BACKGROUND:During fracture healing, in addition to the need for appropriate biomechanical environment, the role of cytokines is also increasingly attracted attention.
OBJECTIVE:To study the effect of nerve growth factor and alpha-lipoic acid on fracture healing in rat models of femoral fracture.
METHODS:Sprague-Dawley rat models of femoral fracture were established. Seventy-two rats were randomly divided into three groups. In the control group, rats were intramuscularly injected with physiological saline. In the nerve growth factor group, rats were intramuscularly injected with nerve growth factor 200 ng/kg, once a day. In the combined therapy group, rats were intramuscularly injected with nerve growth factor 200 ng/kg and oral y taken alpha-lipoic acid 25 mg/kg, once a day. At 1, 2 and 3 weeks after administration, bony cal us volume was measured. Enzyme linked immunosorbent assay was used to measure serum bone morphogenetic protein-2 levels. Western blot assay was utilized to detect bone morphogenetic protein-2 protein expression at the broken end of fracture. Semi-quantitative RT-PCR was applied to examine vascular endothelial growth factor mRNA expression.
RESULTS AND CONCLUSION:(1) At 1 week after administration, no significant difference in bony cal us volume was detected among the three groups. Serum bone morphogenetic protein-2 level, bone morphogenetic protein-2 protein expression, and vascular endothelial growth factor mRNA expression were significantly higher in the nerve growth factor group and combined therapy group compared with the control group (P<0.05), but no significant difference was found between the two groups. (2) At 2 weeks after administration, the amount of cal us, serum bone morphogenetic protein-2 levels, bone morphogenetic protein-2 protein expression, and vascular endothelial growth factor mRNA levels were significantly higher in the nerve growth factor group and combined therapy group compared with the control group (P<0.05). Above expression levels were higher in the combined therapy group than in the nerve growth factor group (P<0.05). (3) At 3 weeks after administration, serum bone morphogenetic protein-2 levels, bone morphogenetic protein-2 protein expression, and vascular endothelial growth factor mRNA levels were significantly decreased in the nerve growth factor group. However, above expression levels were stil high in the combined therapy group, and significantly higher than in the nerve growth factor group (P<0.05). (4) These results indicate that nerve growth factor combined with alpha-lipoic acid had better effects on the fracture healing compared with the nerve growth factor alone.

Objective: To investigate the clinical effect of plasma exchange (PE) versus double plasma molecular adsorption system combined with PE (DPMAS+PE) in the treatment of toxic hepatic failure. Methods: A total of 67 patients with toxic hepatic failure who were admitted during the same period of time were divided into PE group, DPMAS+ PE group, and control group. The 22 patients in the PE group were treated with PE alone, and the 24 patients in the DPMAS+PE group were given DPMAS combined with PE. The clinical out-come was compared between the three groups. Results: Both treatment groups had significantly higher clinical response rate and 24-week survival rate than the control group. After treatment, both treatment groups had significant reductions in the serum levels of total bilirubin (TBil) , direct bilirubin (DBil) , alanine aminotransfer-ase (ALT) , and aspartate aminotransferase (AST) , and the PE group had significant reductions in the albumin (Alb) level and activated partial thromboplastin time (APTT) (P<0.05) ; the DPMAS+PE group showed no sig-nificant changes in the Alb level and APTT (P>0.05). There were no significant differences in TBil, DBil, ALT, and AST between the two treatment groups after treatment (P>0.05). After treatment, the PE group had significantly higher Alb level and APTT than the DPMAS + PE group (P<0.05). Compared with the control group, both treatment groups had significant reductions in TBil, DBil, ALT and AST after treatment (P<0.05). Conclusion The two artificial liver support techniques can significantly improve patients' liver function and in-crease their survival rate, and the combined artificial liver support technique can reduce the amount of plasma used.

Nonunion is the interruption of fracture healing process for a variety of reasons.The cause of the disease is different,and the treatment method is also different.Non-infective nonunion is that there are no local infection factors when nonunion occurs after wound and fracture,and it is most common in all nouunion.However,it is still a difficult problem for clinical orthopaedics.With the development of medical technology orthopaedics attach great importance to this kind of nonunion and study it deeply,its incidence is getting lower and lower.Despite brilliant results,the treatment for this kind of nonunion remains tricky.The treatment of non-infective nonunion can be divided into conservative treatment and surgical treatment,and the latter is still the main treatment.This article gives a systematic review of the treatment of non-infective nonunion.

Objective To investigate the clinical efficacy of bone grafts containing bone morphogenetic protein 2 (Bone Conduction) treating of nonunion of femoral fracture after intramedullary nailing.Methods The clinical data of 49 patients with nonunion of femoral fracture after intramedullary nailing from August 2008 to August 2016 were analyzed retrospectively.They were divided into experimental group and control group according to different bone grafting methods.The experimental group (n =23) was treated with Bone Conduction combined with allograft bone grafting.The control group (n =26) was treated with autogenous bone grafting.The autogenous bone was taken from the ipsilateral ilium.The two groups were compared operative time,intraoperative blood loss,postoperative wound complications,hospitalization time,postoperative visual analog scale,mean image healing time and the score for distal femoral fractures after the operation.All patients were followed up for 12 to 24 months.Follow-up methods were divided into telephone follow-up and outpatient follow-up.The patients were followed up for outpatients before fracture healing.The patients were followed up by telephone after fracture healing.The healing time of fracture,the flexion and extension activities of the knee joint at 9 months after operation were recorded.SPSS19.0 statistical software was used to analyze the data.Measurement data were expressed as ((x) ±s).The independent sample t test was adopted in measurement data and the counting data was tested by Chi-squared test.Result In the experimental group,operative time was (138.7 ± 34.6) minutes,intraoperative blood loss was (315.4 ± 52.8) ml,postoperative wound complications was 0 case,hospitalization time was (8 ± 3) days,postoperative visual analog scale was 5 scores,but in the control group,operative time was (170.5 ± 32.5) minutes,intraoperative blood loss was (367.2 ± 56.4) ml,postoperative wound complications was 3 cases,hospitalization time was (13 ± 2) days,postoperative visual analog scale was 8 scores.There were significant differences between the two groups,P ＜0.05.All patients who followed up for 12-24 months were recovered,with an average follow-up of 15 months.Mean image healing time in the experimental group and control group was separately(4.9± 2.5) months,(5.2 ± 2.8) months.The excellent and good rates ofthe score for distal femoral fractures 9 months after the operation was separately 95.7％,96.2％,there was no significant difference between the two groups,P ＞ 0.05.Conclusions Bone graft material containing bone morphogenetic protein 2 (Bone Conduction) has the advantages of simple operation,less trauma,less complications,high osteogenic activity and good bone graft effect are equalled with iliac bone graft,the bone graft material containing bone morphogene protein is an effective method to treat nonunion of femoral fracture after intramedullary nail.

Human challenge trial (HCT) is a test in which human volunteers are intentionally infected with pathogens in order to evaluate the efficacy of candidate preventive or therapeutic drugs. During the COVID-19 pandemic, the HCT of vaccines has aroused people's attention due to its significant advantages over clinical trial. This paper introduces the concept, development and application of HCT, the advantages and limitations of HCT for vaccine evaluation, and the consideration of future HCT of COVID-19 vaccine in China.

Lipid nanoparticles(LNPs),composed of ionizable lipids,are currently the most promis-ing non-viral nucleic acid drug delivery vectors in clinical practice,and have great potential in gene ther-apy drug delivery and vaccine delivery.Ionizable lipids,the main components of LNPs,play a decisive role in the endosome escape rate,transfection efficiency,organ targeting and safety of LNPs.Among them,the hydrophilic head group of ionizable lipids contains tertiary amine groups,which can improve the buffering capacity of LNPs and thus change the pKa value,and imidazole can enhance the stability and transfection activity of mRNA-LNP.The ligand contains ester groups,which can induce gene silencing efficiently and improve the degradation rate and safety.When the number of hydrophobic tails is 3-4,with 1-2 unsaturation and 8-18 carbon chain length,LNPs can effectively induce gene silencing.Meanwhile,the presence of branching or asymmetric hydrophobic tails can improve the transfection efficiency of LNPs.Based on the chemical structure of ionizable lipids,this review summarizes the influ-ence of the structure of ionizable lipids on the transfection efficiency and safety of nucleic acid carrying drugs LNPs,and the structure-activity relationship of ionizable lipids so as to provide reference for studies on novel ionizable lipids.

Objective:To investigate the incidence and determinants of vaccine hesitancy towards national immunization program in China and understand the current status of parents' hesitancy to different vaccines used in national immunization program.Methods:A cross-sectional survey was conducted in Beijing, Sichuan and Gansu. The methods of proportional probability sampling and convenience sampling were used to select the eligible study subjects for questionnaire surveys.Results:A total of 3 592 parents were enrolled in the study, in whom 38.22% fully accepted all the vaccines, 59.35% agreed to let their children to receive all the vaccines but showed slight concern, and 2.42% had hesitancy to the vaccines. The vaccine with the most hesitancy was polio vaccine (0.89%), followed by diphtheria pertussis tetanus vaccine (0.70%) and hepatitis A vaccine (0.64%). The dominant reason for vaccine hesitancy was the risk-benefit perception of vaccination (31.03%), followed by the low awareness of the parents (21.84%) and the inconvenience caused by distance and time (21.84%).Conclusions:The incidence of vaccine hesitancy towards national immunization program was low in parents in China, but over 50% of the parents showed concern to the vaccines. It is essential to improve the service quality of national immunization program and strengthen the health education about the vaccination to reduce the incidence of vaccine hesitancy in parents.