Purpose: Our previous study showed that circulating tumor cell (CTC) count combined with gene mutation detection might help differentiate benign and malignant pulmonary nodules (PNs). Herein, we aimed to expand the study cohort and conduct further sequencing analysis. Materials and Methods: Patients with PNs were included, and CTCs were identified before operation. Low-coverage whole-genome sequencing (LC-WGS) and lung cancer-related targeted gene sequencing were performed on CTCs. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve. The differences in CTC counts among subgroups classified by demographic–clinical characteristics were analyzed. LC-WGS–based copy number variation (CNV) analysis and targeted gene mutation analysis were conducted. Results: A total of 172 patients were included. CTC count of 2.5 was identified by the ROC curves as the optimal diagnostic cutoff. The sensitivity and specificity of CTC count for differentiating benign and malignant PNs were 54.2% and 78.6%, respectively. The diagnostic sensitivity and specificity of combined CTC count, radiological nodule type, and any malignant imaging features were 84.7% and 71.4%, respectively. The CTC counts were significantly greater in patients with aggressive tumors, later stage, and spread through air spaces. CTCs from malignant cases had more CNVs than those from benign cases. Conclusion CTC count can be used in identifying malignant PNs. The diagnostic efficacy can be improved if combined with computed tomography imaging characteristics. Further CNV analysis might help differential diagnosis. Greater CTC count might suggest more aggressive tumors. CTC detection can provide important information and guidance for subsequent management of PNs.

Objective To observe the value of venous phase CT radiomics for diagnosing colorectal cancer(CRC)complicated with tumor deposit(TD)and/or lymph node metastasis(LNM).Methods Totally 263 CRC patients were retrospectively enrolled and divided into TD(+)LNM(+)group(group A,n=103),TD(+)LNM(-)group(group B,n=63)and TD(-)LNM(+)group(group C,n=97)based on pathological results,also randomly divided into training set(n=210)and test set(n=53)at the ratio of 8∶2.Radiomics features of CRC were screened based on venous phase CT images.Radiomics models were constructed with support vector machine(SVM),multilayer perceptron(MLP)and K-nearest neighbor(KNN),respectively,and their diagnostic efficacy were analyzed.Results In both training set and test set,SVM model had the highest overall efficacy for diagnosing CRC complicated with TD and/or LNM.Due to the uneven distribution of sample sizes among 3 groups,DeLong test was performed on the micro-averaged area under the curve(Micro AUC),which was more robust for handling class imbalance problems.In training set,significant differences were found between SVM and MLP models,as well as between SVM and KNN models(both P＜0.05),while in test set,significant differences were observed between each 2 models(all P＜0.05).Conclusion Venous phase CT radiomics models,especially SVM model was helpful for diagnosing CRC complicated with TD and/or LNM.

Objective:To analyze and summarize the clinical features and short-medium term follow-up results of children with multisystem inflammatory syndrome（MIS-C）following coronavirus infection.Methods:The data of six children with MIS-C admitted to the Intensive Care Unit of Shanghai Children's Medical Center from January to March 2023 were retrospectively analyzed.Results:All six cases were in shock，requiring vasoactive drugs，and one case required invasive mechanical ventilation.All the six patients had multiple organ function injury and increased inflammation indicators.After admission，they received organ support，glucocorticoids and gamma globulin treatment.Two patients were treated with biological agents.Both organ function and inflammation indicators showed significantly improvement after therapy.Six patients had mild coronary artery widening.All patients had good prognosis following short-medium term follow-up.Conclusion:Children with severe MIS-C may suffer life-threatening hemodynamic instability.Timely assessment，active anti-inflammatory and organ support therapy can obtain favorable prognosis.

Aim To investigate the regulatory mecha-nisms of donepezil on the expression and enzymatic ac-tivity of cytochrome P450 3A4(CYP3A4),elucidate the synergistic impact of hypoxia on CYP3A4 function,and reveal its potential association with drug-induced cardiotoxicity,particularly QT interval prolongation.Methods Western blot,co-immunoprecipitation,and gene knockdown techniques were employed to evaluate the effects of donepezil and hypoxia on CYP3A4 pro-tein expression.CYP3A4 enzymatic activity was as-sessed using an in vitro incubation system with rat liver microsomes combined with high-performance liquid chromatography(HPLC),and the half-maximal inhib-itory concentration(IC50)was determined.Results Donepezil(10 μmol·L-1)and hypoxia reduced CYP3A4 protein expression to 31.75％and 45.90％of the control levels,respectively.Both interventions activated the gp78-mediated ubiquitin-proteasome path-way,significantly increasing CYP3A4 ubiquitination levels by 2.1-fold compared to the control group,thereby promoting proteasomal degradation.Donepezil inhibited CYP3A4 enzyme activity with an IC50 of 83.4μmol·L-1,and hypoxia synergistically enhanced this inhibitory effect,reducing the IC50 to 20.79 μmol·L-1.Conclusion Donepezil downregulates CYP3A4 function through dual mechanisms involving ubiquitin-mediated proteasomal degradation and direct enzymatic inhibition.Hypoxia potentiates this effect,leading to impaired metabolism of CYP3A4 substrate drugs,ele-vated plasma drug concentrations(1.6-2.3-fold in-crease compared to normal metabolic conditions),and an increased risk of QT interval prolongation and other forms of cardiotoxicity.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To explore the prognostic value of a combined model of baseline 18F-FDG PET/CT tumor metabolic parameters and clinical factors for predicting progression-free survival (PFS) in Hodgkin′s lymphoma (HL). Methods:From January 2014 to May 2023, 171 HL patients (102 males, 69 females; median age 40 years) who underwent 18F-FDG PET/CT before treatment at the First Affiliated Hospital of Nanjing Medical University and Nanjing Drum Tower Hospital were retrospectively collected. HL patients from the First Affiliated Hospital of Nanjing Medical University were classified as the training set (101 patients) and HL patients from Nanjing Drum Tower Hospital were classified as the validation set (70 patients). Clinical factors and tumor metabolic parameters associated with PFS were determined by multivariate Cox regression analysis, and then the combined model and the independent model of each factor were constructed respectively. The consistency index (C-index) and AUC were used to evaluate the predictive efficacy of models, and nomogram was constructed based on the optimal model, and calibration curves were used to assess the goodness of fit of the models. The differences in Kaplan-Meier survival curves of the high-risk and low-risk groups were compared using log-rank test. Results:The multivariate Cox regression analysis indicated that the independent prognostic factors associated with PFS were the Lugano staging (hazard ratio ( HR)=3.10, 95% CI: 1.17-8.23, P=0.023), total metabolic tumor volume (TMTV) ( HR=2.65, 95% CI: 1.23-5.74, P=0.014), and maximum distance between tumors ( Dmax) ( HR=2.23, 95% CI: 1.02-4.85, P=0.044). These factors were used to construct the combined model, with the highest prognostic efficacy of the C-index for the training and validation sets of 0.692 and 0.653, and the AUC of 0.732 and 0.697, respectively. The calibration curves demonstrated that the predictions made by the combined model were in high agreement with the actual results in both the training and validation sets. The Kaplan-Meier analysis revealed a significantly lower PFS rate in the high-risk group compared to the low-risk group both in training and validation sets ( χ2 values: 5.88 and 4.52, P values: 0.015 and 0.033). Conclusion:The combined model incorporating tumor metabolic parameters and clinical factors improves prognostic efficacy in predicting PFS in HL patients.

Objective:To explore the value of baseline 18F-FDG PET/CT metabolic parameters and related clinical factors in the prognostic assessment of patients with angioimmunoblastic T-cell lymphoma (AITL). Methods:From July 2013 to December 2023, 70 patients with AITL (44 males, 26 females, age (63.9±9.6) years) from Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University (32 cases) as well as the First Affiliated Hospital of Nanjing Medical University (38 cases) who were diagnosed pathologically and underwent PET/CT imaging prior to treatment were retrospectively analyzed. PET/CT metabolic parameters (calculated using the 41%SUV max threshold method) and related clinical factors were collected. The optimal cut-off values of metabolic parameters were determined by using the ROC curve analysis. Cox proportional risk regression models were used for prognostic analyses, prediction models were constructed and efficacies were assessed by calibration curves and time-dependent ROC curves. Results:With the follow-up of 19.0(10.0, 33.3) months, disease progression or recurrence occurred in 51 patients, and 28 patients died. ROC curves showed that the optimal cut-off values on diagnosing AITL of total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and SUV max were 767.1cm 3, 2159.6g and 13.0, respectively. TMTV (hazard ratio ( HR)=0.485, 95% CI: 0.252-0.935, P=0.031) and gender ( HR=0.441, 95% CI: 0.236-0.824, P=0.010) were independent risk factors for progression-free survival (PFS); TMTV ( HR=0.422, 95% CI: 0.178-0.997, P=0.049) and treatment regimen ( HR=0.346, 95% CI: 0.154-0.777, P=0.010) were independent risk factors for overall survival (OS). Time-dependent ROC curves indicated that the combined model of TMTV combining gender or treatment regimen had better prognostic results in predicting PFS (AUCs: 0.67-0.82) or OS (AUCs: 0.62-0.80) in patients with AITL. The calibration curve showed the predicted values of the combined models were in good consistency with the actual values. Conclusions:The metabolic parameter TMTV is an independent risk factor for PFS and OS in patients with AITL. The combined model of TMTV combining gender or treatment regimen can effectively improve the prognostic prediction efficacy of PFS or OS in patients with AITL.

Objective:To investigate the value of a cross-combination machine learning approach in constructing a PET radiomics score (RadScore) for predicting early treatment response and prognosis in patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).Methods:This retrospective cohort study was conducted on 108 patients (59 males and 49 females, age (55.6±12.1) years) diagnosed with PGI-DLBCL between November 2016 and December 2021 at Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University ( n=85) and West China Hospital, Sichuan University ( n=23). Patients were divided into a training set ( n=86) and a validation set ( n=22) with the ratio of 8∶2 using stratified random sampling method. Seven machine learning models were employed to generate 49 feature selection-classification candidates, and the optimal candidate was selected to construct the RadScore, with five-fold cross-validation applied to determine the best-performing model. Logistic regression analysis was performed to identify risk factors for early treatment response, and a radiomics nomogram was developed by integrating RadScore with clinical predictors. Survival results between different groups of RadScore was compared by log-rank test. Results:Nineteen predictive features were selected from 111 radiomic features to construct the RadScore. In the training set, lactate dehydrogenase (LDH) (odds ratio ( OR)=3.53, 95% CI: 1.21-10.31, P=0.021), intestinal involvement ( OR=3.04, 95% CI: 1.04-8.88, P=0.042), total lesion glycolysis (TLG; OR=6.73, 95% CI: 2.23-20.29, P<0.001) and RadScore ( OR=15.11, 95% CI: 3.95-57.80, P<0.001) were identified as independent risk factors for predicting early treatment response. The combined model integrating RadScore, LDH, intestinal involvement, and TLG demonstrated good discriminatory ability for early treatment response (AUC=0.860 in the training set; AUC=0.902 in the validation set). Significant differences were observed in progression-free survival (PFS) and overall survival (OS) between different RadScore groups ( χ2 values: 13.92 and 8.56, both P<0.01). Conclusions:The machine learning-based RadScore may effectively predict survival outcomes in patients with PGI-DLBCL. The combined model integrating RadScore, clinical factors, and metabolic indicators can predict early treatment response in PGI-DLBCL patients.

Objective To observe the effects of electroacupuncture at the Hegu(LI4)acupoint on refractive parame-ters and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)in the retinal tissue of mice with form-deprivation myopia(FDM).Methods Forty-eight SPF-grade,3-week-old healthy male C57BL/6J mice were ran-domly divided into four groups:normal control group,FDM group,sham acupuncture group,and Hegu group.Experimen-tal myopia was induced in the right eyes of mice in the latter three groups by wearing translucent diffuser goggles.Mice in the Hegu group received electroacupuncture stimulation at the Hegu(LI4)acupoint,while those in the sham acupuncture group received intervention with a non-penetrating blunt needle at the same location.Body weight,refractive error,and axial length were recorded for all mice before modeling and at 2 and 4 weeks after modeling.At 4 weeks post-modeling,mice were euthanized.Real-time quantitative PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of TNF-α and IL-1β,respectively,in the right retinal tissues.Retinal cell apoptosis was assessed by TUNEL staining.Results At 2 weeks post-modeling,compared with the normal control group,the refractive error of the right eyes was significantly decreased and the axial length was significantly increased in the FDM,sham acupuncture,and Hegu groups(all P＜0.01).At 4 weeks post-modeling,compared with the normal control group,the refractive error was significantly decreased and the axial length was significantly increased in the FDM and sham acupuncture groups(all P＜0.001).Compared with both the FDM and sham acupuncture groups,the Hegu group showed a significant increase in re-fractive error and a significant decrease in axial length(all P＜0.001).At 4 weeks post-modeling,RT-qPCR and Western blot results showed that the mRNA and protein expression levels of TNF-α and IL-1 β in the retina were significantly higher in the FDM and sham acupuncture groups compared to the normal control group(all P＜0.05).In contrast,the protein ex-pression level of TNF-α and the relative mRNA and protein expression levels of IL-1β in the Hegu group were significantly lower than those in the FDM group(all P＜0.05).TUNEL staining results showed that the retinal cell apoptosis rate was significantly higher in the FDM and sham acupuncture groups compared to the normal control group(all P＜0.001).Com-pared with the FDM and sham acupuncture groups,the retinal cell apoptosis rate was significantly lower in the Hegu group(all P＜0.001).Conclusion Electroacupuncture at the Hegu(LI4)acupoint can significantly inhibit the progression of myopia in mice.The mechanism may be related to the downregulation of TNF-α and IL-1β expression in the retinal tissue,thereby inhibiting retinal cell apoptosis.

Objective To observe the effects of electroacupuncture at the Hegu(LI4)acupoint on refractive parame-ters and the expression of tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)in the retinal tissue of mice with form-deprivation myopia(FDM).Methods Forty-eight SPF-grade,3-week-old healthy male C57BL/6J mice were ran-domly divided into four groups:normal control group,FDM group,sham acupuncture group,and Hegu group.Experimen-tal myopia was induced in the right eyes of mice in the latter three groups by wearing translucent diffuser goggles.Mice in the Hegu group received electroacupuncture stimulation at the Hegu(LI4)acupoint,while those in the sham acupuncture group received intervention with a non-penetrating blunt needle at the same location.Body weight,refractive error,and axial length were recorded for all mice before modeling and at 2 and 4 weeks after modeling.At 4 weeks post-modeling,mice were euthanized.Real-time quantitative PCR(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of TNF-α and IL-1β,respectively,in the right retinal tissues.Retinal cell apoptosis was assessed by TUNEL staining.Results At 2 weeks post-modeling,compared with the normal control group,the refractive error of the right eyes was significantly decreased and the axial length was significantly increased in the FDM,sham acupuncture,and Hegu groups(all P＜0.01).At 4 weeks post-modeling,compared with the normal control group,the refractive error was significantly decreased and the axial length was significantly increased in the FDM and sham acupuncture groups(all P＜0.001).Compared with both the FDM and sham acupuncture groups,the Hegu group showed a significant increase in re-fractive error and a significant decrease in axial length(all P＜0.001).At 4 weeks post-modeling,RT-qPCR and Western blot results showed that the mRNA and protein expression levels of TNF-α and IL-1 β in the retina were significantly higher in the FDM and sham acupuncture groups compared to the normal control group(all P＜0.05).In contrast,the protein ex-pression level of TNF-α and the relative mRNA and protein expression levels of IL-1β in the Hegu group were significantly lower than those in the FDM group(all P＜0.05).TUNEL staining results showed that the retinal cell apoptosis rate was significantly higher in the FDM and sham acupuncture groups compared to the normal control group(all P＜0.001).Com-pared with the FDM and sham acupuncture groups,the retinal cell apoptosis rate was significantly lower in the Hegu group(all P＜0.001).Conclusion Electroacupuncture at the Hegu(LI4)acupoint can significantly inhibit the progression of myopia in mice.The mechanism may be related to the downregulation of TNF-α and IL-1β expression in the retinal tissue,thereby inhibiting retinal cell apoptosis.