Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Fracture healing is a complex process that necessitates the synergistic action of various cells and molecules. Macrophages play an indispensable and crucial regulatory role in the process of fracture repair, influencing stages such as inflammatory modulation, angiogenesis, and tissue remodeling. This article delves into the functional characteristics of macrophages and their roles at different stages of fracture healing. Additionally, it explores the impact of aging macrophages on the healing process. Furthermore, the potential of emerging therapies, such as hydrogel-based treatments and exosomes, in modulating macrophage responses is analyzed. This study provides a theoretical foundation for the development of innovative therapies aimed at enhancing the efficacy of fracture healing.

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.

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.

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.

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.

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.

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.

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.

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.