Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P＜0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.

Objective:To investigate the correlation between leucine-rich α2 glycoprotein (LRG) and endoscopic activity in patients with Crohn′s disease (CD), based on the assessment of inflammation in small intestinal lesion by double-balloon enteroscope (DBE).Methods:From 15 August 2022 to 22 August 2023, the clinical data of 139 patients with small bowel CD diagnosed by DBE at the First Affiliated Hospital of Anhui Medical University were prospectively collected, which included fecal calprotectin (FC), C-reactive protein (CRP), white blood cell count, hemoglobin, albumin, Crohn′s disease activity index (CDAI), and simple endoscopic score for Crohn′s disease (SES-CD). According to the SES-CD, endoscopic activity was classified as mucosal healing (0), endoscopic remission (0 to 2), mild activity (3 to 6), moderate activity (7 to 15), and severe activity (≥16). LRG levels were detected in all patients. Spearman rank correlation was used to analyze the correlation between LRG, clinical biochemical parameters and endoscopic scores. Receiver operating characteristic curve (ROC) was performed to determine the optimal cut-off value of LRG for evaluating endoscopic mucosal healing. Mann-Whitney U test, Kruskal-Wallis H test, and Bonferroni corrected test were used for statistical analysis. Results:Among 139 patients with small bowel CD, the LRG level was 17.3 (13.0, 25.2) mg/L, and SES-CD was 5 (1, 9); 32 patients achieved mucosal healing, 50 patients achieved endoscopic remission; 39 patients had mild activity, 40 patients had moderate activity, and 10 patients had severe activity. The SES-CD was negatively correlated with both hemoglobin and albumin ( r=-0.177 (95% confidence interval, 95% CI: -0.334 to -0.011), -0.293 (95% CI: -0.438 to -0.133)), with statistical significance ( P=0.037, <0.001). The SES-CD was positively correlated with CRP, CDAI, LRG and FC ( r=0.344 (95% CI: 0.188 to 0.482), 0.429 (95% CI: 0.282 to 0.556), 0.525 (95% CI: 0.393 to 0.636), 0.661 (95% CI: 0.556 to 0.745)), with statistical significant (all P<0.001). For the 64 small bowel CD patients with CRP in the normal reference value, SES-CD was positively correlated with CDAI, LRG and FC ( r=0.296 (95% CI: 0.054 to 0.505), 0.364 (95% CI: 0.129 to 0.559), 0.547 (95% CI: 0.348 to 0.699)), with statistical significance ( P=0.017, =0.003, <0.001). The LRG level of patients with endoscopic mucosal healing was significantly lower than that of patients with endoscopic remission (11.5 (10.1, 17.2) mg/L vs. 17.3 (13.4, 23.5) mg/L), with statistical significance ( Z=-3.25, P<0.001). ROC analysis showed that the area under the curve (AUC) of LRG in predicting endoscopic mucosal healing was 0.81 (95% CI: 0.73 to 0.89), with an optimal cut-off value of 15.27 mg/L. The sensitivity, specificity, positive predictive value and negative predictive value were 0.757, 0.718, 0.900 and 0.469, respectively. The accuracy of the combination of LRG and FC (AUC was 0.88, 95% CI: 0.82 to 0.94) in predicting endoscopic mucosal healing was higher than that of LRG alone (AUC was 0.81, 95% CI: 0.73 to 0.89), and the difference was statistically significant ( P=0.011). Conclusion:Based on the results of DBE, LRG may be a reliable biomarker for predicting endoscopic remission and mucosal healing in patients with small bowel CD.

Objective To investigate the anti-tumor mechanism of natural compound toosendanin(TSN)combined with olaparib in triple-negative breast cancer(TNBC).Methods Human TNBC cell line MDA-MB-231 was cultured in vitro.Effects of TSN combined with olaparib on autophagy levels and cell viability in MDA-MB-231 cells were evaluated using 0.5,1.0,and 5.0 μmol/L olaparib alone or in combination.Surgical specimens from four TNBC patients who had residual tumors after neoadjuvant chemotherapy were selected to establish patient-derived organoid(PDO)models.The drug sensitivity of TSN combined with olaparib in TNBC patients was detected.Whether TSN combined with olaparib can exert autophagy inhibitory effects and tumor-killing effects in organoid model was verified.Results Olaparib induced autophagy in MDA-MB-231 cell line,and the combination of TSN and olaparib inhibited the proliferation of MDA-MB-231 cells(P＜0.01).In the TNBC PDOs model,the therapeutic effect of olaparib combined with TSN can significantly reduce the proliferation ability of tumor cells compared with olaparib alone.Conclusion The tumor-killing effect of TSN combined with olaparib is superior to that of olaparib alone,and the mechanism may be related to autophagy inhibition.

Objective:To investigate the correlation between leucine-rich α2 glycoprotein (LRG) and endoscopic activity in patients with Crohn′s disease (CD), based on the assessment of inflammation in small intestinal lesion by double-balloon enteroscope (DBE).Methods:From 15 August 2022 to 22 August 2023, the clinical data of 139 patients with small bowel CD diagnosed by DBE at the First Affiliated Hospital of Anhui Medical University were prospectively collected, which included fecal calprotectin (FC), C-reactive protein (CRP), white blood cell count, hemoglobin, albumin, Crohn′s disease activity index (CDAI), and simple endoscopic score for Crohn′s disease (SES-CD). According to the SES-CD, endoscopic activity was classified as mucosal healing (0), endoscopic remission (0 to 2), mild activity (3 to 6), moderate activity (7 to 15), and severe activity (≥16). LRG levels were detected in all patients. Spearman rank correlation was used to analyze the correlation between LRG, clinical biochemical parameters and endoscopic scores. Receiver operating characteristic curve (ROC) was performed to determine the optimal cut-off value of LRG for evaluating endoscopic mucosal healing. Mann-Whitney U test, Kruskal-Wallis H test, and Bonferroni corrected test were used for statistical analysis. Results:Among 139 patients with small bowel CD, the LRG level was 17.3 (13.0, 25.2) mg/L, and SES-CD was 5 (1, 9); 32 patients achieved mucosal healing, 50 patients achieved endoscopic remission; 39 patients had mild activity, 40 patients had moderate activity, and 10 patients had severe activity. The SES-CD was negatively correlated with both hemoglobin and albumin ( r=-0.177 (95% confidence interval, 95% CI: -0.334 to -0.011), -0.293 (95% CI: -0.438 to -0.133)), with statistical significance ( P=0.037, <0.001). The SES-CD was positively correlated with CRP, CDAI, LRG and FC ( r=0.344 (95% CI: 0.188 to 0.482), 0.429 (95% CI: 0.282 to 0.556), 0.525 (95% CI: 0.393 to 0.636), 0.661 (95% CI: 0.556 to 0.745)), with statistical significant (all P<0.001). For the 64 small bowel CD patients with CRP in the normal reference value, SES-CD was positively correlated with CDAI, LRG and FC ( r=0.296 (95% CI: 0.054 to 0.505), 0.364 (95% CI: 0.129 to 0.559), 0.547 (95% CI: 0.348 to 0.699)), with statistical significance ( P=0.017, =0.003, <0.001). The LRG level of patients with endoscopic mucosal healing was significantly lower than that of patients with endoscopic remission (11.5 (10.1, 17.2) mg/L vs. 17.3 (13.4, 23.5) mg/L), with statistical significance ( Z=-3.25, P<0.001). ROC analysis showed that the area under the curve (AUC) of LRG in predicting endoscopic mucosal healing was 0.81 (95% CI: 0.73 to 0.89), with an optimal cut-off value of 15.27 mg/L. The sensitivity, specificity, positive predictive value and negative predictive value were 0.757, 0.718, 0.900 and 0.469, respectively. The accuracy of the combination of LRG and FC (AUC was 0.88, 95% CI: 0.82 to 0.94) in predicting endoscopic mucosal healing was higher than that of LRG alone (AUC was 0.81, 95% CI: 0.73 to 0.89), and the difference was statistically significant ( P=0.011). Conclusion:Based on the results of DBE, LRG may be a reliable biomarker for predicting endoscopic remission and mucosal healing in patients with small bowel CD.

Organoids can well simulate the heterogeneity of tumors,including tumor microenvironment and immune response,which helps to more accurately predict patient responses to drug and treatment effects.Organoids can be used for drug screening before drugs enter body,thus reducing the time and cost of clinical trials.However,research on tissue-organoids still faces some challenges,such as technical limitation and ethical issue.This review mainly introduces the progress in the research of breast cancer organoids,including the definition of organoids,development history,advantages and application in breast cancer research.

Objective:To explore the expression level and clinical significance of low-density granulocytes (LDGs) in peripheral blood of patients with inflammatory bowel disease (IBD) .Methods:A cross-sectional survey was conducted. Clinical data of IBD patients admitted to the Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University from August 2022 to January 2023 were collected. A total of 45 healthy people were enrolled as the normal control group. Simple endoscopic score for Crohn′s disease (SES-CD) was used to evaluate the activity of Crohn′s disease (CD) and Mayo endoscopic score (MES) was used to evaluate the activity of ulcerative colitis (UC). Laboratory indicators included LDGs, white blood cell count (WBC), hemoglobin (HB), platelet count (PLT), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and fecal calprotectin (FC). The difference in LDGs level between IBD patients and the normal control group was statistically analyzed and the relationship between LDGs level and clinical characteristics of IBD patients was analyzed. Receiver operating characteristic (ROC) curve was used to calculate the predictive value of LDGs for the disease activity of IBD.Results:A total of 130 IBD patients were included, including 83 CD patients and 47 UC. Compared with the normal control group, the LDGs levels of patients in the CD group and UC group were respectively higher[CD: 0.53% (0.32%, 1.41%) vs. 0.19% (0.12%, 0.29%), H= 57.71, P<0.001; UC: 0.87% (0.43%, 1.90%) vs. 0.19% (0.12%, 0.29%), H= 73.23, P<0.001]. Compared with the CD patients in remission phase, the level of LDGs in active CD patients was higher ( P<0.001). Compared with the CD patients in mild activity phase, the LDGs levels of CD patients in moderate and severe activity phases were higher (all P<0.05). In terms of different disease behaviours, the level of LDGs in stricturing CD patients was the highest [1.37% (0.91%, 3.06%), all P<0.05]. Compared with the UC patients in remission phase, the level of LDGs in active UC patients was higher ( P<0.001). Compared with the UC patients in mild activity phase, the LDGs levels of UC patients in moderate and severe activity phases were higher (all P<0.05). In the CD group, LDGs level was positively correlated with CRP, FC, NLR, PLT, simple Crohn′s disease activity index (CDAI), and SES-CD ( r= 0.374, 0.548, 0.345, 0.284, 0.764, 0.721, all P<0.05). In the UC group, LDG levels was positively correlated with CRP, FC, NLR, Sutherland disease activity index (DAI), and MES ( r= 0.325, 0.666, 0.474, 0.638, 0.740, all P<0.05). In CD patients, the cut-off value of LDGs was 0.565%, with the area under curve (AUC) of 0.873, sensitivity of 73.50%, and specificity of 99.30%. In UC patients, the cut-off value of LDGs was 0.545%, with the AUC of 0.877, sensitivity of 76.90%, and specificity of 100.00%. Conclusion:The expression of LDGs in IBD patients is significantly high, which correlates with the disease activity and may be used as a biological marker for the clinical evaluation of IBD patients.

Objective:To explore the expression level and clinical significance of low-density granulocytes (LDGs) in peripheral blood of patients with inflammatory bowel disease (IBD) .Methods:A cross-sectional survey was conducted. Clinical data of IBD patients admitted to the Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University from August 2022 to January 2023 were collected. A total of 45 healthy people were enrolled as the normal control group. Simple endoscopic score for Crohn′s disease (SES-CD) was used to evaluate the activity of Crohn′s disease (CD) and Mayo endoscopic score (MES) was used to evaluate the activity of ulcerative colitis (UC). Laboratory indicators included LDGs, white blood cell count (WBC), hemoglobin (HB), platelet count (PLT), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and fecal calprotectin (FC). The difference in LDGs level between IBD patients and the normal control group was statistically analyzed and the relationship between LDGs level and clinical characteristics of IBD patients was analyzed. Receiver operating characteristic (ROC) curve was used to calculate the predictive value of LDGs for the disease activity of IBD.Results:A total of 130 IBD patients were included, including 83 CD patients and 47 UC. Compared with the normal control group, the LDGs levels of patients in the CD group and UC group were respectively higher[CD: 0.53% (0.32%, 1.41%) vs. 0.19% (0.12%, 0.29%), H= 57.71, P<0.001; UC: 0.87% (0.43%, 1.90%) vs. 0.19% (0.12%, 0.29%), H= 73.23, P<0.001]. Compared with the CD patients in remission phase, the level of LDGs in active CD patients was higher ( P<0.001). Compared with the CD patients in mild activity phase, the LDGs levels of CD patients in moderate and severe activity phases were higher (all P<0.05). In terms of different disease behaviours, the level of LDGs in stricturing CD patients was the highest [1.37% (0.91%, 3.06%), all P<0.05]. Compared with the UC patients in remission phase, the level of LDGs in active UC patients was higher ( P<0.001). Compared with the UC patients in mild activity phase, the LDGs levels of UC patients in moderate and severe activity phases were higher (all P<0.05). In the CD group, LDGs level was positively correlated with CRP, FC, NLR, PLT, simple Crohn′s disease activity index (CDAI), and SES-CD ( r= 0.374, 0.548, 0.345, 0.284, 0.764, 0.721, all P<0.05). In the UC group, LDG levels was positively correlated with CRP, FC, NLR, Sutherland disease activity index (DAI), and MES ( r= 0.325, 0.666, 0.474, 0.638, 0.740, all P<0.05). In CD patients, the cut-off value of LDGs was 0.565%, with the area under curve (AUC) of 0.873, sensitivity of 73.50%, and specificity of 99.30%. In UC patients, the cut-off value of LDGs was 0.545%, with the AUC of 0.877, sensitivity of 76.90%, and specificity of 100.00%. Conclusion:The expression of LDGs in IBD patients is significantly high, which correlates with the disease activity and may be used as a biological marker for the clinical evaluation of IBD patients.

Objective:To study on the effects of gastrointestinal function and portal vein hemodynamics applicated with abdominal hot compressing with evodiae fructus and crude salt after hepatectomy.Methods:A total of 60 patients who underwent hepatectomy were randomly divided into 2 groups by random number table method, with 30 in each group. The control group was treated with conventional basic western medicine, while the treatment group was treated with medicinal evodiae fructus and crude salt hot compress on abdomen on the basis of the control group. The portal vein diameter (PVD), portal venous flow velocity (PVV), recovery time of main clinical indexes, clinical symptom scores and liver function indexes were dynamically monitored at different observation time points.Results:The scores of abdominal distension, nausea and vomiting in the treatment group were significantly lower than those in the control group 3 days after treatment ( t values were -3.489 and -2.740, respectively, all Ps<0.05). The recovery time of bowel sounds, first exhaust time and first defecation time in the treatment group were significantly earlier than those in the control group ( t values were -3.622, -4.297 and -4.151, respectively, all Ps<0.01). With the extension of treatment time, ALT in 2 groups showed a gradual downward trend ( P<0.05 or P<0.01), DBIL in control group was significantly higher at 3 days after treatment than before ( t=-2.157, P=0.039), and TBIL was significantly lower at 7 days after treatment than before ( t=2.175, P=0.038). The PVD ( t values were 3.528, 2.160) and PVV ( t values were 11.096, 4.264) of the treatment group were significantly higher than those of the control group 3 and 5 days after treatment ( P<0.01 or P<0.05). Conclusion:Early application of abdominal hot compressing with evodiae fructus and crude salt hot compress on abdomen after hepatectomy can improve the portal vein blood circulation and promote the rehabilitation of gastrointestinal function in patients with hepatectomy.

Objective: To investigate the clinicopathological, and molecular characteristics of myoepithelial tumors (MTs) of salivary glands. Methods: A total of 37 MTs cases including 13 malignant epithelial tumors (MMTs) and 24 benign epithelial tumors (BMTs) of salivary glands were identified from the archives of the Department of Pathology, General Hospital of Eastern Theater Command, dating from 2006 to 2016. Clinical features, histological patterns, immunohistochemical characteristics and status of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) analysis were reviewed in all cases. Results: Clinically, 37 MTs cases mainly occurred in the parotid glands, when most of the patients presented with painless masses. Of the 13 MMTs cases, male to female ratio was 7∶6, and the median age was 62 years old. Of the 24 BMTs cases, male to female ratio was 5∶7, and the median age was 54 years old. Immunohistochemically, 37 MTs cases were positive for CKpan, and at least one myoepithelial marker. Twenty six of 37 MTs cases were analyzable for the EWSR1 gene break by FISH. Based on the previous evaluation criterion, the EWSR1 translocation was detected in 4 cases of 11 MMTs, and 4 cases of 15 BMTs. According to the main histological composition of tumor cells, 4 EWSR1-positive MMTs covered 2 clear-cell cases and 2 epithelioid-cell cases, when 4 EWSR1-positive BMTs covered 2 clear-cell cases, 1 plasmacytoid-cell case, and 1 spindle-cell case. Conclusions Males and females are affected equally. MTs express immunoreactivity for CKpan, and at least one myoepithelial marker. The EWSR1 rearrangement is present in a subset of MTs, with variable morphological characteristics, and has no statistical significance on clinical behavior.