BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

BACKGROUND:Titanium elastic intramedullary nailing for the treatment of significantly displaced midshaft clavicle fractures has the characteristics of minimally invasive and elastic fixation.The displacement of the fracture is closely related to the later function.However,there are few studies on the three-dimensional displacement analysis of the fracture ends before surgery and after intramedullary fixation such as titanium elastic intramedullary nailing.OBJECTIVE:To explore the three-dimensional displacement of fracture ends after midshaft clavicle fracture and fixation with titanium elastic intramedullary nails,and to analyze the risk factors.METHODS:A total of 91 patients with midshaft clavicle fracture(fracture end shortening ≥15 mm)admitted to Wendeng Orthopedic Hospital of Shandong Province from April 2019 to April 2024 were selected,including 57 males and 34 females,aged(51.73±10.21)years old.All patients received closed reduction and internal fixation with titanium elastic intramedullary nail.CT scans of the affected clavicle were performed before and on the first day after surgery.The CT data were imported into Mimics software for modeling.The length of the clavicle,lateral displacement of the fracture end,and rotation of the distal end of the fracture along the X,Y,and Z axes were measured and recorded before and after surgery.Pearson correlation coefficient was used for correlation analysis of various parameters,and generalized linear regression was used to evaluate risk factors.RESULTS AND CONCLUSION:(1)Preoperatively,the variable that increased the risk of lateral displacement was the number of comminuted bone fragments,the variable that increased the risk of shortening displacement was male patients,and the variable that increased the risk of Z-axis rotation was the left limb.Shortening displacement was significantly positively correlated with lateral displacement(r=0.715,P＜0.001);shortening displacement was significantly positively correlated with X-axis rotation displacement and Y-axis rotation displacement(r=0.265,P=0.028;r=0.303,P=0.011);lateral displacement was significantly positively correlated with Y-axis rotation and Z-axis rotation(r=0.258,P=0.032;r=0.250,P=0.038);X-axis rotation was significantly positively correlated with Y-axis rotation(r=0.382,P=0.001),and Z-axis rotation was significantly positively correlated with Y-axis rotation(r=0.280,P=0.020).(2)Postoperatively:The number of scapula fractures and comminuted bone fragments were variables that increased the risk of postoperative shortening and lateral displacement:Preoperative X-,Y-,and Z-axis rotation displacements were risk variables that increased postoperative X-,Y-,and Z-axis rotation displacements,respectively.Postoperative lateral displacement was significantly positively correlated with postoperative shortening and displacement(r=0.584,P=0.000),and postoperative lateral displacement was also significantly positively correlated with postoperative Y axis rotation and Z axis rotation(r=0.360,P=0.002;r=0.250,P=0.038).Postoperative Y axis rotation was significantly positively correlated with postoperative Z axis rotation(r=0.248,P=0.040).(3)The results showed that the three-dimensional displacement of the clavicle end before and after surgery was affected by many factors,especially the number of comminuted bone fragments,scapula fractures,gender,and original rotation displacement.At the same time,there were complex correlations between various displacements,especially the correlation between shortening displacement and lateral displacement was the strongest.

Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Objective To explore the clinical and immunological significance of CCDC97 in hepatocellular carcinoma (HCC). Methods Clinical data and RNA sequencing results from HCC patients were retrieved from TCGA and ICGC databases. Bioinformatics analysis and in vitro experiments were performed to investigate the role of CCDC97 in HCC. Results The expression level of CCDC97 was elevated in HCC patients and HCC cells, closely associated with pathological features and prognosis. CCDC97 was identified as a novel prognostic biomarker. It is linked to the spliceosome pathway, which is significantly active in tumors and potentially promotes carcinogenesis. CCDC97 is also highly expressed in various immune cells and is associated with microenvironment. Furthermore, knocking down CCDC97 in vitro suppressed cell migration, invasion, and proliferation. Conclusion CCDC97 plays a critical role in HCC progression and the immune microenvironment, making it a potential target for prognosis and therapeutic intervention.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Tumor Microenvironment/genetics* ; Cell Movement/genetics* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics* ; Male

In recent years, the widespread application of chest computed tomography (CT) screening has led to a significant increase in the detection rate of pulmonary nodules. As a critical diagnostic tool for early-stage lung cancer, video-assisted thoracic surgery (VATS) has emerged as the preferred therapeutic approach for pulmonary nodules. Clinical evidence demonstrates that precise preoperative localization significantly enhances surgical success rates (reducing conversion to thoracotomy), minimizes complications, and shortens operation time. This comprehensive review systematically evaluates six cutting-edge localization techniques: percutaneous puncture-assisted localization, electromagnetic navigation bronchoscopy (ENB) localization, 3D-printed auxiliary localization, basin-analysis-based localization, robotic navigation system localization, and mixed reality (MR)-guided localization. By critically analyzing their operational principles, efficacy, safety profiles, and clinical applicability, this paper aims to provide evidence-based recommendations for optimizing clinical decision-making in pulmonary nodule management.
.
Humans ; Lung Neoplasms/diagnosis* ; Solitary Pulmonary Nodule/diagnostic imaging* ; Thoracic Surgery, Video-Assisted/methods* ; Multiple Pulmonary Nodules/diagnostic imaging* ; Tomography, X-Ray Computed

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Objective:To evaluate the efficacy and safety of dupilumab in the treatment of moderate-to-severe atopic dermatitis (AD) in infants aged 6 months to 2 years.Methods:A prospective cohort study was conducted. Children aged 6 months to 2 years with moderate-to-severe AD were enrolled from the Department of Dermatology, Children′s Hospital of Chongqing Medical University between July 2022 and March 2023. Children weighing 5 to < 15 kg received subcutaneous injections of dupilumab at a dose of 200 mg every 4 weeks, while those weighing 15 to < 30 kg received subcutaneous injections of dupilumab at a dose of 300 mg every 4 weeks. Three age-matched healthy children were recruited as controls at the same time. Clinical assessments were performed at weeks 0, 2, 4, 8, 12, and 16 by using the parameters scoring AD (SCORAD), eczema area and severity index (EASI), investigator′s global assessment (IGA), body surface area (BSA) involvement, patient-oriented eczema measure (POEM), pruritus numerical rating scale (NRS), sleep NRS, and infants′ dermatitis quality of life (IDQoL) index. The primary efficacy endpoint was the proportion of patients achieving an IGA score of 0 or 1 (IGA0/1) at week 16, and the key secondary efficacy endpoint was the proportion of patients achieving at least 75% improvement from baseline in EASI (EASI75) at week 16. In addition, serum immunoglobulin (Ig) E, IgG, IgM, and IgA levels and peripheral blood eosinophil counts were measured at weeks 0, 4, and 16. Peripheral blood T helper (Th) cell subsets were analyzed in 10 AD patients and 3 healthy children at baseline by flow cytometry, and 6 AD patients underwent repeat testing at week 16. Adverse reactions were recorded throughout treatment. Changes in clinical scores over time after dupilumab treatment were analyzed using repeated-measures analysis of variance, and changes in serum total IgE levels were analyzed using generalized estimating equations.Results:A total of 12 children with AD were enrolled, including 8 males and 4 females, aged 1.5 ± 0.3 years, and the baseline SCORAD was 64.8 ± 9.9 points. Compared with baseline, SCORAD, EASI, IGA, BSA, POEM, pruritus/sleep NRS, and IDQoL scores were all significantly reduced at week 2 (all P < 0.05), and continued to decrease at weeks 4, 8, 12, and 16. At week 16, the IGA scores decreased from 3.9 ± 0.3 points at baseline to 1.7 ± 0.9 points, with 9 patients achieving IGA0/1; the EASI scores decreased from 28.1 ± 12.4 points at baseline to 4.9 ± 5.4 points, with 9 patients achieving EASI75. Compared with baseline, serum total IgE levels were significantly reduced at weeks 4 and 16 (Wald χ2 = 11.51, P = 0.003). At baseline, the proportion of Th2 cells among total CD3 +CD4 + T cells in patients was significantly higher than that in healthy controls (6.3% ± 1.3% vs. 4.3% ± 0.8%, t = 2.45, P = 0.032) ; at week 16, the proportion of Th2 cells in patients (5.3% ± 2.0%) was significantly lower than that at baseline ( t = 5.56, P = 0.003). The proportion of Th1/17 cells increased from 2.2% ± 1.5% at baseline to 3.9% ± 2.1% at week 16 ( t = 3.51, P = 0.007), whereas the proportions of Th1 and Th17 cell subsets showed no statistical significance compared with baseline (both P > 0.05). One patient experienced an injection-site reaction and another developed fever, but no treatment-related serious adverse reactions were observed. Conclusions:Dupilumab demonstrated favorable efficacy and safety in infants aged 6 months to 2 years with moderate-to-severe AD. In addition, dupilumab could decrease the proportion of Th2 cell subsets and serum levels of total IgE.