Latest ArticlesThe Omicron variant of SARS-CoV-2 is a new variant of concern after Alpha, Beta, Gamma and Delta variants. The amino acid mutations in the viral antigens, especially in the receptor binding region (RBD) of spike protein, were significantly more than those of other variants, which lead to the significant increase of infectivity, transmissibility and immune escape of Omicron variant. In addition, those spike mutations impaired the protective effect of vaccination. When compared to the infection of other variants, the latency of Omicron variant infection was significantly shortened, and the pathogenicity decreased markedly, which is in consistence with the fact that the vast majority of infected individuals showed no symptoms or only mild disease. Exacerbations in patients infected by Omicron variant were often associated with the progress of underlying disease. Early detection and medical isolation of infected persons, careful personal protection measures to cut off transmission routes, and active vaccination to protect susceptible people are key measures to prevent the spread of Omicron variant epidemic. A small number of patients infected with Omicron variant may develop so-called long COVID-19, post-COVID-19 syndrome, or post-COVID-19 condition, which means that long-term follow-up is needed in those patients. Effective anti-Omicron variant therapy can shorten the course of infection, promote the recovery from infection, and also contribute to the control of infection. Therefore, the development of antiviral drugs with ideal cost-benefit ratio and convenient administration is one of the research hotspot in the future.
Objective To observe the effects of free sound field blast shock waves on damage effect and neuro behavior in rats, so as to provide the experimental basis for evaluating the biological damage effect of ammunition and proposing the related protective and treatment measures. Methods Ninety SD rats were randomly divided into trinitrotoluene (TNT) explosion group(n=40), thermobaric (TB) explosion group (n=40) and control group (n=10) according to ammunition type and laying distance(18, 20, 25, 30 m). TNT and TB ammunition were detonated in the free field and the shock wave parameters at different distances from the explosion source were measured by pressure transducers. The degree index of injury of rats was evaluated by grass anatomy, histopathology and adjusted severity of injury index (ASII) scoring system. Behavioral changes of the rats were evaluated with Open field test and Morris water maze test. Results The peak pressure and impulse of explosion shock wave decreased continuously with increasing distance from the explosion center in TNT explosion group and TB explosion group. The rats in TNT explosion group died at 18 m (3/10) and 20 m (1/10), while all rats in TB explosion group survived. The dead rats showed a combined lung blast injury. HE staining showed widened alveolar septa and infiltration of red blood cells and inflammatory cells, and no obvious pathological changes were found in brain tissue 24 hours after explosion. Significant correlation existed between ASII score and shock wave peak pressure in TNT explosion groups (r=0.81, P<0.05) and TB explosion groups (r=0.70, P<0.05). The parameters of total move time and total move distance of rats in different positions were shorter in TNT explosion group than in control group, but without statistical significance (P>0.05). Compared with the control group, the move time and distance of rat in 20 m central region were shorter in TNT explosion group (P<0.05). Compared with the control group, the escape latency of rats in TNT explosion group 18 m and TB explosion group 20 m was shortened, the platform crossing time increased, and the residence time in target quadrant prolonged (P<0.05). Conclusions The injury degree of free-field blast shock wave in rats is related to the distance to explosion center with a shock wave peak pressure and impulse dependence. The blast shock wave can affect the behavior and spatial memory ability of rats.
Sepsis and its development of multiple organ dysfunction pose a serious threat to human life and health. Sepsis is a hot issue that experts in the critical field are committed to solve. It is a heterogeneous, infection-induced systemic inflammatory response syndrome based on endothelial dysfunction, and it is still a huge burden on the global health system. As a well recognized immune cell, the endothelium is the primary site of attack by pathogens, toxins, or endogenous injury signals, which cause activation of endothelial cells and consequently damage to their function or structure. Although the latter may help to eliminate the infection and limit the dissemination of the infection to some extent, the excessive and persistent inflammatory response will also lead to a subsequent storm of cytokine and organ damage, causing irreversible damage to the organism. Glycocalyx is the first barrier on the surface of endothelial cells, it is also the first line of defence for endothelial cells under attack in sepsis, which has a great significance on endothelial function. Many studies have found that a variety of immune inflammatory responses involving the glycocalyx also play a key role in the development of sepsis. This review will give a brief overview of the factors, mechanisms and various treatments targeting glycocalyx injury in sepsis at present.
Glioma is of the most common malignant tumors in the central nervous system. The prognosis of patients is poor, and its effective treatment has always been a major clinical challenge. In tumor cells, genetic instability often leads to a large number of mutations. The expression of nonsynonymous mutations can produce tumor-specific antigens, called neo-antigens, which have high immunogenicity. They could activate specific T cells to produce an immune response and become a new tumor immunotherapy target. Among the tumor vaccines targeting neo-antigens, the mRNA tumor vaccine has obvious advantages: easy access, low cost, high safety, and great stability. Therefore, a neo-antigen mRNA vaccine is likely to become an effective treatment for glioma. At present, some clinical trials have proved the safety and effectiveness of these vaccines. This article reviews the research progress of the neo-antigen tumor mRNA vaccine and its application in glioma therapy, and predict the direction of future research.
Objective To explore the effect of hsa-microRNA-203-3p (miR-203) targeted-regulating Cullin2 (CUL2) on the biological characteristics of human papillomavirus 16 (HPV16) positive cervical cancer cells. Methods A total of 10 patients underwent cervical cancer screening from September 2018 to September 2019 in the Department of Obstetrics and Gynecology, the Second Hospital of Shanxi Medical University. HPV genotyping was performed as single HPV16 positive, and pathological examination showed cervical squamous cell carcinoma (SCC). Ten corresponding paracancer normal tissue samples were collected as control group. Real-time quantitative reverse transcription PCR (qRT-PCR) was performed to detect the expression of miR-203 in cervical squamous cell carcinoma and corresponding adjacent tissues, cervical cancer cell line (SiHa) and human immortal keratinocyte line (HaCaT) cells. GO and KEGG enrichment were applied to analyze the functions and pathways miR-203 involved. The regulatory relationship between miR-203 and CUL2 were verified via TargetScan website and dual luciferase reporter assay. The miR-203 mimics or inhibitor were transfected into SiHa cells to establish cell models of high and low expression of miR-203,and the expressions of CUL2 mRNA and protein were detected by qRT-PCR and Western blotting. The proliferation, migration and apoptosis of SiHa cells were assessed by CCK-8, scratch assay and Annexin V-APC/PI double staining, respectively. Results Results of qRT-PCR indicated that, compared with the corresponding adjacent tissues and HaCaT cells, the relative expression level of miR-203 decreased obviously in both cervical SCC tissues and SiHa cells (P<0.01). The results of GO and KEGG enrichment methods showed that miR-203 was widely involved in the ubiquitination process and the signaling pathways involved in the malignancies. TargetScan website and dual-luciferase reporter assay showed that the targeting regulatory relationship existed between miR-203 and CUL2 (P<0.01). qRT-PCR and Western blotting indicated that overexpression of miR-203 reduced the expressions of CUL2 mRNA and protein (P<0.05 or P<0.01); While low expression of miR-203 up-regulated the expressions of CUL2 mRNA and protein (P<0.01). CCK-8, scratch experiments and Annexin V-APC/PI double staining method confirmed that overexpression of miR-203 decreased proliferation rate and migration rate of SiHa cells (P<0.01), and elevated cell apoptosis rate (P<0.05). In contrast, low expression of miR-203 increased the proliferation rate and migration rate of SiHa cells (P<0.01), and reduced the apoptosis rate(P<0.01). Conclusion The miR-203 might suppress the biological characteristics of HPV16-positive cervical cancer cells SiHa by targeting CUL2, and it was expected to become a new candidate gene in diagnosis and treatment of cervical cancer.
Objective To observe the effects and possible mechanism of exposure to high altitude environment on liver function in rats. Methods Forty-eight healthy male SD rats were randomly divided into plain group, plateau 1-month group, plateau 2-month group and plateau 4-month group (12 each). Rats in plain group were fed at an altitude of about 500 m for 1 month, and in the plateau groups were fed in a simulated chamber of high altitude (5000 m) for 1 month, 2 months and 4 months, respectively. Serum and liver tissue were collected at the end of the model. The contents of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were measured with automatic biochemical analyzer. The pathological morphology of liver tissue was observed by HE staining. The levels of reduced glutathione (GSH) and superoxide dismutase(SOD) in liver tissue were measured by ELISA. The ultra structural changes of hepatocytes were observed by transmission electron microscope. The relative expressions of autophagy associated proteins LC3-Ⅱ and Beclin-1 were determined by Western blotting. Results Compared with the plain group, the serum levels of ALT, AST and TBIL significantly increased in the plateau 2-month group (P<0.05); compared with the plateau 2-month group, the serum levels of ALT, AST and TBIL significantly decreased in the plateau 4-month group (P<0.05). HE staining showed that the lobule structure of liver tissue in each group was clear without obvious inflammatory infiltration, cell edema or necrosis. The results of transmission electron microscope showed that the number of autophagy corpuscles in hepatocytes of rats was significantly higher in plateau 1-month group and plateau 2-month group than in plain group, and was significantly lower in plateau 4-month group than in plateau 2-month group. Western blotting and ELISA results showed that the relative expression levels of LC3-Ⅱ and Beclin-1 protein increased significantly, while the GSH and SOD levels decreased significantly in plateau 1-month group and plateau 2-month group than in the plain group (P<0.05); the relative expression levels of LC3-Ⅱ and Beclin-1 protein significantly decreased, and the levels of GSH and SOD significantly increased in plateau 4-month group than in plateau 2-month group (P<0.05), but no significant differences compared with those in plain group(P>0.05). Conclusion In the process of adapting to hypobaric and hypoxic environment, abnormal changes of liver function indexes of rats occurred, the mechanism may be related to the changes of oxidative stress level and autophagy of hepatocytes.
Nuclear transcription factor TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA binding protein commonly expressed and highly conserved in evolution. In physiological state, TDP-43, when localized mainly in nucleus and cytoplasm (no more than 30%), may play a physiological role, such as participating in mRNA transcription, splicing, translation, transport and maintaining the stability of mRNA, while its mislocalization in mitochondria might play a corresponding pathological role. Recent researches found that, in addition to produce a marked effect in neurodegenerative diseases, TDP-43 also plays an important role in the pathological process of tumors, male infertility, osteoarthritis (OA) and other diseases. Therefore, the gene expression, subcellular organelle translocation, function and the relationship with diseases of TDP-43 have attracted more and more attention. The research progress of pathological effects of TDP-43 has been reviewed in present paper, so as to provide more help for diagnosis and treatment of related diseases.
Surgery and resuscitation are the core capabilities of combat casualty care. Early treatment should be carried out within 3 hours, and divided into two phases, emergency treatment and surgical resuscitation, emphasizing the capability building of resuscitation and surgery. This paper interprets the capability requirements of the early casualty care level. According to the domestic and international progress in the care of civilian trauma and combat casualty, the relationship between "surgery" and "resuscitation" in the early treatment level of combat casualty, and the key technological progress are summarized, indicating that only the coordinated development of surgery and resuscitation ability and mutual support can provide safe, standardized and efficient treatment and reduce the death rate of the combat casualties.
Objective To investigate the effect and mechanism of homocysteine on apoptosis and proliferation of cardiomyocytes. Methods Cardiomyocytes were stimulated with homocysteine at the concentration of 3 mmol/L for 24 h. Cells were divided into control group and homocysteine group (Hcy group). Western blotting was detected the expression of TLR4,Myeloid differentiation factor 88 (MyD88), NF-κB, p-NF-κB, the expression of apoptosis related proteins Bax, cleaved-caspase-3 and anti-apoptotic protein Bcl-2; Flow cytometry was detected the apoptosis rate of cardiomyocyte, EdU staining was observed the proliferation of cardiomyocytes. After TLR4 interference fragment was transfected into cardiomyocytes, the interference fragment was verified by Western blotting. The cells were transfected with si-NC or si-TLR4 and treated with Hcy. Western blotting was detected the expression of MyD88, NF-κB and p-NF-κB, the expression of apoptosis related protein and anti-apoptosis protein in cardiomyocytes; The apoptosis rate of cardiomyocytes was detected by flow cytometry; The apoptosis of cardiomyocytes was observed by EdU staining. Results Compare with control group, Western blotting showed that TLR4, MyD88 and p-NF-κB significantly increased in Hcy group (P<0.01); The expression of apoptosis related proteins Bax and cleaved-caspase-3 increased and the expression of anti-apoptotic protein Bcl-2 was decreased (P<0.01); Compared with si NC+Hcy group, the expression of TLR4, MyD88 and p-NF-κB decreased (P<0.01), the expression of apoptosis related protein decreased (P<0.01), and the expression of anti-apoptosis protein increased in si-TLR4+Hcy group (P<0.01); Compare with control group, the results of flow cytometry showed that the apoptosis rate of cardiomyocytes increased in Hcy group (P<0.01); Compared with si-NC+Hcy group, the apoptosis rate of si-TLR4+Hcy group decreased (P<0.01). Compared with control group, EdU staining showed that the number of positive cells decreased in Hcy group (P<0.01); Compared with si-NC+Hcy group, the number of positive cells increased in si-TLR4+Hcy group (P<0.01). Conclusion Hcy can induce apoptosis and inhibit proliferation of cardiomyocytes, the mechanism may have something to do with TLR4/NF-κB signaling pathway.
Objective To explore the cumulative metabolic indicators and the related risk factors for restenosis after intervention of lower extremity arteriosclerosis obliterans (LEASO). Methods Data were collected of 110 patients with arterial occlusive symptoms of low limbs who admitted to the Department of Hypertension and Endocrinology, Army Characteristic Medical Center, Army Medical University from January 2007 to July 2021 and met the criteria. All patients underwent low limbs interventional surgery and were followed up for more than 2 years. CT angiography (CTA) and ultrasound of both low limbs arteries were performed 2 years after surgery to clarify whether restenosis occurred and, based on the results of CTA and ultrasound, patients were divided into restenosis group (n=37) and non-restenosis group (n=73). The patients' basic information, pre- and post-operative hematological indices at 6 months, 1 year and 2 years were collected to compare and analyze the differences in basic clinical information, baseline values of metabolic indices (Xbaseline) and cumulative exposure values (Xcum) between patients in the restenosis group and non-restenosis group, and binary logistic regression models were used to analyze the risk factors for post-interventional revascularization in patients with LEASO. Results The incidence was 33.6% of restenosis 2 years after intervention in patients with lower extremity arterial occlusive disease. The percentage of patients with smoking, the percentage of patients with Pan Atlantic Collaborative Group (TASC) typeⅡ (hereafter referred to as TASC type Ⅱ) C or D femoropopliteal artery lesions(hereafter referred to as TASC typeⅡ), hypersensitive C-reactive protein (hs-CRP), cumulative hypersensitive C-reactive protein(hs-CRPCum), cumulative low-density lipoprotein cholesterol (LDL-CCum), and cumulative triacylglycerol (TGCum) were significantly higher in restenosis group than those in non-restenosis group (P<0.05). The percentage of patients with regular postoperative use of antiplatelet agents and ankle-brachial index (ABI) were significantly lower than those in non-restenosis group (P<0.05). Binary logistic regression analysis showed that smoking (OR=4.158, P=0.040), TASC Ⅱ typing (OR=4.3, P=0.036), hs-CRPCum (OR=1.160,P=0.013), LDL-CCum (OR=2.313, P=0.003), and TGCum (OR=1.668, P=0.015) were the risk factors for restenosis 2 years after surgery, and regular postoperative use of antiplatelet drugs was a protective factor (OR=0.038, P=0.000). Conclusions Smoking,TASC Ⅱ typing, hs-CRPCum, LDL-CCum, and TGCum were the risk factors for restenosis of blood vessels after intervention in patients with lower extremity atherosclerotic occlusive disease. The regular use of postoperative antiplatelet drugs was a protective factor. Continuous smoking cessation, intensive lipid lowering, and anti-inflammation are the key factors to reduce the occurrence of postoperative restenosis, and early intervention of vascular lesions (TASC A-B) has better long-term effects.