Predisposing Factors for Granulomatous Lobular Mastitis: A Case-Control Study.

Background: Despite the rising incidence rate of granulomatous lobular mastitis (GLM), uncertainties persist about its etiologic and predisposing factors to guide clinical treatment and early prevention. The objective of this study is to explore the predisposing factors for GLM. Patients and methods: This case-control study was conducted from 2018 to 2021 at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Patients with GLM (cases) were matched with healthy examinees (controls) in a 1:1 ratio according to gender and living area. We analyzed their demographic features and investigated 75 factors that may be relevant to GLM using a standard questionnaire. Univariate and multivariable binary conditional logistic regression analyses were used to compare the differences between the two groups and evaluate the predisposing factors that may induce GLM. Results: There were 594 female GLM patients and 594 matched controls included in the study. The average age of the cases was 32.78 years (mainly 20 to 40). The incidence was high within five years after childbirth, and lesions were mainly in the unilateral breast. Univariate and multivariable conditional logistic regression analyses obtained six relevant factors and six high-risk factors. The six relevant factors included age, marriage, emotional abnormality, high prolactin, psychiatric drug intake, and sex hormone intake. Additionally, the independent high-risk factors for GLM included gestation, nipple invagination, blunt trauma, non-iatrogenic massage, lactation disorder, and nipple discharge (odds ratio (OR)=17.378, 8.518, 4.887, 3.116, 2.522, 1.685, P<0.05). Menopause was an independent protective factor (OR=0.249, P<0.05). Conclusion: The factors that increase milk and secretion production in the mammary duct are the main risk factors of GLM, especially when the nipples are invaginated. These factors can obstruct the duct and induce inflammation. Additionally, hormonal disorders, extrinsic trauma, and emotional abnormalities can accelerate the occurrence of GLM.

[The role of heme oxygenase-1 in non-alcoholic steatohepatitis].

OBJECTIVE: To investigate the potential role of heme oxygenase-1 on preventing non-alcoholic steatohepatitis (NASH) in mice. METHODS: Experimental models of NASH were established by feeding male C57BL/6J mice with choline-methionine deficient diet (MCD) for four weeks. Control animals were fed with choline-methionine supplemented diet. The treatment groups were fed with MCD diet combined with HO-1 inducer hemin or inhibitor zinc protoporphyrin IX (ZnPP-IX). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested by enzymic method with automatic biochemistry analyzer. The degree of hepatic steatosis, inflammation and fibrosis were examined under HE staining. The hepatic mRNA and protein expressions of HO-1, TNFalpha and IL-6 were analyzed by RT-PCR and Western blot respectively. MCD fed mice showed increased serum ALT and AST levels and moderate to severe hepatic steatosis with inflammatory infiltration, hepatic spot or focal necrosis, light portal and sinus hepaticus fibrosis in the liver sections, which associated with enhanced expression of HO-1, TNFalpha and IL-6 mRNA and protein (1.13+/-0.11, 1.74+/-0.05; 0.20+/-0.01, 1.92+/-0.10; 0.58+/-0.02, 2.06+/-0.05 vs 0.43+/-0.02, 0.75+/-0.05; 0.08+/-0.00, 0.59+/-0.02; 0.22+/-0.01, 0.91+/-0.02). Administration of hemin significantly decreased serum ALT and AST levels and attenuated hepatic steatosis and necroinflammation which associated with up-regulation of antioxidative gene HO-1 and down-regulation of pro-inflammatory cytokines TNFalpha and IL-6 (P < 0.01). A contrary effect on serum aminotransferase levels and liver histopathology was observed in mice injected with ZnPP-IX (P < 0.01). CONCLUSIONS: The effect was associated with suppressed HO-1 expression and increased TNFaLPHA and IL-6 expression. The data provided a biochemical, morphological and molecular biological evidence for the protective role of HO-1 in ameliorating hepatic steatosis, necroinflammation in experimental nutritional steatohepatitis.

Antioxidants vitamin E and 1-aminobenzotriazole prevent experimental non-alcoholic steatohepatitis in mice.

OBJECTIVE: Hepatic oxidative stress plays a key role in the development of non-alcoholic steatohepatitis (NASH). However, the protective effects of antioxidants on NASH are largely unknown. The aim of this study was to elucidate the effect and mechanism of antioxidants on NASH in mice. MATERIAL AND METHODS: C57BL6/J mice were fed a methionine-choline-deficient (MCD) diet for 10 days or 3 weeks to induce steatohepatitis. Antioxidants (vitamin E, ABT, or vitamin E plus ABT) were supplemented in mice fed a MCD diet, respectively. The effect of antioxidants on oxidative stress and apoptosis was assessed, and activation of adiponectin and expressions of inflammatory factors, apoptosis-related genes, and fibrosis-related genes were assayed. RESULTS: MCD feeding in mice showed increasing serum alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) levels, and progressive hepatic injury including hepatic steatosis and inflammatory infiltration. Administration of antioxidants vitamin E and/or ABT significantly lowered serum ALAT and ASAT levels (p<0.001) and ameliorated hepatic steatosis and necroinflammation. These effects were associated with repressed hepatic lipid peroxides through reducing hepatic MDA content and enhancing hepatic superoxide dismutase (SOD) activity; down-regulated inflammatory factor COX-2, lowered activity of NF-kappaB, up-regulated anti-apoptotic gene Bcl-2, and down-regulated pro-apoptotic gene Bax suppressed expression of the fibrotic genes TGF-beta1 and MMP2. Moreover, expression of the anti-inflammatory factor adiponectin was also induced by vitamin E or ABT. A combination of vitamin E and ABT showed an additive effect on preventing liver injury. CONCLUSIONS: The present study provides morphological and molecular biological evidence for the protective role of the antioxidant vitamins E and ABT in ameliorating oxidative stress, hepatic apoptosis, and necroinflammation in experimental nutritional steatohepatitis.