Identification and validation of miR-29b-3p and LIN7A as important diagnostic markers for bone non-union by WGCNA.

Bone non-union is a common fracture complication that can severely impact patient outcomes, yet its mechanism is not fully understood. This study used differential analysis and weighted co-expression network analysis (WGCNA) to identify susceptibility modules and hub genes associated with fracture healing. Two datasets, GSE125289 and GSE213891, were downloaded from the GEO website, and differentially expressed miRNAs and genes were analysed and used to construct the WGCNA network. Gene ontology (GO) analysis of the differentially expressed genes showed enrichment in cytokine and inflammatory factor secretion, phagocytosis, and trans-Golgi network regulation pathways. Using bioinformatic site prediction and crossover gene search, miR-29b-3p was identified as a regulator of LIN7A expression that may negatively affect fracture healing. Potential miRNA-mRNA interactions in the bone non-union mechanism were explored, and miRNA-29-3p and LIN7A were identified as biomarkers of skeletal non-union. The expression of miRNA-29b-3p and LIN7A was verified in blood samples from patients with fracture non-union using qRT-PCR and ELISA. Overall, this study identified characteristic modules and key genes associated with fracture non-union and provided insight into its molecular mechanisms. Downregulated miRNA-29b-3p was found to downregulate LIN7A protein expression, which may affect the healing process after fracture in patients with bone non-union. These findings may serve as a prognostic biomarker and potential therapeutic target for bone non-union.

Evaluating the ability of the NLHA2 and artificial neural network models to predict COVID-19 severity, and comparing them with the four existing scoring systems.

To improve the identification and subsequent intervention of COVID-19 patients at risk for ICU admission, we constructed COVID-19 severity prediction models using logistic regression and artificial neural network (ANN) analysis and compared them with the four existing scoring systems (PSI, CURB-65, SMARTCOP, and MuLBSTA). In this prospective multi-center study, 296 patients with COVID-19 pneumonia were enrolled and split into the General-Ward-Care group (N = 238) and the ICU-Admission group (N = 58). The PSI model (AUC = 0.861) had the best results among the existing four scoring systems, followed by SMARTCOP (AUC = 0.770), motified-MuLBSTA (AUC = 0.761), and CURB-65 (AUC = 0.712). Data from 197 patients (training set) were analyzed for modeling. The beta coefficients from logistic regression were used to develop a severity prediction model and risk score calculator. The final model (NLHA2) included five covariates (consumes alcohol, neutrophil count, lymphocyte count, hemoglobin, and AKP). The NLHA2 model (training: AUC = 0.959; testing: AUC = 0.857) had similar results to the PSI model, but with fewer variable items. ANN analysis was used to build another complex model, which had higher accuracy (training: AUC = 1.000; testing: AUC = 0.907). Discrimination and calibration were further verified through bootstrapping (2000 replicates), Hosmer-Lemeshow goodness of fit testing, and Brier score calculation. In conclusion, the PSI model is the best existing system for predicting ICU admission among COVID-19 patients, while two newly-designed models (NLHA2 and ANN) performed better than PSI, and will provide a new approach for the development of prognostic evaluation system in a novel respiratory viral epidemic.

Choose the appropriate implantation position of the Femoral Neck System in the femoral neck: a finite-element analysis.

PURPOSE: There is no specific literature on the best implantation position of the Femoral Neck System (FNS) for treating Pauwels type III femoral neck fracture in young adults. METHODS: Use finite-element analysis to compare the mechanical properties of implantation positions: FNS in the central position, FNS in the low position, and FNS in the low position combined with cannulated screw (CS). The CT data of the femur were imported into the mimics20.0 to obtain the three-dimensional model of the femur; imported into geomagic2017 and SolidWorks 2017 for optimizations; models of FNS and CS are built on the basis of the device manuals. Grouping is as follows: FNS group, FNS-LOW group, and FNS-CS group. Assemble and import them into abaques6.14 for load application. The displacement distribution and von Mises Stress value of them were compared. RESULTS: On femoral stability and stress distribution, the FNS-CS group performs best, followed by the FNS-LOW group, and finally FNS group. The FNS-LOW group has an improvement over the FNS group but not by much. CONCLUSION: In operations, when the implantation position of the central guide wire is not at the center of the femoral neck but slightly lower, it is recommended not to adjust the wire repeatedly in pursuit of the center position; for femoral neck fractures that are extremely unstable at the fracture end or require revision, the insertion strategy of FNS in the low position combined with CS can be adopted to obtain better fixation effects.

Role of hsa_circ_0066966 in proliferation and migration of hepatitis B virus-related liver cancer cells.

A large proportion of liver cancer cases is caused by hepatitis B virus (HBV) infection. In recent years, an increasing number of reports have indicated that circular RNAs (circRNAs) exert regulatory effects in cancer development, whereas the role of circRNAs in HBV-positive liver cancer requires further investigation. In the present study, abnormally expressed circRNAs were identified in HBV-positive liver cancer cells through microarray analysis. A total of 1,493 differentially expressed circRNAs [absolute fold-change (FC) ≥2] in HBV-positive liver cancer cells were detected, of which 171 were upregulated and 1,322 were downregulated. Subsequently, Gene Ontology enrichment analysis indicated that the genes of dysregulated circRNAs were mainly involved in regulating Sertoli cell differentiation and development, as well as telomeric DNA binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that most of these genes were enriched in cancer-related signaling pathways, including the MAPK and Hippo signaling pathways. Next, the expression levels of the top-10 dysregulated circRNAs were verified in HBV-positive liver cancer cells through reverse transcription-quantitative PCR. Among them, hsa_circ_0066966 had the highest absolute Log2FC value and was abnormally increased in HBV-positive liver cancer cells. Functional experiments further verified that knockdown of hsa_circ_0066966 had a significant inhibitory effect on the proliferation and migration of HBV-positive liver cancer cells. By contrast, overexpression of hsa_circ_0066966 in HBV-negative liver cancer cells resulted in the opposite effect. In conclusion, in the present study, comprehensive circRNA profiling in HBV-positive liver cancer cells indicated that hsa_circ_0066966 may regulate the progression of HBV-positive liver cancer.

Low Molecular Pectin Inhibited the Lipid Accumulation by Upregulation of METTL7B.

Inhibition of lipid accumulation is the key step to prevent nonalcoholic fatty liver (NAFL) progressing to nonalcoholic steatohepatitis. We aimed to study the effect of low-molecular-weight citrus pectin (LCP) against lipid accumulation and the underlying mechanism. Oleic acid (OA)-induced lipid deposition in HepG2 cells was applied to mimic in vitro model of lipid accumulation. Oil Red O (ORO) stain result showed lipid accumulation was significantly reduced, and levels of adipose triglyceride lipase (ATGL) and carnitine palmitoyltransferase-1 (CPT-1), involved in triacylglycerol catabolism and fatty acid ß-oxidation, detected by RT-qPCR were increased after OA-stimulated HepG2 cells treated with LCP. RNA sequencing analysis identified 740 differentially expressed genes (DEGs) in OA-stimulated HepG2 cells treated with the LCP group (OA+LCP group), and bioinformatics analysis indicated that some DEGs were enriched in lipid metabolism-related processes and pathways. The expression of the top 8 known DEGs in the OA+LCP group was then verified by RT-qPCR, which showed that fold change (abs) of METTL7B was the highest among the 8 candidates. In addition, overexpression of METTL7B in HepG2 cells significantly inhibited the lipid accumulation and enhanced levels of ATGL and CPT-1. In conclusion, LCP inhibited lipid accumulation through the upregulation of METTL7B, and further enhancement of ATGL and CPT-1 levels. LCP is expected to develop as a promising agent to ameliorate fat accumulation in NAFL.

Clinical and genetic characterization of measles viruses isolated from adult patients in Shanghai in 2006.

BACKGROUND: In recent years there has been an increase in adult measles cases in Shanghai, and an outbreak occurred in 2005. Although there have been many studies analyzing the genotype of measles virus from pediatric patients in various parts of China, there is little information on the clinical findings and genetic makeup of adult measles. OBJECTIVES: Clinical information and phylogenetic analysis of adult measles infection in Shanghai. STUDY DESIGN: Blood, urine, throat swabs, and clinical information were collected from adult measles patients reporting to three major hospitals in Shanghai. Measles virus was isolated in Vero-SLAM cells. The C-terminus of the N gene of the isolates was sequenced and analyzed with reference to sequences obtained from GenBank. RESULTS: More than half of the patients developed severe clinical symptoms. None of the patients knew their measles vaccination history. All measles virus isolates had the same amino acid substitutions as the two standard H1a measles strains at position 484 and were classified as H1a genotype and could be further divided into three small clusters. CONCLUSIONS: The genotype of the predominant measles virus causing disease in adults in Shanghai is H1a.

[Role of platelet activating factor in hepatorenal syndrome].

OBJECTIVE: To investigate the relationship between platelet activating factor (PAF) and occurrence of hepatorenal syndrome (HRS). METHODS: A total of 57 cases of patients with liver cirrhosis or hepatitis gravis were enrolled. The serum concentrations of PAF, lipopolysaccharide (LPS) and prothrombin activity (PTA), total bilirubin, and serum creatinine were detected in patients combined with HRS and in patients without HRS in hospital at the term. The correlations among the PAF, LPS, and the function of liver and kidney were analyzed. RESULTS: The concentrations of PAF and LPS in the patients combined with HRS were significantly higher than those patients without HRS. There were linear correlations between the PAF and LPS level, the total bilirubin level and PAF level, the PAF level and serum creatinine level. CONCLUSION: The PAF associates with the occurrence of HRS. The PAF may mediate the occurrence of HRS induced by LPS. The PAF level may forecast whether patients with liver failure will take place HRS.

Zebrafish as a new model for phenotype-based screening of positive inotropic agents.

The zebrafish-based assay is a widely used animal model system for cardiovascular research. In this study, we investigated the cardiac defects caused by terfenadine and tested the pharmacological response of digoxin to zebrafish with cardiac defects. The study suggested that zebrafish could be a suitable model for phenotype-based screening and evaluation of positive inotropic agents. This phenotype-based heart failure zebrafish model system was then utilized in in-house library screen. Some positive inotropic compound was discovered, which could attenuate the cardiac defects by increasing the flow velocity of caudal artery blood.

Treatment of middle-super thoracic fractures associated with the sternum fracture.

To analyze the characteristics and treatment of middle-super thoracic fractures associated with the sternum fracture, twenty six patients with middle-super thoracic fractures associated with the sternum fracture were retrospectively reviewed. The intimate information of patients including age, gender, cause of injury, site of the sternal fracture, level and type of thoracic vertebral fracture, spinal cord injury and associated injuries were included in the analysis. There were 12 compressed fractures, 11 fracture-dislocations, two burst fracture and one burst-dislocation in this study. Six patients had a complete lesion of the spinal cord, nine sustained a neurologically incomplete injury and 11 were neurologically intact. Nine patients were treated non-operatively and 17 were underwent surgery. All patients were followed up for 8~99 months. Our results showed that road traffic accidents (RTA) and fall were the dominated in the causes. All six patients with a complete paralytic lesion were not recovered with any significant function. Four out of eleven neurologically intact patients had local pain although ten of them remained normal function and one patient turn up tardive paralysis. One of nine patients with incomplete paraplegia returned to normal and four recovered with some function. These study suggested that the sternum is one of the important parts in constructing thoracic cage and plays an important role in maintain the stabilization of the thoracic vertebra. Because of the unique anatomy and biomechanics of the thoracic cage, the classification commonly applied to thoracic vertebra fractures is not suitable for middle-super thoracic fractures associated with the sternum fracture. Middle-super thoracic fractures associated with the sternum fracture was marked by violent force, severe fractures of spine, severe injuries of spinal cord and high incidence of associated injuries. These cases confirm the existence and clinical relevance of the fourth column of the thoracic spine and its role for spinal stability in the patient with middle-super thoracic fracture.

Fast pinless external fixation for open tibial fractures: preliminary report of a prospective study.

A major drawback of conventional fixator system is the penetration of fixator pins into the medullary canal. The pins create a direct link between the medullary cavity and outer environment, leading to higher infection rates on conversion to intramedullary nailing. This study was designed to prospectively evaluate the role of new rapid pinless external fixators in primary stabilization of open tibial shaft fractures. In our study, a prospective study of 96 consecutive patients of open tibial shaft fractures treated with new rapid pinless external fixator and reamed intramedullary nail was carried out. The bone healing status, ability to maintain alignment were examined for radiologic outcome, whereas initial management, length of hospital stay, associated morbidity, range of knee and ankle motion, time to partial and full weight-bearing, employment status and perioperative and postoperative complications were used for clinical evaluation. We followed up for over two years for the patients underwent clinical and radiologic after the surgery. The mean hospital stay was 15 days (ranges, 8-68). Bone healing was achieved for all cases except 3 patients who were lost to follow-up study. No patient suffered compartment syndromes. There was no statistically significance in range of motion among the knees of injury and uninjured limbs at final follow-up (P > 0.05). To the last follow-up, there were no cases of deep infection or implant-related fractures. Seventy-one patients who were employed before the injury returned to work after the operation, 16 had changed to less strenuous work. We concluded that better results can be achieved on clinical and radiologic evaluation of primary stabilization with rapid pinless external fixator and early exchange reamed intramedullary nail for suitable patients with open tibial shaft fractures. The incident rate of relative complications is low. The rapid pinless external fixator can be combined favorably with the reamed intramedullary nail and is a valuable addition to the conventional external fixator systems.

Full-Genome Analysis of Influenza A(H7N9) Virus from Shanghai, China, 2014.

We analyzed the complete genome sequence of the A/Shanghai/01/2014 (H7N9) strain, which will provide a better understanding of the evolution of influenza A(H7N9) virus.