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.

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.

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: Lateral patellar compression syndrome (LPCS) is characterized by a persistent abnormally high stress exerted on the lateral articular surface of the patella due to lateral patellar tilt without dislocation and lateral retinaculum contracture, leading to anterior knee pain. The purpose of this study is to evaluate the efficacy and prognosis of lateral retinaculum release (LRR) combined with chondroplasty in the treatment of LPCS. METHODS: This retrospective study evaluated 40 patients who underwent LRR combined with chondroplasty for LPCS between 2020 and 2021. The assessment included improvement in postoperative tenderness and knee joint function. Patients were evaluated using the Lysholm, Tegner, and International Knee Documentation Committee 2000 scoring systems, as well as the visual analog scale, both preoperatively and postoperatively, with the paired comparisons analyzed using a t-test. Additionally, intraoperative observations were made regarding knee joint lesions, including cartilage damage and osteophyte formation, with analysis by the Chi-square test. RESULTS: The visual analog scale score for tenderness showed a significant decrease after surgery (p < 0.001). Evaluation of knee joint function also indicated significant improvements, as demonstrated by increased Lysholm, Tegner, and International Knee Documentation Committee 2000 scores postoperatively (p < 0.001, p = 0.011, p < 0.001, respectively). Furthermore, all LPCS patients included in the study presented with cartilage injuries and osteophyte formation. Significant differences were noted in the incidence of cartilage damage and osteophyte formation at different locations within the knee among patients with LPCS. CONCLUSION LRR combined with chondroplasty is an effective surgical approach for treating patients with LPCS, with satisfactory recovery observed at the 1-year follow-up. Additionally, the incidence of cartilage damage and osteophyte formation in LPCS patients varies significantly depending on the specific location within the knee joint.
Humans ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Patella/surgery* ; Knee Joint/physiopathology* ; Recovery of Function ; Young Adult ; Treatment Outcome ; Cartilage, Articular/surgery* ; Adolescent

Objective To investigate the effects of isoflurane anesthesia on cognitive function and the hippocampal nerve growth factor(NGF)and tyrosine receptor kinase A(TrkA)signaling pathway in Alzheimer's disease(AD)mice,while explore the role of G protein inhibitory α subunit 1/3(Gαi1/3)in this pathway.Methods Twelve wide-type mice and 48 APP/PS1(AD)mice(all males)were respectively assigned into a control group and 4 experimental groups,including AD,AD+postoperative cognitive dysfunction(POCD)group,empty adenovirus group,and Gαi1/3 overexpression group,with 12 mice in each group.Morris water maze and novel object recognition tests were conducted to assess the learning and memory function of each group;Western blotting was applied to detect the expression of amyloid P-protein 1-42(Aβ1-42),IL-6,TNF-α,synaptotagmin-1,synapsin-1,and NGF,p-TrkA,Gαi1/3,and p-Gab1 in hippocampal tissues.Results Compared with the control group and AD group,the avoidance incubation period in the AD+POCD group is significantly extended from days 2 to 4(P＜0.05),enhanced expression of Aβ1-42,IL-6,and TNF-α(P＜0.05),and reduced expression of synaptotagmin-1,synapsin-1,NGF,p-TrkA,Gαi1/3,and p-Gab1(P＜0.05).When compared with the AD+POCD group and the empty adenovirus group,the avoidance latency in the Gαi1/3 overexpression group was significantly shorted on days 2 to 4(P＜0.05),down-regulation of Aβ1-42(2.00±0.39 vs 3.38±0.38),IL-6(1.65±0.37 vs 3.36±0.39),and TNF-α(1.58±0.30 vs 2.90±0.31,P＜0.05),and up-regulation of synaptotagmin-1,synapsin-1,Gαi1/3,and p-Gab1(P＜0.05).Conclusion Isoflurane anesthesia can exacerbate POCD in AD mice,and overexpression of Gαi1/3 can improve cognitive function by activating the phosphorylation of Gab1.

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 evaluate the efficacy and safety of systemic thrombolysis(ST)and standard anticoagulation(SA)in the treatment of lower extremity fracture complicated with distal deep vein thrombosis(DDVT).Methods We retrospectively analyzed the clinical data of 60 patients with lower extremity fracture complicated with DDVT treated from January 2021 to December 2023.When the lower limb venography indicated a calf thrombus burden score ≥3 points,a retrievable inferior vena cava filter(IVCF)was successfully placed in the healthy femoral vein before orthopedic surgery.The patients who received further anticoagulant or thrombolytic therapy after surgery were allocated into a ST group(n=30,urokinase ST and SA)and a SA group(n=30,only SA).The two groups were compared in terms of calf thrombus burden score,thrombus dissolution rate,IVCF placement time,IVCF retrieval rate,intercepted thrombi,hemoglobin level,platelet count,D-dimer level,and complications.Results There was no statistically significant difference in the calf thrombus burden score between the two groups before treatment(P=0.431).However,after treatment,the scores in both groups decreased(both P<0.001),with the ST group showing lower score than the SA group(P=0.002).The thrombus dissolution rate in the ST group was higher than that in the SA group(P<0.001).There was no statistically significant difference in the IVCF placement time between the two groups(P=0.359),and the IVCF retrieval rate was 100% in both groups.The ST group had fewer intercepted thrombi than the SA group(P=0.002).There was no statistically significant difference in hemoglobin level(P=0.238),platelet count(P=0.914),or D-dimer level(P=0.756)between the two groups before treatment.However,after treatment,both groups showed an increase in platelet count(both P<0.001)and a decrease in D-dimer level(both P<0.001).There was no statistically significant difference in the occurrence of complications between the two groups(P=0.704).Conclusions Both SA and ST demonstrate safety and efficacy in the treatment of lower extremity fractures complicated with DDVT,serving as valuable options for clinical application.Compared with SA,ST not only enhances the thrombus dissolution in the calf but also mitigates the risk of thrombosis associated with IVCF.
Humans ; Venous Thrombosis/therapy* ; Retrospective Studies ; Thrombolytic Therapy/methods* ; Male ; Female ; Middle Aged ; Fractures, Bone/complications* ; Lower Extremity/injuries* ; Anticoagulants/therapeutic use* ; Aged ; Treatment Outcome ; Adult

BACKGROUND: Non-invasive computed tomography angiography (CTA)-based fractional flow reserve (CT-FFR) could become a gatekeeper to invasive coronary angiography. Deep learning (DL)-based CT-FFR has shown promise when compared to invasive FFR. To evaluate the performance of a DL-based CT-FFR technique, DeepVessel FFR (DVFFR). METHODS: This retrospective study was designed for iScheMia Assessment based on a Retrospective, single-center Trial of CT-FFR (SMART). Patients suspected of stable coronary artery disease (CAD) and undergoing both CTA and invasive FFR examinations were consecutively selected from the Beijing Anzhen Hospital between January 1, 2016 to December 30, 2018. FFR obtained during invasive coronary angiography was used as the reference standard. DVFFR was calculated blindly using a DL-based CT-FFR approach that utilized the complete tree structure of the coronary arteries. RESULTS: Three hundred and thirty nine patients (60.5 ±10.0 years and 209 men) and 414 vessels with direct invasive FFR were included in the analysis. At per-vessel level, sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of DVFFR were 94.7%, 88.6%, 90.8%, 82.7%, and 96.7%, respectively. The area under the receiver operating characteristics curve (AUC) was 0.95 for DVFFR and 0.56 for CTA-based assessment with a significant difference (P < 0.0001). At patient level, sensitivity, specificity, accuracy, PPV and NPV of DVFFR were 93.8%, 88.0%, 90.3%, 83.0%, and 95.8%, respectively. The computation for DVFFR was fast with the average time of 22.5 ± 1.9 s. CONCLUSIONS The results demonstrate that DVFFR was able to evaluate lesion hemodynamic significance accurately and effectively with improved diagnostic performance over CTA alone. Coronary artery disease (CAD) is a critical disease in which coronary artery luminal narrowing may result in myocardial ischemia. Early and effective assessment of myocardial ischemia is essential for optimal treatment planning so as to improve the quality of life and reduce medical costs.

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL