BACKGROUND: Mechanisms related to bone fracture and nonunion have been clarified, but the healing time and treatment strategy of delayed union remain controversial. OBJECTIVE: To establish a reliable model of femoral delayed union using external fixation in the New Zealand white rabbit. METHODS: Seventy-two New Zealand white rabbits were randomized to three groups. After removal of 10-mm femoral middle bone cortex with internal and external periosteum and bone marrow, a uniplanar external fixator was used. There was a 1 mm gap between broken ends (group A), and the broken ends were sealed by bone wax (group B). For controls, only bone cortex was cut and then fixed to contact the broken ends. The gross, radiological and histological observations were performed to observe the bone healing at 4, 8 and 12 weeks after modeling. RESULTS AND CONCLUSION: The control group achieved bone healing at the 4th week, which was considered as the normal time of bone healing. The groups A and B achieved healing at the 12th week, which was remarkably longer than that in the control group. The rabbit femoral delayed union model showed the typical X-ray imaging and pathological features of delayed union. Our results suggest that the model is reasonable and reliable, which can provide reference for clinical research.

BACKGROUND: Many methods have been developed to establish a rabbit VX2 tumor model, but the reliability of each method has not been explored. In order to develop a reliable method, we made some improvements based on the existing methods. OBJECTIVE: To investigate the reliability of rabbit VX2 tumor tissue block implantation and cell suspension via modified and traditional implantation to make the rabbit tibia VX2 tumor model. METHODS: Forty healthy adult New Zealand white rabbits were randomly divided into two groups. Group A was treated with tissue block implantation for tibia VX2 tumor modeling, and group B was treated with cell suspension for tibia VX2 tumor modeling. Modified and traditional implantation was performed on the left and right tibia of the experimental animals, respectively. One hour after successful modeling, ultrasound examination of the puncture site was performed to determine whether there is hematoma. All experimental animals were sacrificed at 3 weeks. X-ray examination of the bilateral tibia was performed to confirm the tumor growth range. Tumor tissue and soft tissue around the puncture site were taken for general and pathological observation to compare the size of the tumor and identify whether there is tumor cell metastasis. RESULTS AND CONCLUSION: One rabbit died in the tissue block group, and all the experimental animals in the cell suspension group survived. X-ray examination indicated the tumors in the tissue block group invaded the cortex, but the tumors in the cell suspension group did not invade the cortex. Gross observation revealed that the tumor volume of the tissue block group was greater than that of the cell suspension group. In the tissue block group, there were one and seven cases of hematoma around the puncture site at 1 hour after modified and traditional implantation, respectively. In the cell suspension group, there were two and nine cases of hematoma around the puncture site at 1 hour after modified and traditional implantation, respectively. Pathological examination showed that local tumor invasion was found in 1 and 8 cases in the tissue block group as well as in 2 and 11 cases in the cell suspension group at 3 months after modified and traditional implantation, respectively. Our findings indicate that the tissue block implantation method is easier and more convenient than the cell suspension method for making rabbit VX2 bone tumors, and the tumor invasion rate of the tissue block implantation method is lower than that of the cell suspension method. Improved tissue block implantation can effectively reduce the tumor invasion rate during modeling.

Objective To study the expression of interleukin-1β (IL-1β) in synovia and synovium of rats after high intensity exercise.Methods 24 healthy male Sprague-Dawley rats were randomly divided into control group and high intensity group, and the latter were forced to run 60 min at the speed of 28 m/min for 6 weeks. The histological changes of cartilage from the lesion areas of medial femoral condyle and synovium of knee joint were examined with HE stain and the expression of IL-1β in synovium with immunohistochemistry, in synovial fluid with the enzyme-linked immunosorbent assay (ELISA). Results The articular cartilage of knee were injured and synovitis were found in high intensity group. The expression of IL-1β both in synovial fluid and in synovium of the knee were more in high intensity group than in control group (P<0.05). Conclusion High intensity exercise could cause aticular cartilage injury, synovitis and over expression of IL-1β in synovia and synovium, which may associated with post-traumatic osteoarthritis.

Objective:To establish a reliable approach for measuring proximal femoral 3 dimensional anatomy, and to compare post-operative differences of proximal femoralanatomy in the inter-trochanter fractures with two kinds of antegrade nailings.Methods: Some computer assisted design ( CAD ) soft-wares, e.g.Mimics, were used to establish a reliable approach for measuring proximal femoral 3 dimen-sional (3D) anatomy.Intra-class correlation coefficient ( ICC) was used to test the reliability of intra-and inter-observers.The post-operative pelvic CT data of 19 cases of inter-trochanter fracture patients treated with InterTAN nailing and 21 cases of inter-trochanter fracture patients treated with proximal femo-ral nail anti-rotation ( PFNA) were retrospectively analysed and used to measure bilateral proximal femo-ral anatomical parameters, including 2D and 3D femoral neck-shaft ( NS) angle and femoral neck ante-version (NA) angle, and 2D and 3D anteversion angles of the intramedullary (IM) nailings.ICC was used to test the consistency of the NA angles in the different groups, and the paired student T-test was used to test the differences of the paired quantitative data.Results:The established measurement method hasdexcellent consistency within the intra-and inter-observers, with all the ICCs higher than 0.9.The paired student T-test showed no significant difference between the post-operative bilateral 2D or 3D NA angles.The ICCs results showed that there were no consistency between the post-operative bilateral 2D or 3D NA angles (P values were 0.099 and 0.055, respectively), but the excellent consistency between the 2D injured side NA angle and 2D IM nailing’ s NA angle, or between the 3D injured side NA angle and 3D IM nailing’s NA angle (the ICCs were 0.81 and 0.8, respectively, P values <0.001).In PF-NA group, 57%of the differences between the 2D post-operative injured side’s and intact side’s NA an-gles were higher than 15°, which was more than 15.78%in InterTAN group.The paired student T-test showed no significant difference between the post-operative injured side’ s 2D or 3D NS angles and the in-tact side’s respective 2D or 3D angles in PFNA group (P values were 0.925 and 0.367, respectively), but in InterTAN group, the post-operative injured side’s 2D or 3D NS angles were significantly smaller than the intact side’s respective angles (P values were 0.033 and 0.009, respectively).Conclusion:By analyzing and comparing bilateral proximal femoral anatomical parameters after two kinds of IM nailings procedures, the differences between the bilateral post-operative NA angles in PFNA group were significantly larger than those in InterTAN group.There was significant correlation between the NA angles of the injured sides and NA angles of IM nailings in both the groups.

Objective To investigate the dynamic expression of the drug resistance protein P-glycoprotein (P-gp) within 72 hours in the pentylenetetrazol (PTZ)-induced status epilepticus (SE) model, and to identify the optimal detection time to inhibit P-gp. Methods mRNA and protein expressions of P-gp in rats hippocampal tissue were detected by using immunohistochemistry , RT-qPCR and Western blot at different time points after modeling (0, 3, 6, 12, 24, 48, 72 h). Results The mean density of P-gp protein in the hippocampus of status epilepticus model was 0.325 1 ± 0.008 2 at 24 h, and was 0.396 3 ± 0.016 8 at 48 h, which were consistently higher than those of the control group (P < 0.05, P < 0.01, respectively). Results of qRT-PCR showed that MDR1a expression was significantly upregulated at 24 h and at 48 h (P < 0.05, P < 0.01, respectively). Western blot assay revealed that P-gp protein was also significantly increased at 48 h after seizures (P < 0.05). Conclusions The upregulation of P-gp after SE peaked at 48 h, which maybe the optimal detection time to detect drug resistant after SE.

Sepsis can cause life-threatening organ dysfunction and is one of the leading causes of death in critically ill patients. Early diagnosis and correct treatment of sepsis are the key to reducing the fatality, however, there is no golden standard for diagnosis at present. The ideal sepsis biomarker can be used for early diagnosis and predicting poor prognosis with good sensitivity and specificity. There are many candidate biomarkers for sepsis. This article reviews the latest developments on acute phase proteins, soluble receptors, non-coding RNAs and other candidate biomarkers of sepsis that attracted more recent attention.

ObjectiveTo observe the effects of the water extracts of Trichosanthis Radix-Polygonati Rhizoma at different ratios on glucose and lipid metabolism in KKAy mice with spontaneous type 2 diabetes and explore the mechanism of the extract in alleviating insulin resistance based on phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead box O1 （FoxO1） signaling pathway. MethodThe 8-week-old C57BL/6J male mice were taken as the normal control group， and KKAy male mice of the same age were randomly assigned into a model group， a metformin group， Trichosanthis Radix-Polygonati Rhizoma groups at the ratios of 1∶1 （Trichosanthis Radix 30 g， Polygonati Rhizoma 30 g）， 1∶3 （Trichosanthis Radix 15 g， Polygonati Rhizoma 45 g）， and 1∶5 （Trichosanthis Radix 10 g， Polygonati Rhizoma 50 g） according to blood glucose level and body weight， with 6 mice in each group. The administration lasted for 8 weeks， and the body weight （BW） and fasting blood glucose （FBG） of mice were recorded at the same time points of the 2nd， 4th， 6th， and 8th weeks， respectively. Oral glucose tolerance test （OGTT） was performed at the 7th week. After drug administration， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， and fasting insulin （FINS） were measured， and homeostasis model assessment-insulin resistance （HOMA-IR） index was calculated. The liver tissue samples were stained with hematylin-eosin （HE） and periodic acid-Schiff （PAS） for observation of the fat distribution and glycogen content. The protein levels of PI3K， Akt， p-Akt， FoxO1， and p-FoxO1 in the liver were determined by Western blot. ResultCompared with the normal group， the model group showed increased food intake， FBG， glucose tolerance， FINS， HOMA-IR， TC， TG， and LDL-C （P<0.01）， and down-regulated protein levels of PI3K， Akt， phosphorylaison （p）-Akt， FoxO1， and p-FoxO1 in the liver （P<0.01）. Compared with the model group， Trichosanthis Radix-Polygonati Rhizoma lowered FBG and HOMA-IR （P<0.05， P<0.01）. In particular， the combination at the ratio of 1∶3 showed the best performance （P<0.01） comparable to metformin. Furthermore， Trichosanthis Radix-Polygonati Rhizoma at different ratios lowered blood glucose at different time points of OGTT （P<0.05） and TC and LDL-C （P<0.01）. Additionally， the combination at the ratio of 1∶3 reduced TG （P<0.01）. The liver of mice in the drug administration groups showed regular morphology， with few lipid droplets and rich glycogen. Western blot showed that Trichosanthis Radix-Polygonati Rhizoma up-regulated the protein levels of PI3K and p-Akt， down-regulated the protein level of FoxO1， and up-regulated the protein level of p-FoxO1 （P<0.05）. ConclusionTrichosanthis Radix-Polygonati Rhizoma， especially at the ratio of 1∶3， lowered the FBG， TC， LDL-C， and HOMA-IR index， promoted liver glycogen synthesis， and reduced steatosis in KKAy mice， which may be related to the regulation of PI3K/Akt/FoxO1 signaling pathway in the liver.

COVID-19 ; Coronavirus Nucleocapsid Proteins ; Humans ; Nucleocapsid Proteins ; Phosphoproteins ; SARS-CoV-2