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Xian-ling-gu-bao (XLGB) is a well-known patented traditional Chinese prescription widely used to treat osteoporosis, osteoarthritis, aseptic bone necrosis, or climacteric syndrome. However, recent reports have suggested that XLGB may cause liver injury in humans. In the present study, we aimed to evaluate the efficacy of XLGB in the prevention of osteoporosis in the zebrafish and ovariectomized (OVX) rats, both of which have been used as osteoporosis models. The safety of XLGB after long-term administration to OVX rats was also assessed. OVX rats were administered by oral gavage 270 mg/kg (recommended daily dose), 1350 mg/kg, and 1800 mg/kg of XLGB for 26 weeks. Bone mineral density, relative bone surface to bone volume, relative bone volume to total volume, trabecular number, mean trabecular thickness, and mean trabecular spacing in OVX rats were examined at the end of the 26-week dosing period. Additionally, OPG and RANKL expression in the femur were determined by western blot and immunohistochemical staining. To evaluate the safety of XLGB, body weight, hematology, serum biochemistry markers related to toxicology, and organ histopathology were determined in each group of OVX rats. Conversely, the zebrafish was treated with prednisolone to induce osteoporosis in the embryo. Disodium etidronate was used as a treatment control. XLGB was shown to be effective in preventing osteoporosis in both the OVX rats and the prednisolone-treated zebrafish. Similarly, XLGB increased OPG protein and decreased RANKL protein in OVX rats. Interestingly, no obvious toxicity was observed in the heart, liver, kidney, small intestine, or stomach at dosages of up to 1800 mg/kg after treating the OVX rats for 26 weeks. XLGB was shown to be very effective in treating osteoporosis in OVX rats. No obvious toxicity or adverse effects developed in OVX rats at dosages up to 1800 mg/kg, which is equivalent to six times the daily-recommended dose. Therefore, XLGB should be considered a good option for the treatment of post-menopausal osteoporosis.

Previously we have found vicagrel, a new acetate derivative of clopidogrel, underwent hydrolysis to 2-oxo-clopidogrel and subsequent conversions to its pharmacological active metabolite (AM) and inactive carboxylic acid metabolite (CAM). This study demonstrated the interspecies differences of the vicagrel bioactivation by comparing the critical vicagrel metabolites formation in rats, dogs and human. The pharmacokinetic studies with rats and dogs were conducted after intragastric administration of vicagrel, followed by in vitro metabolism investigation in venous system, intestinal/hepatic microsomes from rats, dogs and human. An obvious disparity was observed in system exposure to AM (99.0 v.s 635.1μg∙h/L, p

BackgroundCoronavirus disease 2019 (COVID-19) has developed into a worldwide pandemic. This study aimed to retrospectively describe the use of corticosteroids in treating COVID-19.MethodsFor this multicenter retrospective study, medical records from 488 symptomatic COVID-19 patients were reviewed. Patients were divided into severe and nonsevere groups. Baseline characteristics, signs and symptoms, laboratory findings, treatments, and disease outcomes were compared. Specific data for corticosteroid treatment were further analyzed.ResultsFour hundred fifty COVID-19 patients were included in this study, including 82 severe patients and 368 nonsevere cases. Out of the 450 patients, 126 (28.0%) received corticosteroid treatment. In the 126 patients treated with corticosteroids, the median daily dose of corticosteroid therapy was 56.6 [interquartile range (IQR): 40.0–78.4] mg and median corticosteroid therapy duration was 5.0 (IQR: 3.0–7.0) days. Among nonsevere cases, patients treated with corticosteroids were significantly older in comparison with patients who did not receive corticosteroid treatment (p0.05).ConclusionOur study indicates that corticosteroids are regarded as one of treatments in the general clinical practice of COVID-19. However, corticosteroid use may be accompanied by increased use of antibiotics, longer hospitalization, and prolonged viral shedding.

BackgroundWe explored the therapeutic and prognostic effect of YAP/TAZ intensityinHER2-positive breast cancer patients. We also investigated the relationship between YAP/TAZ expression and Trastuzumab-resistance.MethodsWe collected clinicopathological information from 397 cases. We evaluated therapeutic and prognostic effect of YAP/TAZ and other variables. We also cultivated Trastuzumab-resistance cell lines and explored relationship between YAP/TAZ and Trastuzumab-resistance.ResultsOver-expression of YAP/TAZ was remarkable in Trastuzumab-resistant cells, and so did HER3 and HER2/HER3 heterodimer. Inhibition of YAP/TAZ expression reversed Trastuzumab-resistance.YAP/TAZ deficiency contributed to favorable therapeutic response, and so did hormone receptor insufficiency and chemotherapy dosage inferiority. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival. Over-expression of YAP/TAZ was obvious in recurrent cases in comparison with their matching primary lesions. Prognostic superiority of insufficient YAP/TAZ intensity was more outstanding in hormone receptor negative cases. Over-expression of YAP/TAZ and HER3 was generally synchronous. Absence of HER3 expression in residual lesions might correlate with better breast cancer-free survival.ConclusionsOver-expression of YAP/TAZ as well as HER-3 and HER2/HER3 heterodimer was synchronously remarkable in Trastuzumab-resistant cell lines. Inhibition of YAP/TAZ expression reversed Trastuzumab resistance. Deficient YAP/TAZ intensity as well as insufficient hormone receptor intensity and high chemotherapy dosage contributed to favorable therapeutic response. Deficient YAP/TAZ intensity and abundant hormone receptor intensity contributed to better survival, and so did absence of HER3expression in residual lesions. Prognostic superiority of YAP/TAZ expression depended on hormone receptor status. Cases with synchronous over-expression of YAP/TAZ and HER3 suffered poor survival, which revealed the potential effect of YAP/TAZ-HER2/HER3 crosstalk in prognosis of HER2-positive patients.

Xiaochaihutang (XCHT) is one of classic prescriptions in Treatise on Febrile Diseases in China which was reported to have the effect of anti-hepatic fibrosis in vivo. Activation of hepatic stellate cells (HSCs) is now well established as a central driver of fibrosis in liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important element for anti-oxidative damage which is one of the key factors responsible for occurrence. This study was to investigate the effect of XCHT compound serum on HSCs activation and focus on the Nrf2 pathway. Rats in treatment groups were given the appropriate doses of XCHT granules (5 g/kg) and Silybin (50 mg/kg) for 6 days, and the serum were obtained. The compound serum was used to intervene HSCs. The results found that XCHT compound serum significantly inhibited the proliferation of HSCT6 cells. The number of α-SMA positive stained cells in HSCT6 cells and the content of Collagen type I (collagen-I) in supernatant were significantly decreased indicating suppression of activated HSCs. Compared with the control group, the nuclear transcription of Nrf2 and the expressions of Nqo1, GCLC, and GCLM were significantly increased in XCHT group. However, the effects of XCHT were inhibited in Nrf2-siRNA transfected HSCT6 cells. These studies demonstrated that XCHT could inhibit HSCT6 cell proliferation and activation. The mechanism might be related to up-regulation of the Nrf2 pathway against oxidative stress.