Multicenter outcomes of robotic reconstruction during the early learning curve for minimally-invasive pancreaticoduodenectomy

Background

Perceived excess morbidity during the early learning curve of minimally-invasive pancreaticoduodenectomy (MIPD) has limited widespread adoption. It was hypothesized that robot-assisted reconstruction (RA) after MIPD allows anastomotic outcomes equivalent to open pancreaticoduodenectomy (PD).

Comparative efficacy,safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1–7 trials

In individuals with type 2 diabetes, glycaemic control and cardiovascular risk factor management reduces the likelihood of late-stage diabetic complications. Guidelines recommend treatment goals targeting HbA_1c, body weight, blood pressure, and low-density lipoprotein cholesterol. Development of new treatments for type 2 diabetes requires an understanding of their mechanism and efficacy, as well as their relative effects compared to other treatment choices, plus demonstration of cardiovascular safety. Subcutaneous semaglutide is a glucagon-like peptide-1 receptor agonist currently approved in several countries for once-weekly treatment of type 2 diabetes. Semaglutide works via the incretin pathway, stimulating insulin and inhibiting glucagon secretion from the pancreatic islets, leading to lower blood glucose levels. Semaglutide also decreases energy intake by reducing appetite and food cravings, and lowering relative preference for fatty, energy-dense foods. Semaglutide was evaluated in the SUSTAIN clinical trial programme in over 8000 patients across the spectrum of type 2 diabetes. This review details the efficacy and safety profile of semaglutide in the SUSTAIN 1–5 and 7 trials, and its cardiovascular safety profile in the SUSTAIN 6 trial. Semaglutide consistently demonstrated superior and sustained glycemic control and weight loss vs. all comparators evaluated. In SUSTAIN 6, involving patients at high risk of cardiovascular disease, semaglutide significantly decreased the occurrence of cardiovascular events compared with placebo/standard of care (hazard ratio 0.74, P < 0.001 for non-inferiority). Through a comprehensive phase 3 clinical trial program, we have a detailed understanding of semaglutide’s efficacy, safety, cardiovascular effects and comparative role in the treatment of type 2 diabetes.     

Altered erythrocyte Na+ + K+ pump in adolescent obesity

The number of $\text{Na}\text{K}$ pump units and the cation transport activity of the pump were measured in erythrocytes from two etiologically different groups of obese adolescents and a group of normal controls. There was a significant reduction in the number of pump units, as measured by saturation ouabain binding, in erythrocytes from adolescents with idiopathic, early onset obesity. Individuals whose obesity developed subsequent to the appearance of a variety of hypothalamic lesions showed no reduction in the red cell complement of $\text{Na}\text{K}$ pump when compared to controls and the cation transport activity of their cells was higher than both the controls and the subjects with idiopathic obesity. These results support data obtained in adults that reduced red cell $\text{Na}\text{K}$ pump levels are seen in a group of individuals with idiopathic obesity. They further suggest that such reductions are not likely to be secondary to the obese state per se.     

Triggering Apoptotic Death of Human Epidermal Keratinocytes by Malic Acid: Involvement of Endoplasmic Reticulum Stress- and Mitochondria-Dependent Signaling Pathways

Malic acid (MA) has been commonly used in cosmetic products, but the safety reports in skin are sparse. To investigate the biological effects of MA in human skin keratinocytes, we investigated the potential cytotoxicity and apoptotic effects of MA in human keratinocyte cell lines (HaCaT). The data showed that MA induced apoptosis based on the observations of DAPI staining, DNA fragmentation, and sub-G1 phase in HaCaT cells and normal human epidermal keratinocytes (NHEKs). Flow cytometric assays also showed that MA increased the production of mitochondrial superoxide (mito-SOX) but decreased the mitochondrial membrane potential. Analysis of bioenergetics function with the XF 24 analyzer Seahorse extracellular flux analyzer demonstrated that oxygen consumption rate (OCR) was significantly decreased whereas extracellular acidification rate (ECAR) was increased in MA-treated keratinocytes. The occurrence of apoptosis was proved by the increased expressions of FasL, Fas, Bax, Bid, caspases-3, -8, -9, cytochrome c, and the declined expressions of Bcl-2, PARP. MA also induced endoplasmic reticulum stress associated protein expression such as GRP78, GADD153, and ATF6α. We demonstrated that MA had anti-proliferative effect in HaCaT cell through the inhibition of cell cycle progression at G0/G1, and the induction of programmed cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways.     

马融教授治疗小儿癫痫经验简析

癫痫是一种发作性神志异常的疾病,具有突然性、短暂性、反复发作的特点。此病多因情志失宜,饮食失调,六淫所伤等引起,还与先天因素关系密切。基本病机是顽痰内伏、瘀血停积、气机逆乱,而痰随气逆,瘀血阻络,清阳蒙蔽,引动肝风,发为癫痫。中医学中大多医家从风、痰、瘀入手辨治癫痫。马融教授根据患儿不同的发作形式、诱因、体质特点及脑电图表现,灵活选用涤痰汤、柴胡桂枝龙骨牡蛎汤、凉膈散、风引汤等系列方药,以中医、中西医结合方法治疗小儿癫痫,屡获效验。     

Evaluation for effects of severe acidosis on hemostasis in trauma patients using thrombelastography analyzer

Objective

To investigate effects of metabolic acidosis on hemostasis function in trauma patients using thromboelastography analyzer.

马融教授治疗小儿癫痫经验简析

癫痫是一种发作性神志异常的疾病,具有突然性、短暂性、反复发作的特点。此病多因情志失宜,饮食失调,六淫所伤等引起,还与先天因素关系密切。基本病机是顽痰内伏、瘀血停积、气机逆乱,而痰随气逆,瘀血阻络,清阳蒙蔽,引动肝风,发为癫痫。中医学中大多医家从风、痰、瘀入手辨治癫痫。马融教授根据患儿不同的发作形式、诱因、体质特点及脑电图表现,灵活选用涤痰汤、柴胡桂枝龙骨牡蛎汤、凉膈散、风引汤等系列方药,以中医、中西医结合方法治疗小儿癫痫,屡获效验。     

Palmitic acid induces autophagy in hepatocytes via JNK2 activation

Aim： Free fatty acid-induced lipotoxicity plays a crucial role in the progression of nonalcoholic fatty liver disease （NAFLD）. In the present study we investigated the effects of a high-fat diet and free fatty acids on the autophagic process in hepatocytes in vivo and in vitro and the underlying mechanisms.
Methods： LC3-II expression, a hallmark of autophagic flux, was detected in liver specimens from patients with non-alcoholic steatohepatitis （NASH） as well as in the livers of C57BL/6 mice fed a high-fat diet （HFD） up to 16 weeks. LC3-II expression was also analyzed in human SMMC-7721 and HepG2 hepatoma cells exposed to palmitic acid （PA）, a saturated fatty acid. PA-induced apoptosis was detected by Annexin V staining and specific cleavage of PARP in the presence and absence of different agents.

Results： LC3-II expression was markedly increased in human NASH and in liver tissues of HFD-fed mice. Treatment of SMMC-7721 cells with PA increased LC3-II expression in time- and dose-dependent manners, whereas the unsaturated fatty acid oleic acid had no effect. Inhibition of autophagy with 3MA sensitized SMMC-7721 cells to PA-induced apoptosis, whereas activation of autophagy by rapamycin attenuated PA-induced PARP cleavage. The autophagy-associated proteins Beclin1 and Atg5 were essential for PA-induced autophagy in SMMC-7721 cells. Moreover, pretreatment with SP600125, an inhibitor of JNK, effectively abrogated PA-mediated autophagy and apoptosis. Specific knockdown of JNK2, but not JNK1, in SMMC-7721 cells significantly suppressed PA-induced autophagy and enhanced its pro-apoptotic activity; whereas specific knockdown of JNK1 had the converse effect. Similar results were obtained when HepG2 cells were tested.

Conclusion： JNK1 promotes PA-induced lipoapoptosis, whereas JNK2 activates pro-survival autophagy and inhibits PA lipotoxicity. Our results suggest that modulation of autophagy may have therapeutic benefits in the treatment of lipid-related metabolic diseases.