[Purpose]To analyze the changes in the incidence trend of thyroid cancer from 1990 to 2021,and to predict the future incidence from 2022 to 2030.[Methods]We collected data related to the incidence of thyroid cancer among Chinese residents from 1990 to 2021 in the Global Bur-den of Disease 2021(GBD 2021)study,analyzed the trend of thyroid cancer incidence using the Joinpoint regression model,and constructed a Bayesian age-period-cohort(BAPC)model to pre-dict the future incidence of thyroid cancer during the years of 2022-2030,based on the inci-dence data during the years of 1990-2021.[Results]From 1990 to 2021,the age-standardized incidence rate(ASIR)of thyroid cancer in China showed a fluctuating upward trend,and the ASIR of thyroid cancer in China in 2021 was 2.47/105,slightly lower than the global average(2.91/105)in the same year.In 2021,there were significant differences in new cases and incidence rate of thyroid cancer between men and women,with the incidence rate of women being higher than that of men.Among them,the number of new cases in women was 27 915,the crude incidence rate was 4.02/105,and the ASIR was 2.87/105;in men,the number of new cases was 20 189,the crude incidence rate was 2.77/105,and the ASIR was 2.11/105.Between 1990 and 2021,the increase in the number of new cases,the crude incidence rate,and the ASIR of men in China was much larger than that of women.The ASIR of thyroid cancer in both male and female showed an in-creasing trend,while the average annual percentage change(AAPC)in female was lower than that in male.There were significant gender differences in the age-specific incidence rates of thyroid cancer.In 2021,the incidence rate of women was higher than that of men in the Chinese population＜75 years old,whereas the incidence rate of men was higher than that of women in the population≥75 years old.From 1990 to 2021,the incidence rates of the Chinese male population aged 45～59 years old and ≥75 years old increased significantly;and the incidence rate of the Chinese fe-male popu-lation aged 50～74 years old increased significantly.Projections showed that the ASIR of overall,male and female standardized incidence rates in 2030 increased to 2.90/105,2.44/105 and 3.26/105 respectively.[Conclusion]The incidence rate of thyroid cancer in China is on the rise,with the incidence rate of women being higher than that of men,but the incidence rate of men has increased more than that of women,and the gap between the incidence rates is narrow-ing,and the peak age of incidence of men is mostly in the senior age group.

Objective To investigate the interaction between a novel antimicrobial compound,HL-J6,and penicillin-binding protein 1(PBP1)of Staphylococcus aureus.Methods With MRSA252 genomic DNA as the template and PBP1F and PBP1R as primers,the expression plasmid pET30a-pbp1-39-608 was constructed by amplifying the target gene fragment followed by cloning into the Nde I/Xho I restriction sites of the pET30a vector.Then the obtained plasmids were transformed into Escherichia coli for the expression of PBP1-39-608 protein,and the product was purified by affinity chromatography.The inhibitory effect of HL-J6 on the transpeptidase activity of PBP1-39-608 was measured using peptidoglycan side chain backbone peptide,with thiol ester analog S2d as the substrate.The affinity between HL-J6 and PBP1-39-608 was detected using microscale thermophoresis(MST),and the binding interaction was confirmed by cellular thermal shift assay(CETSA).Molecular docking and dynamics simulation were performed using AutoDock Vina and Desmond software,respectively,to elucidate the binding mode of HL-J6 with the PBP1-39-608 protein and the key amino acid residues involved.Results The recombinant plasmid pET30a-pbp1-39-608 was successfully constructed,and PBP1-39-608 protein was produced after induction and purified,yielding a protein with an approximate molecular mass of 65×103.HL-J6 inhibited the transpeptidase activity of PBP1-39-608 in a time-dependent manner(P<0.001).The dissociation constant Kd of the binding between HL-J6 and PBP1-39-608 was 64.92 μmol/L.Molecular docking results showed that HL-J6 bound to the active pocket of PBP1-39-608 by interacting with key residues such as ILE-348,ASN-370,THR-516 and PHE-423,with a binding score of-8.38 kcal/mol(<-5.00 kcal/mol).Dynamics simulation results indicated that the complex became stable after 50 ns.Conclusion HL-J6 effectively inhibits the transpeptidase activity of Staphylococcus aureus PBP1,and shows stable interaction with the protein.

Objective: To construct a Family with sequence similarity 50 member A(FAM50A) gene knockout mouse insulinoma pancreatic β-cell line Beta-TC-6 using CRISPR/Cas9 gene editing technology and to prepare polyclonal antibodies specifically recognizing FAM50A. Methods: Two guide RNAs(sgRNAs) targeting the FAM50A gene were designed,and a recombinant plasmid expressing blue fluorescent protein(BFP) was constructed for gene knockout.The successfully constructed plasmid was transfected into Beta-TC-6 cells,and BFP-positive single cells were isolated for clonal expansion.The expanded monoclonal cell lines were genotyped by Sanger sequencing,and FAM50A protein expression was assessed by Western blot.Purified human recombinant FAM50A protein was used to immunize New Zealand rabbits for the preparation of a polyclonal antibody.The specificity of the prepared antibody was then validated using the successfully established FAM50A knockout cell line. Results: A monoclonal cell line with a successful knockout of the FAM50A gene was identified.Sanger sequencing confirmed base deletions at the target site.Western blot analysis showed a complete absence of FAM50A protein expression in this cell line.The prepared polyclonal antibody successfully recognized endogenous murine FAM50A protein in wild-type Beta-TC-6 cells and in hTERT-RPE1 cells overexpressing human FAM50A-GFP fusion protein,while no signal was detected in the FAM50A knockout cells. Conclusion This study successfully established a FAM50A gene knockout Beta-TC-6 cell model and generated a FAM50A polyclonal antibody,providing powerful tools for future research.

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

[Purpose]To analyze the changes in the incidence trend of thyroid cancer from 1990 to 2021,and to predict the future incidence from 2022 to 2030.[Methods]We collected data related to the incidence of thyroid cancer among Chinese residents from 1990 to 2021 in the Global Bur-den of Disease 2021(GBD 2021)study,analyzed the trend of thyroid cancer incidence using the Joinpoint regression model,and constructed a Bayesian age-period-cohort(BAPC)model to pre-dict the future incidence of thyroid cancer during the years of 2022-2030,based on the inci-dence data during the years of 1990-2021.[Results]From 1990 to 2021,the age-standardized incidence rate(ASIR)of thyroid cancer in China showed a fluctuating upward trend,and the ASIR of thyroid cancer in China in 2021 was 2.47/105,slightly lower than the global average(2.91/105)in the same year.In 2021,there were significant differences in new cases and incidence rate of thyroid cancer between men and women,with the incidence rate of women being higher than that of men.Among them,the number of new cases in women was 27 915,the crude incidence rate was 4.02/105,and the ASIR was 2.87/105;in men,the number of new cases was 20 189,the crude incidence rate was 2.77/105,and the ASIR was 2.11/105.Between 1990 and 2021,the increase in the number of new cases,the crude incidence rate,and the ASIR of men in China was much larger than that of women.The ASIR of thyroid cancer in both male and female showed an in-creasing trend,while the average annual percentage change(AAPC)in female was lower than that in male.There were significant gender differences in the age-specific incidence rates of thyroid cancer.In 2021,the incidence rate of women was higher than that of men in the Chinese population＜75 years old,whereas the incidence rate of men was higher than that of women in the population≥75 years old.From 1990 to 2021,the incidence rates of the Chinese male population aged 45～59 years old and ≥75 years old increased significantly;and the incidence rate of the Chinese fe-male popu-lation aged 50～74 years old increased significantly.Projections showed that the ASIR of overall,male and female standardized incidence rates in 2030 increased to 2.90/105,2.44/105 and 3.26/105 respectively.[Conclusion]The incidence rate of thyroid cancer in China is on the rise,with the incidence rate of women being higher than that of men,but the incidence rate of men has increased more than that of women,and the gap between the incidence rates is narrow-ing,and the peak age of incidence of men is mostly in the senior age group.

Objective:To investigate the correlation between immune function and age-related pulmonary fibrosis, as well as the potential impact of bacterial lysates on this condition.Methods:Twenty-four healthy male C57BL/6 mice, aged 24, were randomly divided into three groups: a control group(Group N), a pulmonary fibrosis group(Group M), and a pulmonary fibrosis+ bacterial lysis product intervention group(Group P). Mice in Groups M and P were intratracheally injected with bleomycin(5 mg/kg)to induce a mouse pulmonary fibrosis model, while mice in Group N were injected with saline.After modeling, mice in Group P were orally administered 0.4 ml of a bacterial lysis product once a day.After 28 days, lung tissue and blood samples were collected for analysis.Pathological changes in lung tissue were assessed using hematoxylin and tosin staining(HE)and Masson staining and the Ashcroft score.The expression of CD4+ and CD8+ in lung tissue was evaluated using immunohistochemistry.The levels of serum interferon-γ(INF-γ), interleukin-3(IL-13), and immunoglobulin A(IgA)protein were measured using Enzyme-linked Immuno Sorbent Assay(ELISA). The levels of INF-γ and IL-13 mRNA in lung tissue were determined using Real-Time Quantitative Transcription PCR(RT-qPCR). Additionally, the protein expression levels of matrix metalloprotein-9(MMP-9)and tissue inhibitor of metalloproteincise 1(TIMP-1)in lung tissue were assessed using blot analysis.Results:The degree of lung fibrosis was significantly reduced in mice in group P compared with group M when treated with bacterial lysis products.Group M showed a significant decrease in the expression of CD4+ T cells and an increase in the expression of CD8+ T cells( P<0.05)compared to group N. Additionally, the content of IgA was decreased( P<0.05)in group M. On the other hand, group P showed a significant increase in the expression of CD4+ T cells and a decrease in the expression of CD8+ T cells( P<0.05)compared to group M. Furthermore, the content of IgA was elevated( P<0.05)in group P. After bacterial lysis product intervention, mRNA and protein expression levels of IFN-γ were elevated( P<0.05), while mRNA and protein expression levels of IL-13 were reduced( P<0.05). Moreover, protein expression of MMP-9 and TIMP-1 was significantly up-regulated in group M compared with group N( P<0.05), and decreased after bacterial lysis product intervention( P<0.05). Conclusions:It is well-known that immune mechanisms play a crucial role in the development of pulmonary fibrosis.The use of bacterial lysates has been found to effectively regulate immune balance and mitigate the severity of pulmonary fibrosis in elderly mice.

Objective To elucidate the regulatory effects of Glycerol Kinase(GLPK)on the inflammatory response induced by lipopolysaccharide(LPS)in mouse Raw264.7 macrophages.Methods Raw264.7 macrophages were cultured in vitro,and an inflammatory model was established through LPS induction.The transcriptional levels of inflammatory cytokines NF-κB,TNF-α,IL-6,and IL-1β were quantified using RT-qPCR.The expression and localization of GLPK were examined via Western blot and immunofluorescence.Additionally,Western blot analysis was employed to detect the levels of cellular pan-succinylation and H3K23su expression.ChIP-qPCR was utilized to assess the enrichment of H3K23su modification at the IL-10 promoter.The total reactive oxygen species production was measured using DCFH-DA probes,while mitochondrial ROS levels were determined with Mito-SOX probes.Mitochondrial membrane potential changes,indicative of mitochondrial dysfunction,were evaluated using JC-1 fluorescent probes.Furthermore,GLPK overexpression plasmids were transfected into cells to investigate the effects of GLPK on inflammatory responses,mitochondrial function,and epigenetic modifications.Results LPS treatment led to mitochondrial dysfunction,inflammatory responses exacerbation,succinylation modifications reduction,and GLPK protein expression decrease in Raw264.7 cells.Overexpression of GLPK in LPS-treated cells improved mitochondrial function and reduced the transcription of pro-inflammatory cytokines.ChIP-qPCR analysis revealed that GLPK overexpression could reverse the LPS-induced suppression of H3K23su modification at the IL-10 promoter,thereby attenuating the inflammatory response.Conclusion LPS mediates inflammatory responses in Raw264.7 macrophages through a GLPK-dependent H3K23 succinylation modification mechanism.

BackgroundThe occurrence rate of dangerous behaviors in patients with severe mental disorders is higher than that of the general population. In China， there is limited research on the prediction of dangerous behaviors in community-dwelling patients with severe mental disorders， particularly in terms of predicting models using data mining techniques other than traditional methods. ObjectiveTo explore the influencing factors of dangerous behaviors in community-dwelling patients with severe mental disorders and testing whether the classification decision tree model is superior to the Logistic regression model. MethodsA total of 11 484 community-dwelling patients with severe mental disorders who had complete follow-up records from 2013 to 2022 were selected on December 2023. The data were divided into a training set （n=9 186） and a testing set （n=2 298） in an 8∶2 ratio. Logistic regression and classification decision trees were separately used to establish predictive models in the training set. Model discrimination and calibration were evaluated in the testing set. ResultsDuring the follow-up period， 1 115 cases （9.71%） exhibited dangerous behaviors. Logistic regression results showed that urban residence， poverty， guardianship， intellectual disability， history of dangerous behaviors， impaired insight and positive symptoms were risk factors for dangerous behaviors （OR=1.778， 1.459， 2.719， 1.483， 3.890， 1.423， 2.528， 2.124， P<0.01）. Being aged ≥60 years， educated， not requiring prescribed medication and having normal social functioning were protective factors for dangerous behaviors （OR=0.594， 0.824， 0.422， 0.719， P<0.05 or 0.01）. The predictive effect in the testing set showed an area under curve （AUC） of 0.729 （95% CI： 0.692~0.766）， accuracy of 70.97%， sensitivity of 59.71%， and specificity of 72.05%. The classification decision tree results showed that past dangerous situations， positive symptoms， overall social functioning score， economic status， insight， household registration， disability status and age were the influencing factors for dangerous behaviors. The predictive effect in the testing set showed an AUC of 0.721 （95% CI： 0.705~0.737）， accuracy of 68.28%， sensitivity of 64.46%， and specificity of 68.60%. ConclusionThe classification decision tree does not have a greater advantage over the logistic regression model in predicting the risk of dangerous behaviors in patients with severe mental disorders in the community. ［Funded by Chengdu Medical Research Project （number， 2020052）］

Objective:To study the role of special microbial communities in the development of periodontitis in type 2 diabetes melli-tus(T2DM)patients.Methods:40 subjects aged 20-70 years were included and divided into 3 groups:moderate to severe periodon-titis with T2DM(SP.T2DM,n=15),moderate to severe periodontitis group(SP,n=15)and normal healthy group(N,n=10).The basic information,periodontal clinical indicators and blood sugar of the subjects were recorded.Subgingival plaque samples were col-lected,DNA samples of the plaque were extracted,and sequenced by Illumina NovaSeq6000 platform.The microbial diversity,eco-logical characteristics and functions of the plaque were analyzed by Uparse,SPSS and other softwares.Results:481 species in 22 phyla,30 classes,73 orders,129 families and 265 genera were obtained from the samples.Beta polymorphism analysis showed that the species composition of CP.T2DM group and CP group was similar.Alpha polymorphism analysis showed that the species richness and evenness in CP.T2DM group and CP group were higher than those in N group(P＜0.01).Venn diagram analysis showed that the species richness of the plaque in CP.T2DM group was the highest,followed by CP group and the lowest in N group.At the genus lev-el,Klebsiella and Bifidobacterium in CP.T2DM group were larger than those in CP group and N group(P＜0.05),and between group CP and N,P＞0.05.At the species level,the Capnocytophaga leadbetteri in CP.T2DM group was higher than that in CP group and N group(P＜0.05),between group CP and N,P＞0.05;There were some differences in the microbial community structure of subgingival plaque among the 3 groups.The species richness of subgingival flora in patients with CP and T2DM was higher than that in patients with CP and healthy people.Conclusion:The increase of Klebsiella,Bifidobacterium and Capnocytophaga leadbetter in subgingival flora of patients with moderate and severe periodontitis may be related to the development of T2DM.

Aim To investigate the relationship between fibrinogen(FIB)and the progression of coronary plaque stenosis rate in patients with type 2 diabetes mellitus(T2DM).Methods Hospitalized T2DM patients who underwent two or more coronary CT angiography(CCTA)examinations in the First Affiliated Hospital of Xi'an Jiaotong U-niversity from January 2015 to December 2020 were included.The subjects were divided into high FIB and low FIB groups according to the median of FIB.The differences in the progression of coronary plaque stenosis rate and other clini-cal characteristics were compared between the two groups,and the relationship between FIB level and the progression of coronary plaque stenosis rate was analyzed by Spearman's correlation analysis and Logistic regression.Results A total of 145 patients were included,73 in the high FIB group and 72 in the low FIB group at baseline,with a median follow-up time of 25(18,40)months between CCTA.The age,proportion of women,and the progression of coronary plaque ste-nosis rate were higher in the high FIB group than those in the low FIB group,and the differences were statistically signifi-cant(P＜0.05).FIB level was positively correlated with the change in coronary plaque stenosis rate(r2=0.308,P＜0.001).Multivariate Logistic regression analysis showed that FIB level was a risk factor for the progression of coronary plaque stenosis rate in patients with T2DM(OR=5.25,95％CI:1.97～14.02,P＜0.001),after adjusting for age,sex and other clinical risk factors.Conclusion High baseline FIB level is an independent risk factor for the progression of coronary plaque stenosis rate in patients with T2DM,and monitoring FIB level is beneficial to cardiovascular risk stratifica-tion in patients with T2DM.