Objective:To explore the effects of hyperoxic environments on renal metabolites to understand the potential mechanisms that contribute to pathologic retinal vascular neovascularization and renal injury through metabolomic studies in a mouse model of oxygen-induced retinopathy (OIR) model.Methods:Sixteen C57/B6J mice pups born to day 7 (P7) were randomly and equally divided into an OIR model group and a normal control group using a randomized numerical table of mother mice.Mice were reared standardly from birth until day 7 (P7), then mice and their mother mice in the OIR group were placed in a hyperoxic (75±2)% chamber until day 12 (P12) and then reared normally.Mice in the normal control group were reared normally throughout.Mice in two groups were killed by carbon dioxide euthanasia on postnatal day 17 (P17). The mice retinal wholemount from the two groups were made and stained with isolectin B4 (IB4) to observe the morphology of retinal vessels, central non-perfusion area and pathological neovascularization.The kidney tissue of P17 mice was analyzed by liquid chromatograph mass spectrometer.After anticoagulant treatment, the whole blood of mice was centrifuged and precipitated, and the obtained plasma without cellular components was analyzed by targeted metabonomics.Mass spectral information was interpreted using metabolomics data processing software Progenesis QI v2.3.Overall differences in metabolic profiles were distinguished by unsupervised principal component analysis and orthogonal partial least squares analysis (OPLS-DA). The fold change and P values of metabolites were compared between the two groups.The variable importance of projection value>1 and P value<0.05 was used to screen out differential metabolites.Metabolic pathway enrichment analysis of differential metabolites was performed based on the KEGG database.The feeding and use of animals were strictly in accordance with the requirements of the Ethics Committee of Jinan University, and the research protocol was reviewed and approved by the Ethics Committee of Jinan University (No.20200401-54). Results:The IB4 staining of retinal wholemounts showed that the retinal blood vessels were evenly distributed in the P17 mice from control group.The peripheral retinal vessels were tortuous and disordered with a large non-perfusion area in central region in P17 mice from OIR group, and a large number of neovascularization clusters were formed at the junction of the nonperfusion area and the vascular area of the retina, showing strong fluorescent staining.The relative area of retinal nonperfusion area in OIR group was (25.16±3.50)%, which was significantly larger than (0.63±0.30)% in normal control group ( t=12.07, P<0.001). The OPLS-DA parameter R2X cum (0.578), interpretation rate R2Y cum (0.978) and prediction rate Q2 cum (0.857) values were all greater than 0.5, indicating that the OPLS-DA model had a good predictive ability.A total of 26 main differential metabolites were found, among which 17 were up-regulated and 9 were down-regulated, including glycerophospholipids (PC 20∶4(5Z, 8Z, 11Z, 14Z)/0∶0, PC 22∶6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)/0∶0, PC 14∶1(9Z)/20∶2(11Z, 14Z), PE P-18∶0/20∶4(6E, 8Z, 11Z, 14Z)(5OH[S]), amino acid metabolites (arginine, ornithine, pipecolic acid, and hydroxylysine), purines (guanine, hypoxanthine, hydroxypurinol), and fatty acids (methyl 15-palmitate, 2, 6, 8, 12-tetramethyl-2, 4-tridecadien-1-ol), and so on.Differential metabolites were mainly enriched in ABC transporters (L-arginine, taurine, inositol, adenosine, N-acetyl-D-glucosamine, L-glutamine), aminoacyl-tRNA biosynthesis (L-isoleucine, L-proline, L-arginine, L-histidine, L-glutamine), arginine biosynthesis (L-arginine, L-ornithine, L-glutamine) metabolic pathways.The plasma targeted metabonomics showed that the differential amino acid metabolites were mainly enriched in metabolic pathways such as aminoacyl-tRNA biosynthesis, arginine biosynthesis and metabolism, and ABC transporters. Conclusions:ABC transporter, aminoacyl-tRNA biosynthesis, and arginine biosynthesis metabolic pathways in OIR mice may participate in the pathological changes of renal injury and neovascularization in retinopathy of prematurity.

Objective To investigate the effects of eicosanoic acid(C20DC)on the proliferation and migration of human retinal endothelial cells(HRECs)and its mechanism.Methods The optimal working concentration of C20DC in human retinal pigment epithelium 19(ARPE-19)cells and HRECs was determined as 30 mg·L-1 and 25 mg·L-1,respec-tively.HRECs were divided into the C20DC treatment group(HRECs treated with C20DC)and the control group[HRECs treated with dimethyl sulfoxide(DMSO)].The effects of C20DC on the migration and proliferation of HRECs were detec-ted by cell proliferation and migration experiments.The molecular docking method was used to simulate the binding ability of C20DC to peroxisome proliferator-activated receptor δ(PPARδ).ARPE-19 cells were divided into the C20DC+ARPE-19 group(ARPE-19 cells treated with C20DC)and the DMSO+ARPE-19 group(ARPE-19 cells treated with DMSO).The ex-pression levels of PPARδ and angiopoietin-like protein 4(ANGPTL4)in ARPE-19 cells and ANGPTL4 protein in HRECs were detected using Western blot.The ANGPTL4 protein expression levels in ARPE-19 cells and HRECs were quantitatively analyzed using enzyme-linked immunosorbent assay(ELISA).Results Compared with the control group,the prolifera-tion and migration of cells in the C20DC treatment group significantly increased(both P＜0.05),and C20DC could stably bind to PPAR8(binding energy:-7.20 kcal·mol-1).Western blot showed that the expression level of ANGPTL4 protein in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group,and the difference was statistically sig-nificant(P＜0.05);there was no statistically significant difference in the expression level of PPARδ receptor protein be-tween the two groups(P＞0.05).The expression level of ANGPTL4 protein in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P＜0.05).ELISA quantitative analysis showed that the expression level of ANGPTL4 in the C20DC+ARPE-19 group was higher than that in the DMSO+ARPE-19 group(P＜0.001);the expression level of ANGPTL4 in the C20DC treatment group was higher than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion C20DC can promote the expression of ANGPTL4 pro-tein by binding to PPARδ and thus increase the proliferation and migration of retinal related cells(HRECs and ARPE-19 cells).Its mechanism may be related to the increased angiogenesis in retinopathy of prematurity.

Background::Circular RNAs (circRNAs) are endogenous non-coding RNAs, some of which have pathological roles. The current study aimed to explore the role of circRNA BTG3-associated nuclear protein (circ-BANP) binding with let-7f-5p and its regulation of the toll-like receptor 4 (TLR4)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in residual hepatocellular carcinoma (HCC) after insufficient radiofrequency ablation (RFA).Methods::Circ-BANP, let-7f-5p, and TLR4 expressions in HCC samples were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Bioinformatics prediction, RNA pull-down assay, and dual luciferase reporter gene assay were used to analyze the relationships among circ-BANP, let-7f-5p, and TLR4. Huh7 cells were used to generate an in vitro model of residual HCC, defined as Huh7-H cells, which were transfected with either a plasmid or the sequence of circ-BANP, let-7f-5p, or TLR4. Expression of circ-BANP, let-7f-5p, and TLR4 mRNA was determined by RT-qPCR. TLR4, STAT3, p-STAT3, vascular endothelial growth factor A, vascular endothelial growth factor receptor-2, and epithelial-mesenchymal transformation (EMT)-related factors proteins were determined by Western blotting. Cell proliferation was determined by cell counting kit-8 and 5-Ethynyl-2’-deoxyuridine (EdU) assay and cell migration and invasion by Transwell assay. Animal studies were performed by inducing xenograft tumors in nude mice. Results::Circ-BANP and TLR4 mRNAs were upregulated in HCC tissues (the fold change for circ-BANP was 1.958 and that for TLR4 was 1.736 relative to para-tumors) and expression further increased following insufficient RFA (fold change for circ-BANP was 2.407 and that of TLR4 was 2.224 relative to para-tumors). Expression of let-7f-5p showed an opposite tendency (fold change for let-7f-5p in HCC tissues was 0.491 and that in tumors after insufficient RFA was 0.300 relative to para-tumors). Competitive binding of circ-BANP to let-7f-5p was demonstrated and TLR4 was identified as a target of let-7f-5p (P < 0.01). Knockdown of circ-BANP or elevation of let-7f-5p expression inhibited the TLR4/STAT3 signaling pathway, proliferation, invasion, migration, angiogenesis, and EMT in Huh7 and Huh7-H cells ( P < 0.01). The effects induced by circ-BANP knockdown were reversed by let-7f-5p inhibition. Overexpression of TLR4 reversed the impact of let-7f-5p upregulation on the cells ( P < 0.01). Silencing of circ-BANP inhibited the in vivo growth of residual HCC cells after insufficient RFA ( P < 0.01). Conclusions::Knockdown of circ-BANP upregulated let-7f-5p to inhibit proliferation, migration, and EMT formation in residual HCC remaining after insufficient RFA. Effects occur via regulation of the TLR4/STAT3 signaling pathway.

Objective:To evaluate the deformity changes in the treatment of congenital clubfoot in infants by ultrasound, and to explore its clinical application value.Methods:Seventeen infants with congenital clubfoot treated in the Department of Pediatric Orthopaedics of the Third Affiliated Hospital of Zhengzhou University from March 2020 to June 2021 and 27 normal infants in the same period were selected. The distance between medial malleolus and scaphoids (MM-N distance) of all feet was measured by ultrasound. The distance from the tangent line of the lateral edge of calcaneus to the midpoint of the lateral edge of the chondroid bone (C-C distance), medial soft tissue thickness and tibial calcaneal angle were measured by ultrasound. The data before, after treatment and during follow-up were statistically analyzed.Results:A total of 88 feet of 44 infants were evaluated. The mean number of cast was 4.7±1.1, the follow-up time was (96.9±59.3)days. The MM-N distance, C-C distance and posterior tibial calcaneal angle in the clubfoot group were improved after treatment and at the last follow-up, and the differences were statistically significant (all P<0.01). During the treatment, 1 case had false correction, and 2 cases recurred in the last follow-up. Conclusions:Ultrasound can clearly display the medial, dorsal, lateral and posterior articular structures of normal and clubfoot, and can observe the deformity changes of clubfoot during the correction process, which can provide guidance for the clinical treatment of clubfoot.

Objective: To introduce a new surgical technique for the correction of congenital syndactyly without skin grafts. Methods: The technique consists of a dorsal double-wing flap created from the dorsal skin of the metacarpophalangeal joint to cover the newly released web space and zigzag incisions in the fingers, thus avoiding the use of skin grafts in this area. Results: From May 2010 to October 2016, 35 web spaces in 24 patients were treated using this technique. There were no complications such as haematoma, infection or flap necrosis. The average follow-up time was 54 months (range, 6 months to 60 months). One of the 35 webs developed web creep. No patients developed flexion contractures. All webs had good appearance with 45 degrees inclination from dorsal to palmar. All fingers had no obvious scar, and the flexion and abduction function were good. Conclusions The technique is simple, rapid, safe and easily performed and does not require the use of skin grafts.

Gut microbiota(GM)consists of a complex community of microorganism species that live in the digestive tracts of animals including humans. Dysbiosis is believed to involve in the development of some diseases. Recently dysbiosis in the patients with Alzheimer′s disease(AD)and AD rat models was reported. GM may influence the pathogenesis and development of AD in several ways. Some neurotoxic substances produced by GM can invade into the brain via circulation and impair the neural functions. These sub?stances include ammonia,cyanobacteria-producedβ-N-methylamino-L-alanine,saxitoxin,anatoxin-αand amyloid. The decrease in brain-derived neurotrophic factor(BDNF)in hippocampus and cerebral cortex induced by dysbiosis contributes to the cognitive dys?function. Dysbiosis related endotoxin can induce inflammation,which is one important risk factor for obesity,insulin resistance(IR) and type 2 diabetes mellitus(TIDM). AD and diabetes have good correlation and similarity. Probiotics,prebiotics and Chinese herbal medicines can rebuild GM and have been reported to ameliorate the memory loss of AD patients or model rats. However ,whether and how their preventative and therapeutic effects on AD mediated by GM are worthy of further investigation.

BACKGROUND:Flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures are two common methods in the clinic. It remains controversial which fixation methods are better. OBJECTIVE:To systematicaly evaluate the therapeutic effects of flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures. METHODS: A computer-based search was performed on PubMed, Embase, Medline, and Cochrane library for literatures on clinical controled trials of flexible intramedulary nailing and external fixation for pediatric femoral shaft fractures published before November 25, 2014. Literature language was not limited. The age of subjects was from 3 to 15 years. Modified Jadad was utilized to assess methodological quality of the included studies. Meta-analysis was carried out using Stata 12.0 software. RESULTS AND CONCLUSION:Six papers involving 237 patients were included. Meta-analysis results showed that compared with external fixation, a low incidence of overal complications [relative risk (RR)=0.30, 95% confidence interval (CI): 0.19-0.46;P < 0.001] and pin-hole infection (RR=0.286, 95%CI: 0.13-0.61;P= 0.001), but a high risk of needle tail irritation (RR=1.86, 95%CI: 1.35-2.56;P < 0.001) were found folowing flexible intramedulary nailing. No significant differences in other complications were found between the two groups. These results confirm that compared with external fixation, elastic intramedulary nail has fewer complications and faster fracture healing. Elastic intramedulary nail is recommended for single pediatric femoral shaft fractures. However, external fixation is a better option for high energy injury of lower limbs, multiple trauma or severely soft tissue injury.

Oxycodone,an opioid receptor agonist,is one of potent narcotic analgesics. Despite its potent analgesic effect,the tolerant and dependent liability of oxycodone as well as its inhibition on gas-trointestinal motility strongly restricts its clinical application. Since the end of the last century,antipyretic, opioid receptor agonist,opioid receptor antagonist and dopamine receptor antagonist have been used to in combination with oxycodone at different ratios as complex prescriptions,the aim of which is to enhance the effect of oxycodone,decrease the dosage of oxycodone,and prevent the adverse effect and the tendency for misuse. Here we reviewed the development of oxycodone compositions in the recent years,hoping to provide more data for its potential clinical application.

Objective:To establish an improved model of mouse partial hepatectomy for study on liver regeneration .Methods :Healthy 8~10 week old male C57BL/6 mice were anesthetized by intraperitoneal injection .Then ,common hepatic pedicle of left lateral lobe of liver and middle lobe of liver was wrapped around with 6-0 proline suture .6-0 proline was fixed on the sur-face of right middle lobe of liver ,which was 0 .2 cm away from the hepatic pedicle .Hepatic pedicle was ligated and left lateral lobe and middle lobe of liver were resected 0 .2 cm away from ligature .The postoperative survival rate and the situation of liver weight vecovery at 3rd day ,7th day ,and 14th day after the operation were observed .Results:An improved mouse model of partial hepatectomy ,of which left lateral lobe of liver and middle lobe of liver were resected ,was established .The weight of removed liver accounted for 66 .7% of total liver and the survival rate of mice was 100% .After liver resection ,the compensa-tory regeneration of remaining liver achieved 58 .2% of the total liver weight at the 3rd day ,78 .0% at the 7th day ,and 93 .2%at the 14th day after the operation .Conclusions :An improved mouse model of partial hepatectomy was successfully established for study on liver regeneration ,which has advantages such as simplicity ,operability and high success rate .

Objective:To study the expression of UHRF1 and its relationships with the clinicopathological characteristics in hepatocellular carcinoma(HCC) .Methods :The expression of UHRF1 was analyzed in 556 cases of tumor tissues and peritumor tissues of HCC by immunohistochemistry .The relationships of UHRF1 with the clinicopathological characteristics of HCC were assayed .Results:Immunohistochemistry showed that positive staining of UHRF1 located in the nucleus of HCC cells .The ex-pression levels of UHRF1 protein were higher in tumor tissues than in peritumor tissues .HCC patients with positive expression of UHRF1 protein accounted for 59% of the whole cohort .The expression of UHRF1 protein was significantly correlated with the size of tumor ( P<0 .01) ,differentiation (P<0 .05) and microvessel invasion(P<0 .01) .Conclusions :The overexpression of UHRF1 is correlated with the malignant phenotypes of HCC and probably implicated in the invasion and metastasis of HCC .