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 analyze the clinical efficacy of Yunnan Baiyao in middle aged and elderly lung cancer patients undergoing the uniportal video-assisted thoracoscopic.Methods A total of 90 patients with non-small cell lung cancer meeting the criterias were screened and divided into two groups according to random number table method,which respectively received conventional treatment(control group)and Yunnan Baiyao treatment(experimental group).The perioperative period related indexes,coagulation function related indexes,and the occurrence rate of complications were observed and compared between the two groups.Results The intraoperative bleeding volume and thoracic drainage volume for the first day of experimental group were significantly lower than control group(P＜0.05).However,there were no significant difference in the coagulation function related indexes between two groups before and after surgery(P＞0.05).Additionally,there were also no significant difference in the occurrence rate of complication between two groups(P＞0.05).Conclusion Yunnan Baiyao can reduce intraoperative bleeding volume and chest tube drainage volume for the first day,promots the recovery of patients,and has a good clinical application value.

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.

AIM:To investigate the role and possible mechanisms of disulfiram(DSF)in a rat model of heart failure with preserved ejection fraction(HFpEF)induced by high-fat diet(HFD)and nitric oxide blocker Nω-nitro-L-argi-nine methyl ester(L-NAME).METHODS:The HFpEF rat model was constructed using HFD and L-NAME.Sprague-Dawley rats were randomly divided into 3 groups:control group(fed with a normal diet and water),HFpEF group(fed with HFD and drinking water containing 0.5 g/L L-NAME),and DSF+HFpEF group(treated with DSF in addition to HFD and L-NAME).After 5 weeks,cardiac function of the rats was examined using echocardiography and exercise test.Myo-cardial pathological changes were detected using hematoxylin-eosin and wheat germ agglutinin staining,the degree of car-diac fibrosis was assessed using Masson staining,and apoptosis levels were observed using TUNEL staining.Western blot was performed to detect the expression of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),cleaved caspase-1,gasdermin D N-terminal fragment(GSDMD-N)in the myocardium,and serum level of N-terminal pro-brain natriuretic peptide(NT-proBNP),and interleukin(IL)-1β and IL-18 in the myocardium were detected by ELISA.RESULTS:Compared with control group,the rats in HFpEF group showed increased body weight,systolic blood pres-sure,diastolic blood pressure,E/E′ ratio,left ventricular anterior wall thickness at diastole and serum NT-proBNP level(P<0.05),and decreased E/A ratio and absolute value of global longitudinal strain(GLS;P<0.05).In contrast,the rats in DSF+HFpEF group showed decreased body weight,E/E′ ratio,diastolic blood pressure and serum NT-proBNP level(P<0.05),and increased E/A ratio and absolute value of GLS(P<0.05),with no significant changes in systolic blood pressure,left ventricular posterior wall thickness at diastole and left ventricular ejection fraction(P>0.05).The rats in HFpEF group had increased myocardial fibrosis area,cardiomyocyte cross-sectional area,and apoptotic rate compared with control group(P<0.05),while these indexes were reduced in DSF+HFpEF group(P<0.05).The results of Western blot and ELISA showed that the levels of NLRP3,cleaved caspase-1,GSDMD-N,IL-1β and IL-18 were increased in the myocardium of rats in HFpEF group compared with control group(P<0.05),but decreased in DSF+HFpEF group com-pared with HFpEF group(P<0.05).CONCLUSION:Disulfiram improves cardiac function and attenuates myocardial remodeling in HFpEF rats.The mechanism may be related to the modulation of NLRP3/caspase-1/GSDMD signaling path-way and the reduction of myocardial inflammatory response.

Objective:To investigate the value of conventional ultrasound combined with shear wave elastography (SWE) in the differential diagnosis of non-mass ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) . Methods:A total of 102 patients with non-mass breast cancer admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from March 2019 to April 2022 were selected as the study objects, including 32 cases of DCIS and 70 cases of IBC. Conventional ultrasound parameters echo, microcalcification, location, posterior echo, blood flow, axillary lymph node, breast imaging reporting and data system (BI-RADS) score and SWE-related parameters maximum shear wave velocity (SWV max), minimum shear wave velocity (SWV min), mean shear wave velocity (SWV mean) and median shear wave velocity (SWV median) were compared between patients with non-mass DCIS and IBC. Binary logistic regression was used to analyze the independent factors for the differential diagnosis of non-mass DCIS and IBC. Based on the results of multivariate analysis, a nomogram prediction model was constructed and the predictive efficacy of the prediction model was evaluated by receiver operator characteristic (ROC) curve. Calibration curve and decision curve analysis (DCA) were used to evaluate the accuracy and practicability of the model. Results:There were statistically significant differences in blood flow ( χ2=8.47, P=0.004), axillary lymph nodes ( χ2=9.11, P=0.003), SWV max ( Z=-3.32, P<0.001), SWV mean ( t=3.00, P=0.003), SWV median ( Z=-2.69, P=0.007) between patients with non-mass DCIS and IBC. Multivariate analysis showed that, blood flow ( OR=3.56, 95% CI: 1.28-9.89, P=0.015), axillary lymph nodes ( OR=3.04, 95% CI: 1.10-8.42, P=0.032) and SWV max ( OR=1.40, 95% CI: 1.13-1.73, P=0.002) were independent factors for distinguishing non-mass DCIS from IBC. A nomogram prediction model was constructed based on blood flow, axillary lymph nodes and SWV max. ROC curve analysis showed that, the area under the curve of blood flow, axillary lymph nodes, SWV max, and prediction model for differential diagnosis of non-mass DCIS and IBC were 0.64 (95% CI: 0.52-0.76), 0.66 (95% CI: 0.55-0.77), 0.71 (95% CI: 0.60-0.81), and 0.79 (95% CI: 0.70-0.88), respectively, and the differential diagnostic value of prediction model was higher than that of blood flow ( Z=2.92, P=0.004), axillary lymph nodes ( Z=2.94, P=0.003), and SWV max ( Z=1.88, P=0.060) alone. The C-index of the prediction model for the differential diagnosis of non-mass DCIS and IBC was 0.77, and the calibration curve showed that the prediction probability of the prediction model was close to the actual probability. DCA showed that this prediction model could provide higher clinical net benefit and had certain clinical practicability. Conclusion:Blood flow and axillary lymph nodes in conventional ultrasound parameters and SWV max of SWE-related parameters are independent factors in the differential diagnosis of non-mass DCIS and IBC. The nomogram prediction model constructed by this method has a high value in the differential diagnosis of non-mass DCIS and IBC.

Objective To develop a new model for predicting recurrence after liver transplantation for hepatocellular carcinoma (HCC) beyond Milan criteria based on related preoperative and postoperative indicators. Methods A retrospective analysis was performed for the clinical data of the patients with HCC beyond Milan criteria who underwent orthotopic liver transplantation for the first time in Tianjin First Central Hospital from August 2014 to July 2018, and according to the presence or absence of recurrence during follow-up, the patients were divided into recurrence group and no-recurrence group. The t -test or the Mann-Whitney U test was used for comparison of continuous data between groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used for comparison of survival curves. Univariate and multivariate Cox proportional hazards regression analyses were used to identify the risk factors for recurrence-free survival after surgery. A new model was developed for recurrence after liver transplantation in the patients with HCC beyond Milan criteria based on the risk factors identified. The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive performance, and the Hosmer-Lemeshow test was used to assess the goodness of fit of the model. Results A total of 117 patients with HCC beyond Milan criteria were enrolled in this study, with a median follow-up time of 24 (1-74) months. A total of 53 patients (45.3%) experienced recurrence after surgery, among whom 52 (98.1%) had recurrence within 3 years after surgery, with a median time to recurrence of 6 (1-52) months. The Cox proportional hazards regression analysis showed that preoperative serum alpha-fetoprotein (AFP) >769 ng/mL, neutrophil-lymphocyte ratio (NLR) >3.75, and ki67 index >0.25 were independent risk factors for recurrence-free survival after liver transplantation. The model established based on these three risk factors had an AUC of 0.843, with good sensitivity (88.7%) and specificity (70.3%). The optimal cut-off value was selected according to the maximization of Youden index, and then the patients were divided into low-risk group (0-1 point) and high-risk group (1.5-4 points). The log-rank test showed that the low-risk group had significantly higher 3-and 5-year recurrence-free survival rates than the high-risk group (84.1%/72.0% vs 10.9%/10.9%, χ 2 =29.425, P < 0.001). Conclusion Liver transplantation for HCC beyond Milan criteria should be performed with caution, and the predictive model established based on preoperative AFP, NLR, and ki67 index can accurately assess the indication for liver transplantation in such patients.