Objective To investigate the toxic effect of hemin on primary cultured neurons,astrocytes,and brain capillary endothelial cells (BCECs),and the damage effect of hemin with different concentrations on the above cells. Methods (1) Primary cultured neurons,astrocytes and BCECs from the cortex of rats were exposed to different doses of hemin for 2 h,and continue culture of these cells for 24 to 96 h after withdrawing hemin was performed; the cellular morphology was examined under phase-contrast microscope; cellular survival rate was measured with Alama blue staining; and the releasing rate of lactate dehydrogenasing (LDH) was detected with regular biochemical method. (2) Primary cultured cells were exposed to different doses of hemin for 2 h,and continue culture of the cells for 4 h was performed after washing out the hemin; and then,concentrated formic acid was employed to dissociate the cells, and heme content in dissociated cells was measured with spectrophotometer. (3) Primary cultured cells was exposed to different doses ofhemin for 30,60 and 120 min,respectively,and continue culture of the cells for 4 h was performed after washing out hemin; and then,intracellular Fe3+was examined with Prussian blue staining. Results (1) Cultured neurons were injured by a low dose ofhemin (5 mmol/L) with a decreased survival rate by 40.2％ and an increased LDH releasing rate by 22.2％; and the pathological changes of cellular morphology were severe after 24 h of exposure to hemin.Following the increased doses ofhemin and time of post-exposure,the cellular death and LDH releasing were increased,and the morphological changes of cells were much severe. (2) The low and medium doses of hemin (5 mmol/L and 25 mmol/L) did not induce cellular death, LDH releasing and morphological changes in astrocytes; and a high dose ofhemin (50 mmol/L) could induce a death rate of astrocytes decreasing by 52.4％, a LDH releasing rate increasing by 31％ and obvious morphological changes of astrocytes; however, the injured astrocytes could regenerate fluent cellular monolayer 96 h after exposing to high dose of hemin treatment.(3) Hemin with either low or high dose did not induce any changes in cellular survival,LDH releasing and cellular morphology of BCECs.(4) The heme content in cultured neurons was significantly higher than that in astrocytes and BCECs after hemin treatment for 2 h.(5) The blue Fe3+ stained granules appeared in neurons as early as 30 min after neurons being exposed to hemin, and Fe3+ stained positive cells in neurons were significantly higher than those in astrocytes and BCECs at any dose ofhemin and any time point ofhemin treatment. Conclusion Hemin is highly toxic to neurons, but it can only injure astrocytes at a high dose and it can not induce direct damage in BCECs; free hemin could rapidly enter and accumulate in neurons,but less accumulate in astrocytes and not accumulate in BCECs.

OBJECTIVETo investigate the effect of Shuganlipi decoction on Th1/Th2 cytokines, liver function and HBV replication in patients with chronic hepatitis B (CHB).

METHODSEighty-six confirmed CHB cases were randomly divided into control group (n=42) and experimental group (n=44) for treatment with routine western medication and additional treatment with Shuganlipi decoction, respectively. The production of IFN-γ, IL-2, IL-6, IL-10 and liver function, HBV DNA, and HBeAg were detected in all the patients.

RESULTSThe total response rate to the treatment was significantly higher in the experimental group than in the control group (78.13% vs 57.14%, P<0.01). ALT, AST, TBIL and ALB were all improved obviously in the two groups after the treatments (P<0.01). In terms of ALT and ALB, the experimental group showed more obvious improvement than the control group(P<0.05). The treatments also resulted in significant increases of IFN-γ and IL-2 levels and reductions of IL-6 and IL-10 levels in the two groups (P<0.01).

CONCLUSIONShuganlipi decoction can improve the liver function and activity of Th1/Th2 cytokines to promote the clearance of liver cell HBV infection.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; Hepatitis B, Chronic ; drug therapy ; immunology ; virology ; Humans ; Interleukin-10 ; immunology ; Interleukin-2 ; immunology ; Interleukin-6 ; immunology ; Male ; Middle Aged ; Phytotherapy

Objective To study the secular changes on both morphological development and nutritional status among Tibetan students, from 1985 to 2005. Methods Data from the Chinese national survey on students' physical fitness and health in 1985, 1995, 2000 and 2005 were used to analyze and find out the difference of the morphological development and nutrition status of Tibetan students aged 7-18 years in different years. Results From 1985 to 2005, the height and weight of Tibetan students had a growing trend. The height and weight of schoolboys and schoolgirls aged 7-18 years increased 3.94 cm, 5.08 kg, 2.25 cm, and 4.24 kg respectively, while the circumference decreased without significance. The prevalence rates of underweight and malnutrition in Tibetan students further went down along with the improvement of their nutritional status. However, the prevalence rates on both overweight and obesity increased continuously, affecting the health status of Tibetan students. Conclusion From 1985 to 2005, the morphological development of Tibetan students had a growing trend and their nutrition status improved. However, the prevalence of overweight and obesity continuously increased.

Objective To explore the clinical features and echocardiographic characteristics of cardiac papillary fibroelastoma (CPF) in adults.Methods Clinical features,echocardiographic characteristics,surgical procedures and outcomes were retrospectively evaluated in 13 patients with CPF confirmed by pathology.Results The clinical features of CPF were atypical.The most common symptoms were chest distress and short breath.All the 13 patients were single lesions,9 cases (9/13,69.23％) involved the valves (4 on the aortic valve,3 on the mitral valve,2 on the tricuspid valve) and 4 cases (4/13,30.77％) involved the chambers (2 in the right atrium,1 in the right ventricle,1 in the left ventricle).The largest diameters of ＞2 mm were in 8 cases and ≤2 mm were in 5 cases.Eight cases were detected by echocardiographic examination and 5 cases were missed.Surgical excision was performed in 8 patients and prosthetic valve replacement was performed in 5 patients.Conclusion The clinical symptoms of CPF are variable.When the size of CPF is too small,echocardiography is difficult to detect.Most of CPFs originate on the valves,predominantly on the aortic valve.The prognosis of CPF is excellent.

Purpose/Significance To explore the characteristics and clinical significance of differentially expressed genes closely re-lated to HPV E6/E7 by using bioinformatics.Method/Process The cervical tissue and clinical information of cervical cancer in TCGA and GTEx of UCSC are used as the training set.The expression profile chip GSE63514 related to cervical cancer in GEO is used as the validation set.Firstly,the limma package of R software is used to screen DEGs of tumor and normal samples,and Venn map of genes re-lated to E6/E7 protein in MigDB is made.Survival analysis is performed by survival kit and verified by ROC and protein expression lev-els.Secondly,key genes are obtained by copy number variation and methylation correlation.Finally,the specific co-expression network is constructed and enrichment analysis and immune infiltration analysis are performed.Result/Conclusion There are 101 differentially expressed genes related to HPV E6/E7 protein,and three genes are found to have significance after screening,namely E2F1,MCM4 and PCNA.At the same time,it is found that the genes in the specific coexpression network are significantly enriched in the DNA replication and chromosome organization pathways.Immune correlation analysis shows that key genes are significantly associated with CD4 T cells,B cells and neutrophils.DNA replication,chromosome organization,etc.,are the molecular mechanisms and key genes significantly related to the development of cervical squamous cell carcinoma and HPV E6/E7 encoded proteins.

Objective:To identify differentially expressed genes (DEGs) associated with the progression of synovitis in RA by using bioinformatics analysis and explore the effects of DMARDs such as methotrexate, tocilizumab and rituximab on the DEGs in RA synovium.Methods:RA expression profile microarray data GSE7307、GSE12021、GSE55457、GSE55235、GSE77298、GSE89408 were acquired from the public gene chip database (GEO), including 113 synovial tissue samples from RA and 70 healthy controls (HC). At the same time, synovial expression microarrays GSE45867, GSE24742 and GSE97165 after DMARDs treatment were obtained. These data included 8 samples treated with methotrexate, 12 treated with tocilizumab, 12 treated with rituximab and 19 treated with combined tDMARDs. R software was used to screen DEGs and Venn plots using gene ontology function enrichment and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Hub genes were selected by STRING online analysis tool and Cytoscape software.Results:Compared with HC, 797 DEGs were up-regulated and 434 DEGs were down-regulated in the synovial tissue of RA. These DEGs were mainly enriched in T cell activation, immune response-activating cell surface receptor signaling pathway. Using Cytoscape and cytoHubba to obtain 5 sets of DEGs based on the STRING database model, the degree algorithm screened out 10 hub genes: LCK, SYK, PTPRC, HLA-DRA, LYN, NCAPG, TOP2A, JUN, CXCR4, CCNB1. Methotrexate treatment significantly up-regulated 20 DEGs and down-regulated 30 DEGs. Rituximab treatment up-regulated 100 DEGs and down-regulated 55 DEGs. Tocilizumab treatment up-regulated 91 DEGs and down-regulated 317 DEGs. These altered DEGs were enriched in regulating cell adhesion, leukocyte-cell adhesion, leukocyte transfer, and insulin-like growth factor receptor signaling pathways. It was worth noting that after treatment, a total of 306 high-expressing DEGs were down-regulated, and 36 low-expressing DEGs were up-regulated.Conclusion:LCK, insulin-like growth factor receptor signaling pathway, etc. are the responsible molecular mechanisms and key pivot genes for the occurrence and development of RA, and the treatment of DMARDs, which are closely related to the response of RA to the treatment of DMARDs.

Neuropsychiatric disorders are the leading cause of mental and intellectual disabilities worldwide. Current therapies against neuropsychiatric disorders are very limited, and very little is known about the onset and development of these diseases, and their most effective treatments. MIR137 has been previously identified as a risk gene for the etiology of schizophrenia, bipolar disorder, and autism spectrum disorder. Here we generated a forebrain-specific MIR137 knockout mouse model, and provided evidence that loss of miR-137 resulted in impaired homeostasis of potassium in mouse hippocampal neurons. KCC2, a potassium-chloride co-transporter, was a direct downstream target of miR-137. The KCC2 specific antagonist VU0240551 could balance the current of potassium in miR-137 knockout neurons, and knockdown of KCC2 could ameliorate anxiety-like behavior in MIR137 cKO mice. These data suggest that KCC2 antagonists or knockdown might be beneficial to neuropsychiatric disorders due to the deficiency of miR-137.

The brain pericyte is a unique and indispensable part of the blood-brain barrier (BBB), and contributes to several pathological processes in traumatic brain injury (TBI). However, the cellular and molecular mechanisms by which pericytes are regulated in the damaged brain are largely unknown. Here, we show that the formation of neutrophil extracellular traps (NETs) induces the appearance of CD11b⁺ pericytes after TBI. These CD11b⁺ pericyte subsets are characterized by increased permeability and pro-inflammatory profiles compared to CD11b^- pericytes. Moreover, histones from NETs by Dectin-1 facilitate CD11b induction in brain pericytes in PKC-c-Jun dependent manner, resulting in neuroinflammation and BBB dysfunction after TBI. These data indicate that neutrophil-NET-pericyte and histone-Dectin-1-CD11b are possible mechanisms for the activation and dysfunction of pericytes. Targeting NETs formation and Dectin-1 are promising means of treating TBI.
Blood-Brain Barrier/metabolism* ; Brain/pathology* ; Brain Injuries, Traumatic/metabolism* ; Extracellular Traps/metabolism* ; Histones ; Humans ; Lectins, C-Type ; Pericytes/pathology*

Objective:Compare the effects of 3 administration methods (tracheal perfusion, tail vein injection and aerosol inhalation) with bleomycin (BLM) in inducing pulmonary fibrosis in rats, in order to find out the optimal administration methods. Method:Eighty sprague-dawley (SD) male rats with SPF were randomly divided into aerosol inhalation blank group, single tracheal perfusion group(10 mg·kg^-1), multiple tracheal perfusion group(5 mg·kg^-1), single intravenous injection group(150 mg·kg^-1), multiple intravenous injection group(50 mg·kg^-1), single aerosol inhalation group (30 min)and multiple aerosol inhalation group(30 min). The mortality and body weight of rats in each group were observed at 7 d, 14 d and 28 d after the administration. And 28 days later after the administration, the lung coefficients of rats in each group were observed, paraffin sections were prepared, hematoxylin-eosin staining (HE) and Masson staining were performed, and the contents of hydroxyproline (HYP) and plasminogen activator inhibitor-1 (PAI-1) in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA), so as to evaluate the alveoli inflammation and pulmonary fibrosis of rats in each group. Result:Compared with the aerosol inhalation blank group, the rats in the trachea perfusion group had the highest mortality among the drug treatment groups. The pulmonary coefficients of rats in the multiple intravenous injection group and the multiple inhalation group were significantly higher than those in the blank group(P<0.05,P<0.01). The multiple inhalation group was higher than the other model group and the single atomization model group. The results of HE and Masson staining showed thickening of pulmonary septum and higher degree of pulmonary interstitial fibrosis in tracheal perfusion group, intravenous injection group and multiple inhalation group. The degree of pulmonary fibrosis in the multiple inhalation group was more obvious than that in other groups. The results of ELISA showed that the levels of HYP and PAI-1 in lung tissues of rats in aerosol inhalation group and tracheal perfusion group were significantly higher than those in control group(P<0.05). The multiple inhalation group and the single atomization inhalation group were significantly higher than other modules. Conclusion:Bleomycin was inhaled repeatedly to establish pulmonary fibrosis model. The pathological injury and physiological indexes of the model rats were relatively stable, which conforms with the evolution process of pulmonary fibrosis.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.