Extracellular signal-regulated kinase (ERK) is a kind of serine/threonine protein kinase. As a key downstream protein in RAS-RAF-MEK-ERK signaling pathway, its abnormal activation plays an important role in the development of tumors. Selective ERK1/2 inhibitors can block ERK signaling pathway while overcoming drug resistance caused by upstream target mutation. In this paper, the components of MAPK signaling pathway, the structure and functions of ERK and the role of ERK signaling pathway in tumor development are summarized, and some representative ERK inhibitors in clinical or preclinical studies are emphasized.

Fatigue, which is one of the most commonly reported symptoms in cancer, can negatively impact the functional status and the health-related quality of life of individuals. Although awareness and
study of CRF have grown in recent years,the biological mechanisms and risk factors that induce CRF remain unclear.This paper systematically reviews the available evidence on the biological mechanisms and the risk factors to guide the development of targeted, individualized interventions for cancer-related fatigue.

Objective To investigate the prevention and management of perioperative complications of intertrochanteric fractures in elderly in-hospital patients(aged≥80 years).Methods Clinical data of 103 intertrochanteric fracture patients(31 male and 72 female)undergoing surgical treatment at our hospital from May 2010 to Nov.2015 were retrospectively analyzed.Their ages ranged from 80 to 99 years,with an average of 86.2 years.There were 3 Evan type Ⅰ cases,25 type Ⅱ cases,36 type Ⅲ cases,37 type Ⅳ cases and 2 type V cases.Of these,82 received epidural anesthesia and 21 had general anesthesia.Intertrochanteric fractures were treated with proximal femoral nail(PFN) internal fixation in 101 patients and dynamic hip screw(DHS)internal fixation in 2 patients.Results The average operation duration and blood loss were 30 min and 60 ml in the PFN internal fixation group and 60 min and 150 ml in the DHS internal fixation group,respectively.The average hospitalization time was 16.7 days.One patient (0.9％) died after operation,10 (9.7％) had preoperative complications of bed rest with 3 cases involving the central nervous system and 4 cases involving the respiratory system,and 38 cases (36.9％)had postoperative complications with 13 involving the central nervous system.The average time from admission to operation was 6 days,with 65 cases above the average and 38 cases below the average,and there was a statistically significant difference in the incidence of postoperative complications between the two subgroups(30/65 or 46.2 ％for the former and 8/38 or 21.1％ for the latter,x2＝6.49,P＜0.05).Conclusions Elderly patients with intertrochanteric fractures should undergo surgery as soon as possible,preferably with epidural anesthesia.Proficiency in surgical kills,short operation time,close monitoring of preoperative and postoperative conditions,and proper and timely treatment are the key to ensuring surgical success.

Objective To investigate the levels of cancer related fatigue (CRF) and the correlations between CRF and serum inflammatory factors and hypothalamus-pituitary-adrenal (HPA) axis in patients with gastrointestinal cancer.Methods The CRF level was assessed by brief fatigue inventory (BFI).The level of C-reactive protein (CRP) was measured by immunoturbidimetry, and the level of cortisol was measured by electrochemiluminesence.The levels of interleukin (IL)-6, IL-1β, tumor necrosis factor-α (TNF-α), adrenocorticotropic hormone (ACTH) and norepinephrine (NE) were measured by enzyme-linked immunosorbent assay (ELISA).Results The average total score of CRF was 3.15±1.93, and the degree was mild to moderate, which was positively correlated with the CRP (r=0.321, P=0.000), TNF-α (r=0.265, P=0.000), NE (r=0.174, P=0.015) and ACTH (r=0.257, P=0.000), but was not correlated with the cortisol (r=0.033, P=0.652).Eastern Cooperative Oncology Group (ECOG) score (t=8.081, P=0.000), education (t=-4.244, P=0.000), treatment (t=4.563, P=0.000), time from diagnosis to sampling (t=3.453, P=0.001) and CRP (t=2.837, P=0.006) were important factors of CRF.Conclusion The CRF status is common in gastrointestinal cancer patients.The CRF is correlated with the NE and ACTH of HPA axis.Medical staff should pay attention to the inflammatory factors and hormone levels to improve the fatigue status and the quality of patients.

Fatigue is commonly experienced in patients with advanced kidney disease and associated with poor outcomes. The purpose of this review was to discuss the prevalence, assessment methods and contributing factors of fatigue in patients with end-stage renal disease (ESRD), and also examined possible interventions to improve fatigue and concludes by defining some future research directions.

OBJECTIVETo study whether previously intravenous injection of anisodamine can prevent endotoxemia of heat stroke of rats.

METHODSExperimental animals were randomly divided into two groups, their average artery pressure, heart rate, survival time, survival rate and rectal temperature were measured at an environmental temperature of 38 degrees C-40 degrees C and 50%-60% retative humidity. Blood samples for endotoxins analyses were taken both before and after heat-stress.

RESULTSDuring heat stress, the animals of rectal temperature of the experimental and control groups continuously increased and two hours later, separately to (42.7 +/- 0.6) degree C and (43.1 +/- 0.5) degree C, without statistic difference(P > 0.05), and to (44.6 +/- 0.4) degree C and (44.2 +/- 0.3) degree C prior to death, with statistic difference(P < 0.05). Before the experiment, the contents of endotoxins of portal vein blood were (45.7 +/- 5.2) pg/ml and (42.6 +/- 5.4) pg/ml, and that of systemic blood was (14.8 +/- 4.5) pg/ml and (13.9 +/- 7.2) pg/ml, without statistic difference(P > 0.05). Two hours later, the contents of portal vein blood separately increased to (122.2 +/- 16.7) pg/ml and (49.7 +/- 10.2) pg/ml, obviously higher than that before heat-stress(P < 0.01). And there were clear statistic difference between the two groups(P < 0.01). The changing tendency of the heart rhythm is almost the same in two groups, that is, first rose and then fell. But it is without statistic difference before and two hours later(P > 0.05): before heat-stress, the average artery pressures were (13.3 +/- 0.6) kPa and (13.6 +/- 0.5) kPa, without statistic difference(P > 0.05), and two hours later, were (9.6 +/- 0.5) kPa and (8.6 +/- 0.6) kPa, with obvious statistic difference(P < 0.01). The survival time of the animals were (166.5 +/- 16.9) min and (144.5 +/- 18.2) min with obvious statistic difference(P < 0.01), the survival rate of heat stressed rats in the experimental group were obviously higher than control group(P < 0.01 or P < 0.05).

CONCLUSIONSAnisodamine can prevent endotoxemia in rats suffering heat stroke.

Animals ; Blood Pressure ; Body Temperature ; Endotoxemia ; prevention & control ; Endotoxins ; blood ; Heat Stress Disorders ; drug therapy ; mortality ; physiopathology ; Hot Temperature ; Rats ; Solanaceous Alkaloids ; therapeutic use ; Survival Rate

Wound healing is a dynamic process which involves interaction of various types of cells, cytokines, and extracellular matrix. Among them, epithelial cells and mesenchymal cells are the key components which involve in wound healing and scar formation. Related scholars had done a great number of studies about the functions of epithelial cells and fibroblasts(Fbs) in wound healing and scar formation. The results showed that under the stimulation of complex microenvironment, epithelial cells would lose their epithelial characteristics and acquire the typical characteristics and migration ability of mesenchymal cells. At the same time, with the complex changes of cell structure and cell behavior, they would participate in the process of tissue wound repair, including normal or fibrotic repair, by covering the wound with migration. Fbs are the key cells for the wound fibrotic repair, and play important roles in the process of wound healing, including excessive wound healing or delayed wound healing. In the recent years, the researchers realized that the cross-talk between epithelial cells and Fbs in wound healing, which is referred to as epithelial-mesenchymal interaction, significantly changes the biological behaviors of these two cell types, which affects the dermal remodeling and re-epithelialization quality of wound. Epithelial-mesenchymal interaction plays an important role in skin morphogenesis during embryonic development and maintaining the structural integrity of adult skin. In the process of re-epithelialization, Fbs could promote the proliferation and migration of keratinocytes, meanwhile keratinocytes would receive the signals from Fbs to reconstruct functional epithelium, which has become a hot topic in the field of wound healing at present. In this paper, a comprehensive analysis of the literature on the role of epithelial-mesenchymal interaction in wound healing and scar formation at home and abroad in recent years is presented for the reference of relevant scholars.

The healing after skin injury is a dynamic process of the interaction of various cells, cytokines, and extracellular matrix, and the abnormality of any link will affect the speed and quality of wound healing. Circadian rhythm is a spontaneous periodic oscillation cycle in organisms, which plays an important role in maintaining homeostasis and regulating physiological activities. Studies have shown that circadian rhythm genes play a key role in wound healing. This review summarizes the effects of circadian rhythm genes on different stages of wound healing and its possible mechanism of action, in order to provide a new perspective for wound healing and provide theoretical basis for formulating more effective treatment strategies for refractory wounds.

Abdominal aortic aneurysm (AAA) and atherosclerosis (AS) have considerable similarities in clinical risk factors and molecular pathogenesis. The aim of our study was to investigate the differences between AAA and AS from the perspective of metabolomics, and to explore the potential mechanisms of differential metabolites via integration analysis with transcriptomics. Plasma samples from 32 AAA and 32 AS patients were applied to characterize the metabolite profiles using untargeted liquid chromatography-mass spectrometry (LC-MS). A total of 18 remarkably different metabolites were identified, and a combination of seven metabolites could potentially serve as a biomarker to distinguish AAA and AS, with an area under the curve (AUC) of 0.93. Subsequently, we analyzed both the metabolomics and transcriptomics data and found that seven metabolites, especially 2'-deoxy-D-ribose (2dDR), were significantly correlated with differentially expressed genes. In conclusion, our study presents a comprehensive landscape of plasma metabolites in AAA and AS patients, and provides a research direction for pathogenetic mechanisms in atherosclerotic AAA.

Objective:To explore the influence of human amniotic mesenchymal stem cells (hAMSCs) on the in vivo and in vitro regulation of macrophage phenotypes and inflammatory factors associated with wound healing of full-thickness skin wounds in mice.Methods:Fresh amniotic membrane discarded from full-term delivery by 5 healthy pregnant women in the Department of Obstetrics and Gynecology of the Affiliated Hospital of Zunyi Medical University was used for the isolation and culture of hAMSCs by enzyme digestion method. The third passage of cells was used for identification of adipogenic and osteogenic differentiation. The fourth passage of cells was used for identification of hAMSCs surface markers. Ten C57BL/6 mice (all male, aged 6 to 8 weeks, the same gender and age below) were selected for extracting mouse peritoneal macrophages by intraperitoneal lavage, and M1-type macrophages were induced by Dulbecco′s modified eagle medium (DMEM) medium containing interferon-γ. The M1-type macrophages were divided into hAMSCs+ macrophage group and macrophage alone group. Then 1×10 4 hAMSCs/per well of fourth passage were added to macrophage in hAMSCs+ macrophage group and cultured in 2 mL DMEM medium for routine culture. In macrophage alone group, each well was only added with 2 mL DMEM medium for routine culture. On day 1 and 7 in culture, the content of interleukin-12 (IL-12), arginase 1, and IL-10 in the cell culture supernatant of the 2 groups were detected by enzyme-linked immunosorbent assay with sample number of 6/per group. (2) Full-thickness skin wound model was reproduced in the back of 56 C57BL/6 mice, which were divided into hAMSCs group and phosphate buffer solution (PBS) group using the random number table, with 28 mice in each group. Mice in hAMSCs group were subcutaneously injected with 100 μL of cell suspension containing 1×10 7 hAMSCs per mL in PBS suspension along the wound edge. While mice in PBS group were only subcutaneously injected with 100 μL PBS along the wound edge. On post injection day (PID) 1, 3, 7, and 14, 7 mice in the two groups were sacrificed respectively. Histopathological observation was performed with hematoxylin-eosin staining. The expressions of macrophage surface markers [CD68 and inducible nitric oxide synthase (iNOS) double positive cells and CD68 and arginase 1 double positive] in the wounds were detected by immunofluorescent staining. The mRNA expressions of IL-10, macrophage inflammatory protein 1α (MIP-1α), and MIP-2 in the wounds were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction. Data were statistically analyzed with analysis of variance for factorial design, t test, and Bonferroni correction. Results:(1) On day 1 in culture, the content of IL-12 and arginase 1 in the cell culture supernatant of the two groups were similar ( t=0.448, 0.536, P>0.05), and the content of IL-10 in the cell culture supernatant of hAMSCs+ macrophage group was significantly lower than that in macrophage alone group ( t=14.722, P<0.01). On day 7 in culture, the content of IL-12 in the cell culture supernatant of hAMSCs+ macrophage group was significantly lower than that in macrophage alone group ( t=13.226, P<0.01), and the content of arginase 1 and IL-10 was significantly higher than that in macrophage alone group ( t=30.172, 31.406, P<0.01). (2) On PID 1, a large number of inflammatory cells infiltration were observed in the skin wounds of both groups. On PID 3, the inflammatory cells infiltration in the skin wounds increased in both groups, and the inflammatory cells infiltration in hAMSCs group was less than that in the PBS group. On PID 7, the inflammatory cells infiltration in the wounds decreased in both groups, and the inflammatory cells infiltration in hAMSCs group was less than that in the PBS group. On PID 14, no obvious inflammatory cells infiltration was observed in the wounds in the two groups. (3) On PID 1 and 14, the percentages of CD68 and iNOS double positive cells and CD68 and arginase 1 double positive cells in the wounds were similar in the two groups ( t1 d=0.134, 0.693, t14 d=1.146, 2.585, P>0.05). On PID 3 and 7, the percentages of CD68 and iNOS double positive cells in the wounds in hAMSCs group were significantly lower than those of PBS group ( t=6.396, 4.787, P<0.01), while the percentages of CD68 and arginase 1 double positive cells were significantly higher than those of PBS group ( t=3.928, 4.473, P<0.01). (4) On PID 1, the mRNA expressions of IL-10 in the wounds of mice in the two groups were similar ( t=2.005, P>0.05). On PID 3, 7, and 14, the mRNA expressions of IL-10 in the wounds of mice in hAMSCs group were significantly higher than those of PBS group ( t=7.758, 124.355, 80.823, P<0.01). On PID 1, 3, 7, and 14, the mRNA expressions of MIP-1α and MIP-2 in the wounds of mice in hAMSCs group (0.341±0.212, 0.648±0.004, 0.611±0.106, 0.763±0.049, 1.377±0.099, 1.841±0.042, 1.181±0.035, 0.553±0.028) were significantly lower than those of PBS group (3.853±0.035, 6.914±0.163, 3.648±0.113, 2.250±0.046, 11.119±0.495, 8.634±0.092, 5.722±0.021, 4.862±0.036, t=43.198, 101.904, 51.845, 58.231, 51.074, 177.501, 291.752, 251.614, P<0.01). Conclusions:hAMSCs demonstrates biological effects of promoting the transformation of M1-type macrophages into M2-type macrophages in full-thickness skin wounds of mice. They can up-regulate the expression of anti-inflammatory and anti-fibrotic factor IL-10, and down-regulate the expression of important inflammation mediated factors MIP-1α and MIP-2.