Prognostic significance of circulating tumor cell measurement in the peripheral blood of patients with nasopharyngeal carcinoma.

OBJECTIVE: Nasopharyngeal Carcinoma (NPC) is lethal cancer. Typically, relapse and metastasis are the outcomes of most patients. Against this backdrop, this study aimed to investigate the correlation between Circulating Tumor Cell (CTC) profiles and clinicopathological features in patients with NPC. PATIENTS AND METHODS: A total of 119 blood samples from 79 patients were collected from patients with NPC during treatment. CanPatrolTM CTC enrichment and RNA In Situ Hybridization (RNA-ISH) were used to characterize CTCs, including epithelial, Mesenchymal (MCTCs), and epithelial/mesenchymal mixed types according to their surface markers. RESULTS: The number of CTCs and MCTCs in the pre-treatment group was significantly higher than that in the post-treatment group (p < 0.05). The total number of CTCs and MCTCs cell numbers was significant correlation with Tumor-Node-Metastasis (TNM) staging (p < 0.05), Progression-Free Survival (PFS), and Overall Survival (OS). The PFS of patients with > 7 CTCs or > 5 MCTCs per 5 mL blood was significantly shorter PFS than those patients with ≤ 7 CTCs or ≤ 5 MCTCs (p < 0.05). Patients treated with targeted therapy combined with chemoradiotherapy had poorer PFS and OS rates than those treated with chemoradiotherapy (p < 0.05). The Kaplan-Meier survival analysis also demonstrated that patients with changes in CTC > 4 were strongly associated with PFS and OS rates (p < 0.05). CONCLUSION: CTC and MCTC number detection in patients with NPC is a useful biomarker for predicting patient progress. Patients with more than 7 CTCs or 5 MCTCs in 5 mL of blood had shorter PFS and OS rates. CTC and MCTC count changes were also significantly associated with the patient's therapy.

Prognostic significance of circulating tumor cell measurement in the peripheral blood of patients with nasopharyngeal carcinoma

Abstract Objective: Nasopharyngeal Carcinoma (NPC) is lethal cancer. Typically, relapse and metastasis are the outcomes of most patients. Against this backdrop, this study aimed to investigate the correlation between Circulating Tumor Cell (CTC) profiles and clinicopathological features in patients with NPC. Patients and methods: A total of 119 blood samples from 79 patients were collected from patients with NPC during treatment. CanPatrol™ CTC enrichment and RNA In Situ Hybridization (RNA-ISH) were used to characterize CTCs, including epithelial, Mesenchymal (MCTCs), and epithelial/mesenchymal mixed types according to their surface markers. Results: The number of CTCs and MCTCs in the pre-treatment group was significantly higher than that in the post-treatment group (p < 0.05). The total number of CTCs and MCTCs cell numbers was significant correlation with Tumor-Node-Metastasis (TNM) staging (p < 0.05), Progression-Free Survival (PFS), and Overall Survival (OS). The PFS of patients with > 7 CTCs or > 5 MCTCs per 5 mL blood was significantly shorter PFS than those patients with ≤ 7 CTCs or ≤ 5 MCTCs (p < 0.05). Patients treated with targeted therapy combined with chemoradiother-apy had poorer PFS and OS rates than those treated with chemoradiotherapy (p < 0.05). The Kaplan-Meier survival analysis also demonstrated that patients with changes in CTC > 4 were strongly associated with PFS and OS rates (p < 0.05). Conclusion: CTC and MCTC number detection in patients with NPC is a useful biomarker for predicting patient progress. Patients with more than 7 CTCs or 5 MCTCs in 5 mL of blood had shorter PFS and OS rates. CTC and MCTC count changes were also significantly associated with the patient's therapy.

[Expression, purification, and characterization of cell-permeable fusion antioxidant enzyme sensitive to matrix metalloproteinases-2/9].

Antioxidant enzymes fused with cell-penetrating peptides could enter cells and protect cells from irradiation damage. However, the unselective transmembrane ability of cell-penetrating peptide may also bring antioxidant enzymes into tumor cells, thus protecting tumor cells and consequently reducing the efficacy of radiotherapy. There are active matrix metalloproteinase (MMP)-2 or MMP-9 in most tumor cellular microenvironments. Therefore, a fusion protein containing an MMP-2/9 cleavable substrate peptide X, a cell-penetrating peptide R9, a glutathione S-transferase (GST), and a human Cu, Zn superoxide dismutase (SOD1), was designed and named GST-SOD1-X-R9. In the tumor microenvironment, GST-SOD1-X-R9 would lose its cell-penetrating peptide and could not enter tumor cells due to the cleavage of substrate X by active MMP-2/9, thereby achieving selected entering normal cells. The complete nucleotide sequence of SOD1-X-R9 was synthesized and inserted into the prokaryotic expression vector pGEX-4T-1. The pGEX4T-1-SOD1-X-R9 recombinant plasmid was obtained, and soluble expression of the fusion protein was achieved. GST-SOD1-X-R9 was purified by ammonium sulfate precipitation and GST affinity chromatography. The molecular weight of the fusion protein was approximately 47 kDa, consistent with the theoretical value. The SOD and GST activities were 2 954 U/mg and 328 U/mg, respectively. Stability test suggested that almost no change in either SOD activity or GST activity of GST-SOD1-X-R9 was observed under physiological conditions. The fusion protein could be partially digested by collagenase Ⅳ in solution. Subsequently, the effect of MMP-2/9 activity on transmembrane ability of the fusion protein was tested using 2D and 3D cultured HepG2 cells. Little extracellular MMP-2 activity of HepG2 cells was observed under 2D culture condition. While under the 3D culture model, the size and the MMP-2 activity of the HepG2 tumor spheroid increased daily. GST-SOD1-R9 proteins showed the same transmembrane efficiency in 2D cultured HepG2 cells, but the transmembrane efficiency of GST-SOD1-X-R9 in 3D cultured HepG2 spheres was reduced remarkably. This study provided a basis for further investigating the selectively protective effect of GST-SOD1-X-R9 against oxidative damage in normal cells.

Circ_0006873 Sponges miR-142-5p to Inhibit Osteoblastic Differentiation of hBMSCs via Regulating PTEN/Akt Signaling Pathway.

OBJECTIVE: Osteoporosis is likely becoming a new disease challenge with increasing aging population. Circ_0006873 dysregulation may serve as an event linked to osteoporosis. Thus, this study sought to evaluate the function and mechanism of circ_0006873 on osteoporosis. METHODS: Clinical serum samples collected from 30 osteoporosis patients were utilized to obtain circ_0006873 and miR-142-5p expression data. The link between circ_0006873, miR-142-5p, and phosphatase and tensin homolog (PTEN) was demonstrated via online tools (starBase, circinteractome), RNA Immunoprecipitation (RIP) and dual-Luciferase reporter assays. After knockdown or overexpression, cell counting kit-8 (CCK-8) assay measured cell viability. Alizarin red S (ARS) staining as well Alkaline phosphatase (ALP) staining detected osteoblastic differentiation levels. Quantitative real-time PCR (qRT-PCR) and western blot analyzed expression of RNAs and proteins after transfection or during osteoblastic differentiation. RESULTS: circ_0006873 was upregulated in osteoporosis patients and decreased during osteoblastic differentiation. Following experiments revealed that cell viability, proliferation-related factors, osteogenic marker genes (ALP, Runx2, Bglap) and osteoblastic differentiation degree were promoted after circ_0006873 knockdown but inhibited after overexpression. Circ_0006873 sponged miR-142-5p, which was downregulated in osteoporosis patients and became higher during osteoblastic differentiation. Rescue assay indicated miR-142-5p mimic could reverse the effects of circ_0006873 overexpression on cell viability and osteogenic markers, and also could activate Akt pathway. Furthermore, circ_0006873 can negatively target miR-142-5p via regulating PTEN to inhibit osteoblastic differentiation. CONCLUSION: Circ_0006873 sponges miR-142-5p thereby enhances PTEN expression to suppress osteoblastic differentiation via regulation of Akt signaling pathway, thus, may provide a treatment approach for osteoporosis.

Dietary inflammatory index and cardiorenal function in women with diabetes and prediabetes.

BACKGROUND AND AIMS: Previous studies had shed a new light on the importance of multiple inflammatory mechanisms in the pathogenesis of arterial stiffness. The dietary inflammatory index (DII®) is a new tool for estimating the overall inflammatory potential of the diet. The aim of this study is to assess the association of the inflammatory potential of diet with peripheral arterial stiffness and renal function in women with diabetes and prediabetes. METHODS AND RESULTS: This is an observational cross-sectional study. A total of 2644 females aged 45-75 years were included for the study. Dietary intake in the past 12 months was assessed by a validated China National Nutrition and Health Survey 2002 (CNHS2002) food-frequency questionnaire. Energy-adjusted DII (E-DII) scores were calculated from daily dietary information. In a multivariable linear regression analysis adjusted for potential confounders, E-DII was positively associated with brachial ankle pulse wave velocity (baPWV) in participants with diabetes (ß = 12.820; 95% CI = 2.565, 23.076; P = 0.014) and prediabetes (ß = 29.025; 95% CI = 1.110, 56.940; P = 0.042), but not in females with normal glucose homeostasis. In addition, per unit increase of E-DII was significantly associated with lower eGFR (ß = -1.363; 95% CI = -2.335, -0.392; P = 0.006) in patients with diabetes. CONCLUSION: We identified a direct association between E-DII and arterial stiffness, decreasedeGFR in middle-aged and elderly women with diabetes or prediabetes. Future studies are needed to verify and clarify the role of E-DII as an intervention target for cardiorenal complications of chronic hyperglycemia.

Approach to parathyroid carcinoma (PC): seven cases and a review of the literature.

To summarize the experience in the diagnosis and treatment of seven cases with parathyroid carcinoma (PC). We collect seven parathyroid carcinoma cases of Fujian Provincial Hospital from January 2009 to December 2018. Reviewing and concluding the seven collected cases referring to relative reference domestic and abroad. All of the seven cases have hypercalcemia and a high level of parathyroid hormone (PTH) that were over two folds of the normal upper limit, even over 36 folds. The PC in seven cases were confirmed by routine histopathology and immunohistochemistry. All the cases went through surgery. Parathyroid carcinoma shows no specificity in clinical feature, it usually implicates in skeleton and urinary system. Routine serum calcium examination, serum PTH determination are helpful diagnosing PC before operation. The appropriate surgical procedure is parathyroidectomy combined with ipsilateral total thyroidectomy and neck dissection in levels of II, III, IV, V and VI.

Association between Depression and Renal Hyperfiltration in a General Chinese Population.

BACKGROUND: Depression is prevalent in patients with all stages of CKD and is associated with adverse outcome. Abnormally elevated GFR, or hyperfiltration, may play a crucial role in the initiation and progression of CKD. However, the association between depression and hyperfiltration is not known. The aim of this study is to investigate the relationship between depression and hyperfiltration. METHODS: This was an observational cross-sectional study. A total of 3,716 volunteers (1,303 males and 2,413 females) aged 40-75 years without CKD from a community in China were included for the study. Depressive symptoms and the presence of a minor or major depressive episode were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and Diagnostic and Statistical Manual of Mental Disorders (4th edition)-based structured interview, respectively. RESULTS: The mean age of the participants in the present study was 53.8 ± 9.0 years. 115 participants had clinically relevant depression, and 122 participants had a minor or major depressive episode. In a multivariable logistic regression analysis adjusted for potential confounders, the association between clinically relevant depression and renal hyperfiltration remained significant in men but not in women. As compared with men without depression (PHQ <5) or depressive episodes, those with clinically relevant depression (PHQ ≥10) had a significantly higher risk of renal hyperfiltration. The fully adjusted OR (95% CI) was 4.81 (1.62-14.30, p = 0.005), those with a major depressive episode had a higher risk of renal hyperfiltration (OR 7.45; 95% CI 2.04-27.21, p = 0.002). CONCLUSION: Depressive symptoms and major depressive episodes are associated with renal hyperfiltration in middle-aged and elderly Chinese men without CKD. Future studies are needed to verify and clarify the role of depression in the development of abnormally high eGFR and CKD.

Is waist circumference a negative predictor of calcaneal bone mineral density in adult Chinese men with normal weight?

BACKGROUND: Our study aimed to evaluate the association between waist circumference (WC) and calcaneal bone mineral density (BMD) in adult Chinese men with normal weight. METHODS: This was a cross-sectional study. A total of 4,663 male participants aged 40 years or older residing in Ningde and Wuyishan, two cities locating in Fujian province of China, were randomly recruited between 2011 and 2012. Each participant should complete a standard questionnaire, undergo anthropometric and calcaneus quantitative ultrasound (QUS) measurements and have blood sample taken. Anthropometric, biochemical and calcaneal QUS parameters of 1,583 male participants with BMI ranging from 18.5 to 22.9 were included in the analysis. WC was divided into quartiles (Q1-Q4: <71, 71-75, 75-78, >78 cm). The relationship between WC (quartiles) and BMD was analyzed by multiple linear regression models. RESULTS: Mean age of the whole population was 54.6±9.8 years. Anthropometric and biochemical parameters were almost normal. Multiple linear regression analysis showed that BMD was negatively associated with increasing WC quartiles except for Q2 after adjusting for age and BMI, and this relationship remained negative except for Q2 when further adjustment was made for other covariates. Multiple logistic regression model also showed that the risks of osteopenia and osteoporosis increased across WC quartiles. CONCLUSIONS: The present study indicated that WC was a negative predictor of calcaneal BMD in adult Chinese men with normal weight. It suggests that, even for the normal-weight Asian males, monitoring accrual of abdominal adipose is still helpful for the purpose of preventing bone loss.

RAGE Gly82Ser polymorphism in patients with type 2 diabetes with comorbid Depression.

OBJECTIVE: To examine receptors for advanced glycation end-products Gly82Ser polymorphism in patients of type 2 diabetes with comorbid depression. METHODS: The case-control study was conducted at Fujian Provincial Hospital, Fuzhou, China, between December 2011 and December 2012, and comprised unrelated Chinese Han patients of type 2 diabetes, and diabetics with diagnosed clinical depression. Gly82Ser polymorphism polymorphism was determined using polymerase chain reaction amplification-high resolution melting curve protocol. Serum levels of endogenous secretory receptor for advanced glycation end products were measured using enzyme-linked immunosorbent assay. SPSS 16 was used for data analysis. RESULTS: Of the 114 subjects, 72(63.15%) were clinically depressed. Lower levels of endogenous secretory receptor were found in the depression group compared with the other group (p=0.049). No difference in genotypes or allele frequencies existed between the two groups (p>0.05). Gly82Ser carriers had significantly higher Hamilton Rating Scale scores (p<0.001) and lower serum endogenous secretory receptor (p=0.012) among the depressed diabetics. There were also significant differences in body mass index (p=0.005), abdominal circumference (p=0.038), carotid intima-media thickness (p=0.037) and high-sensitivity C-reactive protein (p=0.005) concentration between the different genotypes.. CONCLUSIONS: Receptors for advanced glycation end-products-ligands system may be involved in type 2 diabetes with comorbid depression at the genetic level.

EXPOSURE TO FAMINE IN EARLY LIFE AND THE RISK OF OSTEOPOROSIS IN ADULTHOOD: A PROSPECTIVE STUDY.

Objective: To assess the association between famine exposure in early life and osteoporosis in adulthood. Methods: A total of 2,292 participants born between 1955 and 1965 in Fujian Province were selected; after 3 years, 1,378 participants attended a follow-up research visit. Calcaneus bone mineral density and bone quality were measured by quantitative ultrasound. The T-score was used to assess bone mineral density, and the parameters quantitative ultrasound index (QUI), speed of sound (SOS), and broadband ultrasonic attenuation (BUA) were used to assess bone quality. A T-score threshold of -1.8 was defined as osteoporosis, and a possible vertebral fracture was considered as a prospective height loss of 0.8 inches or more. Results: Compared with the nonexposed cohort, risks of osteoporosis for fetal-, early childhood, and mid-childhood famine-exposed cohorts in postmenopausal women were adjusted odds ratio (OR), 3.741 (95% confidence interval [CI], 1.233, 11.44) versus OR 2.894 (95% CI, 0.997, 8.571) versus OR 4.699 (95% CI, 1.622, 13.612) by logistic regression but not significant in men. Moreover, the fetal-exposed cohort had a weak negative relation with QUI (ß, -5.07 [-10.226, 0.127]) and BUA (ß, -4.321 [-0.88, 0.238]). The early- and mid-childhood-exposed cohorts had significantly lower QUI (ß, -7.085 [-11.799, -2.372] versus ß, -10.845 [-15.68, -6.01]) and BUA (ß, -6.381 [-10.515, -2.246] versus ß, -8.573 [-12.815, -4.331]) than the nonexposed cohort by linear regression. None of the famine-exposed cohorts had a significant relationship with SOS. Conclusion: Famine exposure during early life is associated with higher risk of osteoporosis in adulthood, which is most obvious in postmenopausal women. Furthermore, famine exposure in early life has adverse effects on bone quality. Abbreviations: BMD = bone mineral density; BUA = broadband ultrasonic attenuation; CI = confidence interval; OR = odds ratio; QUI = quantitative ultrasound index; QUS = quantitative ultrasound; SOS = speed of sound.

Early life exposure to famine and reproductive aging among Chinese women.

OBJECTIVE: To assess the effect of early life exposure to famine, as endured during 1959 to 1961 in China, on reproductive aging in adult women. METHODS: Between 2011 and 2012, 2,868 women born around the Chinese famine period (1956-1964) were enrolled in this study from three communities in China. Age at natural menopause was obtained retrospectively from a structured questionnaire. The associations of early life famine exposure with reproductive aging during adulthood were estimated, with adjustment of socioeconomic status, lifestyle factors, and body mass index. RESULTS: Women exposed to prenatal famine had a higher risk of early menopause (ie, natural menopause <45 years, odds ratio: 1.59, 95% confidence interval [CI]: 1.07, 2.36), and a nonsignificant trend of higher risk of premature ovarian failure (ie, natural menopause <40 y, odds ratio: 1.94, 95% CI: 0.93, 4.00), compared to unexposed women. Exposure to famine during childhood was not significantly associated with reproductive aging. In a secondary analysis focusing on the fetal exposure, prenatal famine exposure was associated with a higher risk of premature ovarian failure (odds ratio: 2.07, 95% CI: 1.08, 3.87), and a nonsignificant trend of higher risk of early menopause (odds ratio: 1.37, 95% CI: 0.98, 1.91), compared to those unexposed to prenatal famine. CONCLUSIONS: Our study showed that fetal exposure to famine was associated with an increased risk of early menopause. Such findings provided evidence in favor of the thrifty phenotype theory in reproductive aging and helped better understand the etiology of early menopause.

Identification of autoimmune type 1 diabetes and multiple organ-specific autoantibodies in adult-onset non-insulin-requiring diabetes in China: A population-based multicentre nationwide survey.

AIMS: To investigate the prevalence of adult-onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ-specific autoantibodies in people with phenotype of type 2 diabetes (T2D). MATERIALS AND METHODS: We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform-8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21-hydroxylase (21-OH) autoantibodies in randomly selected participants with ADM and in age-matched, sex-matched and non-ADM controls with T2D plus controls with NGT. RESULTS: Post-normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3-6.8) in initially non-insulin-requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8-21.8), tTG autoantibodies 2.1% (95% CI 0.0-4.2), and 21-OH autoantibodies 1.8% (95% CI -0.2 to 3.8). Those participants with ADM who were GAD autoantibody-positive had high risk of TPO autoantibody positivity (odds ratio [OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001). CONCLUSIONS: A proportion of people with phenotype of T2D in China have ADM, with diabetes-associated autoantibodies, and may be at risk of developing other organ-specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations.

The improved oval forceps suture-guiding method for minimally invasive Achilles tendon repair.

OBJECTIVE: To discuss the effect and advantage of the improved oval forceps suture-guiding method combined with anchor nail in the treatment of acute Achilles tendon rupture. METHODS: A retrospective research was performed on 35 cases of acute Achilles tendon rupture treated with the improved oval forceps suture-guiding method from January 2013 to October 2016. Instead of the Achillon device, we perform the Achillon technique with the use of simple oval forceps, combined with absorbable anchor nail, percutaneously to repair the acute Achilles tendon rupture. RESULTS: All patients were followed up for at least 12 months (range, 12-19 months), and all the patients underwent successful repair of their acute Achilles tendon rupture using the improved oval forceps suture-guiding method without any major intra- or postoperative complications. All the patients returned to work with pre-injury levels of activity at a mean of 12.51 ±â€¯0.76 weeks. Mean AOFAS ankle-hindfoot scores improved from 63.95 (range, 51-78) preoperatively to 98.59 (range, 91-100) at last follow-up. This was statistically significant difference (P < 0.001). Mean Achilles Tendon Total Rupture Score (ATRS) at final follow-up was 94.87 (range, 90-100). CONCLUSION: The improved oval forceps suture-guiding method could make the advantage of minimally invasive repair with less complications, reduced surgical time and similar functional outcomes compared with the traditional open surgery. In addition, our new technique could save the cost of surgery with the compare of the Achillon device. At the same time for the cases which the remote broken tendon ends were within 2 cm from the calcaneal nodules, because of the less tendon tissue was left in the remote side, traditional percutaneous methods are incapable to ensure the reconstruction strength. By using the anchor nail, the improved technique has better repair capacity and expands the operation indication of oval forceps method.

Self-reported sleep duration and daytime napping are associated with renal hyperfiltration in general population.

STUDY OBJECTIVES: Renal hyperfiltration (RHF) has emerged as a novel marker of early renal damage in various conditions such as diabetes and metabolic syndrome. Aberrant sleep duration and excessive daytime napping may affect the development of chronic kidney disease (CKD). In this study, the association between sleep duration, daytime napping, and renal hyperfiltration was assessed. SETTING: This study was conducted in three communities in China. PARTICIPANTS: A total of 16,119 community volunteers (5735 males and 10,384 females) aged 40-65 years without CKD were included for the study. METHODS AND RESULTS: Participants with short sleep duration (<6 h/day) or long sleep duration (≥10 h/day) were at a significantly increased risk of renal hyperfiltration. The fully adjusted ORs (95% CI) were 2.112 (1.107, 4.031) and 2.071 (1.504, 2.853), respectively (P < 0.05). In addition, those who took naps longer than 1.5 h per day had a higher risk of renal hyperfiltration compared with those without napping (OR 1.400, 95% CI 1.018-1.924). Further joint analysis indicated that participants with long sleep duration (≥10 h/day) had a more than twofold increased risk of RHF regardless of nap status compared with those who slept 8-9 h per day without daytime napping. The association between sleep duration or daytime napping and RHF could not be explained by the influence of sleep quality. Additional subgroup analysis showed long sleep duration (≥9 h/day) and long daytime napping (≥1.5 h) were associated with an increased risk of RHF among individuals with good sleep quality. CONCLUSION: Sleep duration less than 6 h/day or more than 10 h/day and long daytime napping tend to be associated with an increased risk of renal hyperfiltration in middle-aged general population, and this relationship was independent of diabetes, hypertension, obesity, or poor sleep quality.

Comparison of three fixation methods in treatment of tibial fracture in adolescents.

BACKGROUND: Tibial fractures are the most common musculoskeletal injury in adolescents. The optimal management of tibial fractures in adolescents is controversial. In this study, we compared the outcomes including complications of three fixation methods in tibial fractures of adolescents and explored the factors associated with the complications. METHODS: A retrospective cohort study about 83 diaphyseal tibial fractures in 79 children and adolescents, who were treated with plate fixation (PF), elastic stable intramedullary nail fixation (ESINF), or external fixation (EF), was conducted. After adjustment for age, weight, energy of the injury, polytrauma, fracture level and pattern, and extent of comminution, treatment outcomes were compared in accordance with the length of the hospital stay, time to union, and complication rates including many factors. RESULTS: The mean age of the patients was 13.4 years, and their mean weight was 44.2 kg. There was a loss of reduction in two of 33 fractures treated with ESINF and four of 13 treated with EF (P < 0.001). At the time of final follow-up, three patients (two treated with EF and one treated with ESINF) had ≥2.0 cm of shortening. Four of the 32 patients (33 fractures) treated with ESINF underwent a reoperation (two due to loss of reduction and one each because of delayed union and nonunion). Six patients treated with EF required a reoperation (four due to loss of reduction, one for malunion and one for replacement of a pin complicated by infection). Two fracture treated with PF required refixation attributing to nonunion and malunion. A multivariate analysis with adjustment for baseline differences showed that EF was associated with a 7.56-times (95% confidence interval 3.74-29.87) greater risk of loss of reduction and/or malunion than ESINF. CONCLUSIONS: All three treatments had satisfactory outcomes, and EF was correlated with the highest rate of complications in our series of adolescents treated with a tibial fracture. However, we cannot currently recommend that all fractures might be suitable for ESINF. The choice of fixation will remain influenced by surgeon preference in term of expertise and experience, patient and fracture characteristics, and patients and family preferences.

Association Between Bone Mineral Density and Pancreatic ß-Cell Function in Elderly Men and Postmenopausal Women.

PURPOSE: To explore the association between bone mineral density (BMD) and ß-cell function. METHODS: A cross-sectional study was performed in Fujian, China, from 2011 to 2012. The study included 572 elderly men older than age 60 years and 1558 postmenopausal women aged 45 to 86 years, excluding those with diabetes and insulin resistance. Fasting glucose and insulin concentrations were measured. Pancreatic ß-cell function was estimated by using the homeostasis model assessment (HOMA-ß). Calcaneus BMD was measured by using quantitative ultrasonography. Multiple regression analyses were applied to explore the association. RESULTS: Participants with decreased BMD had lower fasting glucose (P < 0.001 in postmenopausal women; P = 0.007 in elderly men) and greater HOMA-ß (P = 0.001 in postmenopausal women; P = 0.008 in elderly men) than those with normal BMD, whereas no statistical differences in insulin were seen among categories of BMD. After adjustment for all confounders, HOMA-ß was still significantly negatively related to BMD in both groups (all P < 0.001), and remarkable positive relationships were found between BMD and fasting glucose. Furthermore, binary logistic regression presented fully adjusted odds ratios for diabetes in those with osteoporosis vs those with normal BMD: 0.60 [95% confidence interval (CI), 0.38 to 0.94] and 0.66 (95% CI, 0.49 to 0.91) in the original selected population of elderly men (n = 1070) and postmenopausal women (n = 2825), respectively. CONCLUSIONS: BMD was independently inversely associated with HOMA-ß and positively associated with fasting glucose in both elderly men and postmenopausal women, suggesting that bone mass may be a predictor of glucose metabolism. Further research is needed to verify the associations and determine the exact mechanism underlying them.

The characteristics of newly diagnosed adult early-onset diabetes: a population-based cross-sectional study.

To investigate the characteristics of newly diagnosed early-onset diabetes in the Chinese population, 2801 newly diagnosed diabetes participants without known diabetes or pre-diabetes in a national cross-sectional survey were analysed. Participants were divided into quartiles (22-43, 44-52, 53-61 and >61 years) according to age of diabetes onset and the first group were defined as early-onset diabetes group. Early-onset diabetes group had lower systolic blood pressure (SBP), total cholesterol, low density lipoprotein cholesterol, 2-hour post prandial blood glucose and urine albumin creatinine ratio. There was no difference in body mass index, Homeostasis model assessment (HOMA) of beta cell function and diabetes family history between early-onset diabetes participants and any other age groups. HOMA of insulin resistance (IR) scores and disposition index 30 minutes after glucose load (DI30) were increased in early-onset diabetes participants. The beta cell function declination was more deteriorated in early-onset diabetes participants. Male gender, triglycerides, HOMA-IR and DI30 were positively associated with an earlier age at diagnosis. In conclusion, patients diagnosed with diabetes at a younger age are characterized by a similar cardiovascular risk profile with increased insulin resistance and more severe beta cell failure than patients diagnosed at a later age.

Distal tibial nonunion using a contralateral anterior L-shaped locking compression plate through a posterior-lateral approach: A retrospective case series.

BACKGROUND: Distal tibial nonunion is usually due to severe open distal tibial fractures with high energy injury. The best surgical treatment is not well established because of the poor soft tissue condition. We retrospectively analyzed a series of patients with distal tibial nonunion after severe open distal tibial fractures; our purpose was to introduce a treatment using a contralateral anterior L-shaped locking compression plate through a posterior-lateral approach with Iliac crest bone graft and evaluate the outcomes of patients. METHODS: All patients with distal tibial nonunion who received a contralateral anterior L-shaped locking compression plate fixation through the posterior-lateral approach with Iliac crest bone graft by a single surgeon from 2014 to 2016 were reviewed. 9 patients met the criteria. Five of nine patients had varus deformities (range, 9-40°) and 4 patients had valgus deformities (range, 5-30°). Postoperative radiographs, Postoperative complications, limb alignment and limb functional outcome information of AOFAS ankle-hindfoot score were recorded. RESULTS: All patients were followed up for at least 8 months (range, 8-16 months). Union was achieved in all patients after the index surgery without postoperative wound complications while one patient came up with checkrein deformity. Average time to radiographic union was 16 weeks (range, 12-24 weeks). All patients had correction to neutral alignment in both coronal and sagittal planes. The average AOFAS ankle-hindfoot score was 90 (range, 77-100) at the last follow-up of patients. CONCLUSIONS: Using a contralateral anterior L-shaped locking compression plate fixation through a posterior-lateral approach with Iliac crest bone graft to reconstruct the distal tibial nonunion is a safe and reliable method that can successfully treat patients with poor soft tissue condition of anterior portion of leg because of its adequate exposure, both tibia and fibula rigid fixation and plenty of bone graft. We believe the application of this method resulting in a high union and low complication rate.

Effect of Hypoxia on Self-Renewal Capacity and Differentiation in Human Tendon-Derived Stem Cells.

BACKGROUND Hypoxic conditions play roles in functioning of human tendon-derived stem cells (hTSCs). The goal of this study was to investigate the effect of various hypoxic conditions in self-renewal capacity and differentiation of TSCs. MATERIAL AND METHODS hTSCs was obtain from supraspinatus tendon donors. Colony formation and cell proliferation assay were used to assess the self-renewal of hTSCs. qRT-PCT and Western blot analysis were used to examine stemness and multi-differentiation potential of hTSCs. RESULTS We found that culturing at 5% O2 is more beneficial for the self-renewal of hTSCs than the other 3 culture conditions, with larger colony size and numbers. The proliferation of hTSCs in 5%, 10%, and 20% O2 cultures increased after seeding. The number of cells in the 5% O2 condition was higher than that in other culture; however, self-renewal capacity of hTSCs in 0.5% O2 was inhibited. The expression levels of stem cell markers, including NS, Nanog, Oct-4, and SSEA-4, were highest in 0.5% O2 culture. Furthermore, hTSCs cultured in 20% O2 exhibited significantly higher expression of the 3 markers (PPAR-γ, Sox-9, and Runx-2). CONCLUSIONS Hypoxic condition of culture encouraged self-renewal capacity of hTSCs, but inhibited their multi-differentiation potential, compared to normoxic condition of culture. Moreover, excessively low oxygen concentration impaired the capacity of hTSCs.

Is ß-cell aging involved in the pathogenesis of diabetes?

BACKGROUND: ß-Cells at different stages have different functions and capacity for proliferation, regenerative and apoptosis. The aim of the present study was to investigate whether there are changes in ß-cell phonotype in the development of diabetes to identify potential ß-cell targets to prevent the progression of diabetes. METHODS: A cross-sectional study was performed on pancreatic tissues obtained from 80 patients classified into three groups: 25 with type 2 diabetes (T2D), 25 with impaired fasting glucose (IFG), and 30 non-diabetics (ND). The ratio of the insulin-positive area to pancreatic area was used as an indirect marker of ß-cell mass. Insulin-positive duct cells and scattered ß-cells were defined as newly generated ß-cells, whereas insulin/neurogenin 3 (Ngn3), insulin/v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) and insulin/P16 double-positive cells were defined as immature, mature, and senescent ß-cells, respectively; Ki67 was used as a marker of cell proliferation, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) was used as a marker of cell apoptosis. Data were analyzed using the Kruskal-Wallis test. RESULTS: There were no significant differences in ß-cell mass, the prevalence of insulin-positive duct cells, scattered ß-cells, or insulin/Ngn3, insulin/MafA, and Insulin/Ki67 double-positive cells among groups. The incidence of insulin/P16 double-positive cells was significantly higher in T2D than ND. ß-Cell apoptosis was significantly higher in T2D and IFG than ND. CONCLUSION: The senescence and apoptosis of ß-cells may be involved in the course of diabetes.