Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

Objective:To explore the association between the systemic immune-inflammation index (SII) and obesity metabolic phenotypes, as well as metabolic features in children and adolescents.Methods:A cross-sectional study was conducted using the random cluster sampling method from March 2023 to May 2024. Children and adolescents aged 9-17 years in Guangzhou were surveyed through questionnaires, physical measurements, and blood tests. According to BMI and metabolic status, participants were classified into normal-weight groups [metabolically healthy normal weight (MHNW) and metabolically unhealthy normal weight (MUNW)] and overweight/obese groups [metabolically healthy overweight/obese (MHO/O) and metabolically unhealthy overweight/obese (MUO/O)]. After natural log-transformation of SII values (lnSII), multinomial logistic regression was used to assess the association between SII and obesity metabolic phenotypes, while binary logistic regression was applied to assess the relationship between SII and metabolic phenotypes in the overweight/obese subgroup. Linear regression model and restricted cubic spline (RCS) were employed to examine the relationship between SII and metabolic features among the entire population.Results:A total of 3 749 participants were included. After adjusting for covariates, for every unit increase in lnSII, the risk of MHO/O and MUO/O increased by 93% ( OR=1.93, 95% CI: 1.56-2.40, P<0.001) and 156% ( OR=2.56, 95% CI: 2.02-3.25, P<0.001), respectively. In the overweight/obesity subgroup, for every unit increase in lnSII, the risk of MUO/O increased by 37% ( OR=1.37, 95% CI: 1.01-1.87, P=0.045). Linear regression model and RCS showed that lnSII was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: β=1.39, 95% CI: 0.67-2.11, P<0.001; DBP: β=1.27, 95% CI: 0.79-1.75, P<0.001). lnSII also had a non-linear relationship with triglyceride ( Pnonlinear=0.032) and high-density lipoprotein cholesterol ( Pnonlinear=0.002). Conclusion:Elevated SII levels are associated with unfavorable obesity metabolic phenotypes, higher blood pressure, and altered lipid profiles in children and adolescents. SII may be a potential driving factor for metabolic heterogeneity in children and adolescents.

Breast cancer, a malignant tumor that significantly endangers women′s health, has shown a gradually rising incidence in recent years. Some breast cancer patients experienced poor prognosis. The commonly used imaging techniques for breast cancer include ultrasound, mammography, and magnetic resonance (MR), which suffer from certain limitations in accurately diagnosing and staging breast cancer. Positron emission tomography/computed tomography (PET/CT) enables tumor imaging at the cellular and molecular levels by utilizing radiolabeled molecular probes targeting different ligands. This technique facilitates precise localization and qualitative diagnosis of lesions to improve the staging accuracy, thereby reducing biopsy frequency and enhancing treatment effects for patients. Therefore, PET/CT has gradually developed into an essential imaging method for breast cancer in clinical practice. It plays a critical role in assessing the extent of lesion invasion, predicting immune subtypes, and estimating targeted therapy efficacy, holding promising application prospects. Recently, significant research breakthroughs have been achieved in this field. This review summarized the advances in clinical applications of different PET/CT molecular probes in the diagnosis and treatment of breast cancer, aiming to enhance the understanding of this aspect.

Objective:To explore the feasibility and clinical outcomes of transperineal prostate multimodal image fusion-targeted biopsy under the day surgery model.Methods:Clinical data of 258 patients who underwent transperineal prostate biopsy at the Second Affiliated Hospital of Xi’an Jiaotong University between December 2022 and June 2024 were retrospectively analyzed. Patients were divided into two groups，and the experimental group（ n = 141）underwent transperineal prostate multi-modal image-fusion targeted biopsy in the day-surgery mode，with age of（70.0 ± 8.8）years，median prostate-specific antigen（PSA）level of 11.10（7.63?17.06）ng/ml，and median Prostate Imaging Reporting and Data System（PI-RADS）score of 4（3，5）. The control group（ n = 117）underwent traditional transperineal systematic biopsy，with age of（69.3 ± 7.4）years，median PSA of 25.20（16.18-54.40）ng/ml，and median PI-RADS score of 4（3，5）. The experimental group was given the day surgery mode：preoperatively，multiparametric magnetic resonance imaging（mpMRI）of the prostate was multimodally fused with ultrasound images，the location of target lesions in the prostate was manually mapped，and a targeted biopsy plan was developed. Intraoperatively，under ultrasound guidance，precise puncture was performed at the lesion sites，followed by systematic biopsy. After the operation，the patients were observed for 4-6 hours，and could be discharged if there were no obvious abnormalities，with the total hospitalization time within 24 hours. For the control group，the conventional biopsy mode was used. Intraoperatively，under ultrasound guidance，the standard 12-core transperineal systematic biopsy protocol was adopted，and sampling was conducted according to the anatomical regions of the prostate（base，midportion，apex，transition zone，and peripheral zone）to cover the entire gland. Patients in this group required routine hospitalization，with a hospital stay of 3-5 days. Operative time，intraoperative pain Numerical Rating Scale（NRS）score，complications within one week postoperatively，treatment costs，overall prostate cancer detection rate，and clinically significant prostate cancer（csPCa，defined as Gleason score ≥ 7 or pathological stage ≥ T 2b）detection rate were compared between the two groups. Results:All procedures were successfully completed without special incidents. The operative time was（13.49 ± 2.00）min in the experimental group and（13.05 ± 2.89）min in the control group，showing no significant difference（ P > 0.05）. The intraoperative pain NRS scores were（3.01 ± 1.17）and（3.10 ± 1.25）in the experimental and control groups，respectively，with no significant difference（ P > 0.05）. Pathological examination revealed that the overall prostate cancer detection rates were 46.8%（66/141）in the experimental group and 42.7%（50/117）in the control group，while the csPCa detection rates were 35.5%（50/141）and 31.6%（37/117），respectively. The differences were not statistically significant（ P > 0.05）. The complication rate was 6.4%（9/141）in the experimental group（including 2 cases of acute urinary retention，3 hematuria，3 fever，and 1 sepsis）and 6.0%（7/117）in the control group（including 3 acute urinary retention，1 hematuria，2 fever，and 1 sepsis），with no significant difference（ P > 0.05）. All complications improved after symptomatic treatment. The treatment costs were（4 063.25 ± 67.26）yuan in the experimental group and（5 185.14 ± 469.15）yuan in the control group，demonstrating a statistically significant difference（ P < 0.05）. Conclusions:Transperineal prostate multimodal image fusion-targeted biopsy can be safely performed under the day surgery model，offering advantages including a relatively high detection rate for csPCa，low complication rate，and better cost-effectiveness.

Breast cancer, a malignant tumor that significantly endangers women′s health, has shown a gradually rising incidence in recent years. Some breast cancer patients experienced poor prognosis. The commonly used imaging techniques for breast cancer include ultrasound, mammography, and magnetic resonance (MR), which suffer from certain limitations in accurately diagnosing and staging breast cancer. Positron emission tomography/computed tomography (PET/CT) enables tumor imaging at the cellular and molecular levels by utilizing radiolabeled molecular probes targeting different ligands. This technique facilitates precise localization and qualitative diagnosis of lesions to improve the staging accuracy, thereby reducing biopsy frequency and enhancing treatment effects for patients. Therefore, PET/CT has gradually developed into an essential imaging method for breast cancer in clinical practice. It plays a critical role in assessing the extent of lesion invasion, predicting immune subtypes, and estimating targeted therapy efficacy, holding promising application prospects. Recently, significant research breakthroughs have been achieved in this field. This review summarized the advances in clinical applications of different PET/CT molecular probes in the diagnosis and treatment of breast cancer, aiming to enhance the understanding of this aspect.

Objective:To explore the association between the systemic immune-inflammation index (SII) and obesity metabolic phenotypes, as well as metabolic features in children and adolescents.Methods:A cross-sectional study was conducted using the random cluster sampling method from March 2023 to May 2024. Children and adolescents aged 9-17 years in Guangzhou were surveyed through questionnaires, physical measurements, and blood tests. According to BMI and metabolic status, participants were classified into normal-weight groups [metabolically healthy normal weight (MHNW) and metabolically unhealthy normal weight (MUNW)] and overweight/obese groups [metabolically healthy overweight/obese (MHO/O) and metabolically unhealthy overweight/obese (MUO/O)]. After natural log-transformation of SII values (lnSII), multinomial logistic regression was used to assess the association between SII and obesity metabolic phenotypes, while binary logistic regression was applied to assess the relationship between SII and metabolic phenotypes in the overweight/obese subgroup. Linear regression model and restricted cubic spline (RCS) were employed to examine the relationship between SII and metabolic features among the entire population.Results:A total of 3 749 participants were included. After adjusting for covariates, for every unit increase in lnSII, the risk of MHO/O and MUO/O increased by 93% ( OR=1.93, 95% CI: 1.56-2.40, P<0.001) and 156% ( OR=2.56, 95% CI: 2.02-3.25, P<0.001), respectively. In the overweight/obesity subgroup, for every unit increase in lnSII, the risk of MUO/O increased by 37% ( OR=1.37, 95% CI: 1.01-1.87, P=0.045). Linear regression model and RCS showed that lnSII was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: β=1.39, 95% CI: 0.67-2.11, P<0.001; DBP: β=1.27, 95% CI: 0.79-1.75, P<0.001). lnSII also had a non-linear relationship with triglyceride ( Pnonlinear=0.032) and high-density lipoprotein cholesterol ( Pnonlinear=0.002). Conclusion:Elevated SII levels are associated with unfavorable obesity metabolic phenotypes, higher blood pressure, and altered lipid profiles in children and adolescents. SII may be a potential driving factor for metabolic heterogeneity in children and adolescents.

Objective:To explore the feasibility and clinical outcomes of transperineal prostate multimodal image fusion-targeted biopsy under the day surgery model.Methods:Clinical data of 258 patients who underwent transperineal prostate biopsy at the Second Affiliated Hospital of Xi’an Jiaotong University between December 2022 and June 2024 were retrospectively analyzed. Patients were divided into two groups，and the experimental group（ n = 141）underwent transperineal prostate multi-modal image-fusion targeted biopsy in the day-surgery mode，with age of（70.0 ± 8.8）years，median prostate-specific antigen（PSA）level of 11.10（7.63?17.06）ng/ml，and median Prostate Imaging Reporting and Data System（PI-RADS）score of 4（3，5）. The control group（ n = 117）underwent traditional transperineal systematic biopsy，with age of（69.3 ± 7.4）years，median PSA of 25.20（16.18-54.40）ng/ml，and median PI-RADS score of 4（3，5）. The experimental group was given the day surgery mode：preoperatively，multiparametric magnetic resonance imaging（mpMRI）of the prostate was multimodally fused with ultrasound images，the location of target lesions in the prostate was manually mapped，and a targeted biopsy plan was developed. Intraoperatively，under ultrasound guidance，precise puncture was performed at the lesion sites，followed by systematic biopsy. After the operation，the patients were observed for 4-6 hours，and could be discharged if there were no obvious abnormalities，with the total hospitalization time within 24 hours. For the control group，the conventional biopsy mode was used. Intraoperatively，under ultrasound guidance，the standard 12-core transperineal systematic biopsy protocol was adopted，and sampling was conducted according to the anatomical regions of the prostate（base，midportion，apex，transition zone，and peripheral zone）to cover the entire gland. Patients in this group required routine hospitalization，with a hospital stay of 3-5 days. Operative time，intraoperative pain Numerical Rating Scale（NRS）score，complications within one week postoperatively，treatment costs，overall prostate cancer detection rate，and clinically significant prostate cancer（csPCa，defined as Gleason score ≥ 7 or pathological stage ≥ T 2b）detection rate were compared between the two groups. Results:All procedures were successfully completed without special incidents. The operative time was（13.49 ± 2.00）min in the experimental group and（13.05 ± 2.89）min in the control group，showing no significant difference（ P > 0.05）. The intraoperative pain NRS scores were（3.01 ± 1.17）and（3.10 ± 1.25）in the experimental and control groups，respectively，with no significant difference（ P > 0.05）. Pathological examination revealed that the overall prostate cancer detection rates were 46.8%（66/141）in the experimental group and 42.7%（50/117）in the control group，while the csPCa detection rates were 35.5%（50/141）and 31.6%（37/117），respectively. The differences were not statistically significant（ P > 0.05）. The complication rate was 6.4%（9/141）in the experimental group（including 2 cases of acute urinary retention，3 hematuria，3 fever，and 1 sepsis）and 6.0%（7/117）in the control group（including 3 acute urinary retention，1 hematuria，2 fever，and 1 sepsis），with no significant difference（ P > 0.05）. All complications improved after symptomatic treatment. The treatment costs were（4 063.25 ± 67.26）yuan in the experimental group and（5 185.14 ± 469.15）yuan in the control group，demonstrating a statistically significant difference（ P < 0.05）. Conclusions:Transperineal prostate multimodal image fusion-targeted biopsy can be safely performed under the day surgery model，offering advantages including a relatively high detection rate for csPCa，low complication rate，and better cost-effectiveness.

Objective:To perform harmonization based on the ComBat method for PET brain imaging scanned by different types of scanners from the same manufacturer and explored its effect on center effect.Methods:The three-dimensional (3D) Hoffman brain model was scanned by two different PET/CT instruments (Siemens Biograph64 TruePoint and Biograph128 mCT). Fourteen healthy subjects (8 males, 6 females, age: (57.7±9.5) years) underwent 18F-FDG PET/CT on Siemens Biograph64 TruePoint and 12 healthy subjects (9 males, 3 females, age: (55.8±10.5) years) underwent 18F-FDG PET/CT on Siemens Biograph128 mCT (all from Huashan Hospital, Fudan University; from November 2020 to March 2023). The whole brain was divided into 116 brain regions based on the anatomical automatic labeling (AAL) brain template. The ComBat method was applied to harmonized the PET data from brain model and healthy subjects. Mann-Whitney U test was performed on the radioactive counts and SUV ratios (SUVR) before and after homogenization acquired by both PET/CT instruments. Voxel-based statistical parametric mapping (SPM) independent-sample t test was also performed on data of healthy subjects. Results:In 3D Hoffman brain model, radioactivity counts (5 590.33(4 961.67, 6 102.95) vs 6 116.03(5 420.97, 6 660.66); z=-9.35, P<0.001) and SUVR (1.35(1.19, 1.47) vs 1.37(1.21, 1.49); z=-3.63, P<0.001) were significantly different between the two PET/CT scanners before harmonization and not after harmonization (radioactivity counts: 5 845.95(5 192.68, 6 378.63) vs 5 859.17(5 193.84, 6 380.52); SUVR: 1.35(1.20, 1.48) vs 1.36(1.20, 1.49); both z=-0.68, both P=0.498). In the healthy subjects, radioactive counts in 19 brain regions (12 422.78(11 181.60, 13 424.28)-18 166.40(15 882.80, 18 666.27); z values: from -3.24 to -2.06, all P<0.05) and SUVR in 40 brain regions (1.46(1.41, 1.52)-2.28(2.16, 2.36); z values: from -3.65 to -1.70, all P<0.05) were significantly different between the two scanners before harmonization, while after homogenization there were no statistical differences for all 116 brain regions (radioactivity counts: 9 243.55(8 502.38, 9 854.87)-20 419.60(19 931.51, 21 179.43); z values: from -0.72 to 0, all P>0.05; SUVR: 1.04(1.01, 1.09)-2.32(2.24, 2.40); z values: from -0.82 to 0, all P>0.05). SPM showed that significant differences of glucose metabolism in the cerebral cortex, basal ganglia, midbrain and cerebellum were found in healthy subjects between the two PET/CT scanners before homogenization, and brain regions with obvious differences reduced after homogenization. Conclusion:ComBat harmonization method is efficient at removing the center effect among different types of PET/CT scanners from the same manufacturer and may provide a simple and easy-to-implement homogenization for multicenter brain imaging studies.

Objective The aim of this study was to screen and verify the proteins interacting with Vimentin,investigate the regulatory relationship between FABP5 and candidate proteins,and further explore the mechanism of FABP5 in hepatocellular carcinoma.Methods Immunoprecipitation combined with tandem mass spectrometry(IP-MS)was used to screen the proteins that bind to FABP5.The binding relationship between FABP5 and candi-date interacting proteins was verified from the exogenous and endogenous levels by Co-immune precipitation assay(Co-IP).RT-qPCR,Western blot and immunofluorescence were used to observe the effect of knockdown FABP5 on the transcription and translation of Vimentin in HCC cells.The effect of overexpressing FABP5 on the cytoskeleton of HCC cell was observed by phalloidin staining.Results 336 potential target proteins that bind to FABP5 were identi-fied through IP-MS.Based on literature,five candidate proteins related to tumors were selected,namely PRDX1,PRSS3,PKM,HSP90AA1,and Vimentin.The binding relationship between FABP5 and Vimentin protein was con-firmed through both exogenous and endogenous Co-IP.Knockdown FABP5 has no significant effect on the expression of Vimentin mRNA,but it can inhibit the expression of Vimentin protein,and overexpression of FABP5 can affect the cytoskeleton of HCC cell.Conclusions FABP5 promotes the migration and invasion of HCC cells by the regula-tion of Vimentin and the influence of cytoskeletal remodeling,and thus it is expected to be a potential target for anti-HCC and provide new ideas for the treatment of HCC.

Objective:To study the mechanistic role of myeloid-specific Notch1 knockout inhibiting STING signaling to regulate hepatocyte lipophagy.Methods:A mouse model of nonalcoholic steatohepatitis (NASH) was established using a high-fat diet (HFD) and mouse bone marrow-derived macrophages (BMMs). Primary hepatocytes were isolated to construct a co-culture system. Twelve Notch1 FL/FL mice were randomly divided into two groups: the Notch1 FL/FL + normal diet (NCD) and the Notch1 FL/FL + HFD group. Further, 12 Notch1 M-KO mice were randomly divided into two groups: Notch1 M-KO + NCD, and Notch1 M-KO + HFD group.Serum alanine aminotransferase (sALT), total cholesterol (TC) and triglyceride (TG) were collected from mice serum samples. Liver tissue samples were collected for H&E staining, immunofluorescence (IF), Western blot and qRT-PCR. Tumor necrosis factor (TNF)-α was detected in the supernatant by enzyme-linked immunosorbent assay (ELISA). The comparison of inter group data was conducted using a t-test. Results:The mouse NASH model, mouse BMMs co-culture system, and primary hepatocytes were successfully constructed. Compared with the Notch1 FL/FL + HFD group, the Notch1 M-KO + HFD group showed a significant increase in serum ALT [(250.02 ± 58.21) U/L vs (370.70 ± 54.57) U/L, t = 3.705, P = 0.004], TG [(29.90 ± 3.54) mg/g vs (43.83 ± 8.56) mg/g, t = 3.685, P = 0.004], and TC [(33.70 ± 8.43) mg/g vs (90.53 ± 12.53) mg/g, t = 9.917, P < 0.001]. HE staining of liver tissue showed remarkable balloon-like alterations in liver cells, while IF staining demonstrated increased macrophage infiltration ( t = 7.346, P < 0.001). Compared with the hepatocyte group co-cultured with Notch1 FL/FL BMMs, the BODIPY probe showed a significant increase in lipid droplet (LDs) deposition in liver cells in the Notch1 M-KO group ( t = 3.835, P < 0.001). The co-localization of lysosomal associated membrane protein 1 (LAMP1), LDs ( t = 7.103, P < 0.001), microtubule-associated protein light chain 3 (LC3) -II/LC3-I ( t = 5.0, P = 0.007), and autophagy associated gene 12 (Atg12) ( t = 28.36, P < 0.001) had decreased expression, while P-62 had increased expression ( t = 3.253, P = 0.03), indicating a decrease in autophagic flow. Additionally, LC3 and LDs colocalization decreased ( t = 5.24, P = 0.0003), indicating reduced lipophagy. Compared with the Notch1 FL/FL group, the Notch1 M-KO BMMS mouse group showed an increase in the expression of p-STING ( t = 5.318, P = 0.006), p-TANK1 binding kinase 1 (TKB1) ( t = 6.467, P = 0.002), p-interferon regulatory factor 3 (IRF3) ( t = 14.61, P < 0.001), and p-P65 ( t = 12.7, P = 0.002) protein, accompanied by mRNA expression of the inflammatory mediators interferon (IFN)-β ( t = 7.978, P < 0.001), TNFα ( t = 8.496, P = 0.001), interleukin-1 β (IL-1 β) ( t = 4.7, P < 0.001), and CXCL-10 ( t = 4.428, P = 0.001). The STING gene was knocked out in the BMMs Notch1 M-KO mice using CRISPR/Cas9. Compared with the CRISPR-Control group, the expression of P-TKB1 ( t = 2.909, P = 0.044), p-IRF3 ( t = 10.96, P < 0.001), p-IRF3 ( t = 10.96, P < 0.001), and p-P65 ( t = 7.091, P = 0.002) proteins was lower in the STING-KO BMMs group. The release of TNF-α in the supernatant was decreased (732.3 ± 129.35 pg/ml vs. 398.17 ± 47.15 pg/ml, t = 4.204, P = 0.014). However, in hepatocytes co-cultured with STING-KO BMMs, LC3-II/LC3-I ( t = 7.546, P = 0.001) increased, p-62 ( t = 10.96, P < 0.001) expression decreased, autophagic flow increased, and the colocalization of LC3 and LDs increased, lipophagy increased, and LDs deposition decreased. Conclusion:Myeloid-specific Notch1 knockout can activate macrophages STING signaling, increase the expression of inflammatory mediator genes, inhibit the occurrence of autophagy flow and lipophagy in hepatocyte cells, and aggravate LDs deposition and NASH progression.