Free fatty acid receptors in the endocrine regulation of glucose metabolism: Insight from gastrointestinal-pancreatic-adipose interactions.

Glucose metabolism is primarily controlled by pancreatic hormones, with the coordinated assistance of the hormones from gastrointestine and adipose tissue. Studies have unfolded a sophisticated hormonal gastrointestinal-pancreatic-adipose interaction network, which essentially maintains glucose homeostasis in response to the changes in substrates and nutrients. Free fatty acids (FFAs) are the important substrates that are involved in glucose metabolism. FFAs are able to activate the G-protein coupled membrane receptors including GPR40, GPR120, GPR41 and GPR43, which are specifically expressed in pancreatic islet cells, enteroendocrine cells as well as adipocytes. The activation of FFA receptors regulates the secretion of hormones from pancreas, gastrointestine and adipose tissue to influence glucose metabolism. This review presents the effects of the FFA receptors on glucose metabolism via the hormonal gastrointestinal-pancreatic-adipose interactions and the underlying intracellular mechanisms. Furthermore, the development of therapeutic drugs targeting FFA receptors for the treatment of abnormal glucose metabolism such as type 2 diabetes mellitus is summarized.

ß-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes.

Fibroblast growth factor 21 (FGF21) is secreted by hepatocytes as a peptide hormone to regulate glucose and lipid metabolism. FGF21 promotes hepatic ketogenesis and increases ketone body utilization in starvation. Histones are the target molecules of nutrients in regulating hepatic metabolic homeostasis. However, the effect of ketone bodies on FGF21 expression and the involvement of histones in it is not clear yet. The present study observed the effects of ß-hydroxybutyrate (ß-OHB), the main physiological ketone body, on FGF21 expression in human hepatoma HepG2 cells in vitro and in mice in vivo, and the role of histone deacetylases (HDACs) in ß-OHB-regulated FGF21 expression was investigated. The results showed that ß-OHB significantly upregulated FGF21 gene expression and increased FGF21 protein levels while it inhibited HDACs' activity in HepG2 cells. HDACs' inhibition by entinostat upregulated FGF21 expression and eliminated ß-OHB-stimulated FGF21 expression in HepG2 cells. Intraperitoneal injections of ß-OHB in mice resulted in the elevation of serum ß-OHB and the inhibition of hepatic HDACs' activity. Meanwhile, hepatic FGF21 expression and serum FGF21 levels were significantly increased in ß-OHB-treated mice compared with the control. It is suggested that ß-OHB upregulates FGF21 expression through inhibition of HDACs' activity in hepatocytes.

α-Lipoic acid up-regulates gene expression but reduces protein levels of fibroblast growth factor 21 in HepG2 cells.

Fibroblast growth factor 21 (FGF21) is a metabolism-regulating hepatokine, and its expression is finely controlled by the nutrients and cellular stressors. α-Lipoic acid (ALA) regulates fuel metabolism as a nutrient, but it also arouses mitochondrial and endoplasmic reticulum (ER) stress as well as oxidative stress in hepatocytes. However, the role of cellular stress in ALA-regulated FGF21 expression has not been demonstrated as yet. The present study found that ALA up-regulated FGF21 gene expression while it reduced FGF21 protein levels in HepG2 cells, which was accompanied by mitochondrial damage that was shown by ATP reduction and ROS elevation. ALA led to mitochondrial stress and ER stress as shown by the increased expression of HSP60, ATF6 and ATF4. Inhibition of ER stress by 4-PBA significantly attenuated ALA-stimulated FGF21 gene expression while it did not influence the reduction of FGF21 protein levels. H2 O2 -induced oxidative stress reduced FGF21 protein levels in HepG2 cells, and anti-oxidation by Tempol blocked ALA-induced reduction of FGF21 proteins. In conclusion, ALA up-regulates FGF21 gene expression through the stimulation of mitochondrial and ER stress while it reduces FGF21 protein levels through the induction of oxidative stress in HepG2 cells. Further studies are needed to demonstrate the in vivo effect of ALA on hepatic FGF21 expression.

Pyruvate Upregulates Hepatic FGF21 Expression by Activating PDE and Inhibiting cAMP-Epac-CREB Signaling Pathway.

Fibroblast growth factor 21 (FGF21) functions as a polypeptide hormone to regulate glucose and lipid metabolism, and its expression is regulated by cellular metabolic stress. Pyruvate is an important intermediate metabolite that acts as a key hub for cellular fuel metabolism. However, the effect of pyruvate on hepatic FGF21 expression and secretion remains unknown. Herein, we examined the gene expression and protein levels of FGF21 in human hepatoma HepG2 cells and mouse AML12 hepatocytes in vitro, as well as in mice in vivo. In HepG2 and AML12 cells, pyruvate at concentrations above 0.1 mM significantly increased FGF21 expression and secretion. The increase in cellular cAMP levels by adenylyl cyclase activation, phosphodiesterase (PDE) inhibition and 8-Bromo-cAMP administration significantly restrained pyruvate-stimulated FGF21 expression. Pyruvate significantly increased PDE activities, reduced cAMP levels and decreased CREB phosphorylation. The inhibition of exchange protein directed activated by cAMP (Epac) and cAMP response element binding protein (CREB) upregulated FGF21 expression, upon which pyruvate no longer increased FGF21 expression. The increase in plasma pyruvate levels in mice induced by the intraperitoneal injection of pyruvate significantly increased FGF21 gene expression and PDE activity with a reduction in cAMP levels and CREB phosphorylation in the mouse liver compared with the control. In conclusion, pyruvate activates PDEs to reduce cAMP and then inhibits the cAMP-Epac-CREB signaling pathway to upregulate FGF21 expression in hepatocytes.

Comparison of the Curative Efficacy of Hemivertebra Resection via the Posterior Approach Assisted With Unilateral and Bilateral Internal Fixation in the Treatment of Congenital Scoliosis.

Objective: This study aimed to compare the curative efficacy of hemivertebra resection via the posterior approach assisted with unilateral and bilateral internal fixation in the treatment of congenital scoliosis (CS). Methods: In this study, 29 children (15 males and 14 females), who underwent hemivertebra resection via the posterior approach and received internal fixation from November 2005 to September 2018, were analyzed retrospectively. The age of these patients ranged from 0.9 to 15 years, with an average of 3.8 years. The follow-up duration ranged from 2 to 12.3 years, with an average of 5.7 years. The patients in group A received unilateral internal fixation, and those in group B received bilateral internal fixation. The operation duration, bleeding volume, and complications during the operation, as well as the Cobb angles of scoliosis and kyphosis before and after the operation and at the last follow-up, were compared between the two groups. Results: In group A, the operation duration was 207.4 ± 54.5 min, and the bleeding volume was 215.3 ± 75.4 ml; in group B, the operation duration was 249.5 ± 51.0 min, and the bleeding volume was 291.3 ± 115.6 ml (P < 0.05). The Cobb angles of segmental scoliosis, segmental kyphosis, cephalic compensatory curve, and caudal compensatory curve were significantly improved in the two groups after operation and at the last follow-up (P < 0.05). The post-operative correction rate of the scoliosis Cobb angle was 67.2% in group A and 79.5% in group B; and the difference was statistically significant (P < 0.05). At the last follow-up, the correction rate of the scoliosis Cobb angle was 72.7% in group A and 76.2% in group B (P > 0.05). After the operation and at the last follow-up, the correction rates of kyphosis were 83.1 and 79.6% in group A and 71.8 and 65.5% in group B (P > 0.05). Conclusion: Hemivertebra resection via posterior approach with unilateral internal fixation can also achieve the effect of bilateral internal fixation in the treatment of CS. It is able to preserve a certain degree of contralateral spinal growth potential and is a feasible method.

Nano-realgar suppresses lung cancer stem cell growth by repressing metabolic reprogramming.

BACKGROUND: Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. METHODS: The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. RESULTS: Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. CONCLUSIONS: These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.

Forecasting seasonal variations in electricity consumption and electricity usage efficiency of industrial sectors using a grey modeling approach.

The aim of this research is to forecast seasonal fluctuations in electricity consumption, and electricity usage efficiency of industrial sectors and identify the impacts of the novel coronavirus disease 2019 (COVID-19). For this purpose, a new seasonal grey prediction model (AWBO-DGGM(1,1)) is proposed: it combines buffer operators and the DGGM(1,1) model. Based on the quarterly data of the industrial enterprises in Zhejiang Province of China from the first quarter of 2013 to the first quarter of 2020, the GM(1,1), DGGM(1,1), SVM, and AWBO-DGGM(1,1) models are employed, respectively, to simulate and forecast seasonal variations in electricity consumption, the added value, and electricity usage efficiency. The results indicate that the AWBO-DGGM(1,1) models can identify seasonal fluctuations and variations in time series data, and predict the impact of COVID-19 on industrial systems. The minimum mean absolute percentage errors (MAPEs) of the electricity consumption, added value, and electricity usage efficiency of industrial enterprises separately are 0.12%, 0.10%, and 3.01% in the training stage, while those in the test stage are 6.79%, 4.09%, and 2.25%, respectively. The electricity consumption, added value, and electricity usage efficiency of industrial enterprises in Zhejiang Province will still present a tendency to grow with seasonal fluctuations from 2020 to 2022. Of them, the added value is predicted to increase the fastest, followed by electricity consumption.

GPR120 Regulates Pancreatic Polypeptide Secretion From Male Mouse Islets via PLC-Mediated Calcium Mobilization.

The free fatty acid receptor G protein-coupled receptor 120 (GPR120) is expressed in pancreatic islets, but its specific cell distribution and function have not been fully established. In this study, a GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhanced green fluorescence proteins (EGFP). EGFP-positive cells collected from KI mouse islets by flow cytometry had a significantly higher expression of pancreatic polypeptide (PP) evidenced by reverse transcriptase (RT)-quantitative polymerase chain reaction (qPCR). Single-cell RT-PCR and immunocytochemical double staining also demonstrated the coexpression of GPR120 with PP in mouse islets. The GPR120-specific agonist TUG-891 significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR120 small interfering RNA treatment. TUG-891-stimulated PP secretion in islets was fully blocked by pretreatment with YM-254890 (a Gq protein inhibitor), U73122 (a phospholipase C inhibitor), or thapsigargin (an inducer of endoplasmic reticulum Ca2+ depletion), respectively. TUG-891 triggered the increase in intracellular free Ca2+ concentrations ([Ca2+]i) in PP cells, which was also eliminated by YM-254890, U73122, or thapsigargin. GPR120 gene expression was significantly reduced in islets of high-fat diet (HFD)-induced obese mice. TUG-891-stimulated PP secretion was also significantly diminished in vivo and in vitro in HFD-induced obese mice compared with that in normal-chow diet control mice. In summary, this study demonstrated that GPR120 is expressed in mouse islet PP cells and GPR120 activation stimulated PP secretion via the Gq/PLC-Ca2+ signaling pathway in normal-chow diet mice but with diminished effects in HFD-induced obese mice.

Prediction of the Number of Patients Infected with COVID-19 Based on Rolling Grey Verhulst Models.

The outbreak of a novel coronavirus (SARS-CoV-2) has caused a large number of residents in China to be infected with a highly contagious pneumonia recently. Despite active control measures taken by the Chinese government, the number of infected patients is still increasing day by day. At present, the changing trend of the epidemic is attracting the attention of everyone. Based on data from 21 January to 20 February 2020, six rolling grey Verhulst models were built using 7-, 8- and 9-day data sequences to predict the daily growth trend of the number of patients confirmed with COVID-19 infection in China. The results show that these six models consistently predict the S-shaped change characteristics of the cumulative number of confirmed patients, and the daily growth decreased day by day after 4 February. The predicted results obtained by different models are very approximate, with very high prediction accuracy. In the training stage, the maximum and minimum mean absolute percentage errors (MAPEs) are 4.74% and 1.80%, respectively; in the testing stage, the maximum and minimum MAPEs are 4.72% and 1.65%, respectively. This indicates that the predicted results show high robustness. If the number of clinically diagnosed cases in Wuhan City, Hubei Province, China, where COVID-19 was first detected, is not counted from 12 February, the cumulative number of confirmed COVID-19 cases in China will reach a maximum of 60,364-61,327 during 17-22 March; otherwise, the cumulative number of confirmed cases in China will be 78,817-79,780.

[The molecular mechanism of fibroblast growth factor 21-inhibited leptin expression in adipocytes].

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.

The GPR120 Agonist TUG-891 Inhibits the Motility and Phagocytosis of Mouse Alveolar Macrophages.

Movement and phagocytosis characterize the fundamental actions of macrophages. Although it is known that the free fatty acid receptor GPR120 is expressed in macrophages and regulates cytokine expression to exert anti-inflammatory activities, the effects of GPR120 activation on the motility and phagocytosis of macrophages are not clear. In this study, mouse alveolar macrophages (AM) were stimulated with the GPR120 agonist TUG-891, and the changes in cell motility, intracellular Ca2+ concentration ([Ca2+]i), and the ability of phagocytosis were measured. Mouse AM in controls exhibited active movement in vitro, and TUG-891 significantly restrained AM movement. Meanwhile, TUG-891 stimulated a quick increase in [Ca2+]i in AM, which was blocked separately by the Gq protein inhibitor YM-254890, the phospholipase C (PLC) inhibitor U73122, or depletion of endoplasmic reticulum (ER) Ca2+ store by thapsigargin. The inhibition of AM movement by TUG-891 was eliminated by YM-254890, U73122, thapsigargin, and chelation of cytosolic Ca2+ by BAPTA. Moreover, TUG-891 inhibited AM phagocytosis of fluorescent microspheres, which was also blocked by YM-254890, U73122, thapsigargin, and BAPTA. In conclusion, GPR120 activation in mouse AM increases [Ca2+]i but inhibits the motility and phagocytosis via Gq protein/PLC-mediated Ca2+ release from ER Ca2+ store.

Characterization of coal-based fulvic acid and the construction of a fulvic acid molecular model.

Fulvic acid (FA) is important in modern agriculture, ecological restoration, life science, and medicine. The precise characterization of the composition and molecular structure of FA has become a key scientific issue in both basic and applied research. In this study, coal-based FA was separated by microwave-assisted oxygenation from lignite originating from Inner Mongolia in China. Through elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy, classical quantitative titration experiments, and quantum chemistry combined with software analysis, the representative microscopic molecular structure of FA was determined. The results show that coal-based FA mainly contains three kinds of benzene ring substituents, ether bonds, hydrogen bonds, carbonyl groups, hydroxyl groups, carboxyl groups, phenolic hydroxyl groups, and semiquinonyl groups. The oxygen content is high, the carbon-to-oxygen ratio is less than 1, and the hydrogen-to-carbon ratio is 1.09. The ratio of aromatic carbon to total carbon is approximately 0.6, and benzene rings are connected to each other by an ether-oxygen bridge. The fat chain length of FA is approximately 0.47. FA has a small molecular structure with many acidic groups, primarily carboxyl groups and phenolic hydroxyl groups. The two-dimensional planar molecular structure of FA was established; the chemical formula is C38H32NO24, and the relative molecular mass is 886. The lowest-energy, structurally optimized three-dimensional characteristic ball-and-stick and stick models were also constructed. The calculated infrared spectrum of the molecular structure matches well with the experimental spectrum of FA, and the types and distributions of functional groups agree with the findings of previous studies. The quantum chemical data confirm that the proposed molecular structure is reasonable. The findings provide a scientific reference for applied research on FA in the future.

Lipopolysaccharide inhibits GPR120 expression in macrophages via Toll-like receptor 4 and p38 MAPK activation.

Free fatty acid receptor G protein-coupled receptor 120 (GPR120) is highly expressed in macrophages and was reported to inhibit lipopolysaccharide (LPS)-stimulated cytokine expression. Under inflammation, macrophages exhibit striking functional changes, but changes in GPR120 expression and signaling are not known. In this study, the effects of LPS treatment on macrophage GPR120 expression and activation were investigated. The results showed that LPS inhibited GPR120 expression in mouse macrophage cell line Ana-1 cells. Moreover, LPS treatment inhibited GPR120 expression in mouse alveolar macrophages both in vitro and in vivo. The inhibitory effect of LPS on GPR120 expression was blocked by Toll-like receptor 4 (TLR4) inhibitor TAK242 and p38 mitogen-activated protein kinase inhibitor LY222820, but not by ERK1/2 inhibitor U0126 and c-Jun N-terminal kinase inhibitor SP600125. LPS-induced inhibition of GPR120 expression was not attenuated by GPR120 agonists TUG891 and GW9508. TUG891 inhibited the phagocytosis of alveolar macrophages, and LPS treatment counteracted the effects of TUG891 on phagocytosis. These results indicate that pretreatment with LPS inhibits GPR120 expression and activation in macrophages. It is suggested that LPS-induced inhibition of GPR120 expression is a reaction enhancing the LPS-induced pro-inflammatory response of macrophages.

Protective effects of GPR120 agonist-programmed macrophages on renal interstitial fibrosis in unilateral ureteral obstruction (UUO) rats.

Macrophages in the kidney play different roles in renal interstitial fibrosis (RIF) depending on their phenotypes. M2 phenotype macrophages are believed to protect the kidney against RIF. Free fatty acid receptor GPR120 is expressed in macrophages, and its activation induces macrophage transition to M2 phenotype. In this study, the effects of GPR120 agonist-programmed macrophages on RIF were investigated. The peritoneal macrophages collected from rats were incubated with GPR120 agonist TUG891 in vitro for 24 h, and then they were transplanted autologously to the kidney with ureteral obstruction by intrarenal injection for 7 days on the same day following unilateral ureteral obstruction (UUO) operation. RIF was identified by Masson trichrome histological staining, and the expression of RIF-related proteins was analyzed by immunohistochemistry and western blot. It was observed that TUG891-programmed macrophages up-regulated the expression of CD206 and arginase-1 while the expression of interleukin-6 and tumor necrosis factor-α were down-regulated. RIF in rats was significantly increased following UUO, which was markedly alleviated by TUG891-programmed macrophages but not untreated macrophages. TUG891-programmed macrophages inhibited the abnormal expression of TGF-ß1 and SMAD2. The abnormal expression of epithelial-mesenchymal transition (EMT)-related proteins including vimentin, α-SMA and ß-catenin was also significantly decreased in rats with transplantation of TUG891-programmed macrophages as compared to UUO rats. This study suggests that autologous administration of peritoneal macrophages programmed in vitro by GPR120 agonist to kidney has a protective effect against RIF following UUO.

Prognostic Value of MicroRNA-15a in Human Cancers: A Meta-Analysis and Bioinformatics.

BACKGROUND: Although several studies have proved the relationship between the prognostic value of miRNA-15a and different types of cancer, the result remains controversial. Thus, a meta-analysis was conducted to clarify the prognostic value of miRNA-15a expression level in human cancers. METHODS: We enrolled appropriate literature by searching the databases of PubMed, Embase, and Web of Science. Subsequently, we extracted HRs and their 95% CIs and calculated pooled results of miRNA-15a for overall survival (OS) and disease-free survival (DFS). Besides, subgroup analysis, sensitivity analysis, and publication bias were also revealed in this study. We also further validated this meta-analysis using the Kaplan-Meier plotter database. RESULT: 10 studies, including 1616 patients, were embraced in our meta-analysis. The result showed the lower expression of miRNA-15a significantly predicted adverse OS (HR=2.17, 95% CI: 1.41-3.34), but there is no significant association between the expressing level and DFS in cancer patient (HR=2.04, 95% CI: 0.60-6.88). Based on Kaplan-Meier plotter database, we found the same results in bladder Carcinoma, head-neck squamous cell carcinoma, liver hepatocellular carcinoma, lung squamous cell carcinoma, pancreatic ductal adenocarcinoma, rectum adenocarcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma, but opposite results were found in cervical squamous cell carcinoma and esophageal carcinoma. CONCLUSION: Low expressing levels of miRNA-15a indicated poor OS, while miRNA-15a can be used as a prediction biomarker in different cancer types.

[Facilitative glucose transporters: expression, distribution and the relationship to diseases].

Facilitative glucose transporters (GLUT) are proteins that mediate glucose transmembrane transport in the form of facilitated diffusion, which play an important role in regulating cell energy metabolism. There are many breakthroughs in researches of facilitative GLUT in recent years. It has been known that there are 14 subtypes of facilitative GLUT with obvious tissue specificity in distribution and physiological function. In the present review, the tissue and cellular distribution, subcellular localization, expression regulation, physiological function and the relationship to diseases of facilitative GLUT subtypes were summarized, in order to further understand their physiological and pathophysiological significances.

Chinese expert consensus on echelons treatment of thoracic injury in modern warfare.

The emergency treatment of thoracic injuries varies of general conditions and modern warfare. However, there are no unified battlefield treatment guidelines for thoracic injuries in the Chinese People's Liberation Army (PLA). An expert consensus has been reached based on the epidemiology of thoracic injuries and the concept of battlefield treatment combined with the existing levels of military medical care in modern warfare. Since there are no differences in the specialized treatment for thoracic injuries between general conditions and modern warfare, first aid, emergency treatment, and early treatment of thoracic injuries are introduced separately in three levels in this consensus. At Level I facilities, tension pneumothorax and open pneumothorax are recommended for initial assessment during the first aid stage. Re-evaluation and further treatment for hemothorax, flail chest, and pericardial tamponade are recommended at Level II facilities. At Level III facilities, simple surgical operations such as emergency thoracotomy and debridement surgery for open pneumothorax are recommended. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.

Chinese expert consensus on echelons treatment of pelvic fractures in modern war.

The characteristics and treatment of pelvic fractures vary between general conditions and modern war. An expert consensus has been reached based on pelvic injury epidemiology and the concepts of battlefield treatment combined with the existing levels of military medical care in modern warfare. According to this consensus, first aid, emergency treatment and early treatment of pelvic fractures are introduced in three separate levels. In Level I facilities, simple triage and rapid treatment following the principles of advanced trauma life support are recommended to evaluate combat casualties during the first-aid stage. Re-evaluation, further immobilization and fixation, and hemostasis are recommended at Level II facilities. At Level III facilities, the main components of damage control surgery are recommended, including comprehensive hemostasis, a proper resuscitation strategy, the treatment of concurrent visceral and blood vessel damage, and battlefield intensive care. The grading standard for evidence evaluation and recommendation was used to reach this expert consensus.

Grifolic acid causes osteosarcoma cell death in vitro and in tumor-bearing mice.

Grifolic acid is a natural compound isolated from the fungus Albatrellus confluens. In the present study, we assessed the effects of grifolic acid on human osteosarcoma cells. We found that grifolic acid dose- and time-dependently induced cell death in the U-2 OS, MG-63, Saos-2, and 143B human osteosarcoma cell lines. Grifolic acid decreased osteosarcoma cell mitochondrial membrane potential, ATP production, and cellular NADH levels, but did not impact mitochondrial membrane potential in isolated mitochondria from human osteosarcoma cells. Intratumoral injection of grifolic acid also promoted tumor cell death and prolonged survival in nude mice bearing human osteosarcoma xenografts. Grifolic acid had no obvious toxicity in mice, with no histological changes in liver, kidney, lung, or heart, and no changes in blood cell counts or levels of plasma total protein, alanine aminotransferase, or aspartate aminotransferase. These results show that grifolic acid induces osteosarcoma cell death by inhibiting NADH generation and ATP production without obvious toxicity. Intratumoral injection of grifolic acid may be a promising anti-osteosarcoma therapeutic option in patients.

Expert consensus on the evaluation and diagnosis of combat injuries of the Chinese People's Liberation Army.

The accurate assessment and diagnosis of combat injuries are the basis for triage and treatment of combat casualties. A consensus on the assessment and diagnosis of combat injuries was made and discussed at the second annual meeting of the Professional Committee on Disaster Medicine of the Chinese People's Liberation Army (PLA). In this consensus agreement, the massive hemorrhage, airway, respiration, circulation and hypothermia (MARCH) algorithm, which is a simple triage and rapid treatment and field triage score, was recommended to assess combat casualties during the first-aid stage, whereas the abbreviated scoring method for combat casualty and the MARCH algorithm were recommended to assess combat casualties in level II facilities. In level III facilities, combined measures, including a history inquiry, thorough physical examination, laboratory examination, X-ray, and ultrasound examination, were recommended for the diagnosis of combat casualties. In addition, corresponding methods were recommended for the recognition of casualties needing massive transfusions, assessment of firearm wounds, evaluation of mangled extremities, and assessment of injury severity in this consensus.