Norlichexanthone purified from plant endophyte prevents postmenopausal osteoporosis by targeting ER

Although different types of drugs are available for postmenopausal osteoporosis, the limitations of the current therapies including drug resistances and adverse effects require identification of novel anti-osteoporosis agents. Here, we defined that norlichexanthone (NOR), a natural product, is a ligand of estrogen receptor-alpha (ER

NSC-640358 acts as RXRα ligand to promote TNFα-mediated apoptosis of cancer cell

Retinoid X receptor α (RXRα) and its N-terminally truncated version tRXRα play important roles in tumorigenesis, while some RXRα ligands possess potent anti-cancer activities by targeting and modulating the tumorigenic effects of RXRα and tRXRα. Here we describe NSC-640358 (N-6), a thiazolyl-pyrazole derived compound, acts as a selective RXRα ligand to promote TNFα-mediated apoptosis of cancer cell. N-6 binds to RXRα and inhibits the transactivation of RXRα homodimer and RXRα/TR3 heterodimer. Using mutational analysis and computational study, we determine that Arg316 in RXRα, essential for 9-cis-retinoic acid binding and activating RXRα transactivation, is not required for antagonist effects of N-6, whereas Trp305 and Phe313 are crucial for N-6 binding to RXRα by forming extra π-π stacking interactions with N-6, indicating a distinct RXRα binding mode of N-6. N-6 inhibits TR3-stimulated transactivation of Gal4-DBD-RXRα-LBD by binding to the ligand binding pocket of RXRα-LBD, suggesting a strategy to regulate TR3 activity indirectly by using small molecules to target its interacting partner RXRα. For its physiological activities, we show that N-6 strongly inhibits tumor necrosis factor α (TNFα)-induced AKT activation and stimulates TNFα-mediated apoptosis in cancer cells in an RXRα/tRXRα dependent manner. The inhibition of TNFα-induced tRXRα/p85α complex formation by N-6 implies that N-6 targets tRXRα to inhibit TNFα-induced AKT activation and to induce cancer cell apoptosis. Together, our data illustrate a new RXRα ligand with a unique RXRα binding mode and the abilities to regulate TR3 activity indirectly and to induce TNFα-mediated cancer cell apoptosis by targeting RXRα/tRXRα.

Analysis of the risk factors of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To identify risk factors of hepatocellular carcinoma (HCC) in cirrhotic patients with chronic hepatitis B (CHB).</p><p><b>METHODS</b>A total of 715 cirrhotic patients with CHB were recruited from the Zhongshan Hospital Affiliated to Fudan University and enrolled in this case-control study between January 2009 and September 2014. All participants were Chinese Han residing in Shanghai and the surrounding areas. The patients were divided into a cirrhosis group (n =281) and a HCC group (n=434). History of hepatitis B infection and HCC, as well as clinical data from serological, imaging and pathological examinations were collected for analysis.SPSS software, version 19.0, was used for all statistical comparisons.</p><p><b>RESULTS</b>Single factor analysis indicated that development of HCC in cirrhotic patients with CHB was significantly associated with male sex, age of 50 years or more, family history of HCC, alcohol consumption,fatty liver, detectable levels of hepatitis B virus (HBV) DNA, and history of HBV infection without effective antiviral treatment. Multivariate logistic regression analysis indicated that age of 50 years or more (P =0.005, odds ratio [OR] =1.766), history of alcohol consumption (P =0.002, Or = 2.570), family history of HCC (P =0.014, Or = 2.268), fatty liver (P =0.023, Or = 3.390), and history of HBV infection without effective antiviral treatment (P < 0.001,Or = 5.389) were risk factors of HCC.The risk factors for development of HCC in cirrhotic patients with hepatitis B after achieving sustained virologic suppression (SVS) were family history of HBV infection (P =0.014, Or = 2.537), family history of HCC (P =0.037,Or = 3.339) and fatty liver (P =0.018, Or = 11.646).</p><p><b>CONCLUSION</b>Risk factors of HCC in cirrhotic patients with CHB include age,drinking history,family history of HCC, fatty liver, and ineffective antiviral treatment of CHB.Family history of HBV infection or HCC, and fatty liver disease, were significantly associated with HCC development after SVS in patients with hepatitis B-related cirrhosis.</p>

Experience of Consumptive Disease Treating Analysis of the Gushi Yijing / 浙江中医药大学学报

[Objective]To explore the consumptive disease treating experience in Gushi Yijing, written by Gu Songyuan who lived in the Qing Dynasty. [Methods]By studying consumptive disease related content in the book, discussing and summing up the consumptive disease treating experience. [Results] On the basis of pointing out seven kinds of error method that doctor treating consumptive disease at that time, Gu Songyuan put forward the opinion that consumptive disease was usual y caused by the internal injury of Zang and Fu organs which resulted into Yin deficiency as the main pathogenesis. The article contained other details as fol ows: the basic symptoms of consumptive disease of the five internal organs, three main therapeutic methods on treatment of consumptive disease, the preference of nourishment combined drugs with food, habit of using some sweet and cold durgs which can clear heat, the use of flesh and blood of sentient beings and so on. So the key idea of this article focused on the method of nourishing Yin to enrich Jing and blood which could cure the consumptive disease effectively.[Conclusion]Gu Songyuan inherited predecessor ’s theory, analysed the etiology of consumptive disease of the five internal organs, pointed out Yin deficiency is the main pathogenesis, and then put forward the therapeutic method, which has some medical knowledge on modern clinic.

Dissecting the retrohepatic inferior vena cava in right hepatectomy: an experience in 77 patients / 中华肝胆外科杂志

Objective To study the technique in isolating the retrohepatic inferior vena cava in right hepatectomy.Methods Anatomical exposure of the right lateral wall of retrohepatic inferior vena cava was performed,followed by isolating its back wall.Results Part of the right liver was rotated out of the incision.The 77 patients recovered smoothly.Conclusion Dividing the right adrenal is the key to free the retrohepatic inferior vena cava.To expose the right side of the retrohepatic inferior vena cava is a standard technique to mobilize the right liver.