Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2.

Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared cisplatin sensitivity between OS stem cells and OS non-stem cells. We confirmed that OS stem cells showed significant cisplatin-resistance compared with the OS non-CSCs. Mechanically, we proved that overexpression of the pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to cisplatin in OS stem cells. As a potential strategy, we found that co-treatment with metformin significantly decreased the half maximal inhibitory concentration (IC50) of cisplatin to HOS OS stem cells by downregulating the expression of PKM2. PKM2 downregulation resulted in, metformin inhibited glucose uptake, lactate production and ATP production in HOS CSCs. Therefore, metformin impaired the resistance of HOS CSCs to cisplatin and promoted cisplatin-induced apoptosis. In addition, antitumor effects of other chemotherapeutic drugs such as doxorubicin and 5-fluorouracil were proved to be enhanced by metformin on OS stem cells.

Volume-Targeted Versus Pressure-Limited Noninvasive Ventilation in Subjects With Acute Hypercapnic Respiratory Failure: A Multicenter Randomized Controlled Trial.

BACKGROUND: Volume-targeted noninvasive ventilation (VT-NIV), a hybrid mode that delivers a preset target tidal volume (VT) through the automated adjustment of pressure support, could guarantee a relatively constant target VT over pressure-limited noninvasive ventilation (PL-NIV) with fixed-level pressure support. Whether VT-NIV is more effective in improving ventilatory status in subjects with acute hypercapnic respiratory failure (AHRF) remains unclear. Our aim was to verify whether, in comparison with PL-NIV, VT-NIV would be more effective in correcting hypercapnia, hence reducing the need for intubation and improving survival in subjects with AHRF. METHODS: We performed a prospective randomized controlled trial in the general respiratory wards of 8 university-affiliated hospitals in China over a 12-month period. Subjects with AHRF, defined as arterial pH <7.35 and ≥7.25 and PaCO2 >45 mm Hg, were randomly assigned to undergo PL-NIV or VT-NIV. The primary end point was the decrement of PaCO2 from baseline to 6 h after randomization. Secondary end points included the decrement of PaCO2 from baseline to 2 h after randomization as well as outcomes of subjects (eg, need for intubation, in-hospital mortality). RESULTS: A total of 58 subjects were assigned to PL-NIV (29 subjects) or VT-NIV (29 subjects) and included in the analyses. The decrement of PaCO2 from baseline to 6 h after randomization was not statistically different between the PL-NIV group and the VT-NIV group (9.3 ± 12.6 mm Hg vs 11.7 ± 12.9 mm Hg, P = .48). There were no differences between the PL-NIV group and the VT-NIV group in the decrement of PaCO2 from baseline to 2 h after randomization (6.4 ± 12.7 mm Hg vs 5.0 ± 15.8 mm Hg, P = .71) as well as in the need for intubation (17.2% vs 10.3%, P = .70), and in-hospital mortality (10.3% vs 6.9%, P > .99). CONCLUSIONS: Regardless of whether a VT- or PL-NIV strategy is employed, it is possible to provide similar support to subjects with AHRF. (ClinicalTrials.gov registration NCT02538263.).

[Modified effect of modified danshou decoction on teratogenicity of bisphenol A intoxicated pregnant rats].

OBJECTIVE: To explore the protective effect of modified danshou decoction (MDD) on teratogenicity of bisphenol A intoxicated pregnant rats. METHODS: Forty-four successfully mated rats were randomly divided into 4 groups, 10 in the blank group and 10 in the model group, 12 in the MDD group and 12 in the positive control group. Bisphenol A (BPA) at the dose of 600 mg/kg was given to rats by gastrogavage in the latter three groups from the 1st day of mating to the 20th day, while the soybean oil was given to rats by gastrogavage in the blank group. No intervention was given to rats in the model group, but the normal saline, MDD condensed decoction, and shoutai pill (STP) condensed decoction was respectively given to rats in the rest three groups during the experimental period. All rats were sacrificed by the 20th pregnancy day. RESULTS: Compared with the model group, the body weight of pregnant rats and fetal rats, body length and tail length of the fetal rats significantly increased in the MDD group (P < 0.05). But the effect of MDD was superior to that of STP (P < 0.05). Moreover, the teratogenic rate was significantly lowered in the MDD group (P < 0.05). CONCLUSION: MDD could promote the weight gaining of pregnant rats and fetal rats, improve the body length and tail length of fetal rats, and lower the teratogenic rate in fetal mice.

[Analysis of adverse effects of cinnabar].

This article made a brief analysis of clinical adverse effects of cinnabar. Except for allergic reaction, almost all the adverse events of cinnabar were caused by unreasonable application. The majority of the poisoning cases were associated with excessive and/or long-term dosage, and improper preparation methods, such as decocting, heating or fumigating. Children showed to be prone to poisoning. The poisoning caused by unreasonable use of cinnabar should be considered to be drug alert, but not advert effect. And the toxicity of cinnabar could be avoided by normalizing the preparation method, controlling the dosage and duration.