Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

Objective To analyze the association between lifestyle and the risk of type 2 diabetes(T2D)among adult residents.Methods The data was sourced from the Shanghai Suburban Adult Cohort and Biobank.A total of 42 096 adult residents who had not developed T2D were recruited from four districts of Shanghai(Songjiang,Jiading,Minhang,and Xuhui)between 2016 and 2019.The follow-up ended on Feb 28,2023.A structured questionnaire was used to collect information on six lifestyle-related items,including smoking,alcohol consumption,BMI,waist circumference(WC),physical activity,and diet.The unhealthy lifestyle scores(UHLS)were calculated by counting the number of all the unhealthy lifestyle items,with a range of 0-6.New-onset T2D events diagnosed by physicians were obtained through the medical information system.Cox proportional hazards regression model and restricted cubic spline model were utilized to evaluate the association between unhealthy lifestyles and the risk of T2D incidence.Results About 28.1%of the participants led 4-6 unhealthy lifestyles.A total of 1 752 new T2D cases were identified during 218 513.4 person-years of follow-up.Analysis of single unhealthy lifestyle showed that abnormal WC(HR=1.5,95%CI:1.4-1.7)and abnormal BMI(HR=1.3,95%CI:1.2-1.5)were associated with an increased risk of T2D.Compared with individuals with a UHLS of 0-1,those with a UHLS of 3 and 4-6 had 30%(95%CI:1.1-1.6)and 50%(95%CI:1.2-1.8)higher risks of T2D,respectively.Each additional unhealthy lifestyle was associated with a 10%increase in T2D incidence risk(HR=1.1,95%CI:1.1-1.2).Conclusion The risk of T2D in adult residents increases with the cumulative number of unhealthy lifestyles.Adult residents with abnormal WC or BMI,or have three or more unhealthy lifestyles accumulated,will increase the risk of new-onset T2D.

Objective:To investigate the impacts of the radiosensitivity of cell lines on a microdosimetric kinetic model (MKM) used in carbon-ion radiotherapy.Methods:The saturation-corrected specific energy ( ) of monoenergetic carbon ions was calculated using the Kiefer-Chatterjee (K-C) track structure model. Correction curve f(LET) was derived from experimental data on relative biological effectiveness (RBE) (RBE DSB-LET) defined based on the double-strand DNA break of the Chinese hamster ovary (CHO) and Fibroblast cell lines irradiated using carbon ions with varying linear energy transfer (LET) values. Then, based on the MKM, the D10-LET curves, as well as α and β databases, of the CHO and Fibroblast cell lines with varying radiosensitivity were determined. Results:Compared to the clinically applied MKM, the predicted D10 after correction while accounting for cell line radiosensitivity agreed better with experimental D10 values of the CHO and Fibroblast cell lines. Specifically, compared to experimental values in the literature, the D10 values calculated in the study and determined using the MKM showed mean squared errors (MSEs) of 0.04 and 0.71, for the CHO cell line and 0.35 and 0.55, respectively, for the Fibroblast cell line. For monoenergetic carbon ions with varying LET values, the calculated α and β values generally increased with cellular radiosensitivity. Conclusions:Incorporating cellular radiosensitivity into the MKM framework serves as a more specific method for RBE assessment while also providing a reference for advancing MKM applications and achieving the fine-scale calculations of RBE in carbon-ion radiotherapy.

Objective:To investigate the action mechanism of formononetin(FN)in regulating T helper type 1(Th1)cell dif-ferentiation and macrophage polarization through JAK/STAT signaling pathways in a mouse model of experimental autoimmune prostati-tis(EAP).Methods:Forty non-obese diabetic(NOD)male mice were randomly divided into four groups:normal control,EAP model control,low-dose FN(LFN,50 mg/kg)and high-dose FN(HFN,100 mg/kg).The EAP model was established in the latter three groups by subcutaneous injection of prostate antigens(PAgs)combined with complete Freund's adjuvant(CFA).After modeling,the mice in the LFN and HFN groups were treated intragastrically with FN at 50 and 100 mg/kg/d,respectively,and those in the nor-mal and model controls groups with carboxymethylcellulose sodium(CMC-Na).At 42 days after treatment,all the animals were killed and relevant tissues collected for observation of the pathological changes in the prostate tissue by HE staining,detection of Th1 cell dif-ferentiation and macrophage polarization in the prostate by immunofluorescence double staining(labeling CD4 and interferon-γ[IFN-γ],inducible nitric oxide synthase[iNOS]and CD206),measurement of the ratio of Th1 cells/macrophages in the spleen by flow cy-tometry and the levels of IFN-γ and tumor necrosis factor-α(TNF-α)in the serum by ELISA,and determination of the expressions of phosphorylated(p)-Janus kinase(JAK)1,JAK1,p-JAK2,JAK2,p-signal transducer and activator of transcription(STAT1)in the prostate tissue by Western blot.Results:Compared with the model controls,the mice treated with low-and high-dose FN exhibited more orderly arrangement of glandular epithelial cells,significantly reduced prostatic tissue inflammation scores(P＜0.05),and de-creased proportion of Th1 cells and expression of M1 macrophages(P＜0.05),but increased expression of M2 macrophages in the prostate and spleen tissues(P＜0.05).Besides,the levels of inflammatory cytokines IFN-γ(P＜0.05)and TNF-α(P＜0.05)in the serum of the mice in the LFN and HFN groups were remarkably reduced,and so were the ratios of p-JAK1/JAK1,p-JAK2/JAK2 and p-STAT1/STAT1 in the prostate tissues at the molecular level(P＜0.05),indicating the therapeutic effect of FN on EAP by regu-lating JAK/STAT signaling pathways,promoting inflammation resolution,and restoring immune balance.Conclusion:FN alleviates EAP by inhibiting JAK/STAT signaling pathways and regulating Th1 cell differentiation and macrophage polarization.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Purpose: This study assessed the performance of the ultrasound-guided attenuation parameter (UGAP) in diagnosing and grading hepatic steatosis in patients with metabolic dysfunctionassociated steatotic liver disease (MASLD). Magnetic resonance imaging proton density fat fraction (MRI-PDFF) served as the reference standard. Methods: Patients with hepatic steatosis were enrolled in this prospective study and underwent UGAP measurements. MRI-PDFF values of ≥5%, ≥15%, and ≥25% were used as references for the diagnosis of steatosis grades ≥S1, ≥S2, and S3, respectively. Spearman correlation coefficients and area under the receiver operating characteristic curves (AUCs) were calculated. Results: Between July 2023 and June 2024, the study included 88 patients (median age, 40 years; interquartile range [IQR], 36 to 46 years), of whom 54.5% (48/88) were men and 45.5% (40/88) were women. Steatosis grades exhibited the following distribution: 22.7% (20/88) had S0, 50.0% (44/88) had S1, 21.6% (19/88) had S2, and 5.7% (5/88) had S3. The success rate for UGAP measurements was 100%. The median UGAP value was 0.74 dB/cm/MHz (IQR, 0.65 to 0.82 dB/ cm/MHz), and UGAP values were positively correlated with MRI-PDFF (r=0.77, P<0.001). The AUCs of UGAP for the diagnoses of ≥S1, ≥S2, and S3 steatosis were 0.91, 0.90, and 0.88, respectively. In the subgroup analysis, 98.4% (60/61) of patients had valid controlled attenuation parameter (CAP) values. UGAP measurements were positively correlated with CAP values (r=0.65, P<0.001). Conclusion Using MRI-PDFF as the reference standard, UGAP demonstrates good diagnostic performance in the detection and grading of hepatic steatosis in patients with MASLD.

Objective:To investigate the impacts of the radiosensitivity of cell lines on a microdosimetric kinetic model (MKM) used in carbon-ion radiotherapy.Methods:The saturation-corrected specific energy ( ) of monoenergetic carbon ions was calculated using the Kiefer-Chatterjee (K-C) track structure model. Correction curve f(LET) was derived from experimental data on relative biological effectiveness (RBE) (RBE DSB-LET) defined based on the double-strand DNA break of the Chinese hamster ovary (CHO) and Fibroblast cell lines irradiated using carbon ions with varying linear energy transfer (LET) values. Then, based on the MKM, the D10-LET curves, as well as α and β databases, of the CHO and Fibroblast cell lines with varying radiosensitivity were determined. Results:Compared to the clinically applied MKM, the predicted D10 after correction while accounting for cell line radiosensitivity agreed better with experimental D10 values of the CHO and Fibroblast cell lines. Specifically, compared to experimental values in the literature, the D10 values calculated in the study and determined using the MKM showed mean squared errors (MSEs) of 0.04 and 0.71, for the CHO cell line and 0.35 and 0.55, respectively, for the Fibroblast cell line. For monoenergetic carbon ions with varying LET values, the calculated α and β values generally increased with cellular radiosensitivity. Conclusions:Incorporating cellular radiosensitivity into the MKM framework serves as a more specific method for RBE assessment while also providing a reference for advancing MKM applications and achieving the fine-scale calculations of RBE in carbon-ion radiotherapy.