Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, damage to bone tissue microstructure, increased bone fragility, and susceptibility to fractures, while sarcopenia is a syndrome characterized by progressive reduction in overall muscle mass and functional decline. Based on the common pathophysiological mechanism and close correlation between the two, the concept of "osteosarcopenia" has gradually emerged to describe the simultaneous attenuation of muscles and bones. Signaling pathways serve as important signal transmission channels between muscles and bones, and if abnormal, they can lead to osteosarcopenia. The aim of this article, therefore, is to review the signaling pathways related to osteogenesis and myogenesis, such as Hedgehog, Hippo, mTOR, MAPK, in order to provide new ideas for targeted treatment of osteosarcopenia.

Objective To study the relation between alcohol-induced osteonecrosis of femoral head (AIONFH) related with high morbidity TCM constitution type with CYP2C8 gene polymorphisms.Methods Totally 152 Han nationality NONFH cases from Feburary 2014 to September 2015 from outpatient and the inpatient departments in Gansu Province Hospital of TCM were collected. 50 AIONFH cases were set as medical case group; meanwhile, 45 healthy volunteers were enrolled as control group. Database for medical materials of all patients and volunteers was established. TCM distribution for AIONFH patients was determined. Solution DNA extraction kit was used to extract DNA, and detect the concentration and purity of DNA. The target gene was amplified by PCR and the target gene was amplified by gel electrophoresis. The length of the fragment was confirmed to conduct target gene sequencing. With the results of sequencing and gel electrophoresis, the relation of AIONFH with CYP2C8 gene polymorphism in AIONFH patients with phlegm-dampness syndrome and the control group.ResultsThe CYP2C8 gene loci rs17110453 gene polymorphism was not statistically significant between the two groups (χ2=0.253,P>0.05). There was no significant difference in allele between the two groups (χ2=0.077,P>0.05). The risk of disease in CC genotype was 1.37 times higher than the AA genotype (95%CI: 0.339-5.540), without statistical significance (P>0.05). There was no significant difference in genotype and allele distribution between AIONFH patients with phlegm-dampness and non-phlegm-dampness and the control group (P>0.05).Conclusion CYP2C8 gene loci rs17110453 gene polymorphism A/C mutation has no obvious relation with AIONFH risk. There is no clear relationship between CYP2C8 gene loci rs17110453 gene polymorphism with AIONFH.

Objective: To investigate the difference of prognostic factors and recurrence rates between papillary thyroid microcarcinoma (PTMC) and lager papillary thyroid carcinoma (PTC) and analyze the clinical pathological characteristics of PTMC suitable for surgery. Methods: A retrospective analysis on the clinicopathological features, expression level of of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E gene mutation and pigment epithelium-derived factor (PEDF), and postoperative follow-up results of the 251 PTC patients who underwent surgical treatment from October 2011 to October 2013, including 169 cases with PTMC and 82 with lager PTC (Tumor diameter>1 cm). Results: The BRAF V600E mutation rates of PTMC and lager PTC patients are 65.1%(110/169)and 78.0% (64/82) respectively, and the difference is statistically significant (P<0.05). The prevalence of extrathyroidal invasion (7.1%) and lymph nodes metastasis (27.2%) of the patients with PTMC were significantly lower than those of the patients with larger PTC (15.9% and 46.3%, respectively)(P<0.01). The follow-up durations for PTMC and lager PTC were (45.6±3.6) months and (45.0±3.4) months, respectively (P>0.05). There was no statistic significance for the difference in age, gender, coexistent hashimoto′s thyroiditis, PEDF expression, and recurrence rate between the patients with PTMC and with larger PTC (P>0.05). The recurrence rate of the patients who have the high risk factors of PTMC was 1.6%(2/122)and that of larger PTC was 4.9% (4/82). Conclusions Extrathyroid invasion, lymph node metastases and BRAF V600E gene mutation are the high risk factors of recurrent PTMC. The same treatment strategy should be considered for PTMC with coexistent high risk factors as that for larger PTC. For PTMC with BRAF V600E gene mutation, earlier surgical treatment is suggested. PTMC patients with BRAF V600E gene mutation and high cell subtype are suggested to undergo total thyroidectomy for the first operation in order to reduce the potential risk of recurrence.

Objective To study the correlation between nontraumatic osteonecrosis of femoral head (NONFH) and ApoA1 polymorphism of blood stasis type.Methods Totally 93 cases of NONFH were selected as the case group, and 83 healthy volunteers were randomly selected as the control group. With TCM constitution questionnaire survey, the case group was screened out 32 cases of blood stasis NONFH type and 61 cases of non blood stasis NONFH type. In the case group and control group, the subjects took blood samples 2 mL, extracted DNA for PCR amplification, PCR products for DNA sequencing. G994T PAF-AH and rs9658282 gene NOS1 site polymorphism were detected for tatistical analysis.Results -75G/A gene AA ApoA1 genotype (OR: 2.578; 95%CI: 1.174-5.663;P=0.018) and A allele (OR: 1.726; 95%CI: 1.121-2.658;P=0.013) may be one of the risk factors of NONFH.Conclusion -75G/A gene ApoA1 may be related to the pathogenesis of NONFH. There was no correlation between the ApoA1 gene polymorphism of -75G/A gene and the pathogenesis of blood stasis NONFH. There was no correlation between the ApoA1 gene polymorphism of +83C/T gene and the pathogenesis of blood stasis NONFH.

Objective To discuss the relationship between TCM constitutional types and the levels of transforming growth factor beta 1 (TGF-β1) of patients with knee osteoarthritis (KOA). Methods A total of 161 patients with KOA as a case group filled out questionnaires about 9 TCM constitution types, and 50 cases of unrelated healthy volunteers were selected randomly as control group. The serum samples of two groups were collected. The levels of TGF-β1 were detected and compared by double antibody sandwich ELISA. Results Compared with the control group, the level of TGF-β1 in the case group decreased, with statistical significance (P<0.05). Compared with the control group, the levels of TGF-β1 significantly decreased in the case group of qi deficiency type, with statistical significance (P<0.05). There were no types of special intrinsic and blood stasis. Compared with the control group, the levels of TGF-β1 in the other six types of patients with KOA had no statistical significance (P>0.05). Conclusion The incidence of KOA with qi deficiency type may be related to the decrease of TGF-β1 level. The decreasing level of TGF-β1 may be one of the mechanisms of molecular biology that qi deficiency was linked to KOA.