ObjectiveTo investigate and manage an imported dengue fever (DF) outbreak in Shanghai in 2024, to summarize the experience and lessons learned from the on-site management, and to provide a reference basis for future prevention and control of DF. MethodsEpidemiological investigation and case search were carried out for an imported DF outbreak in Shanghai, 2024. Real-time fluorescence polymerase chain reaction (RT-PCR) was used to detect dengue virus nucleic acid in the serum samples from cases. Meanwhile, emergency vector surveillance and mosquito control measures were carried out in the affected areas, and the effectiveness of the management was evaluated. ResultsAccording to the epidemiological investigation, it was confirmed that this epidemic was a family cluster of imported DF, with both cases infected in Thailand and developed symptoms successively after returning to Shanghai. Laboratory testing identified the pathogens as dengue virus serotype-3 (DENV-3). In the core and precautionary area, ultra-low-volume space spraying and residual spraying were combined to kill adult mosquitoes, and at the same time, comprehensive cleaning and elimination of mosquito breeding sites was carried out. After 2 weeks, the Breteau Index (BI) in the core area decreased from 20 to 5, and the mosquito net trap index decreased from 2 mosquitoes (net·hour)^-1 to 0.67 mosquitoes (net·hour)^-1. Continuous implementation of mosquito control measures kept the BI and net trap index below the safety thresholds [BI<5 and mosquito net trap index <2 mosquitoes (net·hour)^-1] both in the core and precautionary area. ConclusionEarly diagnosis and isolation of patients, combined with rapid suppression of the density of vector Aedes mosquitoes, are the key measures to prevent the transmission of imported DF cases.

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 analyze the efficacy of endoscopic nasal surgery for sinonasal squamous cell carcinoma (SNSCC) with orbital invasion, the factors affecting the prognosis of patients, and the treatment strategies for preserving the eyeball.Methods:This was a retrospective cohort study, including 60 cases of SNSCC with orbital invasion treated in the Department of Otolaryngology-Head and Neck Surgery, the Second Affiliated Hospital of Harbin Medical University from October 2009 to October 2019. The cohort comprised 39 males and 21 females, aged 33-72 years. Orbital invasion was graded: Grade Ⅰ (destruction of the orbital bone wall), Grade Ⅱ (involvement of the periorbita/orbital fascia, extraconal fat, or medial lacrimal sac), and Grade Ⅲ (involvement of extraocular muscles, eyeball, orbital apex, or optic nerve). All cases underwent multi-disciplinary treatment (MDT), including otolaryngology, ophthalmology and oncology radiotherapy departments, and endoscopic nasal surgery. Survival curves were calculated by Kaplan-Meier method, Log-rank test and Cox risk model were used for univariate and multivariate analysis, respectively.Results:Primary tumor sites were maxillary sinus in 19 cases (31.7%, including 6 cases of pterygopalatine fossa), ethmoid sinus in 25 cases (41.7%, 5 cases with skull base bone involvement but not dura mater), nasal cavity in 11 cases (18.3%), frontal sinus in 3 cases (5.0%), and sphenoid sinus in 2 cases (3.3%). Clinical stages included stage Ⅲ in 53 (88.3%) and stage Ⅳ in 7 (11.7%). The surgical methods of orbital invasion cases were as follows: 18 cases (30.0%) of grade I underwent orbital bone wall resection with orbital fascia and orbital contents preserved; 36 cases (60.0%) in Grade Ⅱ were resected the involved orbital fascia, extra-cone fat and lacrimal sac and preserved the internal cone structure of extra-ocular muscle. Six cases (10.0%) were grade Ⅲ, of which 2 cases were subjected to selective extraocular muscle resection with preserving eyeballs, and 4 cases were subjected to orbital contents removal. The 3-year and 5-year overall survival (OS) rates of all patients were 76.7% and 63.3%, respectively, and the 5-year survival rate of the local recurrence-free group was significantly higher than that of the recurrence group (69.4% vs. 36.4%, χ2=3.91, P=0.048). The 5-year survival rates were significantly negatively correlated with the degrees of orbital invasions (83.3% for grade Ⅰ, 58.3% for grade Ⅱ and 33.3% for grade Ⅲ, ( χ2=10.49, P=0.005). The effects of T stages (66.7% in stage T3 vs. 33.3% in stage T4, χ2=7.21, P=0.007) and clinical stages (67.9% in stage III vs. 28.6% in stage IV, χ2=11.80, P=0.001) on survival rates were statistically significant. The 5-year survival rate of patients with cervical lymph node metastases was significantly lower than that of patients without metastasis (37.5% vs. 67.3%, χ2=8.32, P=0.004). The tumor-free survival rate was 56.7%. Cox multivariate analysis identified T stage [ HR=3.53 (95% CI: 1.31-9.52)] and clinical stage [ HR=35.14 (95% CI: 1.88-658.62)] as independent prognostic factors (both P<0.05). Conclusions:The outcomes of patients with orbital invasion in SNSCC are associated with T stage and clinical stage. If the muscle cone and the structures within the muscle cone are not invaded, eye-preserving surgery is feasible.

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 clinical efficacy of the modified crowbar-assisted minimally invasive Chevron osteotomy for the treatment of hallux valgus.Methods:A total of 42 patients with hallux valgus who underwent modified crowbar-assisted minimally invasive Chevron osteotomy at Huashan Hospital of Fudan University for hallux valgus from January 2019 to July 2022 were retrospectively analyzed. There were 3 males and 39 females, aged 42.3±8.7 years (range, 26-60 years); 18 left-sided and 24 right-sided, with body mass index 22.9±2.3 kg/m 2. According to the size of the hallux valgus angle (HVA), 26 patients were divided into the mild group (15°≤HVA<20°) and 16 patients were divided into moderate group (20°≤HVA≤40°). All patients were treated with modified crowbar-assisted Chevron osteotomy. The preoperative and postoperative HVA, intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), visual analogue scale (VAS) and American Orthopaedic Foot and Ankle Society metatarsophalangeal interphalangeal scale (AOFAS Hallux MTP-IP scale) were compared. Results:All patients successfully completed the operation and were followed up for an average of 22.3±6.5 months (range, 18-30 months). The HVA, IMA, and DMAA in the mild group at the last follow-up were 6.6°±1.8°, 8.1°±1.8°, and 4.3°±1.1°, respectively, which were significantly lower than those before operation 17.8°±1.4°, 12.5°±1.5°, and 7.6°±2.4° ( P<0.05). The HVA, IMA, and DMAA in the moderate group at the last follow-up were 7.6°±2.1°, 8.8°±1.6°, and 4.8°±2.9°, respectively, which were significantly lower than those before operation 32.3°±3.5°, 14.8°±3.5°, and 12.7°±5.4° ( P<0.05). At the last follow-up, there was no significant difference in HVA, IMA, or DMAA between the two groups ( P>0.05). The differences of HVA, IMA, and DMAA before and after operation in the moderate group were 24.7°±2.6°, 6.0°±2.3°, and 7.9°±3.8°, respectively, which were greater than those in the mild group 11.2°±1.7°, 4.4°±1.6°, and 3.3°±1.6°, and the differences were statistically significant ( P<0.05). At the last follow-up, the VAS score of the mild group decreased from 2.6±2.0 before surgery to 0.4±0.2, and the difference was statistically significant ( t=6.014, P<0.001). The VAS score of the moderate group decreased from 3.2±2.2 before surgery to 0.4±0.3, the difference was statistically significant ( t=8.777, P<0.001). The preoperative AOFAS Hallux MTP-IP scale of the toe metatarsal joint in the mild group and the moderate group were 71.6±5.9 and 64.3±7.8, respectively, which increased to 93.3±6.0 and 92.3±6.0 at the last follow-up, and the difference was statistically significant ( P<0.05). At the last follow-up, there was no significant difference in AOFAS Hallux MTP-IP scale between the two groups ( P>0.05). Twenty-two of the 26 patients in the mild group were satisfied, and 14 of the 16 patients in the moderate group were satisfied, and the difference in satisfaction between the two groups was not statistically significant ( P>0.05). Conclusion:The clinical efficacy of the modified crowbar-assisted minimally invasive Chevron osteotomy in the treatment of hallux valgus is satisfactory, and it can effectively correct the hallux valgus deformity and improve the function of the metatarsophalangeal joint.

Objective:To evaluate the role of the TANK-binding kinase 1 (TBK1)/receptor-interacting protein kinase 1 (RIPK1) signaling pathway in postoperative cognitive dysfunction (POCD) in aged mice.Methods:Fifty SPF healthy male C57BL/6 mice, aged 18 months, weighing 20-25 g, were divided into 5 groups ( n=10 each) using a table of random numbers: control group (group C), POCD group, dimethyl sulfoxide group, GSK group and GSK+ Nec-1 group. A mouse model of POCD was established by the closed reduction internal fixation of the left tibial fracture in anesthetized animals. Dimethyl sulfoxide, TBK1 inhibitor GSK8612 and RIPK1 inhibitor Nec-1 (0.5 μl/side) were stereotactically injected into the hippocampal CA1 region at 30 min before operation. Cognitive function was assessed using the contextual fear conditioning test before operation and at 3 days after operation. The mice were then anesthetized and sacrificed, and the hippocampal tissues were obtained for determination of the expression of TBK1, RIPK1, interleukin-lbeta (IL-1β), tumor necrosis factor-alpha (TNF-α), activator protein 1 (AP-1) and Nestin (by Western blot), the expression of Bcl-2, Bax and caspase-3 mRNA (by fluorescent quantitative real-time polymerase chain reaction) and for examination of TBK1/RIPK1 molecular interactions and neural stem cell proliferation in the hippocampal dentate gyrus (DG) region (by immunofluorescent staining). Results:Compared with C group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, RIPK1, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in POCD group ( P<0.05 or 0.01). Compared with POCD group, the percentage of freezing time was significantly decreased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was up-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was down-regulated, and the proliferation of neural stem cells in the hippocampal DG region was decreased in GSK group ( P<0.05 or 0.01). Compared with GSK group, the percentage of freezing time was significantly increased at 3 days after operation, the expression of Bax mRNA, caspase-3 mRNA, IL-1β, TNF-α and AP-1 was down-regulated, the expression of TBK1, Bcl-2 mRNA and Nestin was up-regulated, and the proliferation of neural stem cells in the hippocampal DG region was increased in GSK+ Nec-1 group ( P<0.05 or 0.01). Conclusions:The TBK1/RIPK1 signaling pathway is involved in the pathogenesis of POCD in aged mice.

OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide