Latest ArticlesObjective 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.
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.
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.
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.
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.
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 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 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.
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.
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.