The rapid spread of Coronavirus Disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has had a devastating impact on public health and the global economy. Tremendous efforts had been put on urgent development of prophylactic or therapeutic drugs against SARS-CoV-2,mainly smallmolecule antiviral drugs and monoclonal antibodies,to reduce the impact and burden of COVID-19. Currently,National Medical Products Administration(NMPA)of China or Food and Drug Administration(FDA)of the United States have approved three small-molecule drugs and three monoclonal antibodies for use. This paper reviews the clinical research progress and challenges of the main drugs against SARS-CoV-2 on the market at present.

BACKGROUND:Recently,researches have found that insulin-like growth factor-1(IGF-1)can induce the differentiation of bone marrow-derived mesenchymal stem cells(BMSCs)into chondrocytes,but there are no reports concerning the differentiation of adipose-derived mesenchymal stem cells(ADMSCs)into chondrocytes induced by IGF-1,as well as interaction with transforming growth factor-β1(TGF-β1)during this process.OBJECTIVE:To explore the possibility of inducing ADMSCs chondrogenic differentiation by using IGF-1 and the interaction with TGF-β1 in induction.METHODS:ADMSCs were obtained,and seeded at 2×10~5 cells/cm~2 in culture flask.Insulin-free chondrogenic media containing IGF-1 or(and)TGF-β1 were used to induce ADMSCs.2 weeks later,cells were harvested and stained by using toluidine blue and collagen Ⅱ antibody immunohistochemistry.Intracellular sulfated proteoglycan and collagen Ⅱ coloring were observed.Reverse transcription-polymerase chain reaction(RT-PCR)was used to detect the expression of collagen Ⅱ,aggrecan and Sox9 mRNA.RESULTS AND CONCLUSION:After induced,toluidine blue stain exhibited that the cells in the three induction groups were polygonal,with cytoplasm and cell membrane of blue different dyeing.Immunohistochemistry for type Ⅱ collagen demonstrated that cytoplasm and cell membrane were stained brown in three induction groups.RT-PCR revealed that the expression of collagen Ⅱ,aggrecan,Sox9 mRNA of IGF + TGF group were significantly greater than the IGF and TGF groups,and IGF and TGF groups were significantly stronger than the control group.No significant difference was determined between the IGF and TGF groups.These results indicated that IGF-1 can induce chondrogenic differentiation from ADMSCs,expressing chondrocyte specific cell phenotype.There is synergism of IGF-1 and TGF-01 to induce the differentiation of ADMSCs into chondrocytes.

Objective To identify predictors of prescription initiation and persistence of warfarin in non-valvular atrial fibrillation ( NVAF ) patients with high risk of stroke ( CHA2 DS2-VASc≥2 ) . Methods NVAF patients consulted in our hospital from Aug , 2011 to Apr, 2015 were enrolled.Patients who underwent radiofrequency catheter ablation were excluded . Patients were divided into two groups (warfarin group and non-warfarin group).Logistic regression was used to estimate the predictors of initiation warfarin prescription.Kaplan-Meier survival and Cox proportional hazards model was performed to determine rate of warfarin persistence and its associated factors .Results A total of 622 AF patients were enrolled and 490 patients with CHA2DS2-VASc≥2.Ten patients lost follow up and 480 patients were followed up with a mean follow-up period of ( 40.0 ±11.55 ) months.Of which 245 NVAF patients ( 51%) had a warfarin prescription.Patients with ischemic stroke ( OR 2.447 , 95%CI 1.435-4.171 , P=0.001 ) , heart failure ( OR 2.009 , 95%CI 1.084-3.724 , P=0.027 ) and persistent AF ( OR 2.231 , 95%CI 1.448-3.437 , P=0.0001 ) had a higher likelihood of warfarin prescription .Anemia ( OR 0.479 , 95%CI 0.238-0.964 , P=0.039), concommitant Traditional Chinese Medicine (TCM) use (OR 0.638, 95%CI 0.456-0.891, P=0.008 ) and longer distance to hospital ( OR 0.759 , 95%CI 0.610-0.945 , P=0.014 ) decreased the likelihood of warfarin prescription . One hundred and seventy-six ( 71.8%) warfarin users continued persistent therapy and the overall proportion of warfarin persistence was 78.3% for one year , 71.0% for 3 years.Seventy-six existing warfarin users continued the warfarin therapy (80%, 76/95),one hundred new users showed persistence to therapy ( 66.7%, 100/150 ) .Warfarin use before enrollment significantly increased warfarin persistence than new prescription ( P =0.008 ) .Variables associated with higher discontinuation were new prescription ( HR 1.786 , 95% CI 1.029-3.100 , P=0.039 ) , TCM use ( HR 1.687 , 95%CI 1.201-2.37 , P=0.003 ) and longer distance to hospital ( HR 1.446 , 95% CI 1.121-1.865, P=0.005).Conclusions In anticoagulation clinic, concommitant TCM use, distance to hospital and other factors were associated with warfarin initiation prescription and persistence .Identifying factors associated with warfarin treatment could help in developing adherence of patients .

Objective To investigate the effect of internal fixation with proximal femoral nail antirotation (PFNA) and bone cement on peritrochanteric tumors due to metastatic carcinoma.Methods Clinical data of 19 patients with peritrochanteric tumors due to metastatic carcinoma during June 2007 and July 2013 treated with PFNA and bone cement were retrospectively analyzed.Results Visual analogue scale(VAS) was (8.37 ± 1.12) scores before surgery,and (2.58 ± 1.26) scores after 3 d surgery.There was significant difference (t =22.45,P ＜ 0.05).Conclusion For patients with peritrochanteric tumors due to metastatic carcinoma,internal fixation with PFNA and bone cement is an effective way to relieve pain,restore and improve hmb function and enhance quality of life.

Conventional IgG is composed of heavy and light chains. The light chain has one variable region (VL) and one constant region (CL) domain, whereas the heavy chain has one variable region (VH) and three constant region domains (CH1, CH2 and CH3). Single domain antibody (sdAb) is a kind of antibody that is composed of a variable domain of heavy chain and devoid of the light chain completely. Due to its small size, it is also called as nanobody. Although the sdAb has a simple structure, it can exhibit a comparable even better antigen-binding affinity than conventional antibody. Compared with conventional antibody, the small size, high stability and simplicity in recombinant expression are representative advantages of sdAb. In recent years, scientists are becoming increasingly interested in the roles of sdAb in fundamental biomedical research and clinical application. In this review, we summarized the structural features, physicochemical properties, screening strategies and recent advances in application of sdAb.
Antibodies ; immunology

Objective: To compare the effect of insulin-like growth factor-1 receptor (IGF-1R) inhibitor and insulin on renal interstitial macrophage infiltration in mice with type 2 diabetic kidney disease (DKD) mice. Methods: Twenty-four male C57BL/6 mice were selected. After 1 week of adaptive feeding, 6 rats were randomly selected as the control group. The other mice were intraperitoneally injected with streptozotocin (30 mg/kg) after 8 weeks of high-fat and high-sugar feeding. After 72 h, the type 2 diabetes mellitus (DM) models were successfully established if random blood glucose was greater than 16.7 mmol/L. After 8 weeks, if the proteinuria of DM mice increased, the DKD models were successful. DKD mice were divided into 3 groups by random number remainder method: DKD group (n=6), DKD+insulin group (insulin group, n=6, subcutaneous injection of 1-2 U/d insulin) and DKD+IGF-1R inhibitor (IGF-1R inhibitor group, n=6, administered with 30 mg·kg^-1·d^-1 IGF-1R inhibitor). They were continuously treated for 8 weeks. Random blood glucose was tested by glucometer. Blood and urine were collected, and biochemical indicators, such as serum creatinine, urea nitrogen and urine protein were measured by biochemical analyzer. Renal pathological changes were detected by hematoxylin-eosin staining (HE) and periodic acid-schiff staining (PAS). Suppressor of cytokine signaling 2 (SOCS2) mRNA and insulin-like growth factor-1 (IGF-1) mRNA were detected by in situ hybridization. The protein expressions of SOCS2, F4/80, Toll-like receptor 4 (TLR4) and CD68 were detected by immunohistochemistry. Results: Compared with the control group, blood glucose, serum creatinine, serum urea nitrogen and urinary protein excretion rate were significantly higher in DKD mice (all P<0.05), and CD68⁺ cells number, F4/80⁺ cells number and the expression of TLR4 in the tubulointerstitial of DKD mice were significantly higher (all P<0.05). After intervention with insulin or IGF-1R inhibitor, serum creatinine, serum urea nitrogen and urinary protein excretion rate of DKD mice were significantly reduced (all P<0.05). Insulin intervention could significantly reduce blood glucose in mice (P<0.05), but had no significant effect on macrophages. Although IGF-1R inhibitor did not significantly reduce blood glucose, it could significantly reduce the number of CD68, F4/80 positive cells and the expression of TLR4 protein in renal interstitium of DKD mice (all P<0.05). Compared with the DKD group, insulin intervention significantly reduced the expression of IGF-1 protein and mRNA (both P<0.01), and increased the expression of SOCS2 mRNA and protein (both P<0.01). And the expression of SOCS2 protein was correlated with the number of F4/80⁺ cells in insulin group (R²=0.8461, P=0.005). However, IGF-1R inhibitors had no significant effect on SOCS2 expression, but had better inhibition of macrophage infiltration. Conclusion IGF-1R inhibitor has a better inhibitory effect on DKD renal interstitial macrophage infiltration than insulin. The mechanism may be related to the fact that IGF-1R inhibitor does not up-regulate SOCS2 expression, whereas insulin up-regulates SOCS2 expression to activate some potential pathways.