BACKGROUND: In recent years, with the deepening of medical research, it has been found that PI3K/AKT signaling pathway has a regulatory effect on vascular repair regeneration, osteoblast differentiation and proliferation, and osteoclast bone differentiation. This is very important for the treatment of femoral head necrosis. OBJECTIVE: To provide a brief overview of the main research progress in mechanisms of PI3K/AKT signaling pathway regulating femoral head necrosis in recent years, aiming to provide new ideas for the treatment of osteonecrosis of the femoral head in the future. METHODS: PubMed and MEDLINE database, Wanfang, CNKI, WIPO and CBM database were searched from 2012 to 2019, for relevant domestic and foreign literatures, including: (1) epidemiological study of osteonecrosis of the femoral head and related pathogenesis; (2) PI3K/AKT pathway related mechanism; (3) research literature on the effects of PI3K/AKT on factors related to vascular repair and regeneration; (4) research literature on the regulation of PI3K/AKT on osteoblast differentiation and proliferation-related factors; (5) literature on the regulation of PI3K/AKT on functional factors related to osteoclast differentiation. A total of 62 literatures were included for analysis and summary. RESULTS AND CONCLUSION: (1) The PI3K/AKT signaling pathway has been proven to be effective in the regulation of vascular repair regeneration, osteoblast differentiation, proliferation, apoptosis and osteoclast differentiation. After understanding these pathways, research and development of related drugs to improve the success rate of early conservative treatment of osteonecrosis of the femoral head have great development prospects and potential, opening up a new path for future orthopedic surgeons to treat osteonecrosis of the femoral head, and bringing new hope to patients and their families. (2) According to the different osteonecrosis of the femoral head conditions of patients, how to use PI3K/AKT signaling pathway to guide treatment becomes a breakthrough point and challenge of this technology, and more research is needed later.

Vertebral artery hypoplasia is a congenital vessel variation. Its incidence is from 1. 9 to 26. 5% . In recent years, studies have shown that vertebral artery hypoplasia may be a potential risk factor for posterior circulation infarction, especialy when it coexists with other cerebrovascular risk factors. Vertebral artery hypoplasia may also cause regional hypoperfusion and complex neurovascular regulation, and it also has a certaln link with migralne.

Objective To evaluate the role of mitochondrial fission in anoxia-reoxygenation injury to rat hippocampal neurons.Methods Neurons were enzymatically isolated from hippocampi of newborn Sprague-Dawley rats (less than 24 h old).The primary hippocampal neurons were cultured and seeded in 25 mm × 25 mm culture flasks at a density of 7 × 105/ml.The cultured neurons were randomly assigned into 3 groups (n =18 each) using a random number table:control group (C group),anoxia-reoxygenation group (I/R group),and mitochondrial fission inhibitor mdivi-1 group (M group).In group I/R,the vehicle dimethyl sulfoxide (DMSO,final concentration ＜ 0.1％) was added prior to anoxia and the cells were then incubated for 40 min.In group M,mdivi-1 (dissolved in DMSO,final concentration of DMSO ＜ 0.1％) was added prior to anoxia and the cells were then incubated for 40 min.The hippocampal neurons were subjected to oxygen-glucose deprivation (OGD) for 6 h followed by restoration of O2 supply for 20 h.After 20 h of reoxygenation,the level of reactive oxygen species (ROS) (by ELISA),cell apoptosis (using flow cytometry),and expression of mitochondrial fission protein Drp1,Bcl-2 and Bax (by Western blot) were measured.The apoptosis rate and the ratio of Bcl-2 to Bax were calculated.Results Compared with C group,ROS content and apoptosis rate were significantly increased,the expression of Drp1 and Bax was up-regulated,the expression of Bcl-2 was down-regulated,and the ratio of Bcl-2 to Bax was decreased in I/R group (P ＜ 0.05).Compared with I/R group,ROS content and apoptosis rate were significantly decreased,the expression of Drp1 and Bax was down-regulated,the expression of Bcl-2 was up-regulated,and the ratio of Bcl-2 to Bax was increased in M group (P ＜ 0.05).Conclusion Mitochondrial fission is involved in anoxia-reoxygenation injury to rat hippocampal neurons via mitochondria-mediated apoptotic pathway.

The varicela-zoster virus(VZV) infection causes central vasculopathy,and then leads to stroke onset. This article review s the correlation betw een VZV infection and stroke onset in order to conduct a comprehensive assessment of patients w ith VZV infection, thereby reducing the risk of stroke after VZV infection.

Adult ; Epilepsy ; genetics ; Humans ; Hyperhomocysteinemia ; genetics ; Hypogonadism ; genetics ; Intellectual Disability ; genetics ; Male ; White Matter ; pathology

Thrombolytic therapy is one of the standard treatments of acute ischemic stroke.The patients with acute ischemic stroke often complicated with cerebral microbleed.Whether thrombolytic therapy will increase the risks of bleeding and early neurological deterioration in such patients are not conclusive.This article reviews the impact of cerebral microbleed burden on the outcome after thrombolytic therapy in patients with acute ischemic stroke.

Objective:To explore pathogenesis,characteristic genes and immune infiltration of rheumatoid arthritis(RA)by bioinformatics and machine learning methods,and to find correlation between characteristic genes and immune cells.Methods:Chips related to RA were obtained from GEO database,gene differences were analyzed by R language,and GO and KEGG were enriched and analyzed;machine learning methods,namely LASSO regression and SVM-RFE were used to screen disease characteristic genes,ROC curve and sample chips were used to detect accuracy of characteristic genes,CIBERPORT algorithm was used to analyze immune infiltration of RA,and correlation between characteristic genes and immune cells was analyzed.Results:A total of 90 differen-tial genes were obtained from GSE12021 and GSE55235,including 64 up-regulated and 26 down-regulated differentially expressed genes.A total of 209 main items were obtained by GO analysis,mainly involving leukocyte activation,lymphocyte activation,B-cell receptor signaling pathway,etc;KEGG analysis showed that chemokine signaling pathway,IL-17 signaling pathway,Toll-like recep-tor signaling pathway and PPAR signaling pathway were closely related to RA;ten key genes such as IGHM,SLAMF8,CXCL10,FNDC4,AIM2,EGR1 and AKR1B10 were screened by mechanical learning method.Disease characteristic genes were IGHM,SLAMF8,CXCL10,AIM2 and AKR1B10 by ROC curve and sample chip;immune infiltration results showed that there were signifi-cant differences between synovial tissues of RA and normal tissues in 9 kinds of immune cells,such as plasma cells,CD8 T cell,CD4 T cell and T cell follicle helper.By analyzing correlation between disease characteristic genes and immune cells,it was found that there were significant correlations between 5 characteristic genes and some immune cells.Conclusion:There is a significant correla-tion between characteristic genes and immune cells of RA,which provides a preliminary basis for follow-up in-depth study of targeted diagnosis and treatment of RA.

Massive open online course (MOOC) is an emerging online course model for the public. It is large-scale, open, interactive, etc. Therefore, MOOC has been developing rapidly at home and abroad in recent years. The advanced education philosophy of MOOC has also brought many inspirations to the teaching reform mode of Radiation Medicine. Under the background of the current military reform, the building of the online teaching platform on the basis of MOOC may realize the substantive reform of Radi-ation Medicine teaching, which can improve the comprehensive quality of the teachers and students, and cultivate more excellent military medical talents.

A novel RNA virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the ongoing outbreak of coronavirus disease 2019 (COVID-19). Population genetic analysis could be useful for investigating the origin and evolutionary dynamics of COVID-19. However, due to extensive sampling bias and existence of infection clusters during the epidemic spread, direct applications of existing approaches can lead to biased parameter estima-tions and data misinterpretation. In this study, we first present robust estimator for the time to the most recent common ancestor (TMRCA) and the mutation rate, and then apply the approach to analyze 12,909 genomic sequences of SARS-CoV-2. The mutation rate is inferred to be 8.69 × 10-4 per site per year with a 95％ confidence interval (CI) of [8.61 × 10-4, 8.77 × 10-4], and the TMRCA of the samples inferred to be Nov 28, 2019 with a 95％ CI of [Oct 20, 2019, Dec 9, 2019]. The results indicate that COVID-19 might originate earlier than and outside of Wuhan Seafood Market. We further demonstrate that genetic polymorphism patterns, including the enrichment of specific haplotypes and the temporal allele frequency trajectories generated from infection clusters, are similar to those caused by evolutionary forces such as natural selection. Our results show that population genetic methods need to be developed to efficiently detangle the effects of sampling bias and infection clusters to gain insights into the evolutionary mechanism ofSARS-CoV-2. Software for implementing VirusMuT can be downloaded at https://bigd.big.ac.cn/biocode/tools/BT007081.

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.