Activated transcription factor 6 (ATF6) is a transmembrane glycoprotein located in the endoplasmic reticulum.It exists widely in various tissues including myocardium and participates in endoplasmic reticulum stress (ERS) by regulating the unfolded protein response (UPR) signal pathway, which has become one of the major regulators of organs/tissues homeostasis and is of great significance in signal transduction, gene expression and protein synthesis. A number of studies have shown that ATF6 plays an important regulatory role in the occurrence and development of atherosclerosis, myocardial infarction, cardiac hypertrophy, diabetic cardiomyopathy, arrhythmia and other common cardiovascular diseases (CVD). At present, some studies have proved that ATF6 can regulate its activity and function to intervene the occurrence and development of some CVD. As a result, whether a small molecule regulator can be designed to treat some CVD by regulating ATF6 has become a research hot-spot. ATF6-based therapies have made great progress and have shown promising efficacy in small animal models of CVD and other systemic protein-based diseases. The small molecule regulator to ATF6 has a broad application prospect in cardiovascular disease, but further basic and clinical studies are still needed to lay the theoretical and practical foundation for its application. In present paper, the structure, classification and correlation of ATF6 with CVD are reviewed in order to provide references for experimental researches, clinical diagnoses and treatments of CVD.

Vascular endothelial glycocalyx (VEG), a protein-polysaccharide complex located on the cell membrane of vascular endothelial cell lumen, has physiological effects such as anti-inflammation, anti-thrombosis and protection of endothelium.The structural and functional abnormalities of VEG in pulmonary capillaries play an important role in the occurrence and progression of sepsis-mediated acute lung injury (ALI). On one hand sepsis induces ALI by activating heparanase and destroying glycocalyx; on the other hand, it inhibits the repair of lung tissue by preventing the timely reconstruction of glycocalyx. This article summarizes the recent studies to explore the relationship between the structural and functional impairment of VEG and sepsis-related ALI, as well as the value and prospect of glycocalyx in the diagnosis and treatment of sepsis-related ALI.

Periodontal diseases often cause alveolar bone defects, and clinically, autologous bone graft or bone substitute implantation is mainly used for treatment. However, there are many defects in the existing treatment methods, such as shortage of donors, bone resorption, infection, and bleeding after transplantation. Oral tissue is one of the important sources of stem cells. Oral-derived stem cells can promote the regeneration of blood vessels and periodontal tissues, and has become a research hot-spot recent years in the treatment of periodontal diseases. However, there are many factors that affect the efficacy of stem cells in treatment of periodontal diseases and are not easy to control. In the past, researchers mainly focused on the therapeutic effects and mechanisms of stem cells themselves, and seldom studied the interaction between the recipient or donor microenvironment and stem cells, and how to establish the best therapeutic strategy. The microenvironmental regulation mechanism of periodontal tissue regeneration induced by stem cells has been summarized in present paper, and the influence of the microenvironment on the function, biological behavior and curative effect of stem cells have been expounded from the aspects of hormone levels, metabolic status and immune regulation, so to deepen researchers' understanding of microenvironmental regulation during stem cell therapy, and optimize and construct more effective periodontal disease treatment strategies.

C-type lectin-like receptor 2 (CLEC-2) is a member of the cell surface receptor C-type lectin superfamily. CLEC-2 expressed in platelet surface is a platelet activatory receptor based on the immune receptor tyrosine activation motif, which can participate in platelet activation and aggregation by binding to its ligand. This physiological process can prevent excessive blood loss in the body, but is also the pathological basis of many thromboembolic diseases. CLEC-2 and its ligands are involved in the pathophysiological processes such as atherosclerosis, inflammation thrombotic state, maintenance of vascular integrity, and cancer-related thrombosis. The important role of CLEC-2 in the thrombosis process has been reviewed in present paper from the four aspects mentioned above.

Non-alcoholic fatty liver disease (NAFLD) has gradually become an important factor causing hepatocellular carcinoma (HCC), and the clinical treatment effects of NAFLD-HCC and general liver cancer are significantly different, and there are many differences in drug sensitivity. At present, the pathogenesis of NAFLD-HCC is not yet clear. Therefore, it is particularly important to construct pre-clinical animal models of NAFLD-HCC. There are various induction methods for animal models of NAFLD-HCC, including dietary induction, chemical induction, genetic induction, dietary combined with chemical induction, genetic combined with dietary and other induction methods. More and more studies have found that there are certain differences in the histopathological types of animal models of NAFLD-HCC induced by different methods. Therefore, according to the research problem, choosing the most suitable animal model is of great significance for studying the causes of NAFLD-HCC and subsequent development of new drugs. The mouse models established for preclinical studies of the progression of NAFLD-HCC were summarized in this paper to reveal the pathogenesis of NAFLD-HCC, and to explore possible new targets for prevention or treatment of NAFLD-HCC.

The weapons in modern warfare are different from those in traditional. Along with the increasing use of precision-guided and high-energy explosive weapons, the combat environment and traumatic condition of eye injuries have changed dramatically. Traditional War Injury Treatment System of the Chinese PLA has not been able to better meet the needs of modern warfare. In order to improve the abilities of treating and protecting from combat-related eye injuries, this paper reviews the research advances in the combat-related eye injuries in 21st century through the aspects of epidemiology, combat environment, injury factors, treatment system and protection work. The present situation of the research on the combat-related eye injuries in Chinese PLA is analyzed, and the research directions in the future are prospected.

Objective To investigate whether Huaier can reverse the drug resistance of CEM-C1 cells to glucocorticoid(GC) in human acute T lymphocytic leukemia (T-ALL) and its possible mechanism. Methods CEM-C1 and CEM-C7 cells were set as control group (0 μg/ml) and experimental groups (200 and 600 μg/ml) after treated with different concentrations of Huaier; T-ALL CEM-C1 cells were set as Huaier (100 μg/ml) combined with dexamethasone (DEX)(12.5, 25, 50, 100, 200 μg/ml)groups; CCK-8 was used to detect the affect of Huaier on the inhibition rate to proliferation of each group of cells; Flow cytometry(FCM) was employed to detect the effect of different concentrations Huaier (200 and 600 μg/ml) on the apoptosis and cell cycle of CEM-C1 and CEM-C7 cells; Western blotting was performed to detect the MDR1 and Pim3 protein expression levels in CEM-C1, CEM-C7 cells and CEM-C1 cells treated with different concentrations of Huaier (200 and 600 μg/ml); qRT-PCR was used to detect the expression level of Pim3 mRNA in CEM-C1 and CEM-C7 cells and CEM-C1 cells treated with different concentrations of Huaier(200 and 600 μg/ml). Results Huaier inhibited the proliferation of CEM-C1 and CEM-C7 cells in a dose-dependent manner;For CEM-C1 cells, compared with DEX alone, the drug resistance was reversed by 1.34 times in Huaier+DEX group, and Huaier(100 μg/ml) combined with low concentration of DEX (12.5, 25, 50 μg/ml) increased the proliferation inhibition rate of CEM-C1 cells (P<0.05); the coeffcient of drug interaction (CDI) values of all groups were <1. Compared with control group, the apoptosis rate of CEM-C1 and CEM-C7 cells increased significantly with the increase of Huaier concentration (P<0.05). Compared with control group, the number of CEM-C1 and CEM-C7 cells decreased in G₀/G₁ stage and increased in S stage in 200 and 600 μg/ml Huaier groups. The expression levels of MDR1 and Pim3 protein and Pim3 mRNA in CEM-C1 cells were higher than those of CEM-C7 cells (2.41±0.32 vs. 1.34±0.43; 0.39±0.10 vs. 0.13±0.05; 1.00 vs. 0.37±0.02, respectively, P<0.05). Compared with control group, the expression levels of MDR1 and Pim3 proteins and Pim3 mRNA reduced obviously in CEM-C1 cells after treatment with 200 and 600 μg/ml Huaier (P<0.05). Conclusion Huaier can inhibit the proliferation and promote the apoptosis of CEM-C1 and CEM-C7 cells, and partially reverse the resistance of CEM-C1 cells to GC, the mechanism may be related to the down-regulation of Pim3.

Objective To investigate the effects of Schisandrin C (SchC) on hydrogen peroxide (H₂O₂) treated human immortalized keratinocyte cells (HaCaT) and to understand its potential mechanisms on ageing. Methods HaCaT cells were cultured in vitro and divided into control group, H₂O₂ model group, and SchC treatment group. Cell viability was evaluated by CCK-8 assay. The levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were determined by WST-1 assay. The level of reactive oxygen species (ROS) was determined by chemical fluorescence assay. The mRNA expression of matrix metalloproteinase, cyclooxygenase-2 (COX-2) and apoptosis-related genes were detected by qRT-PCR. The expression of COX-2, matrix metalloproteinase, apoptosis-related protein, ageing-related protein, transcription factor NF-E₂ related factor 2 (Nrf-2), heme oxygenase (HO-1), cytoplasmic transcription factor-κB (NF-κB) and p-NF-κB was detected by Western blotting. Results SchC at the concentration of less than 100 μmol/L had no significant effects on the proliferation of HaCaT cells; while cell viability decreased to (57.0±3.0)% (P<0.001) after treated with 800 μmol/L H₂O₂. Compared with the H₂O₂ model group, the cell viability, SOD, and GSH levels were significantly increased; MDA and ROS levels were significantly decreased (P<0.05 or P<0.01). Western blotting results showed that the expression of P16, P21 and p-NF-κB were significantly down-regulated, and the expression of Nrf-2 and HO-1 were up-regulated by SchC (P<0.05 or P<0.01). qRT-PCR and Western blotting results showed that SchC could up-regulate the expression of caspase-3 and caspase-9, and down-regulate the expression of Bcl-2, matrix metalloproteinase (MMP-1, MMP-9) and inflammatory factor COX-2 by regulating NF-κB pathway (P<0.05 or P<0.01). Conclusion SchC had a protective effect on the aging model of oxidative stress damage of H₂O₂-induced HaCaT cells, which could lay a foundation for the development of anti-ageing products of Schisandra C.

Objective To investigate whether dexmedetomidine alleviates lipopolysaccharide (LPS)-induced acute lung injury(ALI) through alpha-7 nicotinic acetylcholine receptor (α7nAChR) mediated TLR4/NF-κB pathways. Methods Twenty-four Wistar rats were randomly divided into 4 groups: control group (n=6), acute lung injury group (n=6), dexmedetomidine treatment group (n=6), and α7nAChR inhibitor α-BGT group (n=6). After anesthesia, rats in the control group were intraperitoneally injected with normal saline to serve as normal control; the rest rats all received LPS (10 mg/kg) via a femoral vein to induce the ALI model. For the dexmedetomidine treatment group, rats were continuously injected with dexmedetomidine (5 μg/kg per hour) via the femoral vein immediately after LPS administration. For the α7nAChR inhibitor α-BGT group, rats received 1 μg/kg α-BGT half an hour before dexmedetomidine administration as the dexmedetomidine treatment group. The rats were sacrificed 12 hours after LPS injection to collect the blood and lung tissues. Histology of the lungs was examined with HE staining. The lung injury score was calculated. In the blood sample, PaO₂, HCO₃^–, Lac, W/D, MPO activity were measured. The number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) were measured, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10 in serum were measured by ELISA. The protein expression of α7nAChR, TLR4, p-NF-κB were determined by Western blotting. Results Compared with the control group, LPS induced marked lung histological injury, which was less pronounced in the dexmedetomidine treatment group. Compared with the control group, the levels of PaO₂ and HCO₃^– were decreased, Lac, W/D, TNF-α, IL-6, IL-10, MPO, the total number of cells, neutrophils, and macrophages were increased in the acute lung injury group (P<0.01). Compared with the acute lung injury group, PaO₂, HCO₃^– and IL-10 were increased, and Lac, W/D, TNF-α, IL-6, MPO, the total number of cells, neutrophils, and macrophages were decreased in the dexmedetomidine treatment group (P<0.01). Compared with the control group, the protein levels of α7nAChR, TLR4, p-NF-κB were increased in the acute lung injury group (P<0.01). Compared with the acute lung injury group, the protein levels of α7nAChR was increased, and TLR4, p-NF-κB were decreased in the dexmedetomidine treatment group (P<0.01).However, the effect of dexmedetomidine was reversed by the α7nAChR inhibitor α-BGT. Conclusion Dexmedetomidine may reduce LPS-induced ALI through α7nAChR mediated TLR4/NF-κB pathways.

Objective To investigate the changes of cognitive function in early stage of severe heatstroke (HS) in a rat model, and analyze the metabolic changes of central nervous system by ¹H NMR-based metabonomics. Methods Twenty-five male Sprague-Dawley rats were randomly divided into control group (n=11) and HS group (n=14). The rats in HS group were exposed to 40 ℃ heat chamber. When the core temperature reached 42 ℃, they were taken out and rewarmed for 3 h. The rats in control group were placed at (25.0±0.5) ℃. The rats in HS group were evaluated for neurological deficits before modeling and 0 and 3 h after the rewarm by the modified neurological severity score (mNSS); the tissues of the control group (n=3) and HS group (n=3) were taken and HE staining was used to detect the pathological changes; the brain tissues of the rats in control group (n=8) and HS group (n=11)were taken and the MestReNova software (v9.0.1) was used to perform ¹H NMR detection in the NMR spectrometer. The related mechanism of early HS brain injury in rats was expounded from the perspective of metabolomics. Results In the early stage of HS, nerve cell necrosis and apoptosis can be seen in pathological observation. The escape latency time and distance was significantly increased in the HS group compared with control group [(33.14±1.51) s vs. (53.14±2.14) s, P<0.05; (360.79±13.50) cm vs.(693.29±28.63) cm, P<0.05]; the number of platform-crossing and the activity time of target quadrant was significantly reduced in the HS group compared with control [(6.36±0.84) times vs. (2.64±0.75) times, P<0.05; (65.78%±1.06%) vs. (35.81%±1.14%), P<0.05]. The metabolic patterns of central nervous system were significantly changed in early stage of severe heatstroke. Compared to the control group, glutamine, glutamate, lactate and succinate were distinctly increased, while the levels of aspartate, glycine, glutathione and pyruvate were markedly decreased. Conclusions The neurological impairment and cognitive dysfunction can occur in the early stage of severe heat stroke, and the metabolic pattern of central nerve system is changed, resulting disorders of neurotransmitters as amino acids and energy metabolism and oxidative stress.