D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1.

Breast cancer is the most frequent malignancy in women worldwide, and triple-negative breast cancer (TNBC) patients have the worst prognosis and highest risk of recurrence. The therapeutic strategies for TNBC are limited. It is urgent to develop new methods to enhance the efficacy of TNBC treatment. Previous studies demonstrated that D-mannose, a hexose, can enhance chemotherapy in cancer and suppress the immunopathology of autoimmune diseases. Here, we show that D-mannose can significantly facilitate TNBC treatment via degradation of PD-L1. Specifically, D-mannose can activate AMP-activated protein kinase (AMPK) to phosphorylate PD-L1 at S195, which leads to abnormal glycosylation and proteasomal degradation of PD-L1. D-mannose-mediated PD-L1 degradation promotes T cell activation and T cell killing of tumor cells. The combination of D-mannose and PD-1 blockade therapy dramatically inhibits TNBC growth and extends the lifespan of tumor-bearing mice. Moreover, D-mannose-induced PD-L1 degradation also results in messenger RNA destabilization of DNA damage repair-related genes, thereby sensitizing breast cancer cells to ionizing radiation (IR) treatment and facilitating radiotherapy of TNBC in mice. Of note, the effective level of D-mannose can be easily achieved by oral administration in mice. Our study unveils a mechanism by which D-mannose targets PD-L1 for degradation and provides methods to facilitate immunotherapy and radiotherapy in TNBC. This function of D-mannose may be useful for clinical treatment of TNBC.

Electrocatalytic Interconversions of CO2 and Formate on a Versatile Iron-Thiolate Platform.

Exploring bidirectional CO2/HCO2- catalysis holds significant potential in constructing integrated (photo)electrochemical formate fuel cells for energy storage and applications. Herein, we report selective CO2/HCO2- electrochemical interconversion by exploiting the flexible coordination modes and rich redox properties of a versatile iron-thiolate platform, Cp*Fe(II)L (L = 1,2-Ph2PC6H4S-). Upon oxidation, this iron complex undergoes formate binding to generate a diferric formate complex, [(L-)2Fe(III)(µ-HCO2)Fe(III)]+, which exhibits remarkable electrocatalytic performance for the HCO2--to-CO2 transformation with a maximum turnover frequency (TOFmax) ∼103 s-1 and a Faraday efficiency (FE) ∼92(±4)%. Conversely, this iron system also allows for reduction at -1.85 V (vs Fc+/0) and exhibits an impressive FE ∼93 (±3)% for the CO2-to-HCO2- conversion. Mechanism studies revealed that the HCO2--to-CO2 electrocatalysis passes through dicationic [(L2)-•Fe(III)(µ-HCO2)Fe(III)]2+ generated by unconventional oxidation of the diferric formate species taking place at ligand L, while the CO2-to-HCO2- reduction involves a critical intermediate of [Fe(II)-H]- that was independently synthesized and structurally characterized.

Systematic Study of Resveratrol Nanoliposomes Transdermal Delivery System for Enhancing Anti-Aging and Skin-Brightening Efficacy.

Due to the stratum corneum barrier, resveratrol is difficult to be absorbed transdermally, limiting its anti-aging and skin-brightening effects. Furthermore, there is a lack of systematic studies on the efficacy of resveratrol in human skin, especially in three-dimensional skin models and clinical trials. To overcome the low transdermal delivery issue, we encapsulated resveratrol into nanoliposomes using the high-pressure homogenization method to develop an efficient transdermal drug delivery system, and systematically evaluated its anti-aging and skin-brightening efficacy via cell line models, a three-dimensional skin model and human skin. The resveratrol nanoliposomes effectively improved the transdermal penetration and retention of resveratrol and enhanced cellular uptake. In addition, compared to free resveratrol, resveratrol nanoliposomes remarkably enhanced the skin-care effects by promoting the antioxidant capacity and collagen synthesis, inhibiting the secretion of matrix metalloproteinases, tyrosine activity and melanin synthesis. Notably, human clinical trials proved the anti-wrinkle and skin-brightening effectiveness of resveratrol nanoliposomes. Three levels of systematic studies indicated that resveratrol nanoliposomes could be a promising transdermal drug delivery system to enhance the anti-aging and skin-brightening effects of resveratrol.

Identification of crucial circRNAs in skeletal muscle during chicken embryonic development.

BACKGROUND: Chicken provides humans with a large amount of animal protein every year, in which skeletal muscle plays a leading role. The embryonic skeletal muscle development determines the number of muscle fibers and will affect the muscle production of chickens. CircRNAs are involved in a variety of important biological processes, including muscle development. However, studies on circRNAs in the chicken embryo muscle development are still lacking. RESULTS: In the study, we collected chicken leg muscles at 14 and 20-day embryo ages both in the fast- and slow-growing groups for RNA-seq. We identified 245 and 440 differentially expressed (DE) circRNAs in the comparison group F14vsF20 and S14vsS20 respectively. GO enrichment analysis for the host genes of DE circRNAs showed that biological process (BP) terms in the top 20 related to growth in F14vsF20 were found such as positive regulation of transcription involved in G1/S phase of mitotic cell cycle, multicellular organismal macromolecule metabolic process, and multicellular organismal metabolic process. In group S14vsS20, we also found some BP terms associated with growth in the top 20 including actomyosin structure organization, actin cytoskeleton organization and myofibril assembly. A total of 7 significantly enriched pathways were obtained, containing Adherens junction and Tight junction. Further analysis of those pathways found three crucial host genes MYH9, YBX3, IGF1R in both fast- and slow-growing groups, three important host genes CTNNA3, AFDN and CREBBP only in the fast-growing group, and six host genes FGFR2, ACTN2, COL1A2, CDC42, DOCK1 and MYL3 only in the slow-growing group. In addition, circRNA-miRNA network also revealed some key regulation pairs such as novel_circ_0007646-miR-1625-5p, novel_circ_0007646-miR-1680-5p, novel_circ_0008913-miR-148b-5p, novel_circ_0008906-miR-148b-5p and novel_circ_0001640-miR-1759-3p. CONCLUSIONS: Comprehensive analysis of circRNAs and their targets would contribute to a better understanding of the molecular mechanisms in poultry skeletal muscle and it also plays an important guiding role in the next research.

HD-eXplosion: visualization of hydrogen-deuterium exchange data as chiclet and volcano plots with statistical filtering.

SUMMARY: Hydrogen-Deuterium eXchange coupled to mass spectrometry is a powerful tool for the analysis of protein dynamics and interactions. Bottom-up experiments looking at deuterium uptake differences between various conditions are the most common. These produce multi-dimensional data that can be challenging to depict in a single visual format. Each user must also set significance thresholds to define meaningful differences and make these apparent in data presentation. To assist in this process, we have created HD-eXplosion, an open-source, web-based application for the generation of chiclet and volcano plots with statistical filters. HD-eXplosion fills a void in available software packages and produces customizable plots that are publication quality. AVAILABILITY AND IMPLEMENTATION: The HD-eXplosion application is available at http://hd-explosion.utdallas.edu. The source code can be found at https://github.com/HD-Explosion.

miRNA-10a-5p Targeting the BCL6 Gene Regulates Proliferation, Differentiation and Apoptosis of Chicken Myoblasts.

Proliferation, differentiation, and apoptosis are three essential stages in cell development, and miRNAs can achieve extensive regulation of cellular developmental processes by repressing the expression of target genes. According to our previous RNA-seq results, miRNA-10a-5p was differentially expressed at different periods in chicken myoblasts, revealing a possible association with muscle development. In this study, we concluded that miRNA-10a-5p inhibited chicken myoblasts' proliferation and differentiation and promoted chicken myoblasts' apoptosis by directly targeting BCL6, a critical transcription factor involved in muscle development and regeneration. Overexpression of BCL6 significantly facilitated myoblasts' proliferation and differentiation and suppressed myoblasts' apoptosis. On the contrary, knockdown of BCL6 significantly repressed myoblasts' proliferation and differentiation and induced myoblasts' apoptosis. The results above suggest that miRNA-10a-5p plays a potential role in skeletal muscle growth, development and autophagy by targeting the BCL6 gene. We first revealed the functions of miRNA-10a-5p and BCL6 in the proliferation, differentiation, and apoptosis of chicken myoblasts.

Study on the transcriptome for breast muscle of chickens and the function of key gene RAC2 on fibroblasts proliferation.

BACKGROUND: Growth performance is significant in broiler production. In the growth process of broilers, gene expression varies at different growth stages. However, limited research has been conducted on the molecular mechanisms of muscle growth and development in yellow-feathered male chickens. RESULTS: In the study, we used RNA-seq to study the transcriptome of the breast muscle of male Jinghai yellow chickens at 4 (M4F), 8 (M8F) and 12 weeks (M12F) of age. The results showed that 4608 differentially expressed genes (DEGs) were obtained by comparison in pairs of the three groups with Fold Change (FC) ≥ 2 and False Discovery Rate (FDR) ≤ 0.05, and 83, 3445 and 3903 DEGs were obtained separately from M4FvsM8F, M4FvsM12F and M8FvsM12F. Six genes were found as co-differentially expressed in the three age groups, namely SNCG, MYH1A, ARHGDIB, ENSGALG00000031598, ENSGALG00000035660 and ENSGALG00000030559. The GO analysis showed that 0, 304 and 408 biological process (BP) were significantly enriched in M4FvsM8F, M4FvsM12F and M8FvsM12F groups, respectively. KEGG pathway enrichment showed that 1, 2, 4 and 4 pathways were significantly enriched in M4FvsM8F, M4FvsM12F, M8FvsM12F and all DEGs, respectively. They were steroid biosynthesis, carbon metabolism, focal adhesion, cytokine-cytokine receptor interaction, biosynthesis of amino acids and salmonella infection. We constructed short hairpin RNA (shRNA) to interfere the differentially expressed gene RAC2 in DF-1 cells and detected mRNA and protein expression of the downstream genes PAK1 and MAPK8. Results of qPCR showed that RAC2, PAK1 and MAPK8 mRNA expression significantly decreased in the shRAC2-2 group compared with the negative control (NC) group. Western Blot (WB) results showed that the proteins of RAC2, PAK1 and MAPK8 also decreased in the shRAC2-2 group. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay both showed that the proliferation of DF-1 cells was significantly inhibited after transfection of shRAC2-2. CONCLUSIONS: The results of RNA-seq revealed genes, BP terms and KEGG pathways related to growth and development of male Jinghai yellow chickens, and they would have important guiding significance to our production practice. Further research suggested that RAC2 might regulate cell proliferation by regulating PAKs/MAPK8 pathway and affect growth of chickens.

Copeptin combined with National Early Warning Score for predicting survival in elderly critical ill patients at emergency department.

OBJECTIVE: Copeptin, reflecting vasopressin release, as well as the National Early Warning Score (NEWS), reflecting the severity of critical illness, might qualify for survival prediction in elderly patients with critical illness. This prospective observational study aims at assessing the predictive value of copeptin combined with NEWS on the prognosis of elderly critical ill patients at emergency department (ED). METHODS: We analyzed serum copeptin levels and the NEWS at admission to the ED in a prospective, single-center, and observational study comprising 205 elderly patients with critical illness. Death within 30 days after admission to the ED was the primary end point. RESULTS: The serum copeptin levels and the NEWS in the non-survivor patients group were higher than those in the survivor group [30.35 (14.20, 38.91) vs 17.53 (13.01, 25.20), P = 0.001 and 9.0 (7.0-10.0) vs 7.0 (6.0-8.0), P = 0.001]. Multivariate logistic regression analysis showed that copeptin, NEWS and copeptin combined with NEWS were all independent risk factors for 30-day mortality in elderly patients with critical illness. Copeptin, NEWS and copeptin combined with NEWS all performed well in predicting 30-day survival, with area under the ROC curve (AUC) values of 0.766 (95%CI, 0.702-0.822), 0.797 (95%CI, 0.744-0.877) and 0.854 (95%CI, 0.798-0.899) respectively. Using the Z test to compare the areas under the above three curves, copeptin combined with NEWS showed a higher predictive value for 30-day survival (P < 0.05). As we calculated, the optimal cut-off values of copeptin and NEWS using the Youden index were 19.78 pg/mL and 8.5 points, respectively. Risk stratification analysis showed that patients with both copeptin levels higher than 19.78 pg/mL and NEWS points higher than 8.5 points had the highest risk of death. CONCLUSIONS: Copeptin combined with NEWS have a stronger predictive power on the prognosis of elderly patients with critical illness at ED, comparing to either factor individually.

Controllable Preparation of Monodisperse Mesoporous Silica from Microspheres to Microcapsules and Catalytic Loading of Au Nanoparticles.

A unique structural transition from pomegranate-like monodisperse mesoporous silica microspheres (M-MSMs) with tunable mesopores to mesoporous silica microcapsules has been reported. The unique evolution occurred together with varying the cross-linking degrees (CLDs) of templates. Herein, using monodisperse sulfonated cross-linked polystyrene (S-CLPS) as templates, S-CLPS/SiO2 composite microspheres were synthesized by the sol-gel method. Subsequently, the templates were removed by calcination to obtain the M-MSMs or microcapsules. The pore sizes of M-MSMs could be tailored from 3.2 to 7.4 nm by facilely varying the CLDs from 0.5 to 20%. Interestingly, mesoporous silica microcapsules were gradually formed when the CLDs were beyond 20%. Meanwhile, the specific surface area also could be adjusted by this strategy without hardly affecting the monodispersity, and the specific surface area increased to 391.9 m2/g. Significantly, Au@M-MSM was prepared by supporting Au nanoparticles (NPs) on M-MSM and used as nanocatalysts to reduce 4-nitrophenol (4-NP). The ultrathin shell and interconnected three-dimensional (3D) porous structure of M-MSMs can increase the mass transfer and protect the Au NPs from leakage, which reveals high recyclability and high conversion (>95%) after 10 regeneration-catalysis cycles. This approach provides a nanotechnology platform for the preparation of mesoporous silica materials with different microstructures, which will have enormous potential in practical applications involving different molecular sizes.

Favourable clinical outcomes following cemented arthroplasty after metal-on-metal total hip replacement: a retrospective study with a mean follow-up of 10 years.

BACKGROUND: Given the unexpected high rate of failure following metal-on-metal total hip replacement (MoM-THR), it is expected that more MoM-THR patients will experience revision. The long-term outcomes regarding the primary MoM-THR revised to cemented THR (CTHR) remain controversial. The purpose of this retrospective review was to evaluate the long-term outcomes of patients who underwent conversion from MoM-THR to CTHR. METHODS: A total of 220 patients (220 hips) who underwent a conversion of primary MoM-THR to CTHR from March 2006 to October 2016 were retrospectively reviewed. The primary outcomes were the functional outcomes assessed using the Harris hip scores (HHS) and major radiographic outcomes. Follow-ups occurred at 3 months, 6 months, 1 year, 2 years, and then every two years after revision. RESULTS: Mean follow-up was 10.1 years (5-13 years). Distinct improvements were detected in the mean HHS between the preoperative and last follow-up analysis (62.35[±8.49] vs. 84.70[±14.68], respectively, p < 0.001). The key orthopaedic complication rate was 18.2% (27/148). Seven (4.7%) cases experienced a CTHR failure at a mean of 3.4 (±1.2) years after revision MoM-THR, mostly attributed to recurrent dislocation. CONCLUSION: CTHR might yield an acceptable functional score and a low rate of the key orthopaedic complications.

Conversion from a failed proximal femoral nail anti-rotation to a cemented or uncemented total hip arthroplasty device: a retrospective review of 198 hips with previous intertrochanteric femur fractures.

BACKGROUND: At present, it is unclear which device (uncemented or cemented total hip arthroplasty [UTA or CTA, respectively]) is more suitable for the conversion of a failed proximal femoral nail anti-rotation (PFNA). The aim of this review was to assess the outcomes of failed PFNAs converted to a UTA or CTA device in elderly individuals with intertrochanteric femoral fractures (IFFs). METHODS: Two hundred fifty-eight elderly individuals (258 hips) with IFFs who underwent a conversion to a UTA or CTA device following failed PFNAs during 2007-2017 were retrospectively identified from the China Southern Medical Centre (CSMC) database. The primary endpoint was the Harris Hip Score (HHS); secondary endpoint was the key orthopaedic complication rate. RESULTS: The median follow-up was 65 months (60-69 months). Significant distinctions were observed (87.26 ± 16.62 for UTA vs. 89.32 ± 16.08 for CTA, p = 0.021; 86.61 ± 12.24 for symptomatic UTA vs. 88.68 ± 13.30 for symptomatic CTA, p = 0.026). A significant difference in the overall key orthopaedic complication rate was detected (40.8% [40/98] vs. 19.0% [19/100], p = 0.001). Apparent distinctions were detected in terms of the rate of revision, loosening, and periprosthetic fracture (11.2% for UTA vs 3.0% for CTA, p = 0.025; 13.2% for UTA vs 5.0% for CTA, p = 0.043; 10.2% for UTA vs 3.0% for CTA, p = 0.041, respectively). CONCLUSION: For elderly individuals with IFFs who suffered a failed PFNA, CTA devices may have a noteworthy advantage in regard to the revision rate and the rate of key orthopaedic complications compared with UTA devices, and CTA revision should be performed as soon as possible, regardless of whether these individuals have symptoms.

Importin-4 functions as a driving force in human primary gastric cancer.

OBJECTIVES: Importin-4 (IPO4) is responsible for transporting histones H3 and H4 into the nucleus for chromatin assembly. But, the role of IPO4 in cancer, especially in gastric cancer (GC), has not been fully understood. We aim to determine the expression and function of IPO4 in GC. MATERIALS AND METHODS: Bioinformatics analysis was used to study the association of IPO4 and GC using GEO data and the Kaplan-Meier plotter. The quantitative real-time polymerase chain reaction and Western blot analysis were used to determine the IPO4 level in GC cells and tissues. Small interfering RNAs (siRNAs) were used to knockdown endogenous IPO4 expression in GC cells. Cell counting kit-8 (CCK-8), colony formation and transwell assays were used to examine the effect of IPO4 on cell proliferation and migration. RESULTS: IPO4 mRNA is overexpressed in GC tissues using bioinformatics analysis of three groups' transcriptome data, and high level of IPO4 is negatively correlated with poor long-term survival using the Kaplan-Meier plotter analysis. Western blot analysis further shows that IPO4 protein levels are also overexpressed in GC tissues and a number of GC cell lines. Endogenous IPO4 level can be inhibited by specific siRNA effectively. Importantly, CCK-8, colony formation, and transwell assays demonstrate that IPO4 knockdown by siRNA impairs GC cell proliferation and migration. CONCLUSIONS: Our data suggest that IPO4 contributes to GC progression and poor prognosis, and may function as a driving force in GC progression.

Unravelling the Origins of Hydroboration Chemoselectivity Inversion Using an N,O-Chelated Ir(I) Complex: A Computational Study.

It has been widely reported that the transition-metal catalysts can invert the chemoselectivity of hydroboration of multifunctional substrates, but the fundamental reasons for this inversion have rarely been studied. In this work, mechanistic details and chemoselectivity of the hydroboration of various E-C ( E = CH, CH2, O, N, etc.) multiple bonds has been explored through density functional theory calculations, including reactions using free HBCy2 or captured HBCy2 by an N,O-chelated Ir(I) complex which includes a phosphoamidate group. The computational results demonstrate the formation of a 3-center π complex before the 4-center transition state when using free HBCy2. When the Ir(I) complex is added, the HBCy2 would be captured to form a metallaheterocyclic Shimoi-type intermediate in which a δ-[M]···H-B agostic interaction appears. Afterward, the E-C functional group intersects this hemilabile interaction rather than the P═O···B coordination bond, and the following hydride transfer is found to be rate-determining. The frontier molecular orbital analysis discloses that the olefins that have typical delocalized π electrons tend to give more effective overlap with the LUMO of free HBCy2, but the aromatic substituents could significantly reduce its reactivity due to the enhanced electron delocalization. The polarized carbonyl group facilitates σ coordination with the metal center, but the vinyl group favors interaction through π coordination. The superiority of σ coordination results in the priority of hydroboration of aldehyde over the olefins when using the captured HBCy2. Thus, it is the conversion of the more favored bonding groups by the transition metal that should be fundamentally responsible for the chemoselectivity inversion.

Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells.

We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133+ osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma.

Identification of mutations in patients with acquired pure red cell aplasia.

Idiopathic acquired pure red cell aplasia (PRCA) is a rare, autoimmune-related disease. This study aimed to describe the previously unidentified DNA alterations associated with PRCA. Here, next generation sequencing using a panel containing 295 critical genes was applied to detect potentially pathogenic mutations in four patients with PRCA. A total of 529 mutations were identified and further classified into three categories, namely, uncertain (n = 25), likely benign (n = 20) and benign (n = 484) mutations, based on the American College of Medical Genetics and Genomics (ACMG) 2015 guidelines and ClinVar database. The spatial proximity between two loci of the uncertain or benign mutations was evaluated using Hi-C datasets of KBM7 and K562 cell lines, respectively. Significant spatial proximity was observed in uncertain mutation pairs compared with benign mutation pairs. In addition, 17 variants were eventually identified after excluding those with mutant frequencies >0.001, including 7 newly identified variants. FANCF and LRP1B mutations existed twice in patients. FANCF and LRP1B mutations were likely to affect protein stability based on prediction analysis. Taken together, our data may provide valuable information about PRCA. FANCF and LRP1B mutations may be associated with acquired PRCA.

Conversion to total hip arthroplasty after failed proximal femoral nail antirotations or dynamic hip screw fixations for stable intertrochanteric femur fractures: a retrospective study with a minimum follow-up of 3 years.

BACKGROUND: Conversion to total hip arthroplasty (CTHA) is a relatively common procedure after a failed dynamic hip screw (DHS) or proximal femoral nail anti-rotation (PFNA) fixation of intertrochanteric fractures, but there have been far fewer reports specifically describing the long-term results of CTHA after failed treatments of stable intertrochanteric fractures with DHS or PFNA. The aim of the present study was to compare the clinical and radiological outcomes of CTHA after failed PFNA or DHS fixations of stable intertrochanteric fractures after a minimum follow-up of 3 years. METHODS: Between January 2005 and April 2014, we retrospectively reviewed 142 active elderly patients treated at our institution (a single institution study). A total of 72 patients (72 hips; 41 women, 31 men; mean age 76.9 years old; range 60-92 years old) who underwent conversion of a failed PFNA to a THA were compared with 70 patients (70 hips; 36 women, 34 men; mean age 75.0 years old; range 60-90 years old) who underwent CTHA after a failed DHS fixation. The mean follow-up periods were 48 (range 43-52) and 48 (range 44-52) months for the DHS and PFNA groups, respectively. Clinical and radiologic evaluations were performed on all patients. The primary outcome was the Harris Hip Score (HHS). The secondary outcomes were the complication rates. RESULTS: The Harris Hip Score (HHS) improved from 50.61 ± 3.23 preoperatively to 85.28 ± 4.45 at the last follow-up in the PFNA group and from 51.46 ± 3.90 to 84.50 ± 4.34 in the DHS group, with no significant differences noted between the groups at each follow-up (P > 0.05). However, the complication rate in the converted DHS patients was significantly higher (42.9%) than that in the converted PFNA patients (20.8%; P = 0.003). Thirty-seven PFFs (2.4%) occurred during a mean follow-up of 44.4 months. The incidence of periprosthetic fractures was found to be significantly higher (P = 0.021) for the DHS group (15.7%) than for the PFNA group (4.2%). CONCLUSIONS: CTHA after failed DHS fixations of stable intertrochanteric fractures might be associated with a significantly higher complication rate than CTHA after failed PFNA fixations. Therefore, PFNA patients with stable intertrochanteric fractures may be more suitable for CTHA.

Dyslipidaemia for patients with low-energy femoral neck fractures after the treatment of cancellous screws: a retrospective study with a 3-year minimum follow-up.

BACKGROUND: Avascular necrosis of the femoral head (AVNFH) occurs infrequently following femoral neck fracture. The association between AVNFH and dyslipidaemia remains controversial. Although major risk factors for AVNFH have been proposed, most of them remain under discussion. Our purpose herein was to evaluate the association between dyslipidaemia and AVNFH following low-energy femoral neck fractures treated with cancellous screws in elderly patients in our tertiary care centre. METHODS: Four hundred and seventy-two consecutive patients (472 hips) with low-energy femoral neck fractures were identified and treated with cancellous screws from July 2007 to April 2013. Patients underwent evaluations preoperatively and each subsequent postoperative visit (months 1, 6, 12, 18, 24, 30, and 36). Clinical and radiographic evaluations were documented at each visit. The risk factors of AVNFH were assessed by multivariate binary logistic analysis. RESULTS: Follow-up was available for 277 patients, which included 135 patients diagnosed with AVNFH (AVNFH group) and 142 patients without AVNFH (control group). The median follow-up for patients alive at the time of analysis was 40 months (range, 37 to 46 months). The mean total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo-B) values were considerably higher in the AVNFH group compared with those in the control group. The mean high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1(Apo-A1) values were significantly lower in the AVNFH group compared with those in the control group. A multivariate logistic backward regression model showed that HDL-C and LDL-C were the only variables associated with the development of postoperative AVNFH in patients with a femoral neck fracture (Odds ratio[OR] 33.09, 95% Confidence Interval[CI]: 2.65-19.42, p < 0.001 and OR 45.94, 95% CI: 0.47-27.75, p < 0.001, respectively). CONCLUSION: Our results suggest that both low HDL-C and high LDL-C have a tendency to result in the occurrence of AVNFH in elderly patients with low-energy femoral neck fractures treated with cancellous screws.

miRNA-532-5p functions as an oncogenic microRNA in human gastric cancer by directly targeting RUNX3.

Accumulating data reveal that microRNAs are involved in gastric carcinogenesis. To date, no information was reported about the function and regulatory mechanism of miR-532-5p in human gastric cancer (GC). Thus, our study aims to determine the role and regulation of miR-532-5p in GC. Here, we found that transient and stable overexpression of miR-532-5p dramatically increased the potential of colony formation and migration of GC cells, decreased the percentage of cells in G1 phase and cell apoptosis in vitro, and increased the weight of mice lungs and number of lung xenografts in vivo. Gain-of-function, loss-of-function and luciferase activity assays demonstrated that miR-532-5p negatively regulated the expression of RUNX3 and its targets directly. We also found that miR-532-5p level was negatively correlated with RUNX3 gene expression in various GC cell lines. Our results indicate that miR-532-5p functions as an oncogenic miRNA by promoting cell growth, migration and invasion in human GC cells.

The visible and hidden blood loss of Asia proximal femoral nail anti-rotation and dynamic hip screw in the treatment of intertrochanteric fractures of elderly high- risk patients: a retrospective comparative study with a minimum 3 years of follow-up.

BACKGROUND: The purpose of this study was to evaluate whether PFNA-II (Asia proximal femoral nail anti-rotation) and DHS (dynamic hip screw) carry substantial post-operative hidden blood loss and to compare PFNA-II with DHS in terms of post-operative hidden blood loss in elderly high-risk patients with intertrochanteric femur fractures(IFFs). METHODS: The clinical data from Jan 2005 to Apr 2015 of 186 patients with PFNA-II and 177 patients with DHS were analyzed retrospectively. Indexes including pre- and post-operative blood routine, intra- and post-operative blood loss and blood transfusion situation were analyzed. The situation of perioperative blood loss (visible and hidden) was assessed. RESULTS: The intra-operative blood loss in the PFNA-II group was 34.7 ± 2.5 ml, the post-operative visible blood loss was 54.7 ± 2.5 ml, and the hidden blood loss was 277.2 ± 7.6 ml. In the DHS group, the intra-operative blood loss was 102.0 ± 7.0 ml, the post-operative visible blood loss was 78.8 ± 4.7 ml, and the hidden blood loss was 139.3 ± 9.6 ml. The intra-operative blood loss and the post-operative visible blood loss in the PFNA-II group were significantly less than in the DHS group (p < 0.01). However, the post-operative hidden blood loss and the total blood loss in the PFNA-II group were larger than in the DHS group (p < 0.01). CONCLUSION: This study demonstrated that with PFNA-II and DHS, much post-operative hidden blood loss exists in the treatment of intertrochanteric fractures in elderly high-risk patients and DHS is more favourable than PFNA-II in terms of post-operative hidden blood loss.

Proximal femoral nails anti-rotation versus dynamic hip screws for treatment of stable intertrochanteric femur fractures: an outcome analyses with a minimum 4 years of follow-up.

BACKGROUND: Dynamic hip screws (DHSs) and proximal femoral nails anti-rotation (PFNAs) are well-documented implants for stable intertrochanteric femur fractures(IFFs); however, there is no consensus regarding which type of implant is the better option for stable IFFs. This study aimed to compare DHSs with PFNAs in the management of stable intertrochanteric fractures. METHODS: A retrospective study was performed in our institution. Between June, 2005 and November, 2015, 267 patients (267 hips) with stable IFFs (AO/OTA Type 3.1A1) were treated with a DHS or a PFNA. Inclusion and exclusion criteria were designed to focus on isolated stable IFFs in ambulatory patients. Follow-up was undertaken at 1, 3, 12, 15, 18, 21, 24, 36, 48 postoperative months, and at final follow-up. Radiograph outcomes were obtained at all visits. The primary outcome measure was re-operation rate. The secondary outcome was patient function, evaluated using Harris hip score (HHS). Tertiary outcomes included: intra- and post-operative orthopaedic complications. RESULTS: Two hundred twenty two patients (110 in the PFNA group and 112 in the DHS group) were evaluated with a mean follow-up period of 53 months (range, 48-60 months). There was an increased risk of reoperation after DHS in one-year follow-up: 0 % and 5.4 % for PFNA and DHS, respectively (P = 0.029). The difference persisted with time: 6.4 % and 13.4 % at last follow-up (P < 0.05). There are statistical differences in postoperative HHS at 12, 15, 18, 21, 24, 36, 48 months postoperatively and at final follow-up. No statistical differences in medical complications was observed between the two groups. The orthopaedic complications were more in the DHS group (n = 42) compared with the PFNA group (n = 18) (P <0.05). CONCLUSION: Compared with PFNA device, DHS device might not be the preferred implant for stable intertrochanteric femur fractures.