Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.
Humans ; Immunoglobulin G4-Related Disease/metabolism* ; Immunoglobulin G/metabolism* ; Machine Learning ; Animals ; Proteomics/methods*

BACKGROUND: Despite some studies identifying a potential association between obesity and chronic obstructive pulmonary disease (COPD) risk, previous research had overlooked the dynamic nature of body weight over time, leading to inconsistent findings. The purpose of this study is to elucidate the relationship between adult weight change and COPD risk by adjusting for potential confounding factors. METHODS: We conducted a retrospective analysis using data from ten NHANES cycles (1999-2018), including adults aged 40-74 years. Weight change patterns were assessed using BMI at three time points and classified into five categories per period. Absolute weight change was also grouped into five levels. Multivariate logistic regression models, incorporating sampling weights, were used to examine associations between weight change and COPD, adjusting for demographic and lifestyle covariates. RESULTS: Compared with participants who maintained normal weight, stable obesity participants had increased risk of COPD from age 25 years to 10 years before the survey (OR = 1.45, 95% CI = 1.15 to 1.83), in the 10 years period before the survey (OR = 1.75, 95% CI = 1.47 to 2.08), and from age 25 years to survey (OR = 1.84, 95% CI = 1.46 to 2.31). Three periods indicate that weight gain in adulthood was associated with risk of COPD. In addition, substantial weight gain of more than 20 kg was associated with a higher risk of COPD. In stratified analyses, we also observed a more significant association between weight change and the risk of COPD in never smokers compared to former smokers. CONCLUSIONS Our study suggested that stable obesity and weight gain in adulthood were associated with an increased risk of COPD compared to those who maintain a normal weight, and that the association between weight gain and the incidence of COPD appears closer in patients who have never smoked.
Humans ; Pulmonary Disease, Chronic Obstructive/etiology* ; Middle Aged ; Male ; Female ; Adult ; Aged ; Retrospective Studies ; Weight Gain ; Obesity/complications* ; Risk Factors ; United States/epidemiology* ; Nutrition Surveys ; Body Mass Index

Objective To observe the effects of Yixintai on lipid metabolism and the protein expressions of CPT-1 and CD36 in rats with heart failure;To explore the mechanism of its treatment of heart failure.Methods 106 out of 120 SD rats were selected to establish the heart failure model induced by myocardial infarction by ligating the left anterior descending coronary artery,and 14 rats were selected as the sham-operation group.The successful model rats were randomly divided into model group,trimetazidine group and Yixintai low-,medium-and high-dosage groups,with 14 rats in each group.The administration group was given corresponding drugs by gavage once a day for 4 weeks.LVEF,LVFS,LVIDd and LVIDs were measured by color doppler ultrasonography,the contents of ANP,BNP,LA and FFA in serum were detected by ELISA,the contents of TG,TC,LDL and HDL were detected by automatic biochemical analyzer,HE and Masson staining were used to observe the morphology of myocardial tissue,the expressions of CPT-1 and CD36 protein in myocardial tissue were detected by Western blot.Results Compared with the sham-operation group,LVEF and LVFS in the model group decreased(P<0.05),the LVIDs and LVIDd increased(P<0.05);the contents of serum ANP,BNP,LA,FFA,TG,TC and LDL increased(P<0.05),while the content of HDL decreased(P<0.05),with myocardial edema,irregular arrangement of myocardial fibers,increased inflammatory cell infiltration and collagen fiber deposition;the protein expressions of CPT-1 and CD36 in myocardial tissue decreased(P<0.05).Compared with the model group,the LVEF and LVFS in Yixintai each dosage groups and trimetazidine group increased(P<0.05),LVIDs and LVIDd decreased(P<0.05);the contents of ANP,BNP,LA,FFA,TG,TC and LDL in serum of Yixintai medium-and high-dosage groups and trimetazidine group decreased(P<0.05),the content of HDL increased(P<0.05);myocardial edema was improved,inflammatory cell infiltration was reduced,collagen fiber deposition was reduced,and the protein expressions of CPT-1 and CD36 in myocardial tissue increased(P<0.05).Conclusion Yixintai may improve myocardial energy metabolism and treat heart failure by increasing the expression of CPT-1 and CD36 protein in myocardial tissue and promoting fatty acid β oxidation.

This study retrospectively analyzed 12 patients with transfusion-dependent, non-severe aplastic anemia (TD-NSAA) refractory to cyclosporine A (CsA) , who were treated with lusutrombopag monotherapy. These patients either had a variety of chronic comorbidities or medication-related risks, or they were unresponsive to or intolerant of other thrombopoietin receptor agonists (TPO-RA) . The median treatment duration with lusutrombopag was 4 months (range: 3-11 months) , while the median follow-up period was 8 months (range: 6-11 months) . The overall response (OR) rates at months 3, 6, and the end of follow-up were 50.0%, 58.3%, and 50.0%, respectively, with a median time to OR of 2 months (range: 1-4 months) . Complete response (CR) rates were 8.3%, 16.7%, and 16.7% at the same time points, with a median time to CR of 4 months (range: 2-5 months) . Adverse events were all Grade 1, with an incidence rate of 25.0%. During follow-up, one patient experienced a loss of OR after discontinuing treatment, with a relapse rate of 14.3%; no clonal evolution or mortality was observed. These findings suggest that lusutrombopag is both effective and well-tolerated in CsA-refractory TD-NSAA patients and represents a promising therapeutic option for those with poor treatment tolerability.

Objective:To investigate the clinical characteristics and hormonal changes in patients with adrenocorticotropic hormone(ACTH)-suppressed and non-suppressed subclinical Cushing′s syndrome(SCS), to evaluate the influencing factors of ACTH suppression, and to assess the diagnostic efficiency of serum dehydroepiandrosterone sulfate(DHEAS) levels in distinguishing these two groups of SCS patients.Methods:Clinical data of patients diagnosed with SCS in the Department of Endocrinology, Drum Tower Hospital Affiliated to Nanjing University Medical College, between June 2014 and October 2023 were retrospectively collected. A total of 194 cases were included. According to morning(8: 00 AM) plasma ACTH levels, patients were divided into an ACTH-suppressed group(ACTH<2.2 pmol/L) and a non-suppressed group(ACTH≥2.2 pmol/L). Additionally, 194 gender-, age-, and BMI-matched patients with non-functional adrenal tumors(NFA) were enrolled as controls. Clinical characteristics and hormone levels were compared between groups. Logistic regression analysis was performed to identify factors influencing ACTH suppression in SCS patients. Furthermore, receiver operating characteristic(ROC) curve analysis was conducted to evaluate the diagnostic performance of serum DHEAS levels in distinguishing ACTH-suppressed and non-suppressed SCS patients. Results:There were no significant differences in the prevalence of overweight/obesity, hypertension, abnormal glucose metabolism, or bone metabolism disorders between the ACTH-suppressed and non-suppressed groups. The serum cortisol level after the 1 mg-dexamethasone suppression test(DST) was significantly lower in the ACTH non-suppressed group than that in the suppressed group, while the serum DHEAS level was significantly higher in the non-suppressed group(both P<0.01). The area under the curve(AUCs) of serum DHEAS for diagnosing ACTH non-suppressed SCS patients and ACTH-suppressed SCS patients was 0.779(95% CI 0.721-0.837) and 0.874(95% CI 0.831-0.918), respectively. Using a serum DHEAS cutoff of 60.0 μg/dL, the sensitivity and specificity for diagnosing ACTH non-suppressed SCS patients were 66.7% and 76.1%, respectively, while for ACTH-suppressed SCS patients, the sensitivity and specificity were 84.9% and 75.5%, respectively. Conclusion:There were no significant differences in metabolic characteristics between ACTH-suppressed and non-suppressed SCS patients. Serum cortisol level after 1 mg-DST is an independent influencing factor for ACTH suppression status. Low serum DHEAS level serves as a sensitive diagnostic marker for SCS and also demonstrates diagnostic value in ACTH non-suppressed SCS patients.

Objective:To investigate the correlation between serum growth differentiation factor 15 (GDF15) and the clinicopathological characteristics of patients with IgA nephropathy (IgAN), and further explore the relationship of GDF15 with the cardiac and renal prognosis of IgAN patients.Methods:It was a single-center retrospective cohort study. From January 2018 to December 2022, the relevant data were collected from patients who were diagnosed with primary IgAN at the Department of Nephrology, Beijing Anzhen Hospital Affiliated to Capital Medical University, and regularly followed up for at least 1 year. Serum samples were collected at admission and the baseline level of serum GDF15 was measured. Based on the median GDF15 level, IgAN patients were categorized into high-level GDF15 group and low-level GDF15 group, and their clinicopathological characteristics were compared. A multiple linear regression model was then constructed to identify independent factors associated with serum GDF15 level based on these comparisons. Subsequently, Kaplan-Meier survival analysis was performed to investigate the association between serum GDF15 level and the cardiorenal prognosis of IgAN patients.Results:A total of 104 IgAN patients were included in this study. The serum GDF15 level in these IgAN patients was 825.60 (556.84, 1 428.15) ng/L. Serum GDF15 level was positively correlated with 24 h urinary protein ( r=0.405, P<0.001), negatively correlated with estimated glomerular filtration rate (eGFR)( r=-0.606, P<0.001). The serum levels of GDF15 in patients with tubular atrophy or interstitial fibrosis (overall comparison among T0, T1, and T2, H=21.866, P<0.001), crescentic lesions (overall comparison among C0, C1, and C2, H=13.787, P=0.001), or intrarenal arteriolar lesions (overall comparison among none, mild, and moderate-to-severe, H=9.856, P=0.007) were significantly different. Compared with IgAN patients without tubular atrophy or interstitial fibrosis, those with Oxford classification T1 ( Z=-17.326, P=0.042) or T2 ( Z=-42.933, P<0.001) had higher serum GDF15 levels. Compared with IgAN patients without crescentic lesions, those with Oxford classification C2 had higher serum GDF15 levels ( Z=-45.929, P=0.001). Compared with IgAN patients without intrarenal arteriolar lesions, those with moderate-to-severe arteriolar sclerosis had higher serum GDF15 levels ( Z=-26.686, P=0.005). The median GDF15 was used as the cut-off value to divide IgAN patients into a high-level GDF15 group (≥825.60 ng/L, n=52) and a low-level GDF15 group (<825.60 ng/L, n=52). Compared to low-level GDF15 group, IgAN patients in high-level GDF15 group presented with a higher proportion of diabetes mellitus ( χ 2=9.420, P=0.002) and cardiovascular disease ( χ 2=7.792, P=0.005), a higher level of systolic blood pressure ( Z=-2.266, P=0.023), body mass index ( Z=-2.183, P=0.031), 24 h urinary protein ( Z=-3.485, P<0.001), blood total cholesterol ( Z=-2.002, P=0.045) and left ventricular mass index ( Z=-2.649, P=0.008), and a lower level of blood albumin ( Z=-3.053, P=0.002) and eGFR ( Z=6.480, P<0.001). Multiple linear regression analysis showed that serum GDF15 level was independently associated with systolic blood pressure (regression coefficient B=29.453, 95% CI 14.139–44.767, P<0.001), blood albumin ( B=-81.412, 95% CI -113.084–-49.740, P<0.001) and eGFR ( B=-9.797, 95% CI -17.554–-2.040, P=0.014). Moreover, IgAN patients in high-level GDF15 group exhibited significantly poorer cardiac and renal prognosis compared to low-level GDF15 group ( χ 2=9.955, P=0.002). Conclusion:High serum GDF15 level correlates with disease severity in IgAN, and high serum GDF15 level may suggest a poorer cardiorenal prognosis in IgAN patients.

BACKGROUND:Poly(lactic-co-glycolic acid)copolymer with good biosafety,biodegradability,and superior mechanical properties has become a focal point of research in stomatology.OBJECTIVE:To review the advance in stomatology of poly(lactic-co-glycolic acid)copolymer.METHODS:Using a computer-assisted search of relevant literature published in the China National Knowledge Infrastructure(CNKI)and PubMed databases,the search terms included"polylactic acid-hydroxyacetic acid,PLGA,oral defect,tissue engineering"in Chinese,and"PLGA,polylactic acid-hydroxyacetic acid copolymer,poly(lactic-co-glycolic acid)copolymer,dent*,regeneration,caries,periodontal,pulp,implant,alveolar bone"in English.Preliminary screening was conducted by reading titles and abstracts,excluding literature unrelated to the theme of the article.Based on the inclusion and exclusion criteria,a total of 119 articles were included for review.RESULTS AND CONCLUSION:In the field of stomatology,the application scope of poly(lactic-co-glycolic acid)copolymer is rapidly expanding,gradually replacing the traditional therapeutic drugs and restorative materials.Poly(lactic-co-glycolic acid)copolymer nanoparticles/microspheres can carry a variety of hydrophobic and hydrophilic active substances,demonstrating excellent delivery capabilities in caries prevention,root canal disinfection,and pulp capping treatment.In periodontal therapy,poly(lactic-co-glycolic acid)copolymer is widely used as a barrier membrane and drug carrier for periodontal tissue regeneration.Poly(lactic-co-glycolic acid)copolymer used for surface modification of implants not only enhances the antibacterial ability of the implant surface but also improves the bio-inert nature of the implant surface.The effect of pure poly(lactic-co-glycolic acid)copolymer scaffolds on treating bone defects is limited and requires the integration of 3D printing,various bioactive components,and inorganic materials to enhance scaffold performance.The combination of poly(lactic-co-glycolic acid)copolymer and stem cells can improve the effectiveness of nerve therapy,meeting clinical needs.Based on the great potential of poly(lactic-co-glycolic acid)copolymer in the field of stomatology,it is expected that in the future,repair materials with specific functions for different diseases will be produced according to different needs of oral tissue engineering.

OBJECTIVE:Nowadays,machine learning algorithms are gradually being applied to predict stroke and cardiovascular disease.Compared with traditional regression models,machine learning can learn from data to achieve high prediction accuracy by exploring the flexible relationship between a large number of predictive features and outcome variables,providing a new method for the formulation of individualized treatment and rehabilitation programs.This study aims to systematically evaluate stroke functional recovery and prognosis prediction models based on machine learning,comprehensively assessing their predictive performance and clinical application potential to provide references for the development,application,and promotion of related predictive models.METHODS:This review was conducted following the PRISMA(Preferred Reporting Items for Systematic Reviews and Meta-Analyses)guidelines.Relevant literature on stroke prognosis prediction using machine learning methods was selected by searching PubMed,EMbase,Web of Science Core Collection,CNKI,WanFang,and the China Biomedical Literature Database,with the search period from January 1,2014,to July 1,2024.Two researchers independently screened the literature and extracted data based on inclusion and exclusion criteria,using the Prediction model Risk Of Bias ASsessment Tool(PROBAST)to assess model quality.RESULTS:(1)A total of 3 126 articles were obtained in the preliminary search.After screening and exclusion,18 articles were finally included.150 prediction models were constructed using 13 machine learning methods.The three most frequently used methods are Logistic Regression,Random Forest,and Extreme Gradient Boosting(XGBoost).Only one study was externally validated.Eight studies reported how the missing data were handled.(2)In terms of outcome indicators,8 studies used the combination of clinical data and imaging data to build models,9 studies only used clinical data to build models,and 1 study only used imaging data to build models.(3)Each of the 18 studies gave the most important characteristics of the study,with the most mentioned being the National Institute of Health Stroke Scale and age.All studies reported area under curve values ranging from 0.74 to 0.96,with the highest area under curve being 0.96.The overall risk of bias in all models was high.The high risk of bias in the field of model analysis was the main reason for the high risk of overall bias in all models.(4)The results of meta-analysis showed that age and National Institute of Health Stroke Scale score had significant influence on stroke prognosis,with age[MD=8.49,95％CI(6.24,10.75),P＜0.01]and National Institute of Health Stroke Scale score[MD=4.78,95％CI(2.56,7.00),P＜0.01].CONCLUSION:This study systematically evaluated the predictive model of functional recovery and prognosis of stroke based on machine learning,and all the models have good predictive potential.However,future studies should increase the sample size of the included model,adopt prospective studies,and add external validation of the model to improve the stability and prediction accuracy of the model,control the risk of bias,and contribute to the validation and promotion of the model in practical clinical applications.At the same time,the interpolation of missing values is more transparent and accurate.Although existing machine learning models show good predictive performance,it is also important to focus on the functionality and usability of the model,and the inclusion of features will reduce ease of use.We should develop easy to use model interfaces and user-friendly clinical tools to enable medical staff to better apply the model for clinical decision.

The peripheral blood of healthy or ketosis dairy cows was collected,and CD4+T cells were isolated.The expressions of lipid synthesis related proteins fatty acid synthase(FASN),acetyl coenzyme A carboxylase 1(ACC1),cluster of differentiation 36(CD36)and store-operated calcium entry(SOCE)related proteins ORAIl,ORAI2,ORAI3,STIM1,STIM2 were detected by Western blot.IL-17 cells were detected by flow cytometry.CD4+T cells were isolated from the spleen of 1-day-old calves and cultured in vitro.Cells were treated and divided into control(Ctrl)group,si-lenced CD36(siCD36)group,stearic acid(SA)group,and SA+siCD36 group.Cells in the Ctrl and SA groups were transfected with 75 pmol/L negative control siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h;Cells in the siCD36 group and SA+siCD36 group were transfected with 75 pmol/L CD36 siRNA for 48 h,and then stimulated with 200 μmol/L SA for 24 h in the SA+siCD36 group.The protein expression of FASN,CD36,ACC1,ORAI1,ORAI2,ORAI3,STIM1 and STIM2 was detected by Western blot,and IL-17 cells were detected by flow cytometry.The results showed that the expression of IL-17 in peripheral blood CD4+T cells of ketosis dairy cows was significantly increased compared to that of healthy cows(P＜0.01).Additionally,the protein level of FASN,CD36,STIM1(P＜0.05),and ACC1,ORAI2,ORAI3,STIM2(P＜0.01)were up-regulated.Compared with the Ctrl group,the protein expression levels of CD36,ACC1 and ORAI3(P＜0.05)were up-regulated in the SA group,as well as the protein expression of FASN and STIM1(P＜0.01).Additionally,the expression of IL-17 was significantly increased(P＜0.05).Compared with the SA group,there was a decrease in the protein expression of STIM1,ORAI1(P＜0.05)and CD36,ACC1,FASN,ORAI2(P＜0.01)in the siCD36+SA group,as well as IL-17(P＜0.05).These results suggest that SA can promote the expression of IL-17 in CD4+T cells in ketosis cows by regulating fatty acid synthesis and activating SOCE channels through CD36.

Guided by Zhang Zhongjing's axiom that"blood stasis induces water",this study develops stage-specific treatment strategies for edema in Kidney Consumption Disorder by examining its four-stage pathogenic progression:Sluggish Flow → Stagnant Obstruction → Depressed Accumulation → Stasis Congelation.We propose an integrated approach that reinforces the root by warming the kidney and replenishing essence,while addressing the branch by activating blood circulation and promoting diuresis.Stage-specific interventions include:for the Sluggish Flow Phase,warming and tonifying kidney Yang combined with unblocking Yang to promote uri-nation;for the Stagnant Obstruction Phase,warming the kidney and replenishing essence supported by activating blood circulation and freeing the collateral channels;for the Depressed Accumulation Phase,quickening blood and resolving stasis,regulating Qi and trans-forming turbidity,along with warming the kidney and strengthening essence;and for the Stasis Congelation Phase,expelling stagnant accumulations while simultaneously regulating essence and blood.This framework advances novel pattern-determined strategies for Kid-ney Consumption edema management.