Objective:To investigate the predictive value of conventional ultrasound，intratumoral and peritumoral radiomics models based on ultrasound images for the efficacy of neoadjuvant therapy in triple negative breast cancer（TNBC），and to construct a combined model.Methods:A total of 122 patients diagnosed with TNBC and admitted to Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School，Nanjing University between April 2020 and December 2023 were retrospectively selected as study subjects. All patients underwent surgical resection after neoadjuvant therapy and were categorized into two groups：50 cases in the pathological complete remission（pCR）group and 72 cases in the non-pCR group according to surgical pathology. A comprehensive array of clinical data，along with conventional ultrasound imaging findings，was systematically collected from patients prior to treatment and at the conclusion of the second cycle of treatment. The region of interest（ROI）was delineated on the baseline two-dimensional gray-scale ultrasound image using 3D Slicer software on the maximum long-axis section of the lesion. The peri-tumor area was obtained by circularly expanding outward by 5 mm，and the imaging histological features were extracted separately. The dataset was then randomly partitioned into a training set and a validation set，with a ratio of 7∶3. The χ2/ t/Mann-Whitney U tests were used for intergroup comparison of general information. Maximum correlation minimum redundancy and least absolute shrinkage and selection operator regression were used to screen the optimal radiomics feature set，respectively. Variables that exhibited statistically significant differences between group comparisons were then employed to construct combined models，incorporating intratumor and peritumor ultrasonographic models. The predictive efficacy，accuracy，and clinical utility of the models were assessed using ROC curves，calibration curves，and decision curve analysis（DCA），respectively. Results:Subsequent between-group comparisons and multifactorial Logistic regression analysis identified blood flow（ OR=0.213，95% CI=0.062-0.735）and change rate of length diameter（ OR=1.091，95% CI=1.013-1.175）as independent risk factors for predicting pCR. A total of seven and eight radiomics features from each of the intratumoral and peritumoral regions were screened for the construction of intratumoral imaging histology score（RS）and peritumoral RS. The Nomogram model was constructed by combining the blood flow，change rate of length diameter，intratumoral RS，and peritumoral RS，and its AUC values in the training and validation sets were 0.884（95% CI=0.815-0.953）and 0.841（95% CI=0.683-0.940），respectively. The calibration curves demonstrated the Nomogram model's exceptional precision，with a C-index of 0.860 and 0.782 for the training and validation sets，respectively. The DCA revealed that the Nomogram model exhibited the optimal net clinical benefit. Conclusions:Conventional ultrasound，intratumoral and peritumoral radiomics models based on ultrasound images have been shown to possess satisfactory predictive value for the efficacy of neoadjuvant therapy in TNBC，thereby facilitating clinical decision-making.

OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*

OBJECTIVES: To investigate the regulatory role of Ral guanine nucleotide dissociation stimulator-like 1 (RGL1) in metastasis of colorectal cancer (CRC). METHODS: We analyzed the differential expression of RGL1 between metastatic and non-metastatic CRC in GEO database, and examined its expression in 25 patients with metastatic CRC and 25 patients with non-metastatic CRC treated in Zhujiang Hospital between January, 2020 and December, 2022 using quantitative PCR (qPCR) and immunohistochemistry. HCT116 cell lines with stable RGL1 overexpression and SW480 cells with RGL1 knockdown were established using lentiviral vecors, and the changes in invasion and migration abilities of the cells were assessed using Transwell invasion and migration assays. The transduced cells were injected into the serosa of the cecum of nude mice, and tumor growth and liver metastasis were observed 8 weeks later. Fibronectin adhesion assays and immunofluorescence experiments were employed to assess the relationship between RGL1 and focal adhesion formation, and co-immuno-precipitation assays were performed to explore the interaction between RGL1 and GTPase activation. RESULTS: Compared with non-metastatic CRC, metastatic CRC showed significantly upregulated expression of RGL1. HCT116 cells overexpressing RGL1 exhibited obviously enhanced migration and invasion in vitro with increased capacity for liver metastasis in nude mice. RGL1 overexpression strongly accelerated focal adhesion assembly, facilitated the formation of motile focal adhesions, and enhanced the binding of activated CDC42/RAC1 complex to RGL1. CONCLUSIONS RGL1 is highly expressed in metastatic CRC and promotes distant metastasis of CRC by activating the CDC42/RAC1 complex to facilitate the formation of motile focal adhesions. These findings suggest that RGL1 can potentially serve as a therapeutic target for CRC metastasis.
Humans ; Colorectal Neoplasms/metabolism* ; cdc42 GTP-Binding Protein/metabolism* ; Animals ; Mice, Nude ; rac1 GTP-Binding Protein/metabolism* ; Cell Movement ; Mice ; Focal Adhesions/metabolism* ; Neoplasm Metastasis ; Cell Line, Tumor ; HCT116 Cells ; Up-Regulation ; Neoplasm Invasiveness ; Adaptor Proteins, Signal Transducing ; Female ; Rho Guanine Nucleotide Exchange Factors

Immune suppression in the tumor microenvironment (TME) is closely related to abnormal glycolysis. Tumor cells gain metabolic advantages and suppress immune responses through the "Warburg effect". Traditional Chinese medicine (TCM) has been shown to regulate key glycolysis enzymes (such as HK2 and PKM2), metabolic signaling pathways (such as PI3K/AKT/mTOR, HIF-1α) and non-coding RNAs at multiple targets, thus synergistically inhibiting lactate accumulation, improving vascular abnormalities, and relieving metabolic inhibition of immune cells. Studies have shown that TCM monomers and formulas can promote immune cell infiltration and functions, improve metabolic microenvironment, and with the assistance by the nano-delivery system, enhance the precision of treatment. However, the dynamic mechanism of the interaction between TCM-regulated glycolysis and TME has not been fully elucidated, for which single-cell sequencing and other technologies provide important technical support to facilitate in-depth analysis and clinical translational research. Future studies should be focused on the synergistic strategy of "metabolic reprogramming-immune activation" to provide new insights into the mechanisms of tumor immunotherapy.
Humans ; Tumor Microenvironment/immunology* ; Glycolysis/drug effects* ; Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Signal Transduction ; Drugs, Chinese Herbal/pharmacology*

Objective To explore the relationship between serum galactomannano(GM)level and specific antibody level of Aspergillus fumigatus in patients with allergic bronchopulmonary aspergillus(ABPA)recurrence.Methods A total of 124 patients diagnosed with ABPA and treated with hormone therapy in our hospital from June 2020 to June 2023 were retrospectively analyzed.According to the recurrence after treatment,the patients were divided into non-recurrence group(n=72)and recurrence group(n=52).The clinical data,blood routine indicators,GM and Aspergillus fumigatus specific antibody level of the two groups were recorded.Results Age,white blood cell(WBC),neutrophil(NEU),lymphocyte(LYM),eosinophil(EOS),GM,serum total immunoglobulin E(tIgE),Aspergillus fumigatus specific immunoglobulin E(sIgE)and Aspergillus fumigatus specific immunoglobulin G(sIgG)were higher in the recurrence group than in the non-recurrence group(P＜0.05).There was a nonlinear relation-ship between GM and sIgE/sIgG(P＜0.05).GM,sIgE and sIgG were independently correlated with the risk of ABPA recurrence(P＜0.05),and had a nonlinear dose-response relationship with the risk of ABPA recurrence(Pfor non linear＜0.05).Under different GM level,the higher the sIgE and sIgG,the higher the ABPA recurrence rate.There was an interaction between GM and sIgE/sIgG.Conclusions With the increase of GM,sIgE and sIgG level,the recurrence rate of ABPA increases.Serum GM level in ABPA recurrence patients is correlated with Aspergillus fumigatus specific antibody.

Objective To evaluate the effectiveness of bronchial artery embolization(BAE)combined with surgical lobectomy in treating patients with refractory hemoptysis caused by bronchiectasis.Methods The clinical data of 168 patients with bronchiectasis and refractory hemoptysis,who were treated at the Wuhan Jinyintan Hospital of China from January 2018 to January 2022,were retrospectively analyzed.Of the 168 patients,91 underwent lobectomy(control group),and 71 underwent BAE combined with lobectomy(observation group).The therapeutic efficacy,intraoperative blood loss,surgical operation time,postoperative 3-day drainage volume,length of hospital stay,hemoptysis recurrence rate,and complications were compared between the two groups.Results In the observation group,the clinical efficacy was higher than that in the control group,while the intraoperative blood loss,operation time,length of hospital stay,postoperative 3-day drainage volume and recurrence rate were lower than those in the control group(all P＜0.05).No statistically significant difference in the incidence of complications existed between the two groups(P＞0.05).Conclusion In treating patients with refractory hemoptysis due to bronchiectasis,BAE combined with lobectomy can improve the therapeutic efficacy while not increasing the risk of complications.

Objective:To explore the predictive value of ultrasonic shear wave elastography (SWE) parameters and pathological characteristics on the status of human epidermal growth factor receptor 2 (HER2), which is difficult to be determined by immunohistochemistry (IHC) in breast cancer, and to construct a nomogram model.Methods:A retrospective case-control study was conducted. One hundred and fifteen cases of breast cancer diagnosed and treated in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from September 2018 to April 2022 were selected, and their HER2 was evaluated as IHC 2+; the HER2 expression status was determined by fluorescence in situ hybridization (FISH) detection, including 23 HER2 positive cases and 92 HER2 negative cases. The ultrasound SWE parameters [including maximum shear wave velocity (V max), mean shear wave velocity (V mean), median shear wave velocity (V median), minimum shear wave velocity (V min)] and clinicopathological characteristics between HER2 positive and negative groups were compared. The variables with statistically significant differences ( P < 0.05) between groups were included in a multivariate logistic regression model, the independent risk factors for HER2 positivity were screened, and a nomogram model was constructed based on these independent risk factors. With the FISH test results as the gold standard, the efficacy of nomogram in judging HER2 positivity in breast cancer which was difficult to be identified by IHC was evaluated with the receiver operating characteristic (ROC) curve; the accuracy and clinical net benefit of the nomogram model were evaluated using calibration curve and decision curve analysis (DCA), respectively. Results:The patients were all female, aged (56±13) years, ranging from 30 to 88 years old. V max [ M ( Q1, Q3)] [8.54 (7.38, 9.47) m/s vs. 6.46 (5.07, 8.42) m/s], V mean [(5.41±0.78) m/s vs. (4.53±1.22) m/s], V median [5.06 (4.48, 5.52) m/s vs. 4.35 (3.42, 4.96) m/s], V min [3.35 (2.68, 3.88) m/s vs. 2.59 (2.11, 3.34) m/s], the proportion of patients with axillary lymph node metastasis [56.5% (13/23) vs. 22.8% (21/92)], and the Ki-67 positivity index [35% (30%, 55%) vs. 25% (15%, 35%)] in the HER2 positive group were higher than those in the HER2 negative group, and the differences were statistically significant (all P < 0.05); There was no statistically significant difference in age, lesion location, pathological type, vascular invasion, nerve invasion and long diameter, short diameter, echo, regular shape, clear boundary, posterior echo, calcification, blood flow grading, Breast Imaging Report and Data System (BI-RADS) classification detected by ultrasound between the two groups (all P > 0.05). Multivariate logistic regression analysis showed that increased ultrasound V max ( OR = 1.786, 95% CI: 1.283-2.485, P = 0.001) and axillary lymph node metastasis ( OR = 4.185, 95% CI: 1.327-13.197, P = 0.015) and elevated Ki-67 positivity index ( OR = 1.042, 95% CI: 1.014-1.071, P = 0.003) were independent risk factors for HER2 positivity. ROC curve analysis showed that the area under the curve (AUC) of HER2 positive breast cancer which was difficult to be determined by IHC was 0.816 (95% CI: 0.732-0.883), that was higher than 0.712 (95% CI: 0.620-0.794) of V max, 0.601 (95% CI: 0.504-0.692) of axillary lymph node metastasis and 0.706 (95% CI: 0.613-0.788) of Ki-67 positivity index based on the nomogram constructed by the above independent risk factors, with statistically significant differences (all P < 0.05). The calibration curve showed that the predicted probability of the nomogram model was close to the actual probability, and DCA indicated that the clinical net benefit of the model was good. Conclusions:The nomogram constructed based on ultrasonic SWE parameter V max, axillary lymph node metastasis and Ki-67 positivity index has a good predictive effect on HER2 status of breast cancer which is difficult to be determined by IHC.

Objective:To investigate the predictive value of conventional ultrasound，intratumoral and peritumoral radiomics models based on ultrasound images for the efficacy of neoadjuvant therapy in triple negative breast cancer（TNBC），and to construct a combined model.Methods:A total of 122 patients diagnosed with TNBC and admitted to Nanjing Drum Tower Hospital，Affiliated Hospital of Medical School，Nanjing University between April 2020 and December 2023 were retrospectively selected as study subjects. All patients underwent surgical resection after neoadjuvant therapy and were categorized into two groups：50 cases in the pathological complete remission（pCR）group and 72 cases in the non-pCR group according to surgical pathology. A comprehensive array of clinical data，along with conventional ultrasound imaging findings，was systematically collected from patients prior to treatment and at the conclusion of the second cycle of treatment. The region of interest（ROI）was delineated on the baseline two-dimensional gray-scale ultrasound image using 3D Slicer software on the maximum long-axis section of the lesion. The peri-tumor area was obtained by circularly expanding outward by 5 mm，and the imaging histological features were extracted separately. The dataset was then randomly partitioned into a training set and a validation set，with a ratio of 7∶3. The χ2/ t/Mann-Whitney U tests were used for intergroup comparison of general information. Maximum correlation minimum redundancy and least absolute shrinkage and selection operator regression were used to screen the optimal radiomics feature set，respectively. Variables that exhibited statistically significant differences between group comparisons were then employed to construct combined models，incorporating intratumor and peritumor ultrasonographic models. The predictive efficacy，accuracy，and clinical utility of the models were assessed using ROC curves，calibration curves，and decision curve analysis（DCA），respectively. Results:Subsequent between-group comparisons and multifactorial Logistic regression analysis identified blood flow（ OR=0.213，95% CI=0.062-0.735）and change rate of length diameter（ OR=1.091，95% CI=1.013-1.175）as independent risk factors for predicting pCR. A total of seven and eight radiomics features from each of the intratumoral and peritumoral regions were screened for the construction of intratumoral imaging histology score（RS）and peritumoral RS. The Nomogram model was constructed by combining the blood flow，change rate of length diameter，intratumoral RS，and peritumoral RS，and its AUC values in the training and validation sets were 0.884（95% CI=0.815-0.953）and 0.841（95% CI=0.683-0.940），respectively. The calibration curves demonstrated the Nomogram model's exceptional precision，with a C-index of 0.860 and 0.782 for the training and validation sets，respectively. The DCA revealed that the Nomogram model exhibited the optimal net clinical benefit. Conclusions:Conventional ultrasound，intratumoral and peritumoral radiomics models based on ultrasound images have been shown to possess satisfactory predictive value for the efficacy of neoadjuvant therapy in TNBC，thereby facilitating clinical decision-making.

Objective:To explore the predictive value of ultrasonic shear wave elastography (SWE) parameters and pathological characteristics on the status of human epidermal growth factor receptor 2 (HER2), which is difficult to be determined by immunohistochemistry (IHC) in breast cancer, and to construct a nomogram model.Methods:A retrospective case-control study was conducted. One hundred and fifteen cases of breast cancer diagnosed and treated in Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from September 2018 to April 2022 were selected, and their HER2 was evaluated as IHC 2+; the HER2 expression status was determined by fluorescence in situ hybridization (FISH) detection, including 23 HER2 positive cases and 92 HER2 negative cases. The ultrasound SWE parameters [including maximum shear wave velocity (V max), mean shear wave velocity (V mean), median shear wave velocity (V median), minimum shear wave velocity (V min)] and clinicopathological characteristics between HER2 positive and negative groups were compared. The variables with statistically significant differences ( P < 0.05) between groups were included in a multivariate logistic regression model, the independent risk factors for HER2 positivity were screened, and a nomogram model was constructed based on these independent risk factors. With the FISH test results as the gold standard, the efficacy of nomogram in judging HER2 positivity in breast cancer which was difficult to be identified by IHC was evaluated with the receiver operating characteristic (ROC) curve; the accuracy and clinical net benefit of the nomogram model were evaluated using calibration curve and decision curve analysis (DCA), respectively. Results:The patients were all female, aged (56±13) years, ranging from 30 to 88 years old. V max [ M ( Q1, Q3)] [8.54 (7.38, 9.47) m/s vs. 6.46 (5.07, 8.42) m/s], V mean [(5.41±0.78) m/s vs. (4.53±1.22) m/s], V median [5.06 (4.48, 5.52) m/s vs. 4.35 (3.42, 4.96) m/s], V min [3.35 (2.68, 3.88) m/s vs. 2.59 (2.11, 3.34) m/s], the proportion of patients with axillary lymph node metastasis [56.5% (13/23) vs. 22.8% (21/92)], and the Ki-67 positivity index [35% (30%, 55%) vs. 25% (15%, 35%)] in the HER2 positive group were higher than those in the HER2 negative group, and the differences were statistically significant (all P < 0.05); There was no statistically significant difference in age, lesion location, pathological type, vascular invasion, nerve invasion and long diameter, short diameter, echo, regular shape, clear boundary, posterior echo, calcification, blood flow grading, Breast Imaging Report and Data System (BI-RADS) classification detected by ultrasound between the two groups (all P > 0.05). Multivariate logistic regression analysis showed that increased ultrasound V max ( OR = 1.786, 95% CI: 1.283-2.485, P = 0.001) and axillary lymph node metastasis ( OR = 4.185, 95% CI: 1.327-13.197, P = 0.015) and elevated Ki-67 positivity index ( OR = 1.042, 95% CI: 1.014-1.071, P = 0.003) were independent risk factors for HER2 positivity. ROC curve analysis showed that the area under the curve (AUC) of HER2 positive breast cancer which was difficult to be determined by IHC was 0.816 (95% CI: 0.732-0.883), that was higher than 0.712 (95% CI: 0.620-0.794) of V max, 0.601 (95% CI: 0.504-0.692) of axillary lymph node metastasis and 0.706 (95% CI: 0.613-0.788) of Ki-67 positivity index based on the nomogram constructed by the above independent risk factors, with statistically significant differences (all P < 0.05). The calibration curve showed that the predicted probability of the nomogram model was close to the actual probability, and DCA indicated that the clinical net benefit of the model was good. Conclusions:The nomogram constructed based on ultrasonic SWE parameter V max, axillary lymph node metastasis and Ki-67 positivity index has a good predictive effect on HER2 status of breast cancer which is difficult to be determined by IHC.

With the improvement of living standard and dietary changes,metabolic dysfunction-associated steatotic liver disease(MASLD)has become one of the most common chronic liver diseases worldwide.Studies have shown that alterations in gut microflora are associated with the metabolic syndrome,and MASLD is regarded as a manifestation of metabolic syndrome in the liver.In recent years,it has been found that small intestinal bacterial overgrowth(SIBO)is closely related to the development of MASLD.SIBO can contribute to MASLD by disrupting the intestinal mucosal barrier through the gut-hepatic axis,and by altering the intestinal microbiota and its metabolic products.This article reviewed the advances in research on SIBO and MASLD.