Objective:To investigate the association between fibroblast growth factor 21(FGF21)and chronic kidney disease(CKD)in a prediabetic population by conducting a 4-year prospective cohort study among community-dwelling residents aged≥40 years in Guangzhou,China.Methods:A total of 1505 subjects who met the criteria for prediabetes and had complete baseline data were col-lected from the 2012 REACTION cohort,and they were followed up for 4 years to observe newly-onset CKD and the changes in urinary albumin-to-creatinine ratio(UACR)and estimated glomerular filtration rate(eGFR).Results:Among the 1 505 subjects with predia-betes,142 reached the diagnostic criteria for CKD during follow-up,yielding an overall incidence rate of 9.43%(95%CI=7.895%-10.902%).According to baseline serum FGF21 level,the subjects were divided into Q1-Q4 groups,with the lowest level of FGF21 in the Q1 group,and the Q4 group had a significantly higher eGFR than the other groups(P<0.05).After a mean follow-up time of 4 years,UACR was increased by 0.87 mg/g(P<0.001)and eGFR was reduced by 4.8 mL/(min·1.73 m2)(P<0.001).After stratification by FGF21 quartiles,there were differences in the declines of eGFR across groups,with the lowest degree of reduction in the Q2 group.In the multivariate regression model,the serum level of FGF21 was significantly negatively associated with the onset of CKD.When FGF21 was analyzed as a continuous variable in the multivariate lo-gistic regression analysis,FGF21 was still significantly negatively associated with the risk of CKD,which was consistent with the re-sults of the quartile-based analysis.However,restricted cubic spline curves showed an L-shaped non-linear relationship between FGF21 level and the risk of CKD,i.e.,the incidence rate of CKD de-creased with the increase in FGF21 level,but when FGF21 level reached a certain threshold,the risk of CKD no longer changed with FGF21.The linear regression analysis showed that FGF21 was positively associated with UACR and eGFR.Conclusion:In this pro-spective cohort study,FGF21 level might be potentially associated with the future risk of CKD among adults with prediabetes,while fur-ther studies are needed to clarify related mechanisms and clinical value.

Microvascular invasion is one of the critical factors influencing the prognosis of patients with hepatocellular carcinoma.Accurate preoperative prediction for its occurrence holds pivotal significance for the formulation of clinical individualized treatment decisions.Traditional diagnosis primarily relies on the evaluation of postoperative histopathological results,which exhibits a certain degree of lag.However,the emergence of radiomics features and biomarkers offers new insights for the preoperative prediction of mi-crovascular invasion.The preoperative prediction model based on radiomics and biomarkers is capable of precisely analyzing and efficiently predicting the occurrence risk of microvascular invasion from both macro-scopic imaging features and microscopic molecular levels,thereby providing multi-dimensional and precise scientific evidence for clinical decision-making.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective:To investigate the efficacy and safety of dupilumab in the treatment of elderly patients (≥ 60 years old) with atopic dermatitis (AD), with particular attention paid to rare adverse reactions.Methods:A single-center retrospective analysis was conducted on data collected from 281 elderly AD patients who received the standard regimen of dupilumab at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to May 2024. Clinical characteristics such as gender, disease duration, skin lesion manifestations, and itch severity were analyzed. Changes in skin lesions and itch severity, as well as related adverse events were recorded during the follow-up period of 0 - 16 weeks. The efficacy and safety of dupilumab in the treatment of elderly AD patients were evaluated.Results:Among the 281 elderly AD patients, 214 were males (76.16%) and 67 were females (23.84%), with the age being 71.13 ± 7.91 years and the age at onset being 59.92 ± 15.72 years. The disease duration ( M[ IQR]) was 5.00 (13.00) years. After standard-regimen dupilumab treatment, the improvement rates of clinical outcome indicators SCORing Atopic Dermatitis (SCORAD) and pruritus numerical rating scale (NRS) scores gradually increased. At week 16, the improvement rates of SCORAD and NRS scores ( M[ IQR]) reached the maxima of 72.37% (23.89%) and 75.00% (29.72%), respectively. The overall incidence of adverse events was relatively low, with only 16 patients (6.05%) reporting adverse events. Common adverse reactions such as conjunctivitis (2 cases, 0.71%) and facial erythema (1 case, 0.36%) were mild and well-tolerated. Phenotype switching occurred in 10 cases (3.56%) . Conclusion:Dupilumab was an effective and safe treatment for elderly AD, but phenotype switching may occur.

Long non-coding RNA myocardial infarction related transcript(MIAT)is a widely studied lncRNAs,which is closely related to the occurrence and development of many diseases.MIAT is associated with inflammatory responses in a variety of dis-eases through further exploring,including diabetes and its complications,cardiovascular and osteoarticular diseases.However,sys-tematic knowledge of the relationship between MIAT molecules and inflammation in diseases remains unclear.This article will focus on the relationship between MIAT and inflammation in various systemic diseases,especially its role,mechanism and potential clinical ap-plication as a biomarker and therapeutic target of disease inflammation,in order to provide molecular strategies for diagnosis and treat-ment of the inflammatory diseases.

Objective:To investigate the efficacy and safety of dupilumab in the treatment of elderly patients (≥ 60 years old) with atopic dermatitis (AD), with particular attention paid to rare adverse reactions.Methods:A single-center retrospective analysis was conducted on data collected from 281 elderly AD patients who received the standard regimen of dupilumab at the Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2020 to May 2024. Clinical characteristics such as gender, disease duration, skin lesion manifestations, and itch severity were analyzed. Changes in skin lesions and itch severity, as well as related adverse events were recorded during the follow-up period of 0 - 16 weeks. The efficacy and safety of dupilumab in the treatment of elderly AD patients were evaluated.Results:Among the 281 elderly AD patients, 214 were males (76.16%) and 67 were females (23.84%), with the age being 71.13 ± 7.91 years and the age at onset being 59.92 ± 15.72 years. The disease duration ( M[ IQR]) was 5.00 (13.00) years. After standard-regimen dupilumab treatment, the improvement rates of clinical outcome indicators SCORing Atopic Dermatitis (SCORAD) and pruritus numerical rating scale (NRS) scores gradually increased. At week 16, the improvement rates of SCORAD and NRS scores ( M[ IQR]) reached the maxima of 72.37% (23.89%) and 75.00% (29.72%), respectively. The overall incidence of adverse events was relatively low, with only 16 patients (6.05%) reporting adverse events. Common adverse reactions such as conjunctivitis (2 cases, 0.71%) and facial erythema (1 case, 0.36%) were mild and well-tolerated. Phenotype switching occurred in 10 cases (3.56%) . Conclusion:Dupilumab was an effective and safe treatment for elderly AD, but phenotype switching may occur.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Microvascular invasion is one of the critical factors influencing the prognosis of patients with hepatocellular carcinoma.Accurate preoperative prediction for its occurrence holds pivotal significance for the formulation of clinical individualized treatment decisions.Traditional diagnosis primarily relies on the evaluation of postoperative histopathological results,which exhibits a certain degree of lag.However,the emergence of radiomics features and biomarkers offers new insights for the preoperative prediction of mi-crovascular invasion.The preoperative prediction model based on radiomics and biomarkers is capable of precisely analyzing and efficiently predicting the occurrence risk of microvascular invasion from both macro-scopic imaging features and microscopic molecular levels,thereby providing multi-dimensional and precise scientific evidence for clinical decision-making.

Long non-coding RNA myocardial infarction related transcript(MIAT)is a widely studied lncRNAs,which is closely related to the occurrence and development of many diseases.MIAT is associated with inflammatory responses in a variety of dis-eases through further exploring,including diabetes and its complications,cardiovascular and osteoarticular diseases.However,sys-tematic knowledge of the relationship between MIAT molecules and inflammation in diseases remains unclear.This article will focus on the relationship between MIAT and inflammation in various systemic diseases,especially its role,mechanism and potential clinical ap-plication as a biomarker and therapeutic target of disease inflammation,in order to provide molecular strategies for diagnosis and treat-ment of the inflammatory diseases.

Objective To investigate the effects and mechanisms of modified Taohong Siwu Decoction on myocardial ischemia-reperfusion injury in rats based on transcriptome sequencing.Methods Totally 15 SPF rats were randomly divided into sham-operation group,model group and modified Taohong Siwu Decoction group,with 5 rats in each group.The modified Taohong Siwu Decoction group was pre-administered with modified Taohong Siwu Decoction by gavage for 5 days,while the sham-operation group and model group were given equal volume of distilled water by gavage,myocardial ischemia-reperfusion injury rat model was established.The cardiac function of the rats was assessed using echocardiography,serum oxidative stress and inflammatory factor contents were detected using reagent kits,TUNEL staining was used to detect myocardial cell apoptosis,transcriptome sequencing was performed on myocardial tissue,and differential expression genes were analyzed using Venn diagram and heatmap.GO and KEGG pathway enrichment analysis were performed on common differentially expressed genes.RT-qPCR was used to validate differentially expressed genes PTX3 and EGR2.Results Compared with the sham-operation group,the EF and FS of the model group rats significantly decreased(P<0.01),the cells apoptosis rate of myocardial tissue and serum LDH,TNF-α,IL-1β and IL-6 contents significantly increased(P<0.01),and SOD activity and IL-10 content significantly decreased(P<0.01).Compared with the model group,the modified Taohong Siwu Decoction group showed a significant increase in EF and FS(P<0.05),while the cell apoptosis rate of myocardial tissue and serum CK-MB,LDH,TNF-α,IL-1β and IL-6 contents significantly decreased(P<0.01),and SOD activity and IL-10 content significantly increased(P<0.01).Transcriptome sequencing revealed 4 227 differentially expressed genes(2 259 upregulated and 1 968 downregulated)between the sham-operation group and the model group,1 933 differentially expressed genes(1 301 upregulated and 632 downregulated)between the sham-operation group and the modified Taohong Siwu Decoction group,and 94 differentially expressed genes(46 upregulated and 48 downregulated)between the model group and the modified Taohong Siwu Decoction group.There were 35 common differential genes in the three groups,and the differential genes were mainly enriched in signaling pathways such as fluid shear stress and atherosclerosis,ubiquitin mediated proteolysis,C-type lectin receptor signaling pathway,sphingolipid signaling pathway,cell cycle,chemokine signaling pathway,lipid and atherosclerosis.RT-qPCR showed that gene expressions of PTX3 and EGR2 in myocardial tissue of the model group were significantly increased than that of the sham-operation group,and the gene expressions of PTX2 and EGR2 of modified Taohong Siwu Decoction group were significantly decreased than that of the model group(P<0.01).Conclusion Modified Taohong Siwu Decoction exhibits a certain protective effect against myocardial ischemia-reperfusion injury in rats,characterized by improvements in rat cardiac function,reduction in cell apoptosis and inflammatory cytokine release,as well as alleviation of oxidative stress levels.The mechanism may be related to the regulation of PTX3 and EGR2 gene expression.