Impact of Post-Mastectomy Radiation Therapy for Sentinel Lymph Node Micrometastases in Early-Stage Breast Cancer Patients.

BACKGROUND The association of radiotherapy with breast cancer survival in patients who underwent a mastectomy and had micrometastases in the sentinel lymph node is unclear. MATERIAL AND METHODS The survival benefit of radiotherapy was examined in patients with T0/1-T2N1mi breast cancer undergoing mastectomy plus sentinel lymph node biopsy (SLNB). Kaplan-Meier curves were employed for survival analysis and competing risk analysis, and a propensity score matching (PSM) cohort was enrolled to investigate whether such patients benefit from radiotherapy. RESULTS We identified 2864 patients in the SEER database from 2004 to 2015. All eligible patients were divided into the radiotherapy and the no-radiotherapy cohorts. With the median follow-up of 53 months, 5-year breast cancer-specific survival (BCSS) was 94.4% vs 95.2% (P=0.135), and 5-year overall survival (OS) was 91.2% vs 90.1% (P=0.466) in the radiotherapy cohorts and no-radiotherapy cohorts, respectively. The results of the competing risk analysis showed a comparable 5-year cumulative incidence of breast cancer-specific death (BCSD) in the radiotherapy and no-radiotherapy groups (5.5% vs 4.7%, P=0.107) but a higher 5-year cumulative incidence of other causes of death (OCD) in the no-radiotherapy cohort (3.3% vs 5.3%, P=0.011). No significant difference was observed for BCSS or OS in the PSM cohort. CONCLUSIONS Radiotherapy has no benefit for patients with T0/1-T2 breast cancer undergoing mastectomy with N1mi disease on SLNB. This analysis provides evidence that radiotherapy may safely be omitted in this group of patients.

PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes.

Diabetic nephropathy (DN), the primary cause of end-stage renal disease (ESRD), is often accompanied by dyslipidemia, which is closely related to the occurrence and development of DN and even the progression to ESRD. Mitophagy, the selective degradation of damaged and dysfunctional mitochondria by autophagy, is a crucial mitochondrial quality control mechanism, and largely regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin signaling pathway. In the present study, we demonstrated that PA induced mitochondrial damage and excessive mitoROS generation in podocytes. We also found PA treatment resulted in the activation of mitophagy by increasing co-localization of GFP-LC3 with mitochondria and enhancing the formation of mitophagosome, stabilization of PINK1 and mitochondrial translocation of Parkin, which indicated that PINK1/Parkin pathway was involved in PA-induced mitophagy in podocytes. Furthermore, inhibition of mitophagy by silencing Parkin dramatically aggravated PA-induced mitochondrial dysfunction, mitoROS production, and further enhanced PA-induced apoptosis of podocytes. Finally, we showed that PINK1/Parkin pathway were up-regulated in kidney of high fat diet (HFD)-induced obese rats. Taken together, our results suggest that PINK1/Parkin mediated mitophagy plays a protective role in PA-induced podocytes apoptosis through reducing mitochondrial ROS production and that enhancing mitophagy provides a potential therapeutic strategy for kidney diseases with hyperlipidemia, such as DN.

[Diagnostic value of automated breast volume scanner in high-risk and small breast lesions].

OBJECTIVE: To assess the accuracy of detection by automated breast volume scanner (ABVS) in diagnosis of high-risk and small breast lesions. METHODS: One hundred and twelve patients with solid high-risk and small breast lesions were identified by ABVS. The patients were divided into benign lesion group and cancer group after pathological examination. The clinicopathological findings and ultrasonographic features of the lesions were compared. RESULTS: Among the 112 lesions there were 49 benign and 63 malignant lesions. The mean size on ABVS and pathology were (1.59 ± 0.52) cm and (1.52 ± 0.58) cm. There was no significant difference in tumor sizes determined by ABVS and pathology (P = 0.194). The mean age of patients with benign lesions was (38.5 ± 7.4) years and that of malignant lesions was (52.4 ± 13.6) years, showing a significant difference between the two groups (P < 0.001) . The mass shape, orientation, margin, lesion boundary, echo pattern, calcification, BI-RADS category and retraction phenomenon were significantly different of the malignant and benign masses (P < 0.05). But there was no significant difference in the location of lesions and posterior acoustic features (P > 0.05) . Retraction phenomenon was significantly associated with pathological type and histologic grade of the breast cancer (P < 0.01). The specificity, sensitivity and accuracy of retraction phenomenon were 100% (46/46), 73.0% (46/63), and 84.8% (95/112), respectively. CONCLUSIONS: ABVS provides advantages of better size prediction of high-risk and small breast lesions. Furthermore, the retraction phenomenon in coronal plane shows high specificity and sensitivity in detecting breast cancer.

[The significance of urine N-acetyl-beta-D-glucosaminidase in kidney injury with patients acute paraquat poisoning].

OBJECTIVES: To test the hypothesis that urine N-acetyl-beta-D-glucosaminidase (NAG) is a nearly biomarker for acute kidney injury in patients with acute paraquat poisoning. METHODS: Forty-four patients with paraquat intoxication and 40 age and gender-matched healthy control participants were recruited. The urine N-acetyl-beta-D-glucosaminidase was determined by spectrophotometric methods. RESULTS: The urine N-acetyl-beta-D-glucosaminidase activities in the patients with paraquat poisoning were higher than the corresponding values in the control participants (P<0.01); The prevalence rate of mortality was significantly higher in subjects with N-acetyl-beta-D-glucosaminidase activities ≥25 U/g Cr than in those N-acetyl-beta-D-glucosaminidase activities <25 Ulg Cr (34.4% vs 16.7%, P<0.01). CONCLUSIONS: The urine N-acetyl-beta-D-glucosaminidase could be used as an early biomarker for acute kidney injury and predictor of mortality inpatients with acute paraquat intoxication.

Magnetic resonance imaging and contrast-enhanced ultrasound findings of a recurrent primary breast angiosarcoma: A case report.

RATIONALE: Primary breast angiosarcoma (PBA) is a rare and overly aggressive entity and account for less than 1% of all breast cancer cases. PBA had a high rate of delayed preoperative diagnosis due to absent distinctive radiographic characteristics. PATIENT CONCERNS: We report a case of a 47-year-old female patient who had a previous history of luminal cancer in the right breast with mastectomy; the patient complained of asymmetrically diffuse enlarged, accompanying with a painless mass in the left breast 12 years after the mastectomy of her right breast. DIAGNOSES: The tumor mimicked idiopathic granulomatous mastitis on magnetic resonance imaging (MRI) at the first presentation. Contrast-enhanced ultrasound (CEUS) was performed for further lesion characterization and showed heterogeneous rapid hyper enhanced. An ultrasound-guided core needle biopsy was performed, and the pathology report indicated a breast angiosarcoma. INTERVENTIONS: The patient underwent a nipple-sparing simple mastectomy with immediate reconstruction of the left breast. OUTCOMES: After 8 months later, the tumor recurred, CEUS and MRI examination suggested PBA recurrence, then re-excision with implant removal was performed, the patient had a lung metastasis 4 months later eventually died 22 months after diagnosis. LESSONS: It is not easy to diagnose PBA with the radiographic examination. This case's importance is by combining CEUS and MRI to reflect enhanced morphology and hemodynamic characteristics of PBA and help diagnose breast angiosarcomas.

Berberine alleviates palmitic acid­induced podocyte apoptosis by reducing reactive oxygen species­mediated endoplasmic reticulum stress.

Lipid accumulation in podocytes can lead to the destruction of cellular morphology, in addition to cell dysfunction and apoptosis, which is a key factor in the progression of chronic kidney disease (CKD). Berberine (BBR) is an isoquinoline alkaloid extracted from medicinal plants such as Coptis chinensis, which has been reported to have a lipid­lowering effect and prevent CKD progression. Therefore, the present study aimed to investigate the effect of BBR on palmitic acid (PA)­induced podocyte apoptosis and its specific mechanism using an in vitro model. Cell death was measured using the Cell Counting Kit­8 colorimetric assay. Cell apoptotic rate was assessed by flow cytometry. The expression of endoplasmic reticulum (ER) stress­ and apoptosis­related proteins was detected by western blotting or immunofluorescence. Reactive oxygen species (ROS) were evaluated by 2',7'­dichlorofluorescein diacetate fluorescence staining. The results of the present study revealed that BBR treatment decreased PA­induced podocyte apoptosis. In addition, 4­phenylbutyric acid significantly reduced PA­induced cell apoptosis and the expression of ER stress­related proteins, which indicated that ER stress was involved in PA­induced podocyte apoptosis. In addition, N­acetylcysteine inhibited PA­induced excessive ROS production, ER stress and cell apoptosis of podocytes. BBR also significantly reduced PA­induced ROS production and ER stress in podocytes. These results suggested that PA mediated podocyte apoptosis through enhancing ER stress and the production of ROS. In conclusion, BBR may protect against PA­induced podocyte apoptosis, and suppression of ROS­dependent ER stress may be the key mechanism underlying the protective effects of BBR.

[Vacuum-assisted biopsy and wire localization for the diagnosis of non-palpable breast lesions].

OBJECTIVE: To compare the effectiveness and accuracy of the use of vacuum-assisted biopsy (VAB) versus wire localization (WL) in the diagnosis of non-palpable breast lesions (NPBL). METHODS: Ninety-seven consecutive women with NPBL were randomized into VAB group and WL group. All specimens were identified by mammography. The patients were requested to score the cosmetic appearance of their breast after operation, and a numerical rating scale was used to measure pain on the first postoperative day. Underestimation rates for atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) were recorded if open surgical biopsy revealed DCIS and invasive cancer, respectively. Clear margins were also recorded in the two groups. RESULTS: VAB and WL located all the NPBL successfully. In the VAB group, the specimen volume was smaller than that of the WL group (2.3 cm(3) vs. 18.4 cm(3), P = 0.03). Underestimation rates of ADH and DCIS in the VAB group were 16.7% and 11.1%, respectively. The diagnostic accordance rate of VAB was 97.9%, the false negative rate was 2.1%, and there was no false positive case. The means of the numerical rating pain scale were different in both groups (1.7 for VAB vs. 2.5 for WL, P = 0.02). When cosmetic results were taken into account, 40 VAB patients had excellent outcomes and 8 good outcomes, compared with 25 excellent and 24 good for the WL group. There were better cosmetic outcomes with the VAB procedure (P < 0.05). CONCLUSION: VAB is highly reliable and may avoid diagnostic open surgery in the majority of patients with benign lesions. However, because of the underestimation of histologic diagnosis and tumor margin involvement, VAB can not be used to completely substitute wire localization.

Inhibition of soluble epoxide hydrolase attenuates renal tubular mitochondrial dysfunction and ER stress by restoring autophagic flux in diabetic nephropathy.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD), and renal tubular cell dysfunction contributes to the pathogenesis of DN. Soluble epoxide hydrolase (sEH) is an enzyme that can hydrolyze epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids (EpFAs) into the less biologically active metabolites. Inhibition of sEH has multiple beneficial effects on renal function, however, the exact role of sEH in hyperglycemia-induced dysfunction of tubular cells is still not fully elucidated. In the present study, we showed that human proximal tubular epithelial (HK-2) cells revealed an upregulation of sEH expression accompanied by the impairment of autophagic flux, mitochondrial dysfunction, ubiquitinated protein accumulation and enhanced endoplasmic reticulum (ER) stress after high glucose (HG) treatment. Furthermore, dysfunctional mitochondria accumulated in the cytoplasm, which resulted in excessive reactive oxygen species (ROS) generation, Bax translocation, cytochrome c release, and apoptosis. However, t-AUCB, an inhibitor of sEH, partially reversed these negative outcomes. Moreover, we also observed increased sEH expression, impaired autophagy flux, mitochondrial dysfunction and enhanced ER stress in the renal proximal tubular cells of db/db diabetic mice. Notably, inhibition of sEH by treatment with t-AUCB attenuated renal injury and partially restored autophagic flux, improved mitochondrial function, and reduced ROS generation and ER stress in the kidneys of db/db mice. Taken together, these results suggest that inhibition of sEH by t-AUCB plays a protective role in hyperglycemia-induced proximal tubular injury and that the potential mechanism of t-AUCB-mediated protective autophagy is involved in modulating mitochondrial function and ER stress. Thus, we provide new evidence linking sEH to the autophagic response during proximal tubular injury in the pathogenesis of DN and suggest that inhibition of sEH can be considered a potential therapeutic strategy for the amelioration of DN.