OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To explore the value of ultrasound intelligent diagnostic system combined with mammography for differentiating benign and malignant non-mass breast lesions(NMBL).Methods Totally 107 patients with NMBL were retrospectively enrolled,including 64 cases of malignant(malignant group)and 43 cases of benign lesions(benign group).Clinical,routine ultrasound,ultrasound intelligent diagnostic system(artificial intelligence[AI]system)and mammography data were compared between groups.Logistic regression analysis was performed,receiver operating characteristic(ROC)curves were drawn,the areas under the curves(AUC)were calculated,and the efficacy of AI system combined with mammography for differentiating benign and malignant NMBL was analyzed.Results Significant differences of the maximum diameter of lesion,ratio of axillary lymph node enlargement and suspected malignant calcification on mammography,as well as of AI system malignancy risk and AI system breast imaging reporting and data system(BI-RADS)classification were found between groups(all P＜0.05).AI system binary classification was obtained based on AI system malignancy risk.The AUC of suspected malignant calcification on mammography,AI system BI-RADS classification and AI system binary classification for differential diagnosis of benign and malignant NMBL was 0.840,0.810 and 0.817,respectively,while of suspected malignant calcification on mammography combined with AI system BI-RADS classification or AI system binary classification were both 0.856,higher than that of AI system BI-RADS classification/AI system binary classification alone(both P＜0.05)but not significantly different with that of suspected malignant calcification on mammography alone(both P＞0.05).Logistic regression analysis of age,the maximum diameter of lesion,axillary lymph node enlargement and suspected malignant calcification on mammography combined with AI system malignancy risk(model 1),AI system BI-RADS classification(model 2)or AI system binary classification(model 3)showed that suspected malignant calcification on mammography,AI system malignancy risk,AI system BI-RADS classification and AI system binary classification were all independent risk factors of malignant NMBL(all P＜0.05),and AUC of model 1,2 and 3 for differentiating benign and malignant NMBL was 0.966,0.964 and 0.957,respectively.Conclusion Ultrasound intelligent diagnostic system combined with mammography was helpful for differentiating benign and malignant NMBL.Combining with clinical indicators might improve diagnostic efficacy.

With the widespread adoption of lung cancer screening, an increasing number of patients are being diagnosed with early-stage lung adenocarcinoma. For stage ⅠA lung adenocarcinoma, sublobar resection is the primary treatment approach. However, in patients with concomitant spread through air space (STAS), numerous studies advocate for lobectomy as the mainstay of treatment. Due to the limitations in preoperative prediction and intraoperative frozen section evaluation for assessing STAS, current research is largely restricted to using clinical and imaging features to predict STAS occurrence, with results that are inconsistent and unsatisfactory. Furthermore, most studies focus on individual clinical or imaging characteristics, and there is a lack of large-sample investigations. The rise of artificial intelligence in recent years has provided new insights into solving this problem, and existing studies have shown that artificial intelligence demonstrates better performance in STAS prediction compared to conventional methods. This article reviews the value of artificial intelligence in predicting STAS.

Objective To explore the value of ultrasound intelligent diagnostic system combined with mammography for differentiating benign and malignant non-mass breast lesions(NMBL).Methods Totally 107 patients with NMBL were retrospectively enrolled,including 64 cases of malignant(malignant group)and 43 cases of benign lesions(benign group).Clinical,routine ultrasound,ultrasound intelligent diagnostic system(artificial intelligence[AI]system)and mammography data were compared between groups.Logistic regression analysis was performed,receiver operating characteristic(ROC)curves were drawn,the areas under the curves(AUC)were calculated,and the efficacy of AI system combined with mammography for differentiating benign and malignant NMBL was analyzed.Results Significant differences of the maximum diameter of lesion,ratio of axillary lymph node enlargement and suspected malignant calcification on mammography,as well as of AI system malignancy risk and AI system breast imaging reporting and data system(BI-RADS)classification were found between groups(all P＜0.05).AI system binary classification was obtained based on AI system malignancy risk.The AUC of suspected malignant calcification on mammography,AI system BI-RADS classification and AI system binary classification for differential diagnosis of benign and malignant NMBL was 0.840,0.810 and 0.817,respectively,while of suspected malignant calcification on mammography combined with AI system BI-RADS classification or AI system binary classification were both 0.856,higher than that of AI system BI-RADS classification/AI system binary classification alone(both P＜0.05)but not significantly different with that of suspected malignant calcification on mammography alone(both P＞0.05).Logistic regression analysis of age,the maximum diameter of lesion,axillary lymph node enlargement and suspected malignant calcification on mammography combined with AI system malignancy risk(model 1),AI system BI-RADS classification(model 2)or AI system binary classification(model 3)showed that suspected malignant calcification on mammography,AI system malignancy risk,AI system BI-RADS classification and AI system binary classification were all independent risk factors of malignant NMBL(all P＜0.05),and AUC of model 1,2 and 3 for differentiating benign and malignant NMBL was 0.966,0.964 and 0.957,respectively.Conclusion Ultrasound intelligent diagnostic system combined with mammography was helpful for differentiating benign and malignant NMBL.Combining with clinical indicators might improve diagnostic efficacy.

Purpose::Shaping and assembling contemporary external fixators rapidly for the severe mandibular fractures remains a challenge, especially in emergency circumstance. We designed a novel external fixator that incorporates universal joints to provide the stabilization for mandibular comminuted fractures. This study aims to confirm the efficacy of this novel external fixator through biomechanical tests in vitro and animal experiments. Methods::In vitro biomechanical tests were conducted using 6 fresh canine with mandibular defect to simulate critical comminuted fractures. Three mandibles were stabilized by the novel external fixator and other mandibles were fixed by 2.5 mm reconstruction plates. All fixed mandibles were subjected to loads of 350 N on the anterior regions of teeth and 550 N on the first molar of the unaffected side. The stability was evaluated based on the maximum displacement and the slope of the load-displacement curve. In animal experiments, 9 beagles with comminuted mandibular fractures were divided into 3 groups, which were treated with the novel external fixation, reconstruction plate, and dental arch bar, respectively. The general observation, the changes in animals’ weight, and the surgical duration were recorded and compared among 3 groups. The CT scans were performed at various intervals of 0 day (immediately after the surgery), 3 days, 7 days, 14 days, 21 days, and 28 days to analyze the displacement of feature points on the canine mandible and situation of fracture healing at 28 days. The statistical significance was assessed by the two-way analysis of variance test followed by the Bonferroni test, enabling multiple comparisons for all tests using GraphPad Prism10.1.0 (GraphPad Inc, USA). Results::The outcomes of the biomechanical tests indicated that no statistically significant differences were found in terms of the maximum displacement ( p = 0.496, 0.079) and the slope of load displacement curves ( p = 0.374, 0.349) under 2 load modes between the external and internal fixation groups. The animal experiment data showed that there were minor displacements of feature points between the external and internal fixation groups without statistic difference, while the arch bar group demonstrated inferior stability. The CT analysis revealed that the best fracture healing happened in the internal fixation group, followed by the external fixation and arch baring at 28 days after fixation. The external fixation group had the shortest fixation duration (25.67 ± 3.79) min compared to internal fixation ((70.67 ± 4.51) min, p < 0.001) and arch baring ((42.00 ± 3.00) min, p = 0.046). Conclusion::The conclusion of this study highlighted the efficacy and reliability of this novel external fixator in managing mandibular fractures rapidly, offering a viable option for the initial stabilization of comminuted mandibular fractures in the setting of emergency rescue.

Objective:To investigate the value of traditional metabolic parameters, CT features and intratumoral heterogeneity parameters measured by 18F-FDG PET/CT in predicting the mutation status of the epidermal growth factor receptor (EGFR) gene in patients with adenocarcinoma. Methods:A total of 147 patients (73 males, 74 females, age (59.8±10.2) years) with pathological confirmed adenocarcinoma between January 2016 and June 2020 in the Affiliated Hospital of Jining Medical University were retrospectively included. The differences of clinical data (smoking history, tumor location and clinical stage), CT features (maximum diameter, ground-glass opacity content, lobulation, speculation, cavitation, air-bronchogram, pleural retraction and bronchial cut-off sign), 18F-FDG PET/CT traditional metabolic parameters (SUV max, SUV mean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and intratumoral heterogeneity parameters ( CV, heterogeneity index (HI)) were analyzed between patients with EGFR mutation and patients with EGFR wild-type. Independent-sample t test, Mann-Whitney U test and χ2 test were used to analyze the data. Multivariate logistic regression was used to analyze the predictors of EGFR mutation. ROC curve analysis was used to evaluate the predictive value of clinical and PET/CT information. Results:Among 147 patients, 87 were with EGFR mutation and 60 were with EGFR wild-type. There were significant differences in gender (male/female), smoking history (with/without), location (peripheral lesion/central lesion), pleural retraction (with/without), SUV max, SUV mean, TLG, CV and HI ( χ2 values: 4.72-23.89, z values: from -2.31 to 5.74, all P<0.05). Multivariate logistic regression analysis showed that smoking history (odds ratio ( OR)=0.167, 95% CI: 0.076-0.366; P<0.001), pleural retraction ( OR=1.404, 95% CI: 1.115-3.745; P=0.012), SUV max ( OR=0.922, 95% CI: 0.855-0.995; P=0.003), TLG ( OR=0.991, 95% CI: 0.986-0.996; P=0.001) and HI ( OR=0.796, 95% CI: 0.700-0.859; P<0.001) were predictors of EGFR mutation. ROC curve analysis showed the AUC of HI was 0.779, with the sensitivity of 76.67%(46/60) and the specificity of 79.31%(69/87). The predictive model was constructed by combining smoking history, pleural retraction, TLG, SUV max and HI, and the AUC was 0.908, with the sensitivity of 88.33%(53/60) and the specificity of 68.97%(60/87). The difference of AUCs between HI and the predictive model was statistically significant ( z=3.71, P<0.001). Conclusion:HI can predict EGFR mutations better, and the predictive value for EGFR mutations can be enhanced when combining HI with smoking history, pleural retraction, TLG and SUV max.

cGAS-STING signaling pathway is a key signaling molecule of innate immune response in vivo,which can recognize exogenous and endogenous dsDNA abnormalities in cytoplasm and promote the release of immune mediators such as interferon(IFN)-1,thus leading to immune response in the body.Recent studies have suggested that the disturbance of cGAS-STING signal is an important factor in the occurrence and development of colorectal cancer,which can promote tumor growth and metastasis.cGAS-STING signaling is also related to intestinal immune response,and the use of this signaling pathway helps to provide a new target for colorectal cancer immunotherapy.This article reviewed the role of cGAS-STING signaling pathway in the occurrence and development of colorectal cancer and the latest research progress,the application of cGAS-STING signaling pathway modulators and their combined therapy in colorectal cancer,and forecast the future research direction of this signaling pathway in the treatment of colorectal cancer.

cGAS-STING signaling pathway is a key signaling molecule of innate immune response in vivo,which can recognize exogenous and endogenous dsDNA abnormalities in cytoplasm and promote the release of immune mediators such as interferon(IFN)-1,thus leading to immune response in the body.Recent studies have suggested that the disturbance of cGAS-STING signal is an important factor in the occurrence and development of colorectal cancer,which can promote tumor growth and metastasis.cGAS-STING signaling is also related to intestinal immune response,and the use of this signaling pathway helps to provide a new target for colorectal cancer immunotherapy.This article reviewed the role of cGAS-STING signaling pathway in the occurrence and development of colorectal cancer and the latest research progress,the application of cGAS-STING signaling pathway modulators and their combined therapy in colorectal cancer,and forecast the future research direction of this signaling pathway in the treatment of colorectal cancer.

Objective: To investigate the clinicopathologic and molecular genetic characteristics, diagnosis, differential diagnosis, treatment and prognosis of histiocyte-rich rhabdomyoblastic tumor (HRRMT). Methods: The clinical data of two cases of HRRMT diagnosed in Fujian Provincial Hospital and Fujian University of Traditional Chinese Medicine Affiliated People's Hospital from 2020 to 2021 were collected. Histopathology and immunohistochemical (IHC) staining were used to assess morphological changes; the genetic changes were analyzed with next-generation sequencing. The relevant literature was reviewed. Results: Both cases showed well-defined solid nodules and soft masses. Microscopically, the tumors had a fibrous pseudocapsule with lymphocytic aggregation, and locally invaded the surrounding skeletal muscle tissue, and the tumor cells were fusiform to epithelioid with an intensive foamy histiocytic infiltrate. No necrosis or mitosis was observed. Immunophenotyping showed the tumor cells were positive for desmin, either one or both skeletal muscle markers (myogenin or MyoD1), and negative for h-caldesmon, ALK and SMA. The Ki-67 index was<5%. Using next-generation sequencing, one case was found to harbour KRAS (G12D) and MSH3 (Q470^*) mutations. Conclusions: HRRMT is a newly described skeletal muscle tumor with uncertain malignant potential. Its diagnosis and differential diagnosis depend on morphologic and IHC staining. No specific molecular genetics changes have been identified so far.
Biomarkers, Tumor/analysis* ; Diagnosis, Differential ; Histiocytes/pathology* ; Humans ; Molecular Biology ; Muscle Neoplasms/pathology* ; Prognosis

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.
Antibodies, Monoclonal/pharmacology* ; Graft vs Host Disease/metabolism* ; Hematopoietic Stem Cell Transplantation ; Humans ; Killer Cells, Natural ; Retrospective Studies ; Treatment Outcome