Chronic Ethanol Consumption Induces Osteopenia via Activation of Osteoblast Necroptosis.

Chronic high-dose alcohol consumption impairs bone remodeling, reduces bone mass, and increases the risk of osteoporosis and bone fracture. However, the mechanisms underlying alcohol-induced osteoporosis are yet to be elucidated. In this study, we showed that excess intake of ethyl alcohol (EtOH) resulted in osteopenia and osteoblast necroptosis in mice that led to necrotic lesions and reduced osteogenic differentiation in bone marrow mesenchymal stem cells (BMMSCs). We found that EtOH treatment led to the activation of the RIPK1/RIPK3/MLKL signaling, resulting in increased osteoblast necroptosis and decreased osteogenic differentiation and bone formation both in vivo and in vitro. We further discovered that excessive EtOH treatment-induced osteoblast necroptosis might partly depend on reactive oxygen species (ROS) generation; concomitantly, ROS contributed to necroptosis of osteoblasts through a positive feedback loop involving RIPK1/RIPK3. In addition, blocking of the RIPK1/RIPK3/MLKL signaling by necrostatin-1 (Nec-1), a key inhibitor of RIPK1 kinase in the necroptosis pathway, or antioxidant N-acetylcysteine (NAC), an inhibitor of ROS, could decrease the activation of osteoblast necroptosis and ameliorate alcohol-induced osteopenia both in vivo and in vitro. Collectively, we demonstrated that chronic high-dose alcohol consumption induced osteopenia via osteoblast necroptosis and revealed that RIPK1 kinase may be a therapeutic target for alcohol-induced osteopenia.

[Effect of Qilin Pill Combined Metformin on Polycystic Ovaries Induced Infertility Patients].

Objective To observe the effect and clinical efficacy of Qilin Pill (QP) combined met- formin on matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF) , hepatocyte growth factor (HGF) , sex hormones, insulin resistance (IR) related indicators in polycystic ovaries induced infertility women. Methods Totally 58 polycystic ovarian syndrome (PCOS) complicated infertility patients admitted to authors' hospital were serial numbered according to visit sequence. The odd num- bers were recruited as the control group, and the even numbers were recruited as the test group, 29 ca- ses in each group. Patients in the control group took Metformin Hydrochloride Tablets, while those in the test group additionally took QP. All patients received 3 months of treatment. After treatment serum con- tents of VEGF, MMP-9, HGF, sex hormones, IR related indicators, and clinical efficacy were detected in all patients. Results (1) There was no statistical difference in serum contents of MMP-9, VEGF, HGF, sex hormones [luteinizing hormone (LH) , testosterone (T) ] , or serum levels of fasting serum insulin (FINS) and insulin sensitive index (IS]) related indicators between the two groups before treatment (P> 0. 05) ; (2) Compared with before treatment in the same group, there was statistical difference in serum contents of MMP-9, VEGF, HGF, and levels of LH, T, FINS, ISI in the two groups after treatment (P < 0. 05) ; (3) Compared with the control group, patients' serum contents of MMP-9, VEGF, HGF,and levels of LH, T, FINS, ISI were lower in the test group after treatment (P <0. 05) ; (4) After treatment the ovulation rate (93.2%) and the pregnancy rate (48.3%) were higher in the test group than in the control group (P <0.05). Conclusion QP combined metformin could significantly reduce serum levels of LH. FINS and T, contents of VEGF, HGF, and MMP-9, improve IR, and elevate the ovulation rate and the pregnancy rate in PCOS induced infertility patients.

[Effect of ruji recipe on the post-surgical survival of female breast cancer patients].

OBJECTIVE: To observe the effect of Ruji Recipe (RR) in preventing disease recurrence/metastasis and improving quality of life (QOL) for female breast cancer patients after operation. METHODS: Totally 102 female patients with stage I - III breast cancer were retrospectively analyzed. They were assigned to the treatment group (54 cases) and the control group (48 cases) according to whether they would rather accept RR therapy. Estrogen receptor/progesterone receptor (ER/PR) positive patients also accepted endocrine therapy. The overall survival (OS), disease-free survival (DFS), recurrence and metastasis, and QOL were compared between the two groups. RESULTS: Totally 100 patients completed the study. The median follow-up was 59 months. The median OS was 60 months in the treatment group and 52.5 months in the control group (chi2 = 3.274, P > 0.05). The median DFS was 55.0 months in the treatment group and 47.5 months in the control group (chi2 = 10.145, P < 0.01). The DFS rate was 75.9% (41/54) in the treatment group and 54.3% (25/46) in the control group (chi2 = -2.259, P < 0.05). There was statistical difference in the 2-, 3-, and 5-year DFS between the two groups (P < 0.01). There was statistical difference in the 2-year DFS 3-year DFS between stage II and III and stage III (P < 0.05, P < 0.01). There was statistical difference in the ER positive patients between 2-year DFS and 3-year DFS (P < 0.01, P < 0.05). There was statistical difference in the 3-and 5-year distant metastasis rate (DMR) in the treatment group, lower than that of the control group (3.7% vs 31.0%, 20.7% vs 60.7%; P < 0.01). By the end of follow-up, disease progression occurred in 13 cases of the treatment group, local recurrence in 3 cases, single organ metastasis in 7 cases, multi-metastasis in 3 cases, while the corresponding numbers were 21, 1, 11, and 9 in the control group (P < 0.05). As for 1 week before study and at 2-year follow-up using Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B) system, there was statistical difference in the QOL between the two groups (P < 0.05), and better effect was obtained in the treatment group. CONCLUSION: RR, as an assistant therapy, could improve the OS rate, the DFS rate, and the QOL for post-surgical female breast cancer patients in 2 -3 years.