Objective:To explore the degree of change in anteversion angle and related risk factors after intramedullary nail fixation of intertrochanteric femur fracture in the elderly.Methods:The data of 256 elderly patients who underwent intramedullary nail fixation for intertrochanteric fractures of the femur at Tianjin Hospital of Tianjin University from March 2020 to March 2023 were selected, including 114 males and 142 females, with an age of 75.40±10.69 years (range, 65-94 years). The degree of change in the anteversion angle of the affected hip before and after the surgery was measured by CT scan of the hip, the Receiver Operating Characteristic Curve (ROC) was plotted, the area under the ROC curve was analyzed, and the optimal degree of grouping was determined by calculating the Youden Index, then all the patients were divided into two groups. The correlation between various risk factors (age, sex, type of internal fixation, fracture AO type, quality of reduction, fracture medial cortical defect or not, cusp distance) and the change of anterior tilt angle was screened by univariate and multivariate logistic regression analyses.Results:All 256 patients were followed up for 20.7±2.1 months (range, 18-23 months). Anteversion on the healthy side was 12.68°±5.10° (range, 5°-28°); postoperative anteversion on the affected side was 15.04°±7.67° (range, 9°-36°). By comparing the difference in the anterior tilt angle between the affected side and the healthy side, it was found that the anterior tilt angle of 67 patients was completely restored to the healthy side level after the operation. The anteversion angle was enlarged in 131 cases, of which the mildly increased angle (1°-9°) was found in 106 cases, moderately increased (10°-15°) was found in 17 cases, and significantly increased (>15°) was found in 8 cases; 58 patients showed anteversion angle reduction, of which 45 cases were mildly reduced (1°-9°), 13 cases were moderately reduced (10°-14°). The area under the ROC curve for the patient's anteversion angle and its 95% CI were 0.714(0.559, 0.867), and the maximum value of its Youden Index was 0.221, which corresponded to the optimal critical angle of 4°. There was no statistically significant difference in age, gender, reduction quality or fracture AO classification between the group with an anteversion angle>4° and the group with an anteversion angle≤4° ( P>0.05). The types of internal fixation, medial cortical defect and insufficient tip apex distance (TAD) were included in the binary variable logistic regression analysis. The results showed that single-nail internal fixation [ OR=0.412, 95% CI(0.244, 0.695), P=0.007], medial cortical defect [ OR=0.471, 95% CI(0.279, 0.793), P=0.009] and TAD>25 mm [ OR=0.367, 95% CI(0.207, 0.651), P=0.003] are independent risk factors for changes in anteversion angle after intramedullary nail fixation of intertrochanteric femur fractures in elderly. Conclusion:Single-nail internal fixation, medial cortical defect and TAD >25 mm are independent risk factors for the change of anteversion angle after intramedullary nail internal fixation of intertrochanteric fractures in the elderly.

Objective:To explore the protective effects and mechanisms of an indole-3-acetaldehyde (I3A)-loaded inulin-based hydrogel against radiation-induced intestinal injury.Methods:The gelation properties and injectability of the I3A-loaded inulin-based hydrogel were detected using a rheometer, and its biocompatibility was assessed via a CCK-8 assay. Eighteen C57BL/6 mice (aged: 6-8 weeks) were stratified by body weight and randomly assigned into three groups with 6 mice in each group: blank control, irradiation-only, and irradiation+ hydrogel protection. Abdominal irradiation was administered using 137Cs γ-rays at 17 Gy. The irradiation+ hydrogel protection group received 200 μl/day of I3A-loaded inulin-based hydrogel for two days before and 2-3 days after irradiation. Meanwhile, the irradiation-only group was treated with an equivalent volume of sterile water via gavage. The mice were euthanized four days post-irradiation, and their intestinal tissues were harvested. Hematoxylin-eosin (HE) staining, Ki67 immunohistochemistry, and TUNEL immunofluorescence were performed to assess histopathological damage, epithelial cell proliferation, and apoptosis, respectively. Quantitative real-time PCR (qRT-PCR) was employed to measure mRNA levels of inflammatory and antioxidant factors. Gut microbiota composition was analyzed via 16S rRNA sequencing. Results:The test results of the rheometer confirmed successful hydrogel formation. CCK-8 assays demonstrated excellent biocompatibility. Compared with the irradiation-only group, the irradiation+ hydrogel protection group exhibited preserved intestinal histoarchitecture, a 1.5-fold increase in intestinal cell proliferation ( t = 8.35, P < 0.05), and a 2-fold reduction in radiation-induced apoptosis ( t = 7.94, P < 0.05). Moreover, the hydrogel group showed significantly elevated expression of the anti-inflammatory cytokine IL-10 and antioxidant factors NRF-2 and HO-1 ( t = 3.16, 24.83, 5.92, P < 0.05), alongside reduced levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α ( t = 5.15, 3.82, 3.83, P < 0.05). Gut microbiota analysis revealed significant modulation in microbial composition and abundance in the hydrogel group. Conclusions:The I3A-loaded inulin-based hydrogel can significantly promote intestinal cell proliferation, reduce radiation-induced apoptosis, and enhance both anti-inflammatory and antioxidant responses. In addition, it regulates gut microbiota composition and abundance, protecting against radiation-induced intestinal injury.

Objective:To rapidly and accurately detect volumetric modulated arc therapy (VMAT) plans with potentially inaccurate radiation doses.Methods:The measurement-based dosimetric verification result of 196 VMAT plans obtained using ArcCHECK phantoms were retrospectively collected. Independent dosimetric calculation and verification were conducted for these plans using the ArcherQA system based on a fast Monte Carlo algorithm. The gamma passing rates of dosimetric verification using ArcCHECK phantom and the ArcherQA system were compared, followed by their correlation analysis and linear regression fitting. The ArcherQA system′s gamma passing rate threshold used to detect positive dosimetric verification result obtained using ArcCHECK phantoms, as well as the specificity of the detection, were calculated. Based on this gamma passing rate threshold, another 50 VMAT plans were selected as a test set to assess the ArcherQA system′s ability to detect positive measurement-based dosimetric verification result.Results:The average gamma passing rates for the dosimetric verification of the VMAT plans using the ArcherQA system and ArcCHECK phantoms were 97.28% and 96.57% (3%/3 mm, TH=10%), respectively. Both rates had a correlation coefficient of 0.71 ( P < 0.01) and a linear fitting coefficient of 0.54 ( R2=0.51). When the gamma passing rate for dosimetric verification using ArcCHECK phantoms was set at 90% (3%/2 mm, TH=10%), the gamma passing rate threshold for dosimetric verification using the ArcherQA system should be adjusted to 94.8% to detect all VMAT plans with positive dosimetric verification result obtained using ArcCHECK phantoms, with a specificity of 67.8%. Using this threshold, the ArcherQA system detected all VMAT plans in the test set for which ArcCHECK phantom-based measurement yielded positive dosimetric verification result. Conclusions:By determining an appropriate gamma passing rate threshold, the ArcherQA system can rapidly and accurately detect VMAT plans with potentially inaccurate doses, thus ensuring treatment accuracy and improving work efficiency.

Objective:To investigate the effect and preliminary mechanism of hypervirulent Klebsiella pneumoniae (hvKP) on the immune response to sepsis induced by liver abscess in mice. Methods:C57BL/6 mice were intraperitoneally injected with hvKP strain NTUH-K2044 or classical Klebsiella pneumoniae (cKP) strain HS11286 suspension to prepare the model of sepsis. The survivals rates of mice within 24 h were recorded. HE staining was used to observed the inflammatory cell infiltration in mouse liver tissues. The levels of neutrophil marker lymphocyte antigen 6G (Ly6G) in mouse liver tissues were detected by immunohistochemistry. The activity of reactive oxygen species (ROS) in mouse liver macrophages and peripheral blood monocytes was measured by ROS assay kit. The activation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes was detected by Western blot. The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were detected by qRT-PCR and ELISA, respectively. One-way analysis of variance and t test were used for statistical analysis. Results:Compared with cKP, hvKP infection could induce C57BL/6 mice to develop obvious liver abscess with massive inflammatory cell infiltration. Moreover, the level of Ly6G in liver tissues was significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.000 1), but the survival rate of hvKP-infected mice was significantly lower than that of cKP-infected mice ( P<0.000 1). hvKP significantly promoted the ROS activity ( P<0.000 1) and enhanced the phosphorylation of p105/p50 and p65 in NF-κB signaling pathway in mouse liver macrophages and peripheral blood monocytes as compared with cKP ( P<0.001). The expression of IL-1β, IL-6 and TNF-α at mRNA and protein levels in mouse liver macrophages and peripheral blood monocytes were significantly higher in hvKP-infected mice than in cKP-infected mice ( P<0.001). Conclusion:hvKP can promote the development of liver abscess and induce sepsis in mice.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective:To determine the prevalence, risk factors, and longitudinal associations of loneliness during mid- to late pregnancy with anxiety and depressive symptoms in late pregnancy.Methods:In this prospective cohort study, 1 107 pregnant women at 24-28 weeks' gestation were enrolled between June 2021 and December 2022. Psychological status was assessed during mid-pregnancy (24-28 weeks) and late pregnancy (≥32 weeks) using standardized electronic questionnaires, including the Revised University of California Los Angeles Loneliness Scale (UCLA) Loneliness Scale-Short Form (Cronbach's α=0.82), Patient Health Questionnaire-9 ( α=0.86), and Generalized Anxiety Disorder-7 ( α=0.88). Multivariate logistic regression identified independent risk factors for loneliness. Cross-lagged path models analyzed the longitudinal predictions between loneliness and anxiety/depressive symptoms. Results:The prevalence of loneliness decreased significantly from 10.8% (120/1 107) in mid-pregnancy to 4.8% (37/777) in late pregnancy ( χ2=21.81, P<0.001). Multivariate analysis identified independent risk factors for loneliness: age <30 years ( OR=1.70, 95% CI: 1.15-2.50), annual household income <50 000 CNY ( OR=2.53, 95% CI: 1.28-5.02), unemployment during pregnancy ( OR=1.57, 95% CI: 1.03-2.39), history of alcohol consumption ( OR=1.63, 95% CI: 1.03-2.56), and the presence of mid-pregnancy depressive ( OR=2.76, 95% CI: 1.51-5.04) and anxiety symptoms ( OR=1.65, 95% CI: 1.01-2.71) (all P<0.05). Cross-lagged path models indicated bidirectional associations between loneliness and both anxiety ( β=0.32, P<0.01) and depressive symptoms ( β=0.28, P<0.01). However, the predictive effect of loneliness on subsequent depressive and anxiety symptoms ( β=0.28-0.32) was substantially stronger than the reverse prediction (mid-pregnancy anxiety on late-pregnancy loneliness: β=0.12; mid-pregnancy depression on late-pregnancy loneliness: β=0.11). Loneliness demonstrated high temporal stability (autoregressive effects β=0.29-0.32). Conclusion:Loneliness in mid-pregnancy exhibits a symmetric bidirectional association with anxiety and depressive symptoms in late pregnancy, suggesting it may be a core driver in the development of these emotional symptoms. Younger maternal age (<30 years), low household income (<50 000 CNY/year), unemployment during pregnancy, and a history of alcohol consumption were associated with a higher risk of loneliness and should be prioritized for psychological screening and intervention.

Objective To assess the incidence of contrast-induced nephropathy(CIN)in patients with chronic thromboembolic pulmonary hypertension(CTEPH)after receiving balloon pulmonary angioplasty(BPA),and to evaluate the effect of the contrast agents on renal function.Methods A total of 143 CTEPH patients,who received BPA at the China-Japan Friendship Hospital of China from December 2018 to May 2022,were enrolled in this study.The clinical data,hemodynamic indicators,and serum creatinine(SC)concentrations within one week before and 48-72 h after BPA were collected.The estimated glomerular filtration rate(eGFR)was calculated according to the Modification of Diet in Renal Disease(MDRD)formula.The SC concentration and eGFR changes before and after each BPA procedure were compared.The incidence of CIN and its risk factors were evaluated,and the changes in hemodynamics,SC and eGFR after the initial and last time of BPA treatment were analyzed.Results A total of 192 BPA procedures were performed in 115 CTEPH patients,including 88 BPA procedures in males and 103 BPA procedures in females.The mean amount of contrast agent used for each BPA was(145.58±47.26)mL.After BPA,12 patients developed 13 times of CIN,with an incidence of 6.8％.There was no significant differences(P＞0.05)in the baseline characteristics and SC concentration before BPA between CIN patients and non-CIN patients.In terms of the hemodynamic indexes,the mixed venous oxygen saturation(SvO2)in CIN patients was significantly lower than that in non-CIN patients(58.58％±10.38％vs.66.15％±8.02％,P=0.002),and no statistically significant differences(P＞0.05)in the other hemodynamic indexes existed between CIN group and non-CIN group.No statistically significant differences in SC concentration and eGFR existed before and after each BPA procedure.In patients who had received several BPA procedures,significant improvements in the SC[(78.09±18.760)μmol/L vs.(82.26±21.37)μmol/L,P＜0.001]and eGFR[(86.08±21.22)mL/(min·1.73 m2)vs.(82.07±22.05)mL/(min·1.73 m2),P=0.007]was achieved when compared with their baseline values.Conclusion CTEPH patients may develop CIN after receiving BPA treatment.After receiving several BPA treatments the patient's clinical symptoms and hemodynamics can be improved,and the patient's renal function is also significantly improved.

Objective: To study the effect of metformin sensitizing pancreatic cancer cells with radiotherapy, with a focus on elucidating the underlying mechanisms of radiotherapy resistance. In particular, the role of the PERK/P-eIF2/ATF4 signaling pathway in mediating these effects was preliminarily explored. Methods : Pancreatic cancer cell lines(PANC-1 and PANC-2) were categorized into control, radiotherapy, and drug treatment groups. Following the respective treatments, cell proliferation inhibition was assessed using the CCK-8 assay, colony formation assays, and cell death staining. Senescence was quantified by β-galactosidase(SA-β-Gal) staining. The expression of cell cycle regulators(P21, P16, γ-H2AX), apoptosis markers(Bax, Bcl-2, Cleaved caspase-3), and pathway-related proteins(PERK, P-eIF2, ATF4) was evaluated by Western blot and immunofluorescence. To further investigate the role of the PERK/P-eIF2/ATF4 axis in metformin-mediated modulation of pancreatic cancer cell senescence and radiosensitization, selective inhibitors(GSK2606414) and agonists(MK-28) of PERK were employed. Results : Radiotherapy markedly upregulated senescence-associated markers(P21, P16, γ-H2AX, and β-galactosidase activity) in pancreatic cancer cells. Senescent cells exhibited enhanced proliferative activity and increased tumor volume both in vitro and in vivo. Metformin mitigated radiotherapy-induced senescence by reducing the expression of senescence markers and significantly suppressing the clonogenic and proliferative capacity of treated cells. Mechanistically, radiotherapy activated the PERK signaling pathway, leading to increased expression of PERK, P-eIF2, and ATF4, thereby driving cellular senescence. Pharmacological inhibition of PERK reduced β-galactosidase activity, while PERK activation further promoted the expression of senescence-associated proteins—an effect that was reversed by metformin. Conclusion Metformin inhibits the activation of the PERK/P-eIF2/ATF4 signaling pathway in pancreatic cancer cells following radiotherapy, thereby delaying cellular senescence and reducing the associated radiotherapy resistance of senescent cells. This modulation contributes to the sensitization of pancreatic cancer cells to radiotherapy.

Diabetic kidney disease(DKD)with increasing global prevalence lacks effective therapeutic targets to halt or reverse its progression.Therapeutic targets supported by causal genetic evidence are more likely to succeed in randomized clinical trials.In this study,we integrated large-scale plasma proteomics,genetic-driven causal inference,and experimental validation to identify prioritized targets for DKD using the UK Biobank(UKB)and FinnGen cohorts.Among 2844 diabetic patients(528 with DKD),we identified 37 targets significantly associated with incident DKD,supported by both observational and causal evi-dence.Of these,22％(8/37)of the potential targets are currently under investigation for DKD or other diseases.Our prospective study confirmed that higher levels of three prioritized targets-insulin-like growth factor binding protein 4(IGFBP4),family with sequence similarity 3 member C(FAM3C),and prostaglandin D2 synthase(PTGDS)—were associated with a 4.35,3.51,and 3.57-fold increased likeli-hood of developing DKD,respectively.In addition,population-level protein-altering variants(PAVs)analysis and in vitro experiments cross-validated FAM3C and IGFBP4 as potential new target candidates for DKD,through the classic NLR family pyrin domain containing 3(NLRP3)-caspase-1-gasdermin D(GSDMD)apoptotic axis.Our results demonstrate that integrating omics data mining with causal inference may be a promising strategy for prioritizing therapeutic targets.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.