ObjectiveTo investigate the relation between mammographic density (MD) and the efficacy of neoadjuvant chemotherapy (NACT) for patients with breast cancer. MethodsThe clinicopathologic data of patients diagnosed with breast cancer in the Affiliated Hospital of Southwest Medical University from January 2019 to December 2021 and met the inclusion and exclusion criteria of this study were collected. According to the 5th edition of the Breast Imaging-Reporting and Data System, the MD was classified into 4 categories: a, b, c, and d. Based on the pathological evaluation systems of Miller-Payne and Residual Cancer Burden, the new and improved pathological criteria was structured including the residual cancer cell and lymph node statuses to evaluate the pathological changes of breast cancer after NACT. After adjusting the factors affecting MD, the original model (only including MD categories as independent variables), the minimum adjustment model (adding age, body mass index, and menopausal status as independent variables), and the fully adjusted model (further including estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, axillary lymph node status at the initial diagnosis, and NACT regimen) were used to analyze the relation between MD and NACT effect. In the 3 models, the MD category a was used as the reference. ResultsA total of 287 patients with breast cancer were enrolled in this study. Thirty-eight, 76, 114, and 59 of whom with MD category a, b, c, and d respectively, and 14, 74, 117, and 82 of whom with grade L1, L2, L3, and L4 of NACT effect respectively. No matter in integrated patients or premenopausal patients, the results of the fully adjusted model showed that, the regression coefficient of MD classification was negative, and with the increase of MD classification, the odds ratio was <1 and showed a decreasing trend. ConclusionsFrom the results of this study, the increase of MD classification may have a negative impact on the effect of NACT. Namely, effect of NACT is poor in integrated patients or premenopausal patients of whom with higher MD. MD can be used as a predictor of NACT effect, so as to guide doctors in the selection and individual management of neoadjuvant therapy, and improve the prognosis of patients with breast cancer.
Objective To explore the effect of natural hirudin on proliferation of human microvascular endothelial cells (HMVECs) and its preliminary mechanism of promoting angiogenesis. Methods Three-dimensional culture models of HMVECs were established in vitro and observed by inverted phase contrast microscopy after 24 hours of culturing. Then, the three-dimensional culture models of HMVECs were treated with different concentrations (1, 4, and 7 ATU/mL) of the natural hirudin, respectively, and Dulbecco’s modified Eagle’s medium containing 10% fetal bovine serum as control. The cell proliferations of 4 groups were detected by cell counting kit 8 (CCK-8) method at 24, 48, and 72 hours; the angiogenesis of 4 groups were observed by tube formation assay at 24 hours; the expressions of vascular endothelial growth factor (VEGF) and Notch1 of HMVECs in 4 groups were observed by immunofluorescence staining at 24 hours. Results The observation of cells in three-dimensional culture models showed that HMVECs attached to Matrigel well, and the cells formed tube structure completely after 24 hours. The results of CCK-8 test showed that the absorbance (A) value of 1 and 4 ATU/mL groups were higher than that of control group at each time point (P<0.05), andA value of 4 ATU/mL group was the highest. The A value of 7 ATU/mL group was significantly lower than those of 1 and 4 ATU/mL groups and control group (P<0.05). The tube formation assay showed that the tube structure was more in 1 and 4 ATU/mL groups than in 7 ATU/mL group and control group, and in 4 ATU/mL group than in 1 ATU/mL group, showing significant differences (P<0.05). There was no significant difference between 7 ATU/mL group and control group (P>0.05). The results of immunofluorescence staining showed that compared with control group, the Notch1 expression was higher in 1 and 4 ATU/mL groups and lower in 7 ATU/mL group; and there was significant difference between 4 and 7 ATU/mL groups and control group (P<0.05). The VEGF expression was higher in 1, 4, and 7 ATU/mL groups than in control group, in 4 ATU/mL group than in 1 and 7 ATU/mL groups, showing significant differences (P<0.05). Conclusion Natural hirudin can promote angiogenesis at low and medium concentrations, but suppress angiogenesis at high concentrations. Its mechanism may be related to the VEGF-Notch signal pathway.
ObjectiveTo investigate the effect of natural hirudin on revascularization of ischemic skin flap in rats using Micro-CT and three-dimensional (3D) reconstruction.MethodsThirty-two Sprague Dawley rats were prepared a ischemic skin flap (8.0 cm×1.8 cm) model on the back and randomly divided into hirudin group and control group (16 rats in each group). At immediate and within 3 days after operation, the rats were treated with hypodermic injection of natural hirudin 0.3 mL (including natural hirudin 6 ATU) every day in hirudin group and the equal amount of normal saline in control group. At 6 days after operation, the survival rate of skin flap was evaluated, histological changes were observed by HE staining, and the volemia, length of blood vessels, and number of blood vessels were analyzed with Micro-CT 3D reconstruction.ResultsBoth groups of rats survived to the end of the experiment without infection. Different degrees of necrosis occurred in the distal part of the skin flaps in both groups at 6 days after operation, but the flap survival rate of the hirudin group (72.11%±8.97%) was significantly higher than that of control group (58.94%±4.02%) (t=3.280, P=0.008). Histological observation showed that the histological hierarchy of the hirudin group was clearer than that of the control group, with more microangiogenesis and less inflammatory response and inflammatory cell infiltration. Micro-CT 3D reconstruction showed that the flap vessels in the hirudin group were more and denser, and the volemia, length of blood vessels, and number of blood vessels were significantly higher than those in the control group (P<0.05).ConclusionNatural hirudin can reduce the inflammation of tissue, promote the regeneration and recanalization of blood vessels in ischemic skin flap, so as to improve the survival rate of the flap.
Objective To explore the accuracy of contrast-enhanced magnetic resonance imaging (MRI) in predicting pathological complete remission (pCR) in breast cancer patients after neoadjuvant therapy (NAC). Methods The clinicopathological data of 245 patients with invasive breast cancer who had completed the surgical resection after NAC in the Affiliated Hospital of Southwest Medical University from March 2020 to April 2022 were collected retrospectively. According to the results of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) detected by immunohistochemistry, all patients were divided into four subgroups: HR+/HER2–, HR+/HER2+, HR–/HER2+ and HR–/HER2–. The value of MRI in evaluating the efficacy of NAC was analyzed by comparing the postoperative pathological results as the gold standard with the residual tumor size assessed by preoperative MRI. Meanwhile, the sensitivity, specificity and positive predictive value (PPV) of pCR predicted by the evaluation results of enhanced MRI were analyzed, and further analyzed its predictive value for pCR of different subtypes of breast cancer. Results There were 88 cases (35.9%) achieved radiological complete response (rCR) and 106 cases (43.3%) achieved pCR in 245 patients. Enhanced MRI in assessing the size of residual tumors overestimated and underestimated 12.7% (31/245) and 9.8% (24/245) of patients, respectively. When setting rCR as the MRI assessment index the specificity, sensitivity and PPV were 84.2% (117/139), 62.3% (66/106) and 75.0% (66/88), respectively. When setting near-rCR as the MRI assessment index the specificity, sensitivity and PPV were 70.5% (98/139), 81.1% (86/106), and 67.7% (86/127), respectively. The positive predictive value of both MRI-rCR and MRI-near-rCR in evaluating pCR of each subtype subgroup of breast cancer was the highest in the HR–/HER2+ subgroup (91.7% and 83.3%, respectively). In each subgroup, compared with rCR, the specificity of near-rCR to predict pCR decreased to different degrees, while the sensitivity increased to different degrees. Conclusions Breast contrast-enhanced MRI can more accurately evaluate the efficacy of localized breast lesions after NAC, and can also more accurately predict the breast pCR after NAC. The HR–/HER2+ subgroup may be a potentially predictable population with pCR exemption from breast surgery. However, the accuracy of the evaluation of pCR by breast enhancement MRI in HR+/HER2– subgroup is low.
ObjectiveTo investigate the effect of natural hirudin combined with hyperbaric oxygen therapy on the survival of transplanted random-pattern skin flap in rats.MethodsA random-pattern skin flap in size of 10.0 cm×2.5 cm was elevated on the dorsum of 72 Sprague Dawley rats. Then the 72 rats were randomly divided into 4 groups (n=18) according to the therapy method. At immediate and within 4 days after operation, the rats were treated with normal saline injection in control group, normal saline injection combined with hyperbaric oxygen treatment in hyperbaric oxygen group, the natural hirudin injection in natural hirudin group, and the natural hirudin injection combined with hyperbaric oxygen treatment in combined group. The flap survival was observed after operation, and survival rate was evaluated at 6 days after operation. The skin samples were collected for histological analysis, microvessel density (MVD) measurement, and evaluation of tumor necrosis factor α (TNF-α) expression level by the immunohistochemical staining at 2 and 4 days after operation.ResultsPartial necrosis occurred in each group after operation, and the flap in combined group had the best survival. The survival rate of flap was significantly higher in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group, and in combined group than in hyperbaric oxygen group and natural hirudin group (P<0.05). There was no significant difference between hyperbaric oxygen group and natural hirudin group (P>0.05). At 2 days, more microvascular structure was observed in hyperbaric oxygen group, natural hirudin group, and combined group in comparison with control group; while plenty of inflammatory cells infiltration in all groups. At 4 days, the hyperbaric oxygen group, natural hirudin group, and the combined group still showed more angiogenesis. Meanwhile, there was still infiltration of inflammatory cells in control group, inflammatory cells in the other groups were significantly reduced when compared with at 2 days. At 2 days, the MVD was significantly higher in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group (P<0.05); the expression of TNF-α was significantly lower in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group (P<0.05). There was no significant difference in above indexes between hyperbaric oxygen group, natural hirudin group, and combined group (P>0.05). At 4 days, the MVD was significantly higher in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group, in natural hirudin group and combined group than in hyperbaric oxygen group (P<0.05). The expression of TNF-α was significantly lower in hyperbaric oxygen group, natural hirudin group, and combined group than that in control group, in combined group than in natural hirudin group and hyperbaric oxygen group (P<0.05).ConclusionHyperbaric oxygen and natural hirudin therapy after random-pattern skin flap transplantation can improve the survival of flaps. Moreover, combined therapy is seen to exhibit significant synergistic effect. This effect maybe related to promotion of angiogenesis and the reduction of inflammation response.