Screening of Fracture Risk and Osteoporosis Among Older Long-term Care Residents: A Prospective Study.

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.

Subjective Cognitive Complaints: Comparing the Relation between Self-Reported Versus Informant-Reported Subjective Cognitive Complaints and Cognitive Performances in Cognitively Unimpaired, Mild Cognitive Impairment and Populations with Dementia.

BACKGROUND: Subjective cognitive decline is proposed to be associated with future mild cognitive impairment and dementia. A better understanding of the roles of self-reported and informant-reported subjective cognitive complaints can provide a more delicate picture in dementia recognition and early diagnosis. OBJECTIVES: To evaluate the accuracy of self-reported and informant-reported subjective cognitive complaints and the relation of subjective cognitive complaints and neuropsychological function in cognitively unimpaired, mild cognitive impairment and populations with dementia. DESIGN: We conducted a cross-sectional survey and evaluate the relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups. SETTING: We recruited individuals diagnosed with cognitively unimpaired or mild cognitive impairment or dementia with Alzheimer's clinical syndrome from a memory clinic in a tertiary medical center in Taiwan. PARTICIPANTS: Participants, age greater than 50 years old, were enrolled in this study. Participants' informants were also enrolled for the cognitive questionnaire assessment. MEASUREMENTS: Participants' and informants' subjective cognitive complaint scores were collected based on a 12-item questionnaire. Neuropsychological assessments of global cognitive function, memory, language, executive function, visuospatial function and calculation were performed. The relations between subjective cognitive complaint scores and cognitive function in the different diagnostic groups were assessed by linear regression model. RESULTS: There were 1536 individuals and 1028 informants enrolled in this study. Self-reported subjective cognitive complaint scores from early and late mild cognitive impairment and dementia with Alzheimer's clinical syndrome participants showed no significant differences, but informants' subjective cognitive complaint scores showed a significant increase. Informant-reported subjective cognitive complaint scores related to neuropsychological tests in population with dementia. Neither self-reported nor informant-reported subjective cognitive complaint scores related to neuropsychological tests in cognitively unimpaired and mild cognitive impairment populations. CONCLUSIONS: Self-reported subjective cognitive complaints alone may not be sufficient to demonstrate clinical significance in different stages of cognitive impairment. Incorporating informant-reported subjective cognitive complaints, along with considering individual's anxiety and depressive status, are crucial in assessing cognitive statuses in clinical practice.

Assessment of the efficacy of intra-articular platelet rich plasma treatment in an ACLT experimental model by dynamic contrast enhancement MRI of knee subchondral bone marrow and MRI T2∗ measurement of articular cartilage.

OBJECTIVE: The vascularization of subchondral bone plays a significant role in the progression of knee osteoarthritis (OA). Treatment with platelet-rich plasma (PRP) has positive effects on cartilage lesions. However, PRP's efficacy for subchondral bone marrow lesions and the relationship of these lesions to cartilage are still undiscovered. Therefore, our aims were first to longitudinally investigate the change in subchondral flow by dynamic contrast enhanced MRI and degeneration of cartilage by MRI T2∗ in an anterior cruciate transection rodent (ACLT) model, and second to examine changes in parameters after intra-articular PRP injection. DESIGN: A 32-week investigation in 18 rats allocated to sham-control, ACLT with normal saline injection (ACLT + NS), and ACLT with PRP injection groups ended with histological evaluation. Another rat was used as a donor of allogenic PRP. RESULTS: Compared to the sham-control group, the ACLT + NS group had higher subchondral blood volume A (0.051, 95% confidence interval: 0.009, 0.092) and lower venous washout kel (-0.030: -0.055, -0.005) from week 4; lower permeability kep from week 18 (-0.954: -1.339, -0.569); higher cartilage T2∗ values (1.803: 1.504, 2.102) reflecting collagen loss beginning at week 10. For the PRP treatment group, subchondral bone marrow A and cartilage T2∗ decreased from week 10. Histological results confirmed and were correlated with the MRI findings. CONCLUSION: Subchondral hyper-perfusion plays a vital role in the pathogenesis of OA and was associated with cartilage degeneration. The efficacy of PRP can be observed from reduced perfusion and MRI T2∗ values.

ERBB2 gene expression silencing involved in ovarian cancer cell migration and invasion through mediating MAPK1/MAPK3 signaling pathway.

OBJECTIVE: To explore possible mechanism of ERBB2 gene expression silencing mediating mitogen-activated protein kinase 1/mitogen-activated protein kinase 3 (MAPK1/MAPK3) signaling pathway on proliferation, migration, and invasion of ovarian cancer cells. PATIENTS AND METHODS: A total of 240 cancer specimens were collected in patients with epithelial ovarian cancer intraoperatively in our hospital from January 2015 to January 2018. Expressions of ERBB2, MAPK1, and MAPK3 in tissues were detected by immunohistochemistry. Following the culture of ovarian cancer cell lines, target cell line with high expression of ERBB2 was screened by qRT-PCR. Cell grouping was performed with four groups after transfection, including Blank group, negative control (NC) group, ERBB2 shRNA group, and ERBB2 overexpression group (shorted as ERBB2 group). The expression levels of ERBB2, MAPK1, MAPK3, vascular endothelial growth factor (VEGF), metalloproteases-2 (MMP-2), and tissue inhibitor of metalloproteases-2 (TIMP-2) were detected by qRT-PCR in different transfection groups, followed by the detection of protein expressions with Western blot. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to test the proliferation activity of each group after transfection, while transwell assay and scratch test explored cell invasion and migration in each group, respectively. RESULTS: Immunohistochemistry showed that the positive rates of ERBB2, MAPK1, and MAPK3 in ovarian cancer tissues were significantly increased than those in adjacent normal epithelial tissues. In the cell experiment, ERBB2 gene was highly expressed in SKOV3 ovarian cancer cell line. There was no significant difference in each index between Blank group and NC group (p > 0.05). Compared with Blank group and NC group, the expression levels of ERBB2, MAPK1, MAPK3, VEGF, and MMP-2 in ERBB2 shRNA group decreased significantly, TIMP-2 increased markedly, and proliferation, invasion, and migration abilities of cells decreased markedly after transfection, showing statistically significant differences (All p < 0.05). By contrast, the expression levels of ERBB2, MAPK1, MAPK3, VEGF, and MMP-2 increased remarkably in ERBB2 group, while TIMP-2 decreased significantly, and cell proliferation, invasion, and migration ability increased evidently after transfection, with statistically significant differences (All p < 0.05). CONCLUSIONS: Silencing ERBB2 gene expression may inhibit the activation of MAPK1/MAPK3 signaling pathway and thus suppress the proliferation, invasion, and migration of ovarian cancer cells. Overexpression of ERBB2 gene can reverse those trends, which in turn support the role of ERBB2 gene expression silencing in molecular targeted therapy of ovarian cancer.

Hsa_circ_001193 regulates proliferation and apoptosis of nasopharyngeal carcinoma cells through targeting mir-496.

OBJECTIVE: To explore the effects of hsa_circ_001193 on the proliferation and apoptosis of nasopharyngeal carcinoma (NPC) cells. MATERIALS AND METHODS: The messenger ribonucleic acid (mRNA) expression level of hsa_circ_001193 in three NPC cell lines (CNE-1, SUNE-1, and HONE-1) and human normal nasopharyngeal epithelial cell line (NP69) was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). The expression of hsa_circ_001193 was silenced through transient transfection with small-interfering RNA (siRNA). Regulatory effects of hsa_circ_001193 knockdown on the proliferation and apoptosis of HONE-1 cells were determined using cell counting kit-8 (CCK-8) assay, colony formation assay, and flow cytometry. Potential miRNAs binding hsa_circ_001193 were predicted in the StarBase, which was further verified via Dual-Luciferase reporter assay and qRT-PCR. Moreover, the involvement of the predicted target miRNA in the proliferation of HONE-1 cells regulated by hsa_circ_001193 was determined by CCK-8 assay. RESULTS: Compared with that in human normal nasopharyngeal epithelial cell line (NP69), the expression of hsa_circ_001193 was significantly upregulated in NPC cell lines (p<0.05). The results of CCK-8 assay and colony formation assay showed that knockdown of hsa_circ_001193 could significantly suppress the cell proliferation ability and colony formation ability compared with control group (p<0.05). The results of flow cytometry revealed that the apoptosis rate in hsa_circ_001193 knockdown group was remarkably higher than that in control group (p<0.05). Besides, according to the analysis of StarBase database, there were binding sites between hsa_circ_001193 and miR-496. The Dual-Luciferase reporter assay manifested that miR-496 bound hsa_circ_001193 (p<0.05). CONCLUSIONS: Hsa_circ_001193 can serve as the miR-496 sponge, which regulates proliferation and apoptosis of NPC cells through up-regulating miR-496. Our findings provide a new therapeutic target for NPC.

Long noncoding RNA ROR promotes proliferation and invasion of colorectal cancer by inhibiting tumor suppressor gene NF2 through interacting with miR-223-3p.

OBJECTIVE: Colorectal cancer is one of the most common cancers in the world. LncRNA ROR, is a tumor oncogene associated with various human cancers. However, the role of ROR in colorectal cancer cells still remains unknown. The aim of this study was to measure the expression level of ROR and clarify its biological functions in colorectal cancer cells. MATERIALS AND METHODS: The expression level of ROR in colorectal cancer cells was detected using qRT-PCR. We performed CCK8 assay, colony formation assay, cell migration and invasion assays to evaluate the effects of ROR on cell proliferation, migration and invasion of colorectal cancer cells. Then, transfection of ROR, ROR inhibitor, miRNA-223-3p-mimics and miRNA-223-3p-inhibitor, qRT-PCR, and luciferase reporter assay were used to explore the molecular mechanisms. RESULTS: In the present study, Lnc-ROR was highly expressed in colorectal cancers compared with adjacent non-cancerous normal tissues. And the expression level of ROR was also increased in colorectal cancer cells (p < 0.05). CCK8 assay and invasion assay suggested that ROR can promote cell proliferation and invasion. The luciferase reporter assay showed ROR acted as sponge and directly competed with miRNA-223-3p, then decreasing the expression of tumor suppressor gene NF2. CONCLUSIONS: The findings of this study first revealed that ROR was upregulated in colorectal cancer cells and can promote cell proliferation and invasion by inhibiting tumor suppressor gene NF2 through interacting with miR-223-3p.

PTEN expression in U251 glioma cells enhances their sensitivity to ionizing radiation by suppressing DNA repair capacity.

OBJECTIVE: Mutations in phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor gene, lead to altered sensitivity to drugs and radiation in various types of cancer. Restoring PTEN expression in tumor cells can increase radiosensitivity by inhibiting the repair of DNA double-strand breaks (DSBs). Thus, determining the mechanism of action of this protein may lead to novel therapeutic strategies. MATERIALS AND METHODS: In this study, we transduced U251 cells with a lentiviral vector expressing PTEN to examine the mechanism of radiosensitization. Specifically, we examined the formation of radiation-induced DNA DSBs and apoptosis, as well as the expression of several proteins involved in repairing DSBs (p53, ataxia-telangiectasia mutated, DNA-dependent protein kinase C, Ku70-80). RESULTS: Our results showed that PTEN transduction sensitized U251 cells to X-rays, increasing the number of DSBs per cell and fraction of cells undergoing apoptosis. Additionally, the average size of γH2AX nuclear foci was increased following irradiation. These findings were accompanied by a PTEN-dependent irradiation-independent increase in p53 levels and decrease in phosphorylated Ku70/80 levels. CONCLUSIONS: Our results suggest that PTEN affects radiosensitivity by reducing DSB repair and by enhancing the p53 pathway, leading to increased apoptosis.

Serum fibroblast growth factor 23 and mineral metabolism in patients with euthyroid Graves' diseases: a case-control study.

This study investigated the alterations of mineral metabolism in patients with Graves' disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. INTRODUCTION: FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves' disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. METHODS: A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. RESULTS: Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. CONCLUSION: Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. TRIAL REGISTRATION: Registration number: NCT01660308 and NCT02620085.

Prognostic values of STAT3 and HIF-1α in esophageal squamous cell carcinoma.

OBJECTIVE: To investigate the expressions of signal transduction and activator of transcription 3 (STAT3) and hypoxia-inducible factor 1-alpha (HIF-1α) in esophageal squamous cell carcinoma (ESCC), and their potential roles in the pathology of ESCC. PATIENTS AND METHODS: Tumor tissues and clinical data of 202 ESCC patients treated in our hospital from January 2011 to June 2013 were collected. Expressions of STAT3 and HIF-1α in tumor tissues and normal esophageal tissues were detected by immunohistochemical S-P method. Correlation of STAT3 and HIF-1α with clinicopathological parameters and prognosis of ESCC were analyzed. RESULTS: STAT3 was positively expressed in 82/202 ESCC tissues, with a positive expression rate of 40.59%, and HIF-1α was positively expressed in 142/202 ESCC tissues, with a positive expression rate of 70.30%. Both STAT3 and HIF-1α were highly expressed in ESCC tissues than those normal esophageal tissues, showing statistically significant differences (p<0.05). The expression of STAT3 was positively correlated with that of HIF-1α in ESCC tissues (r=0.401, p<0.05). Overall survival (OS) and disease-free survival (DFS) of ESCC patients with positive STAT3 and HIF-1α expression were markedly worse than those with negative expression (p<0.05). STAT3 and HIF-1α were related to the infiltration depth (T stage) of ESCC (p<0.05). Univariate and multivariate analyses revealed that the expression of STAT3 was associated with OS and DFS (p<0.05) and was an independent prognostic factor for ESCC. CONCLUSIONS: High expressions of STAT3 and HIF-1α are closely related to ESCC. STAT3 is an independent prognostic risk factor for ESCC, and HIF-1α may be a poor prognostic survival factor for ESCC, both of which can be used as indicators to predict the prognosis of ESCC patients.

Real time scissor correction in TD-DFT.

We demonstrate how the scissor correction to the optical band gap, common in linear-response time-dependent density functional theory (TD-DFT), may be extended to the domain of real-time TD-DFT. This requires modifying both the eigenvalues and momentum matrix elements of the underlying basis set. It provides a simple and computationally economical approach for calculating accurate electron dynamics in solids. We demonstrate the importance of this correction for prototypical semiconductors, diamond and silicon, where the energy absorption in both the linear and non-linear regimes is examined. We also show that for a particular system, ZnSe, using the adiabatic local density approximation together with a scissor correction can be advantageous over other approximations, as the underlying quasi-particle band structure is more accurate.

LncSNHG14 promotes the development and progression of bladder cancer by targeting miRNA-150-5p.

OBJECTIVE: To elucidate whether lncSNHG14 could influence the proliferative potential and cell cycle progression of bladder cancer cells via binding to microRNA-150-5p (miRNA-150-5p). We aim to investigate the potential mechanism of miRNA-150-5p in the occurrence and progression of bladder cancer (BCa). PATIENTS AND METHODS: Expression levels of SNHG14 and miRNA-150-5p in BCa tissues and normal bladder tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Their expressions in BCa cell lines were detected as well. Regulatory effects of NHG14 and miRNA-150-5p on proliferative potential and cell cycle progression were evaluated by cell counting kit-8 (CCK-8) and flow cytometry, respectively. Through the dual-luciferase reporter gene assay, binding conditions between SNHG14 and miRNA-150-5p, as well as between miRNA-150-5p and synaptic vesicle-associated membrane protein 2 (VAMP2), were verified. Finally, rescue experiments were performed to clarify whether SNHG14 regulated behaviors of BCa cells by absorbing miRNA-150-5p to degrade VAMP2. RESULTS: SNHG14 was highly expressed in BCa tissues and cell lines. The overexpression of SNHG14 accelerated the proliferative potential and cell cycle progression of BCa cells. SNHG14 was confirmed to bind to miRNA-150-5p. MiRNA-150-5p remained a low expression in BCa tissues. Moreover, miRNA-150-5p overexpression suppressed proliferative potential and cell cycle progression of BCa cells, which could reverse the promotive role of SNHG14 on behaviors of BCa cells. Furthermore, VAMP2 was the target gene of miRNA-150-5p. VAMP2 overexpression reversed the biological function of miRNA-150-5p in inhibiting proliferative potential and cell cycle progression of T24 and UC9 cells. CONCLUSIONS: LncSNHG14 overexpression accelerates proliferative potential and cell cycle progression of BCa cells through absorbing miRNA-150-5p to degrade VAMP2 expression.

A Cross-Sectional Study of the Association between Arterial Stiffness and Sarcopenia in Chinese Community-Dwelling Elderly Using the Asian Working Group for Sarcopenia Criteria.

BACKGROUND: Several previous researches had found artery stiffness associated skeletal muscle mass, but not considering muscle strength and physical performance, which also were compositions of sarcopenia. This study aims to reveal the relationship of artery stiffness and sarcopenia using the Asian Working Group for Sarcopenia criteria. METHODS: Study was performed on 1002 Chinese community dwelling participants aged ≥65 years from November 2016 to March 2017. Body composition, muscle strength, physical performance, and brachial-ankle pulse wave velocity (baPWV) considering as artery stiffness index were measured. RESULTS: In multiple regression analysis, baPWV was associated with handgrip (ß=-0.13, P=0.04) and Relative skeletal muscle mass index (ASM/Ht2) (ß=-0.02, P<0.01), but not with 4-meter velocity (P=0.21). Multiple logistic regression analysis showed that 1-SD (3.50m/s) increased in baPWV was still associated with a 11% (CI, 4%-20%; P<0.01) higher odds of being sarcopenia. In the gender subgroup analysis, the relationship of baPWV and sarcopenia remain significant in men (OR, 1.23; 95% CI, 1.07-1.42, P<0.01), but not in women (P=0.07). CONCLUSIONS: High brachial-ankle pulse wave velocity is associated with sarcopenia in Chinese community-dwelling elderly, with gender differences.

Expressions of miR-525-3p and its target gene SEMG1 in the spermatozoa of patients with asthenozoospermia.

BACKGROUND: Semenogelin 1 (SEMG1) is an important secretory protein in spermatozoa involved in the formation of a gel matrix encasing ejaculated spermatozoa. Previous studies show that the SEMG1 gene is highly expressed in spermatozoa from patients with asthenozoospermia (AZS); however, the underlying molecular mechanisms are not yet clear. OBJECTIVES: To study the molecular mechanism of high expression of SEMG1 gene and its potential roles in AZS. MATERIALS AND METHODS: Western blot and real-time PCR were used to detect the expression levels of SEMG1 protein and mRNA in the ejaculated spermatozoa from normozoospermic males and AZS patients. Bioinformatics analysis was used to predict miRNAs targeting for SEMG1 3'-untranslated region detection of the expression levels of all the candidate miRNAs in ejaculatory spermatozoa in AZS patients or normozoospermic volunteers. Luciferase reporter assays were performed to confirm it can directly bind to SEMG1. Correlation of miR-525-3p and SEMG1 mRNA expression with clinical sperm parameters were also analyzed. Finally, we conducted a follow-up study of reproductive history about all the subjects. RESULTS: SEMG1 mRNA and protein level were significantly higher in AZS patients compared to that in normozoospermic volunteers (p < 0.001). Subsequently, microRNA-525-3p (miR-525-3p) which was predicted as a candidate regulator of SEMG1 was found lower expressed in ejaculatory spermatozoa in AZS patients (p = 0.0074). Luciferase experiment revealed that microRNA-525-3p could directly target SEMG1 3'-untranslated region and suppress its expression. Importantly, our retrospective follow-up study showed that both low miR-525-3p expression and high SEMG1 expression level was significantly associated with low progressive sperm motility, abnormal sperm morphology, and infertility. DISCUSSION AND CONCLUSION: The elevated expression of SEMG1 and reduced expression of miR-525-3p are associated with AZS and male infertility. Our study provides a potential therapeutic target for the treatment of male infertility or for male contraception.

CircMTO1 inhibits cell proliferation and invasion by regulating Wnt/ß-catenin signaling pathway in colorectal cancer.

OBJECTIVE: Circular RNAs (circRNAs) play critical roles in disease incidence. However, the roles of circRNAs in colorectal cancer (CRC) progression remain largely unknown. We explored the expression of circMTO1 in CRC and elucidated the underlying molecular mechanisms. PATIENTS AND METHODS: Quantitative Real-time-PCR (qRT-PCR) was used to explore circMTO1 expression in CRC tissues and cell lines. The effect of circMTO1 on the biological function of CRC cells was analyzed by Cell Counting Kit-8 (CCK-8) assay, Edu assay, colony formation assay, wound-healing assay and transwell invasion assay. Gene expression and signaling pathway were detected by qRT-PCR and Western blot. RESULTS: QRT-PCR showed that circMTO1 expression was significantly decreased in CRC tissues and cell lines compared with adjacent non-tumor tissues and human normal colon epithelial cell line (FHC), respectively. Patients with low circMTO1 expression were correlated with advanced TNM stage, lymph node metastasis, and poor overall survival. Function assays demonstrated that circMTO1 inhibition promoted CRC cells proliferation and invasion ability in vitro. In addition, we showed that circMTO1 inhibition could promote CRC progression via activating Wnt/ß-catenin signaling pathway. CONCLUSIONS: We showed that circMTO1 could act as a tumor suppressor affecting the growth and invasion of CRC cells via regulating Wnt/ß-catenin signaling pathway, providing a novel potential biomarker and therapeutic target for CRC treatment.

Staged distraction osteogenesis followed by arthrodesis using internal fixation as a form of surgical treatment for complex conditions of the ankle.

Aims: The aim of this study was to describe the technique of distraction osteogenesis followed by arthrodesis using internal fixation to manage complex conditions of the ankle, and to present the results of this technique. Patients and Methods: Between 2008 and 2014, distraction osteogenesis followed by arthrodesis using internal fixation was performed in 12 patients with complex conditions of the ankle due to trauma or infection. There were eight men and four women: their mean age was 35 years (23 to 51) at the time of surgery. Bone healing and functional recovery were evaluated according to the criteria described by Paley. Function was assessed using the ankle-hindfoot scale of the American Orthopedic Foot and Ankle Society (AOFAS). Results: A solid fusion of the ankle and eradication of infection was achieved in all patients. A mean lengthening of 6.1 cm (2.5 to 14) was achieved at a mean follow-up of 25.2 months (14 to 37). The mean external fixation index (EFI) was 42 days/cm (33.3 to 58). The function was judged to be excellent in six patients and good in six patients. Bone results were graded as excellent in ten patients and good in two patients. The mean AOFAS score was 37.3 (5 to 77) preoperatively and 75.3 (61 to 82) at the final follow-up. Minor complications, which were treated conservatively, included pain, pin-tract infection, loosening of wires, and midfoot stiffness. Major complications, which were treated surgically included grade V pin-tract infection with inflammation and osteolysis, poor consolidation of the regenerate bone, and soft-tissue invagination. The reoperations required to treat the major complications included the exchange of pins and wires, bone grafting and invagination split surgery. Conclusion: The technique of distraction osteogenesis followed by arthrodesis using internal fixation is an effective form of treatment for the management of complex conditions of the ankle. It offers a high rate of union, an opportunity to remove the frame early, and a reduced EFI without infection or wound dehiscence. Cite this article: Bone Joint J 2018;100-B:755-60.

Ketamine alleviates LPS induced lung injury by inhibiting HMGB1-RAGE level.

OBJECTIVE: Inflammatory cytokines secretion is an important reason to promote lung tissue inflammation in acute lung injury (ALI). High mobility group box 1 (HMGB-1) and its receptor for advanced glycation end products (RAGEs) play a role in ALI. Ketamine can significantly alleviate ALI, whereas its specific mechanism has not been fully elucidated. MATERIALS AND METHODS: A total of 60 male Wistar rats were equally randomly divided into three groups, including ALI group which was established by 10 mg/kg LPS femoral vein injection, ketamine group which was constructed by 50 mg/kg ketamine femoral vein injection based on ALI model, and control group. Blood gas analysis was applied to detect arterial blood oxygen partial pressure (PaO2) and pH. Lung tissue wet/dry weight ratio (W/D), myeloperoxidase (MPO) and superoxide dismutase (SOD) activity were detected. Real-time PCR and ELISA were used to test HMGB-1 expression in lung tissue and serum. RAGE and NF-κB changes were determined by Real-time PCR and Western blot. RESULTS: Compared with control, ALI group presented decreased PaO2 and PH, elevated W/D, enhanced MPO activity, declined SOD activity, upregulated HMGB-1 mRNA, increased HMGB-1 secretion, and increased RAGE and NF-κB mRNA and protein (p < 0.05). Ketamine treatment significantly elevated PaO2 and PH, reduced W/D, declined MPO activity, enhanced SOD activity, inhibited HMGB-1 mRNA and secretion, and downregulated RAGE and NF-κB mRNA and protein (p < 0.05). CONCLUSIONS: Ketamine can alleviate LPS induced lung injury through inhibiting HMGB1-RAGE level. It could be treated as a new choice for ALI treatment.