Objective To investigate the effect of oleanolic acid (OA) in the maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) through switching pyruvate kinase type M isoforms. Methods HiPSC-CMs were derived from human induced pluripotent stem cells (hiPSCs), through sequential activation and inhibition of the Wnt signaling pathway. On day 19 hiPSC-CMs were divided into control group (RPMI 1640+B27), DMSO group (RPMI 1640+B27+2 μl DMSO), and 10 μmol/L OA group (RPMI 1640+B27+2 μl 5 mmol/L OA) and treated for 7 days, and the medium was changed every 2 days. Immunofluorescence or RT-qPCR were used to detect the expression of stem factor in hiPSCs and cardiac specific markers in hiPSC-CMs. Western blotting was used to detect the expression of PK and mitofusin 2 (MFN2). Mito-Tracker staining showed the morphology of mitochondria, and transmission electron microscope (TEM) showed the ultrastructure of mitochondria. EDU staining was used to detect cell proliferation, and flow cytometry was used to detect cell cycle. Results Immunofluorescence showed that hiPSCs expressed Nanog and Sox2, and hiPSC-CMs expressed myocardial specific markers cTnT, Cx43 and α-actinin.RT-qPCR showed that, compared with hiPSCs, significant differences (P<0.05 or P<0.01) existed in hiPSC-CMs expressed troponin I3 (TNNI3), myosin heavy chain 6 (MYH6), and myosin heavy chain 7 (MYH7). Immunofluorescence showed that, compared with control group and DMSO group, the cell area increased, sarcomere length increased, and the cell circularity decreased in hiPSC-CMs cultured with OA, and the differences were statistically significant (P<0.05); Western blotting showed that, compared with control group and DMSO group, the ratio of PKM1/PKM2 and the expression of MFN2 increased obviously, and the differences were statistically significant (P<0.05 or P<0.01), the fusion lengthening of mitochondria was observed under electron microscope, and Mito-Tracker staining showed that mitochondria formed more mature structure; EDU staining showed a decreased cell proliferation in hiPSC-CMs cultured with OA group compared with control group and DMSO group, all differences were statistically significant(P<0.05). The flow cytometry results indicated that the number of coenocytes increased in hiPSC-CMs cultured with OA group compared with control group and DMSO group. Conclusion OA can promote the maturation of cell structure, mitochondrial structure and morphology, and also can promote cell multinucleation. OA can promote hiPSC-CMs' maturation by switching pyruvate kinase type M isoforms.

Objective To analyze the expression of circRNA0087432 (hsa_circ_0087432) in serum exosomes of patients with cervical cancer, and explore its possible relationship with cervical cancer metastasis. Methods The cervical cancer tissue and serum of 30 patients, who were diagnosed as cervical squamous cell carcinoma from June 2019 to June 2020 in Guangzhou Panyu District Central Hospital and untreated with radiotherapy and chemotherapy before surgery, were collected as the experimental group.Normal cervical tissue and serum of 30 women without cervical cancer were used as control group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of hsa_circ_0087432 in cervical tissues and serum exosomes of patients with cervical cancer and healthy people; Siha cells were transfected with plasmid to overexpress hsa_circ_0087432. According to different treatments, Siha cells were divided into three groups: control group (untransfected plasmid), vector group (transfected with pLC5-ciR) and hsa_circ_0087432 group (transfected with hsa_circ_0087432-pLC5-ciR). The exosomes were collected and extracted, and the exosyndrome were characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA)and Western blotting; Endothelial cells were divided into three groups according to different treatments: control-Exs group (extracted exosomes from control group), vector-Exs group (extracted exosomes from vector group) and hsa_circ_0087432-Exs group (extracted exosomes from hsa_circ_0087432 group). CCK-8 kit was used to detect the effect of exosomes on proliferation of endothelial cells.The effect of exosomes on the migration of endothelial cells were detected by scratch test and Transwell. Results The results of TEM showed that most of the exosomes of Siha cells were elliptical or round. The particle size analysis showed that their diameters ranged of 30-150 nm. Western blotting showed that the expressions of CD9, CD81 and CD63 in the two groups of vesicles were positive. The qPCR results showed that the expression level of hsa_circ_0087432 in cervical tissue was significantly higher in experimental group than that in control group (4.03±1.51 vs. 1.00±0.26, P<0.01), and the expression level of hsa_circ_0087432 in serum exosomes was also obviously higher in experimental group than that in control group (1.97±0.04 vs. 1.02±0.23, P<0.01); CCK-8 results showed that, compared with the control-Exs group, the proliferation of human umbilical vein endothelial cells was significantly promoted in hsa_circ_0087432-Exs group (1.57±0.04 vs. 1.09±0.11, P<0.05). Scratch experiments showed that, 12 hours after treatment, the healing degree was better in hsa_circ_0087432-Exs group than that in control-Exs group (24.66%±2.92% vs. 15.01%±3.12%, P<0.05); and 24 hours after scratching, the healing degree was even better in hsa_circ_0087432-Exs group than that in control-Exs group (74.84%±13.22% vs. 38.70%±2.12%, P<0.01). Transwell also showed that the counted number of endothelial cells increased obviously in hsa_circ_0087432-Exs group than that in vector-Exs group and control-Exs group (1755.00±97.35 vs. 1218.00±103.53 vs. 1044.00±103.79) with significant difference (P<0.05). Conclusion The hsa_circRNA 0087432 is highly expressed in serum exosomes of patients with cervical cancer, and the exosomes derived from cervical cancer cells which over-pressing the hsa_circ_0087432 can promote the proliferation and migration of human umbilical vein endothelial cells.

Objective To investigate the effects of artemisinin (ART) on vascular endothelial cell injury induced by oxidized low density lipoprotein (ox-LDL), and explore its potential molecule mechanism. Methods The human umbilical vein endothelial cells EA.hy926 in logarithmic phase were treated respectively with 0, 50, 100, 150 and 200 mg/ml of ox-LDL and 0, 1,5, 10 and 20 mmol/L of ART. The cell viability were detected by MTT assay. To detected the effect of ART on cells, the EA.hy926 cells were divided into control group (without any treatment), ox-LDL group (treated with 100 mg/ml ox-LDL), ox-LDL+ART group (treated with 100 mg/ml ox-LDL and 10 mmol/L ART) and ox-LDL+ART+3-methyladenine (3-MA) group (treated with 100 mg/ml ox-LDL, 10 mmol/L ART and 5 mmol/L 3-MA). To detected the effect of transient receptor potential channel vanillic acid receptor subtype Ⅳ (TRPV4) on the cells, the EA.hy926 cells were divided into control group, ox-LDL group, ox-LDL+ART group and ox-LDL+ART+ruthenium red (RR) group (treated with 100 mg/ml ox-LDL, 10 mmol/L ART and 10 mmol/L RR). The cell viability were detected by MTT assay. The expressions of TRPV4, autophagy associated proteins (LC3-Ⅱ/LC3-Ⅰ and p62)and apoptosis associated protein (Bcl-2, Bax) were detected by Western blotting. Cell apoptosis were detected by flow cytometry. Results The cell viability of EA.hy926 decreased with the increase of ox-LDL concentration. The viability of ox-LDL induced cells was significantly upregulated by ART (P<0.05). Compared with the control group, the viability of cells, and the expression levels of p62, Bcl-2 and TRPV4 decreased significantly in the ox-LDL group (P<0.05), but the LC3-Ⅱ/LC3-Ⅰ ratio, cell apoptosis rate and expression level of Bax was significantly up-regulated in ox-LDL group (P<0.05). Compared with the ox-LDL group, the cell viability, LC3-Ⅱ/LC3-Ⅰ ratio, the protein expression levels of Bcl-2 and TRPV4 increased significantly, but the cell apoptosis rate, protein expression levels of p62 and Bax decreased significantly in ox-LDL+ART group (P<0.05). Compared with the ox-LDL+ART group, the cell viability, LC3-Ⅱ/LC3-Ⅰ ratio, and protein expression level of Bcl-2 decreased significantly (P<0.05), but the cell apoptosis rate, protein expression levels of p62 and Bax were up-regulated significantly in ox-LDL+ART+3-MA group and ox-LDL+ART+RR group (P<0.05). Conclusion ART can promote autophagy by activating TRPV4 to reduce ox-LDL induced vascular endothelial cell injury.

Objective To investigate the effects of Toll-like receptors (TLR3/TLR4/TLR5/TLR7) on the development, prognosis and immune characteristics of rectal cancer and to explore the association of genetic variation in the regulation region of TLRs with the risk for rectal cancer. Methods Gene expression profiling interactive analysis (GEPIA) platform was used to analyze the expression of TLRs in rectal cancer and its relationship with prognosis. Transcriptome data and clinical data of rectal cancer were downloaded from TCGA database and the correlation between TLRs expression and pathological stage was analyzed. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype of TLR4 rs1927914 and rs7869402 polymorphism. TaqMan probe method was used to determine the genotypes of TLR3 rs5743303, TLR5 rs1640816 and TLR7 rs7869402 variants. The association of TLRs genetic variants with the rectal cancer risk was analyzed by unconditional logistic regression. The immune cells in rectal cancer samples were scored using ESTIMATE algorithm. Using TIMER online data platform, the relationship between both the expression of TLRs and copy number variation (CNV) of genes and immune infiltrated cells was evaluated. Gene function related to TLR3 expression was evaluated by GO function enrichment analysis, gene set variation analysis(GSVA) was used to predict the regulatory network of TLR3 in rectal cancer. Results TLR3 has a lower expression in rectal cancer tissues than in adjacent tissues, which was related to poor prognosis. Compared with the individuals carrying TLR3 AA genotype, the individuals with at least one TLR3 rs5743303 T allele had significantly higher risk of rectal cancer (OR=1.43, 95%CI 1.07-1.91).The study did not show that TLR4 rs1927914, TLR4 rs7869402, TLR5 rs1640816 and TLR7 rs3853839 polymorphism had effect on the risk for rectal cancer. After stratified analysis, the data showed that TLR3 rs5743303 AT or TT contributed the susceptibility to rectal cancer in males (OR=1.47, 95%CI 1.01-2.11), younger subjects (OR=1.64, 95%CI 1.08-2.47), smokers (OR=2.42, 95%CI 1.37-4.38) and drinkers (OR=2.70, 95%CI 1.52-4.80). ESTIMATE and TIMER analyses showed that TLR3 effected on the immune cell infiltration. The results of GO functional enrichment analysis showed that TLR3 was mainly related to changes in related functions such as receptor ligand activity, antigen binding, immunoglobulin receptor binding, growth factors and cytokines. GSVA results showed that TLR3 inhibited the development of rectal cancer by regulating metabolic or immune-related pathways, such as cell apoptosis, natural killer cell-mediated cytotoxicity, phospholipid metabolism and autophagy regulation. Conclusion TLR3 effects on the occurrence and prognosis of rectal cancer and rs5743303 polymorphism increase the susceptibility to rectal cancer.

Objective To summarize the clinical characteristics of patients suffering from invasive pulmonary aspergillosis(IPA) associated with pulmonary nocardiosis (PN) for improving the level in diagnosis and treatment of the disease. Methods The clinical characteristics, diagnosis and treatment of one patient diagnosed with IPA and PN in the First Medical Center of Chinese PLA General Hospital in January 2017 were reported. Wanfang, CNKI, PubMed, Web of Science and Embase databases were searched, and the clinical characteristics and diagnosis and treatment process of patients with IPA and PN were analyzed together with this patient. Results This patient was a 66-year-old male. His underlying disease was nephrotic syndrome, and long-term treatment with hormones and other immunosuppressive agents. The clinical manifestations were cough, yellow sputum, fever. Chest CT showed multiple nodules in both lungs. Aspergillus and Nocardia were found in the sputum. The patient was clearly diagnosed as "invasive pulmonary aspergillosis combined with pulmonary nocardiosis". After targeted anti-infective treatment, the patient recovered. Combined with the literature, a total of 24 cases of patient, including 16 males and 8 females, were analyzed; except for one patient who was infected after drowning, the other 23 patients had immunological impairment; all the patients received anti-infective treatment against Aspergillus and Nocardia, and a total of 6 deaths. Conclusions Patients with IPA may be associated with PN, and it is prone to occur in immunosuppressed patients. Attention should be paid to differential diagnosis during clinical diagnosis and treatment. Early diagnosis and treatment may have a positive effect on improving the prognosis.

Objective To construct a prediction model based on machine learning algorithm for cirrhosis-related hepatic encephalopathy. Methods A cross-sectional survey was conducted in 1498 patients from 7 medical institutions in Chongqing from June 2019 to June 2020, who were divided into hepatic encephalopathy group (n=285) and non-hepatic encephalopathy group(n=1213) according to whether hepatic encephalopathy occurred. 70% (1048 in total) of the data collected from 1498 patients was randomly chosen as the training set for establishing the prediction model and the rest 30% (450 in total) was used for internal verification. Univariate logistic regression was used to filter input indicators. Logistic regression, random forest, decision tree and XGBoost algorithm based on machine learning were used to construct a diagnostic predictive model. The models constructed by the four methods were compared for predictive and diagnostic value of cirrhosis-related hepatic encephalopathy. Results Logistic regression, random forest, decision tree and XGBoost models all suggested prothrombin activity (OR=0.933, 95%CI 0.921-0.946), age (OR=1.045, 95%CI 1.029-1.061), blood sodium (OR=0.964, 95%CI 0.928-1.000) and urea nitrogen (OR=1.063, 95%CI 1.022-1.105) are important influencing factors of hepatic encephalopathy. The sensitivities of the four models were 0.843, 0.904, 0.759 and 0.892; the specificities were 0.785, 0.695, 0.717 and 0.706; the area under the curve (AUC) were 0.875, 0.883, 0.767 and 0.847 respectively. Conclusions The risk prediction model of cirrhosis-related hepatic encephalopathy established based on machine learning has high diagnostic value. The diagnostic effects of logistic and random forest models are better than those of decision tree and XGBoost models.

Objective To explore the clinical diagnostic value of serum dickkopf-1 (DKK1) level in menopausal women with rheumatoid arthritis (RA) secondary to osteoporosis (OP). Methods A total of 236 menopausal female patients diagnosed in the Second Affiliated Hospital of Nanchang University from May 2019 to September 2020 were collected, including 44 patients with OP secondary to RA set as RA+OP group, 150 patients with RA without OP set as RA group, and 42 patients with OP set as OP group, respectively. At the same time, 43 healthy menopausal women in our hospital at the same period were selected as control group. Serum DKK1 was detected by ELISA. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by capillary method and rate-scattering turbidimetry, respectively; The bone metabolism indexes such as parathyroid hormone(PTH), type Ⅰ procollagen C-terminal propeptide (CTX), 25-hydroxy vitamin D₃ [25-(OH)D₃], type Ⅰ procollagen N-terminal propeptide (PINP) and osteocalcin were detected by electro-chemiluminescence method. While, bone alkaline phosphatase (BALP)was determined by chromatography; The bone mineral density (BMD), Z-score and T-score of total hip joint and lumbar spine L_1-4 in all patients were detected by Lunar Prodigy dual energy X-ray absorptiometry. The area under the ROC curve was used to analyze the diagnostic efficacy of DKK1 in patients with RA combined with OP and those with RA or OP alone. Results DKK1, ESR, CRP, BMI, PTH, CTX, 25-(OH)D₃, total hip BMD, total hip T-score, total hip Z-score, lumber spine L_1-4 BMD, lumber spine L_1-4 T score and lumber spine L_1-4 Z score, CTX and BALP were significantly different among the 4 groups (P<0.01 or P<0.05); The difference of fracture story was statistically significant between RA+OP group and OP group (P<0.01). Bivariate correlation analysis conducted between DKK1 and each index showed that serum DKK1 was positively correlated with ESR, CRP, fracture story and BALP (P<0.05), and negatively correlated with BMI, total hip BMD, total hip T-score, total hip Z-score, lumber spine L_1-4 BMD, lumber spine L_1-4 T-score and lumber spine L_1-4 Z-score, PINP, 25-(OH)D₃ and PTH (P<0.01 or P<0.05). Multiple linear regression analysis showed that DKK1 was positively correlated with CRP and BMI (R²=0.048, β=0.034, P=0.003; and R²=0.008, β=0.178, P=0.042, respectively), and negatively correlated with PINP and total hip T-score (R²=0.003, β=–0.022, P=0.009; and R²=0.235, β=–2.375, P=0.000). ROC curve analysis showed that and the optimal cut-off value of DKK1 in the diagnosis of RA secondary to OP was 9.21 μg/L, the sensitivity was 93.2%, the specificity was 91.1%, and the Kappa consistency index was 0.630. The diagnostic efficiency of DKK1 for OP was higher than that of DKK1 for RA, and the Kappa consistency index was relatively stable. Conclusion The serum level of DKK1 is increased in menopausal women with RA secondary to OP, the detection of DKK1 has good diagnostic efficiency in the diagnosis of menopausal women with RA secondary to OP.

Objective To study the warning indicators and clinical value of coagulopathy related to traumatic lung injury(TLI). Methods The data of 159 patients with TLI from September 2015 to November 2019 in the intensive care unit of the 908th Hospital of Chinese PLA Logistical Support Force were analyzed retrospectively, including their hemoglobin (HGB), platelet (PLT), fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), thrombin time (TT), D-dimer (D-D), antithrombin Ⅲ (AT-Ⅲ), fibrin degradation product (FDP) and thromboelastography.According to the 90-d prognosis of patients with TLI, they were divided into survival group (n=141) and death group (n=18). COX regression analysis and ROC curve analysis were carried out, and the risk factors INR were screened out. The patients were divided into INR≥1.36 group (n=49) and INR<1.36 group (n=110) for analysis. Results In survival group, INR, lactate (Lac), and injury severe score (ISS) score were significantly lower than those in death group (Z=–4.493, –3.481, –3.177, P<0.01); APTT, PT, R time and K time were much shorter than death group (Z=–3.275, –4.325, –3.300, –2.278, P<0.01); Oxygenation index, PLT, HGB, AT-Ⅲ, blood clots maximum intensity (MA), blood clot formation dynamics (Angle) and coagulation index (CI) were significantly better than those in death group (Z/t=–4.053, –2.764, 0.269, –2.159, –3.058, –3.294, –3.016, P<0.01). Cox regression analysis showed that INR (RR=2.18, 95%CI 1.07-4.43, P=0.031) were significantly correlated with the death of TLI patients. ROC curve analysis showed that the area under the curve for INR to judge the death of TLI patients was 0.826 (P<0.0001), the cut-off value was 1.36 (P<0.0001)and the sensitivity and specificity were 0.788 and 0.752, respectively. The survival rate in INR<1.36 group was significantly higher than that in INR≥1.36 group (P<0.0001). Compared with INR<1.36 group, in INR≥1.36 group, the Lac and ISS score significantly increased (P<0.05); APTT, PT and K time significantly prolonged (P<0.05); the oxygenation index, PLT, HGB, AT-Ⅲ, MA, Angle and CI decreased significantly (P<0.05). Conclusions TLI patients with INR≥1.36 can be used as an early warning indicator of TLI-related coagulopathy, and the risk of death of TLI related coagulation disease patients is significantly increased.

Objective To investigate the diagnostic efficacy of serum lipids in patients with neuromyelitis optica spectrum disorders (NMOSD), and to analyze the relationship between serum lipids and clinical features of NMOSD. Methods The clinical and laboratory diagnosis information of 324 patients with NMOSD (NMOSD group), 147 patients with multiple sclerosis (MS, MS group) and 252 healthy controls (HCs, HCs group) were collected from the First Medical Center of PLA General Hospital from January 2018 to July 2020. Logistic regression analysis was used to control the age, gender, disease duration, affected sites and the interaction of various serum lipid indexes. The differences of serum total cholesterol (TC), triglyceride (TG), Apolipoprotein A₁ (Apo A₁), Apolipoprotein B (Apo B), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in three groups of patients were analyzed, and the concentration differences of each index in the acute stage, relapse stage and remission stage of NMOSD were also analyzed. According to the clinical features of NMOSD, such as AQP4 antibody titer and affected sites, the concentration difference of lipid index in different subgroups was analyzed. Results The average disease duration in the NMOSD group was 20 months, and magnetic resonance imaging (MRI) showed that the most affected region is the optic nerve (198/324, 61.1%). In the MS group, the disease duration was longer (48 months) and multiple sites were affected (56/147, 38.1%). There were significant differences in TC, Apo A₁, LDL, TG and Apo B between NMOSD group and MS group or HCs group (P<0.05). Subgroup analysis showed that only Apo B was significantly different in the acute stage, relapse stage and remission stage of NMOSD group (P<0.05). Further analysis on the subgroups of NMOSD showed that there were significant differences in TC, Apo A₁, Apo B, HDL and LDL in different sites(P<0.05). The receiver operating characteristic (ROC) analysis showed that the combination of serum TC, Apo A₁, Apo B and LDL could specifically diagnose NMOSD with the AUC of 0.732, sensitivity of 57.86% and specificity of 81.15%. Conclusion The combination of serum TC, Apo A₁, Apo B and LDL can specifically diagnose NMOSD, and Apo A₁ and Apo B can be used as indicators of affected sites and disease activity of NMOSD respectively.

Objective By literature review to retrospectively study the clinical characteristics, diagnosis and treatment process and prognosis of chronic periaortitis (CP) treated with rituximab (RTX), and to improve the understanding of it. Methods To retrospectively analyze the clinical characteristics, laboratory indicators, changes of imaging findings and adverse reactions before and after RTX treatment of six CP patients admitted in the First Medical Center of Chinese PLA General Hospital from October 2014 to November 2020. The clinical remission was defined as the disappearance of clinical symptoms and hydronephrosis, erythrocyte sedimentation rate (ESR) <15 mm/h and C-reactive protein (CRP) <5 mg/L; complete remission was defined as the clinical remission and the maximum transverse diameter of retroperitoneal mass reduced by 50%. Fifty-eight similar cases were collected by searching the database to investigate the efficacy and safety of RTX in treating patients with CP. Results All the 6 patients were males, aged 49.5 (42.0-62.0) years, with pathogenesis of 60 (30-365) days and mean follow-up time of 25.7 (0.9-66.9)months. Three of the 6 patients had severe cardiovascular disease in the past, one suffered from thoracic aorta involvement. RTX alone was given in 3 patients, and together with prednisone in 3 other patients as induce remission therapy, respectively. Five patients achieved clinical remission, of them one was given small dose of prednisone to maintain long-term remission, the other 4 patients received regular application of RTX to maintain remission. The median remission time was 4.0 (0.5-6.0) months. Three patients got complete remission with the median remission time of 18 months (16-24). No recurrence was observed during follow-up. None of the 6 patients had an infusion-related response. One had pulmonary infection at the 3.5-month after the RTX application. A total of 58 cases were found in literature. Clinical symptoms, laboratory tests and imaging findings were all improved. Five (8.6%) patients were infected, 1 (1.7%) was died and 3 (5.2%) had a recurrence after the treatment of RTX. Conclusion Rituximab is an effective and safe regimen in inducing and maintaining remission for chronic periaortitis patients.

Chronic obstructive pulmonary disease (COPD) is a disease with high prevalence, high disability and high mortality, which endangers patients' health seriously. As a common extrapulmonary complication of COPD, skeletal muscle dysfunction leading to the decline of life quality, and increase of mortality, as well as the acute exacerbation of COPD. Howerer, the molecular mechanism of skeletal muscle dysfunction is unclear. This article reviews the potential molecular mechanisms of skeletal muscle dysfunction caused by COPD to provide certain reference value for clinical diagnosis and treatment.

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.