Denervation can activate the catabolic pathway in skeletal muscle and lead to progressive skeletal muscle atrophy. At present, there is no effective treatment for muscle atrophy. Histone deacetylase 4 (HDAC4) has recently been found to be closely related to muscle atrophy, but the underlying mechanism of HDAC4 in denervation-induced muscle atrophy have not been described clearly yet. In this study, we found that the expression of HDAC4 increased significantly in denervated skeletal muscle. HDAC4 inhibition can effectively diminish denervation-induced muscle atrophy, reduce the expression of muscle specific E3 ubiquitin ligase (MuRF1 and MAFbx) and autophagy related proteins (Atg7, LC3B, PINK1 and BNIP3), inhibit the transformation of type I fibers to type II fibers, and enhance the expression of SIRT1 and PGC-1 α. Transcriptome sequencing and bioinformatics analysis was performed and suggested that HDAC4 may be involved in denervation-induced muscle atrophy by regulating the response to denervation involved in the regulation of muscle adaptation, cell division, cell cycle, apoptotic process, skeletal muscle atrophy, and cell differentiation. STRING analysis showed that HDAC4 may be involved in the process of muscle atrophy by directly regulating myogenin (MYOG), cell cycle inhibitor p21 (CDKN1A) and salt induced kinase 1 (SIK1). MYOG was significantly increased in denervated skeletal muscle, and MYOG inhibition could significantly alleviate denervation-induced muscle atrophy, accompanied by the decreased MuRF1 and MAFbx. MYOG overexpression could reduce the protective effect of HDAC4 inhibition on denervation-induced muscle atrophy, as evidenced by the decreased muscle mass and cross-sectional area of muscle fibers, and the increased mitophagy. Taken together, HDAC4 inhibition can alleviate denervation-induced muscle atrophy by reducing MYOG expression, and HDAC4 is also directly related to CDKN1A and SIK1 in skeletal muscle, which suggests that HDAC4 inhibitors may be a potential drug for the treatment of neurogenic muscle atrophy. These results not only enrich the molecular regulation mechanism of denervation-induced muscle atrophy, but also provide the experimental basis for HDAC4-MYOG axis as a new target for the prevention and treatment of muscular atrophy.

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<p>The aim is to study the potency, purity, safety, and stability of the lyophilized human diploid cell rabies vaccine (HDCV). The viruses were harvested from infected human diploid cells (MRC-5 strain) which were cultured in a microcarrier bioreactor. After harvest, purification, inactivation and lyophilization, HDCV was produced. The potency of vaccines was measured by NIH method; the bovine serum protein residual content and the antibiotic residues were tested by ELISA method; the endotoxin content was detected by semi quantitative gel method; the safety of vaccine was determined <em>in vivo</em>. Among 6 batches of HDCV, the lowest immunizing potency was 4.79 IU/ml, whilst the highest was 6.03 IU/ml; the lowest bovine serum protein residual content was 12.41 ng/dose, whilst the highest was 31.74 ng/Dose; the content of antibiotic residues was from 2.20 ng/ml to 4.00 ng/ml; endotoxin levels were all lower than 50 EU/dose. All the mice and guinea pigs vaccinated were all alive, and the body weight of each mouse also increased. The stability was investigated by determining the water content and potency of the vaccine placed in 37±1 °C for 4 weeks and 2-8 °C for 48 months, respectively. The results indicate all the quality index accords with the standards of “Pharmacopoeia of the People's Republic of China 2010, 3 Volumes”. HDCV shows satisfactory potency, purity, safety, and stability.</p>

Aims The aims of the study were to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of a novel, pegylated recombinant human consensus interferon‐α variant (PEG‐IFN‐SA) in healthy volunteers. A pharmacokinetic and pharmacodynamic comparison of PEG‐IFN‐SA and peginterferon‐α‐2a in healthy subjects was evaluated. Methods A randomized, dose‐escalating, single administration dose phase I clinical study was conducted. Thirty healthy subjects received PEG‐IFN‐SA as a single dose of 0.5–2.0 μg kg−1 by subcutaneous (s.c.) injection in four parallel groups. Eight subjects received peginterferon‐α‐2a as a single dose of 180 μg s.c. Results The incidence rates of adverse events for PEG‐IFN‐SA and peginterferon‐α‐2a were 29 of 30 and 7 of 8, respectively. The adverse events for PEG‐IFN‐SA were mild to moderate and similar to those of peginterferon‐α‐2a. Within 168 h after injection, the mean values of maximal concentration and area under the plasma concentration–time curve from time of dosing to 168 h [AUC(0–168h)] for 2′,5′‐oligoadenylate, neopterin and β2‐microglobulin for PEG‐IFN‐SA at 1.5 μg kg−1 s.c. were similar to or higher than those for peginterferon‐α‐2a at a dose of 180 μg s.c. After s.c. injection of PEG‐IFN‐SA at 1.5 μg kg−1, the mean geometric mean values of plasma half‐life, time to maximal concentration, maximal concentration and AUC(0–168h) were 55.3 h, 26.9 h, 0.53 μg l−1 and 44.0 μg l−1 h, respectively. Conclusions The tolerance, pharmacokinetic and pharmacodynamic characteristics of PEG‐IFN‐SA support its administration by s.c. injection as a single dose of 1.5 μg kg−1 or at 2.0 μg kg−1 per week.

This study was aimed at investigating the application of deep learning 4D computed tomography angiography (CTA) combined with whole brain CT perfusion (CTP) imaging in acute ischemic stroke (AIS). A total of 46 patients with ischemic stroke were selected from the hospital as the research objects. Image quality was analyzed after the 4D CTA images were obtained by perfusion imaging. The results showed that whole brain perfusion imaging based on FCN can achieve automatic segmentation. FCN segmentation results took a short time, an average of 2-3 seconds, and the Dice similarity coefficient (DSC) and mean absolute distance (MAD) were lower than those of other algorithms. FCN segmentation distance was 17.87. The parameters of the central area, the peripheral area, and the mirror area of the perfusion map were compared, and the mean transit time (MTT) and time to peak (TTP) of the lesion were prolonged compared with the mirror area. Moreover, the peripheral CBV was increased, and the differences between the parameters were significant ( P < 0.05 ). In conclusion, using the deep learning FCN network, 4D CTA combined with whole brain CTP imaging technology can effectively analyze the perfusion state and achieve clinically personalized treatment.