI). Improved renal function (IRF) and stable renal function were both associated with a lower risk of a major cardiovascular event.

Relationship between quantitative epicardial adipose tissue based on coronary computed tomography angiography and coronary slow flow.

BACKGROUND: The purpose of this study was to explore the relationship between quantitative epicardial adipose tissue (EAT) based on coronary computed tomography angiography (CCTA) and coronary slow flow (CSF). METHODS: A total of 85 patients with < 40% coronary stenosis on diagnostic coronary angiography were included in this retrospective study between January 2020 and December 2021. A semi-automatic method was developed for EAT quantification on CCTA images. According to the thrombolysis in myocardial infarction flow grade, the patients were divided into CSF group (n = 39) and normal coronary flow group (n = 46). Multivariate logistic regression was used to explore the relationship between EAT and CSF. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of EAT in CSF. RESULTS: EAT volume in the CSF group was significantly higher than that of the normal coronary flow group (128.83± 21.59 mL vs. 101.87± 18.56 mL, P < 0.001). There was no significant difference in epicardial fat attenuation index between the two groups (P > 0.05). Multivariate logistic regression analysis showed that EAT volume was independently related to CSF [odds ratio (OR) = 4.82, 95% confidence interval (CI): 3.06-7.27, P < 0.001]. The area under ROC curve for EAT volume in identifying CSF was 0.86 (95% CI: 0.77-0.95). The optimal cutoff value of 118.46 mL yielded a sensitivity of 0.80 and a specificity of 0.94. CONCLUSIONS: Increased EAT volume based on CCTA is strongly associated with CSF. This preliminary finding paves the way for future and larger studies aimed to definitively recognize the diagnostic value of EAT in CSF.

Altered 5-methylcytosine modification of mRNA is involved in the pathogenesis of pre-eclampsia.

5-Methylcytosine (m5 C) is a prevalent RNA modification in messenger RNAs (mRNAs). Despite its abundance, its role in the decidua of pre-eclampsia (PE) remains elusive. In this study, we utilized methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-sequencing (RNA-seq) to map m5 C peaks and mRNA expression profile in the decidua of human early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses elucidated potential roles of the differentially methylated mRNAs (DMGs) and differentially expressed mRNAs in decidualization pathways. Integrative analysis of MeRIP-seq and RNA-seq data pinpointed 50 candidate genes linked to PE, marked by both differentially methylated m5 C peaks and congruent expression changes. To validate these observations, we selected nine genes for verification via quantitative PCR. Our results underscore the precision and reproducibility of our bioinformatics approach. Importantly, we propose that changes in m5 C modification and expression of relevant mRNA might influence the pathogenesis of PE by hampering decidualization. This work shines light on the distinct mRNA m5 C modification patterns and expression profiles in the decidua of PE, implicating pivotal signaling disruptions and decidualization impediments in the onset of PE.

Coronary slow flow research: a bibliometric analysis.

BACKGROUND: Studies on coronary slow flow are receiving increasing attention, but objective evaluations are still lacking. The purpose of this study was to visualize the current status and research hotspots of coronary slow flow through bibliometric analysis. METHODS: All relevant publications on coronary slow flow from 2003 to 2022 were extracted from the Web of Science Core Collection database and analyzed by VOSviewer and CiteSpace visualization software. Year of publication, journal, country/region, institution, and first author of each paper, as well as research hotspots were identified. RESULTS: A total of 913 publications were retrieved. The journal with the most publications was Coronary Artery Disease. The country/region with the most publications was Turkey, followed by China and the United States. The institution with the largest publication volume was Turkey Specialized Higher Education Research Hospital. The author with the largest publication volume was Chun-Yan Ma from China. Keyword analysis indicated that "treatment and prognosis", "pathogenesis and risk factors" and "diagnosis" were the clustering centers of coronary slow flow, and the research hotspots gradually changed with time, from pathogenesis to treatment and prognosis. CONCLUSION: Future research will focus on the search for effective and non-invasive detection indicators and treatments of coronary slow flow. Collaboration needs to be enhanced between different institutions or countries/regions, which would improve clinical outcomes for patients with coronary slow flow.

Ligustrazine and liguzinediol protect against doxorubicin-induced cardiomyocytes injury by inhibiting mitochondrial apoptosis and autophagy.

Preventing or treating heart failure (HF) by blocking cardiomyocyte apoptosis is an effective strategy that improves survival and reduces ventricular remodelling and dysfunction in the chronic stage. Autophagy is a mechanism that degrades intracellular components and compensates for energy deficiency, which is commonly observed in cardiomyocytes of failed hearts. Cardiomyocytes activated by doxorubicin (DOX) exhibit strong autophagy. This study aims to investigate the potential protective effect of ligustrazine and its derivative liguzinediol on regulating DOX-induced cardiomyocyte apoptosis and explore the use of the embryonic rat heart-derived myoblast cell line H9C2 for identifying novel treatments for HF. The results indicated that it has been demonstrated to reverse myocardial infarction remodelling in failed hearts by promoting autophagy in salvaged cardiomyocytes and anti-apoptosis of cardiomyocytes in granulation tissue. Our study suggests that ligustrazine and liguzinediol can be a promising agents and autophagy is potential pathway in the management of HF.

Longitudinal surveillance of three biomarkers to predict recurrence of hepatocellular carcinoma after radical resection.

BACKGROUND: Radical resection is a curative treatment for patients with hepatocellular carcinoma (HCC), but the incidence of recurrence remains high. We aimed to explore the performance of predicting HCC recurrence by longitudinal surveillance of the protein induced by vitamin K absence (PIVKA-II), alpha- fetoprotein (AFP), and lectin-reactive AFP (AFP-L3) during postoperative follow-up. METHODS: Patients who underwent radical resection for HCC at the Ningbo Medical Centre Lihuili Hospital between January 2015 and December 2020 were included. All enrolled patients regularly monitor PIVKA-II, AFP, AFP-L3 every 3 months during postoperative follow-up. The surveillance performance of PIVKA-II, AFP, AFP-L3 during follow-up for the prediction of HCC recurrence was compared in patients. The generalized estimation equation (GEE) was used to analyze the trends of the tumor biomarkers and interactions with time. Area under the receiver operator characteristic (AUROC) curves, the optimal cut-off value, the sensitivity and specificity were calculated to evaluate the performance of the three biomarkers. The recurrence-free survival (RFS) and overall survival (OS) of patients with any of the elevated biomarkers was analyzed by Kaplan-Meier curves and the log-rank test. Multivariate logistic regression models were used to analyze potential risk factors for recurrence. RESULTS: The GEE analysis indicated that PIVKA-II, AFP, AFP-L3 in the recurrence patients were higher than the no recurrence patients during follow-up, PIVKA-II and AFP showed increasing trends from 6 months before recurrence. In predicting recurrence, the AUROCs for PIVKA-II, AFP, AFP-L3 and their combination were 0.885, 0.754, 0.781 and 0.885 respectively, the optimal cut-off value for PIVKA-II, AFP, AFP-L3 was 29.5 mAU/ml, 10.7 ng/L, 1.5% respectively. The sensitivity in predicting recurrence for PIVKA-II, AFP, AFP-L3 and combination were 75.0, 54.7, 57.8 and 79.7% respectively. The RFS and the OS of patients with any of the biomarkers elevated during the follow-up was significantly shorter than that without elevated biomarkers ( P  < 0.001). Multivariate analysis showed that any of the biomarkers elevated was the independent risk factor of recurrence. CONCLUSION: Longitudinal surveillance of PIVKA-II, AFP and AFP-L3 can effectively predict recurrence of HCC after operation.

Clinical features and relapse risks factors of IgG4 related disease: a single-center retrospective study.

OBJECTIVE: The aim of this study was to observe the demographic and clinical characteristics of immunoglobulin (Ig) G4-related disease (IgG4-RD). We aimed to compare different treatment methods and to identify the risk factors for non-response and relapse after treatment. METHODS: We performed a retrospective study of 201 IgG4-RD patients initially diagnosed and treated at the First Affiliated Hospital of China Medical University from January 2016 to December 2020. Patients' sex, age, clinical manifestations, baseline biochemical values, the number of organs involved, and the type of organ involvement were recorded. All patients received glucocorticoid (GC) monotherapy or GC + immunosuppressant combination therapy. The serum IgG4 concentration as well as the details of clinical response, relapse, and side effects were recorded at 1, 3, 6, and 12 months after treatment. RESULTS: The incidence of IgG4-RD was primarily centered in the age group of 50-70 years old, and the proportion of affected male patients increased with age. The most common clinical symptom was swollen glands or eyes (42.79%). The rates of single- and double-organ involvement were 34.83% and 46.27%, respectively. The pancreas (45.77%) was the most frequently involved organ in cases of single-organ involvement, and the pancreas and biliary tract (45.12%) was the most common organ combination in cases of double-organ involvement. Correlation analysis showed that the number of organs involved was positively related to the serum IgG4 concentration (r = 0.161). The effective rate of GC monotherapy was 91.82%, the recurrence rate was 31.46%, and the incidence of adverse reactions was 36.77%. Meanwhile, the effective rate of GC + immunosuppressant combination therapy was 88.52%, the recurrence rate was 19.61%, and the adverse reaction rate was 41.00%. There were no statistically significant differences in response, recurrence, and adverse reactions. The overall response rate within 12 months was 90.64%. Age (< 50 years old) and aorta involvement were significantly associated with non-response. The overall recurrence rate within 12 months was 26.90%. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement were significantly associated with recurrence. CONCLUSION: The clinical features vary among different age groups and according to gender. The number of organs involved in IgG4-RD is related to the serum IgG4 concentration. Age (< 50 years old), low serum C4 concentration, a high number of involved organs, and lymph node involvement are risk factors for recurrence.