BACKGROUND:The elastic modulus of traditional bone implants is large and does not match the elastic modulus of human bone,which will cause a stress shielding effect and lead to bone resorption.The trabecular scaffold of the triply periodic minimal surface with radial gradient has elastic modulus matching with human cancellous bone,and its yield strength is greater than that of human cortical bone,which provides a new choice for the design of bone scaffold. OBJECTIVE:Triply periodic minimal surface structure with radial gradient was constructed by the implicit surface method.The sample was manufactured by laser selective melting technology,and the quasi-static compression test was carried out to obtain trabecular scaffolds with mechanical properties matching human bones. METHODS:Four types of the trabecular scaffolds of the triply periodic minimal surface with a radial gradient of G,I,P and D were established by the implicit surface method.Samples were manufactured by laser selective melting technology.We observed the surface morphology of the molded sample,evaluated the molding quality,conducted a quasi-static compression test,and evaluated the mechanical properties of the samples. RESULTS AND CONCLUSION:The quasi-static compression test results showed that compared with the four triply periodic minimal surface scaffolds,the platform stress of the G scaffold had less fluctuation and no failure or fracture,indicating that the G scaffold had the best plasticity.The mechanical properties of the G scaffolds with 45%,55%and 65%porosities were analyzed.It was found that the elastic modulus of G scaffolds with 55%porosity was within the range of elastic modulus of human cancellous bone(0.022-3.7 GPa),and the yield strength was close to the maximum yield strength of human cortical bone(187.7-222.3 MPa).In conclusion,G triply periodic minimal surface scaffold with 55%porosity can reduce the stress shielding effect,bear a higher body load,improve the stability of the implant,and prolong the service life of the implant.

Bacterial resistance and excessive inflammation are common issues that hinder wound healing.Antimicrobial peptides(AMPs)offer a promising and versatile antibacterial option compared to traditional antibiotics,with additional anti-inflammatory properties.However,the applications of AMPs are limited by their antimicrobial effects and stability against bacterial degradation.TFNAs are regarded as a promising drug delivery platform that could enhance the antibacterial properties and stability of nanodrugs.Therefore,in this study,a composite hydrogel(HAMA/t-GL13K)was prepared via the photocross-linking method,in which tFNAs carry GL13K.The hydrogel was injectable,biocompatible,and could be instantly photocured.It exhibited broad-spectrum antibacterial and anti-inflammatory properties by inhibiting the expression of inflammatory factors and scavenging ROS.Thereby,the hydrogel inhibited bacterial infection,shortened the wound healing time of skin defects in infected skin full-thickness defect wound models and reduced scarring.The constructed HAMA/tFNA-AMPs hydrogels exhibit the potential for clinical use in treating microbial infections and promoting wound healing.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective:To investigate the diagnostic value of two-dimensional ultrasound combined with volumetric contrast imaging (VCI) and magnetic resonance imaging (MRI) for the developmental abnormalities of the fetal corpus callosum.Methods:Seventy-three fetuses who underwent cranial MRI within 1 week after suspected fetal corpus callosum dysplasia on ultrasound and received a definitive diagnosis in the neonatal period were retrospectively recruited for the study. The fetal corpus callosum was observed in the transverse, coronal, and sagittal views of the fetus, and the hyaline septal cavity, lateral ventricle, third ventricle, and corpus callosum were observed in the MRI scan. The diagnostic results and sensitivity of two-dimensional ultrasound combined with volumetric contrast imaging and MRI were analyzed.Results:Neonatal imaging showed that among 73 fetuses, 32 had agenesis of the corpus callosum, 29 had hypoplasia of the corpus callosum, and 12 had normal development of the corpus callosum. The differences in diagnostic results and sensitivity between 2D ultrasound combined with volumetric contrast imaging and MRI testing for agenesis of the corpus callosum were not statistically significant (all P>0.05), and the differences in diagnostic results and sensitivity for hypoplasia of the corpus callosum were statistically significant ( P<0.05). Conclusions:Both 2D ultrasound combined with volumetric contrast imaging and MRI are of high value for the diagnosis of partial-type agenesis of the corpus callosum, but MRI is more advantageous for the diagnosis of agenesis of the corpus callosum, and MRI can be a useful supplement and verification tool for ultrasound to provide a more accurate clinical diagnosis.

Objective:To investigate the status of binocular visual function before and after operation in children with intermittent exotropia.Methods:Eighty patients with intermittent exotropia admitted to Fuyang People′s Hospital from January 2018 to December 2019 were selected for surgical treatment, and the differences in orthotopic rate, binocular visual function, strabismus and stereoscopic sharpness before and after treatment were observed.Results:The orthostatic rate was significantly higher than that before the operation [88.8%(71/80) vs. 40.0%(32/80)], the undercorrection rate and overcorrection rate were lower than those before the operation [7.5%(6/80) vs. 36.2%(29/80), 3.8%(3/80) vs. 23.8%(19/80)], and there were significant differences ( P<0.05). The rates of simultaneous vision (Ⅰ grade), near stereopsis, fusion faculty (Ⅱ grade), and far stereopsis(Ⅲ grade) after operation were higher than those before operation [91.2%(73/80) vs. 26.2%(21/80), 17.5%(14/80) vs. 5.0%(4/80), 21.2%(17/80) vs. 3.8%(3/80), 33.8%(27/80) vs. 0], and there were significant differences ( P<0.05). The strabismus angle, stereoscopic vision sensitivity, fusion faculty degree after operation were lower than those before operation [(29.5 ± 2.8) Δ vs. (46.2 ± 3.1) Δ, (190.6 ± 19.4)° vs. (240.3 ± 18.5)°, (3.1 ± 0.8)° vs. (4.3 ± 0.6)°], and there were significant differences ( P<0.05). Conclusions:It is very important to adopt appropriate surgical methods for children with intermittent exotropia, which can promote the improvement of orthotopic rate, significantly improve the binocular visual function of children, and achieve ideal therapeutic effect.

Objective To explore the characteristics of immunological changes in tree shrews infected with orthoreovirus, and provide a theoretical basis for the prevention of virus in tree shrews. Methods 40 -50-day-old tree shrews were divided into three groups: MRV1/TS/2011 virus-infected and MRV3/TS/2013 virus-infected groups, and saline-treated control group. On the 1, 8, 14, 21, and 28 days after infection, blood samples were taken from the tail vein and used for RT-PCR, flow cytometry and ELISA detection, to assess the viral load, number of CD4/CD8/CD19 cells, and IFN-gamma expression. Results The MRV1/TS/2011 and MRV3/TS/2013 viral load in the plasma and the number of CD4 +and CD19 +cells reached a peak at the 14th day after infection. At the first day after MRV1/TS/2011 infection, the CD4 +cells had a significantly higher expression compared with the normal group. CD8 +cells and the IFN-gamma expression reached a peak at the 21st day after infection. The expression of CD4 +was even higher after MRV1/TS/2011 infection, and the expression of CD8 +cells was higher after MRV3/TS/2013 infection. Conclusions We would conclude that after MRV1/TS/2011 and MRV3/TS/2011 virus infection, accompanying the changes of viral load, it shows some regularity of the expression of CD4/CD8/CD19 and IFN-gamma in the tree shrews: at the early stage of MRV1/TS/2011 virus infection, humoral immunity is stimulated, and CD4 +cells play a major role. MRV3/TS/2013 virus may mainly affect the cellular immunity, while humoral immunity only plays a role at a high viral expression or the late stage of infection. CD4 +cells may be more sensitive to type 1 reovirus, and CD19 +cells may be more sensitive to type 3 reovirus.

Objective: To explore therapeutic effects of calcium channel blocker combined statins on aged patients with hypertension, and their influence on inflammatory factor levels.Methods: A total of 124 aged patients with hypertension, who were treated in our hospital from Oct 2014 to Oct 2015 , were randomly and equally divided into amlodipine group (received amlodipine therapy based on routine treatment) and combined treatment group (received atorvastatin calcium based on amlodipine group) according to random number table.Levels of blood pressure, C reactive protein (CRP), interleukin (IL)-6, endothelin (ET) and blood lipids before and after treatment, and therapeutic effect and incidence of adverse reactions were compared between two groups.Results: Compared with amlodipine group after treatment, there were significant reductions in levels of systolic blood pressure [(143.57±3.14) mmHg vs.(131.73±3.42) mmHg], diastolic blood pressure [(82.17±3.26) mmHg vs.(76.51±3.27) mmHg], CRP [(7.32±0.71) mg/L vs.(5.57±0.76) mg/L], IL-6 [(133.42±27.31) ng/L vs.(123.73±22.81) ng/L], ET [(50.74±4.96) pg/L vs.(45.71±5.78) pg/L], total cholesterol [(5.32±0.66) mmol/L vs.(4.12±0.52) mmol/L], triglyceride [(1.56±0.42)mmol/L vs.(1.21±0.37) mmol/L] and low density lipoprotein cholesterol [(3.12±0.48) mmol/L vs.(2.43±0.43) mmol/L], and significant rise in high density lipoprotein cholesterol level [(1.41±0.12) mmol/L vs.(1.55±0.17) mmol/L] in combined treatment group, P<0.05 or <0.01.Compared with amlodipine group, there was significant rise in total effective rate (77.4% vs.91.9%) in combined treatment group, P=0.025.There was no significant difference in incidence rate of adverse reactions between two groups (P>0.05).Conclusion: Calcium channel blocker combined statins possesses definite therapeutic effects on aged patients with hypertension.It can reduce levels of blood pressure and blood lipids and inflammations and improve vascular endothelial cell function, which is worth extending.

Objective To establish an osteoporosis model in tree shrews by bilateral ovariectomy.Methods One hundred healthy 6-24 month old female tree shrews were used in this study.The diagnosis and treatment of osteoporo-sis in the model tree shrews was assessed according to the Interpretation of the Clinical Practice Guideines for Primary Oste-oporosis 2011 released by the Chinese Medical Association of Osteoporosis and Bone Mineral Salt Disease Branch.① Ac-cording to the human natural life span, sexual maturation time and peak bone mineral density ( PBMD) and the tree shrew natural life span and sexual maturation time, we estimated the PBMD of tree shrew in the age of months.Six 6-, 12-, 18-and 24-month old tree shrews in each group were randomly taken for measurement of BMD, and compared the differences between groups to verify the PBMD age of tree shrews.②We chose 62 6-month old tree shrews from the rest of tree shrews to measure their BMD to determine the mean and standard deviation of BMD.Then we divided them into study group ( n =32) and control group (n =30).Bilateral ovariectomy was performed in the study group, while omentectomy was done in the control group.BMD was measured at 3, 6, 9, 12 months after the surgery, 6 animals from each group.The animals which met the criteria of guideline were taken for pathological examination.Results ①The PBMD of 6-, 12-, 18-, 24-month old tree shrews was 0.138 ±0.012, 0.143 ±0.010, 0.141 ±0.009, and 0.139 ±0.009) g/cm2 , respectively, showing no significant differences among them (P>0.05).②The mean PBMD of the tree shrews was 0.143 ±0.016 g/cm2 .③In the model groups, the number of tree shrews whose BMD met the criteria of guideline was 0, 5, 4, 5, respec-tively.The pathological examination of the proximal tibia from the model group showed sparse and some disrupted trabecu-lae and enlarged inter-trabecular space.In the control group, the tibia tissues showed normal histology of bone structure and no one tree shrew showed a BMD value which met the criteria of diagnosis of osteoporosis.Conclusions An osteopo-rosis model in tree shrews can be established at 6 months after bilateral ovariectomy, showing similar manifestation of osteo-porosis in postmenopausal women.The success rate of this modeling method is high and the model is stable.

Objective To establish a simple and useful kidney or bladder orthotopic tumor model used in preclinical pharmacodynamic evaluation.Methods Mouse model of orthotopic renal cancer were established by subrenal capsule implantation.After aspirating urine and irrigating bladder with PBS,the bladder urothelium was slightly impaired to establish the orthotopic bladder tumor model.Then, B-Ultrasound and H&E staining were used to confirm the availability.Results Tumors could be seen 2 weeks after surgery, accompanied by body mass loss of the mice.H&E staining showed that the tumor cells acted as infiltrative growth.The growth of tumor was inhibited by NTX in vivo, the tumor mass inhibitory rate of the KCC-853 orthotopic tumor model was 57.5% of 60 mg/kg NTX treatment and 48.8% in the T24 orthotopic tumor model of 30 mg/kg NTX treatment.Conclusion Our methods for establishing the orthotopic kidney or bladder tumor model are simple and practical.The results indicate that nitroxoline has potential antitumor activity.

Tree shrews get more and more concerns due to many of its physiological , biochemical and anatomical characteristics similar to those of human beings .Therefore, tree shrews models of human diseases such as viral diseases , neurological diseases and tumors attract more and more attention of researchers .In this article we will review the recent ad-vances in application of tree shrew models in research on human viral diseases .