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This study aimed to investigate the value and feasibility of combining fractional anisotropy (FA) values from diffusion tensor imaging (DTI) and total kidney volume (TKV) for the assessment of kidney function in chronic kidney disease (CKD). Fifty-one patients were included in this study. All MRI examinations were performed with a 3.0 T scanner. DTI was used to measure FA values, and TKV was obtained from DTI and T2-weighted imaging (T2WI). Patients were divided into three groups (mild, moderate, severe) according to eGFR, which was calculated with serum creatinine. Differences in the FA values of the cortex and medulla were analysed among the three groups, and the relationships of FA values, TKV, and the product of the FA values and TKV with eGFR were analysed. Receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficiency of the FA values, TKV, and the product of the FA values and TKV for kidney function in different CKD stages. Medullary FA values (m-FA), TKV, and the product of the m-FA values and TKV (m-FA-TKV) were significantly correlated with eGFR (r = 0.653, 0.685, and 0.797, respectively; all P

Mimecan encodes a secretory protein that is secreted into the human serum as two mature proteins with molecular masses of 25 and 12 kDa. We found 12-kDa mimecan to be a novel satiety hormone mediated by the upregulation of the expression of interleukin (IL)-1β and IL-6 in the hypothalamus. Mimecan was found to be expressed in human pituitary corticotroph cells and was up-regulated by glucocorticoids, while the secretion of adrenocorticotropic hormone (ACTH) in pituitary corticotroph AtT-20 cells was induced by mimecan. However, the effects of mimecan in adrenal tissue on the hypothalamic-pituitary-adrenal (HPA) axis functions remain unknown. We demonstrated that the expression of mimecan in adrenal tissues is significantly downregulated by hypoglycemia and scalded stress. It was down-regulated by ACTH, but upregulated by glucocorticoids through in vivo and in vitro studies. We further found that 12-kDa mimecan fused protein increased the corticosterone secretion of adrenal cells in vivo and in vitro. Interestingly, compared to litter-mate mice, the diurnal rhythm of corticosterone secretion was disrupted under basal conditions, and the response to restraint stress was stronger in mimecan knockout mice. These findings suggest that mimecan stimulates corticosterone secretion in the adrenal tissues under basal conditions; however, the down-regulated expression of mimecan by increased ACTH secretion after stress in adrenal tissues might play a role in maintaining the homeostasis of an organism's responses to stress.

Previous research has demonstrated aberrations in the levels of inflammatory cytokines in patients with schizophrenia (SCZ), but most of the respective studies have tested a narrow set of inflammatory cytokines. Here, we aimed to analyze broad immune profiles in the peripheral blood of the first-episode drug-free (FEDF) patients with SCZ at baseline and after an 8-week treatment with atypical antipsychotics. Serum samples from 24 FEDF patients with SCZ and 25 healthy control (HC) subjects were tested using Luminex multiplex analysis for 30 cytokines, chemokines, and growth factors. Multiple comparison tests demonstrated that interleukin-2 (IL-2), IL-4, interferon-gamma (IFN-γ), monokine induced by IFN-γ, and granulocyte colony-stimulating factor (G-CSF) levels were significantly increased, whereas those of the epidermal growth factor were significantly decreased in the FEDF patients with SCZ. Moreover, the levels of the 6 dysregulated cytokines as well as those of 12 additional soluble factors in FEDF patients with SCZ were significantly decreased after 8 weeks of antipsychotic treatment. Furthermore, the transcription of G-CSF and IFN-γ was significantly increased in FEDF patients with SCZ when compared with controls, and G-CSF and IFN-γ mRNA levels were highly correlated with their respective protein concentrations. Receiver operating characteristic curves showed that G-CSF and IFN-γ had good performance in differentiating between FEDF patients with SCZ and HC subjects. Taken together, our data revealed that FEDF patients with SCZ were accompanied by a unique pattern of immune profile, and antipsychotic medications seemed to suppress the immune function in these patients, which could be used to develop novel targets for the diagnosis and treatment of SCZ.

The paracaval portion of the caudate lobe is located in the core of the liver. Lesions originating in the paracaval portion often cling to or even invade major hepatic vascular structures. The traditional open anterior hepatic transection approach has been adopted to treat paracaval-originating lesions. With the development of laparoscopic surgery, paracaval-originating lesions are no longer an absolute contraindication for laparoscopic liver resection. This study aimed to evaluate the safety and feasibility of laparoscopic anterior hepatic transection for resecting paracaval-originating lesions. This study included 15 patients who underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection between August 2017 and April 2020. The perioperative indicators, follow-up results, operative techniques and surgical indications were retrospectively evaluated. All patients underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection. The median operation time was 305 min (220–740 min), the median intraoperative blood loss was 400 ml (250–3600 ml), and the median length of postoperative hospital stay was 9 days (5–20 days). No conversion to laparotomy or perioperative deaths occurred. Six patients had Clavien grade III–IV complications (III/IV, 5/1). Two patients developed tumor recurrence after 13 months and 8 months. Although technically challenging, laparoscopic anterior hepatic transection is still a safe and feasible procedure for resecting paracaval-originating lesions in select patients.

Paracaval-originating cancers have been considered a contraindication for laparoscopic liver resection (LLR). This study aimed to explore the safety and feasibility of LLR in the treatment of paracaval-originating cancers. This study included 11 patients who underwent LLR and 20 who underwent open liver resection (OLR) for paracaval-originating cancers between May 2010 and November 2020. The outcomes of the procedures were retrospectively analyzed. There were no cases of perioperative death or conversion to laparotomy. The LLR group had an earlier postoperative feeding time, shorter postoperative hospital stay, and lower total bilirubin levels on the first day after surgery. No significant differences in the incidence of overall postoperative complications were noted between the LLR and OLR groups, but the incidence of grade IIIa complications was significantly higher in the LLR group than in the OLR group. Tumor recurrence occurred in 4 of 11 patients in the LLR group and in 11 of 20 patients in the OLR group. LLR for the treatment of paracaval-originating cancers is safe and feasible in selected patients.

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%–98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%–96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%–87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%–100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.

This retrospective 10-year case study evaluated the perioperative results and long-term efficacy of laparoscopic middle-hepatic-vein-guided hemihepatectomy (L-MHV-H) and traditional anatomical hemihepatectomy (TAH) in the treatment of hepatolithiasis (HL). From January 2010 to December 2019, 99 patients with regional HL underwent laparoscopic anatomical hemihepatectomy (LAH) at our centre, including 43 patients in the L-MHV-H group and 56 patients in the TAH group. All patients in both groups were Child–Pugh grade A before operation. No significant between-group differences in general information, stone distribution, comorbidities, history of previous abdominal surgery or co-occurrence of gallstones and common bile duct stones were observed. The L-MHV-H group exhibited a higher intraoperative stone clearance rate (95.3% vs. 75.0%, p = 0.014) and a lower postoperative complication rate (10.1% vs. 48.2%, p = 0.005) compared with the TAH group. In the median follow-up time of 60 months (range 6–125 months), the L-MHV-H group had lower stone recurrence (2.3% vs. 19.6%, p = 0.013) and cholangitis recurrence (2.3% vs. 17.9%, p = 0.034) rates. No significant between-group differences in the other results were observed. L-MHV-H is safe and feasible for HL with certain advantages over TAH in improving the intraoperative stone clearance rate, reducing postoperative complication incidence and reducing stone and cholangitis recurrence rates.

Background: A functional hypothalamic-pituitary-adrenal (HPA) axis is critical for host defenses to outside stimuli. The adrenal cortex is seemingly endowed with distinct functional units that are regulated by adrenocorticotropic hormone (ACTH). We have found that mimecan, a small leucine-rich proteoglycan expressed in the adrenal gland, has yet to be characterized in functional terms.Results: Herein, we have demonstrated the following properties: 1) adrenal mimecan expression in mouse models is significantly downregulated under hypoglycemia and scalded stress; 2) expression of mimecan in adrenal cells may be downregulated through ACTH or upregulated by glucocorticoid via related receptors (GRs); and 3) mimecan stimulates corticosterone secretion in adrenal tissues. The latter was proven using in vivo and in vitro studies to confirm the ACTH-independent activity of mimecan-maltose-binding protein (-MBP). Relative to litter-mate mice, the basal-state diurnal rhythm of corticosterone secretion is disrupted in mimecan knockout mice, and corticosterone secretion is increased under restraint stress conditions. Conclusions: These findings offer the first evidence that mimecan is key in regulating the HPA axis, assuming a critical role in adrenal responses to stress.

It has been suggested that dysregulation of hormones is associated with schizophrenia (SCZ). This study aimed to measure the serum levels of progesterone and testosterone in 125 SCZ patients at different stages of treatment and 96 healthy control (HC) subjects. Our results showed that first-episode drug-free SCZ patients had significantly increased testosterone levels when compared with HC subjects, and chronic medication, but not short-term medication, further increased the serum testosterone levels in the patients. Further analysis suggested that the sex of the patients did not affect testosterone levels. In contrast, serum progesterone levels did not show significant differences between first-episode, drug-free SCZ patients and controls, and the antipsychotics increased progesterone levels in the male SCZ patients, but not female patients. Interestingly, our analyses demonstrated that the serum progesterone levels were negatively correlated with PANSS total score and PNASS positive score, suggesting a correlation between blood hormone levels and disease severity in SCZ patients. Taken together, our data showed differential changes in serum testosterone and progesterone levels in SCZ patients with or without antipsychotics, and our results suggest that increased sex hormone levels may be a defensive response to protect the human body under stress.

Preclinical and clinical studies suggest that brain-derived neurotrophic factor and nerve growth factor are involved in the pathogenesis of schizophrenia (SCZ). However, the roles of other neurotrophic factors in SCZ remain unclear. The aim of this study was to investigate the blood levels of FGF2 and ADNP in first-episode, drug-free SCZ patients compared with healthy control subjects. 20 SCZ patients, and 20 age and sex matched controls were recruited in this study. Serum FGF2 and ADNP protein levels were measured by ELISA assay, and the results showed that FGF2 levels were significantly increased in patients with SCZ when compared with controls, whereas ADNP protein levels did not significantly associated with SCZ. However, we found that blood ADNP mRNA levels were significantly increased in the patients with SCZ when compared with controls. In addition, subgroup analyses suggested that FGF2 levels were significantly increased in female patients of SCZ, but not in male patients of SCZ. Correlation analyses suggested that age and disease severity (PANSS score) did not have moderating effects on the serum FGF2 levels. Taken together, our results for the first time demonstrated that blood FGF2 was up-regulated in first-episode, drug free-SCZ patients, therefore enhancing the knowledge of neurotrophic factor profile in patients with SCZ.

// Shuo Wang 1, 2, * , Ying-Ying Chen 3, 4, * , Yu-Peng Li 5 , Jun Gu 6 , Shu-Dong Gu 4 , Hai Shi 7 , Xue-Song Li 3 , Xiao-Ning Lu 1, 2 , Xiang Li 8 , Shuang-Long Zhang 1 , Kang-Jun Yu 1 , Kun Liu 1 and Li-Li Ji 2 1 Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China 2 Department of Pathology, Medical School of Nantong University, Nantong, China 3 Department of Immunology, Medical School of Nantong University, Nantong, China 4 Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China 5 Department of Pediatrics, The People’s Hospital of Rizhao, Rizhao, China 6 Department of Respiratory, Affiliated Hospital of Nantong University, Nantong, China 7 Department of Cardiothoracic Surgery, The Third People's Hospital of Nantong, Nantong, China 8 Department of Otorhinolaryngology, Maternal and Child Health Care Hospital of Nantong, Nantong, China * These authors have contributed equally to this work Correspondence to: Kun Liu, email: ntliukun@163.com Li-Li Ji, email: kevin08lily@163.com Keywords: non-small cell lung cancer, DISC1, GSK3β, β-catenin, proliferation Received: February 15, 2017 Accepted: April 27, 2017 Published: May 22, 2017 ABSTRACT Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/β-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3β) phosphorylation, and may promote neural progenitor cell and pancreatic β-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3β, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis. siRNA-mediated DISC1 silencing increased p-GSK3β expression and decreased expression of β-catenin and Cyclin D1, while DISC1 upregulation produced the opposite results. DISC1 knockdown also reduced NSCLC cell proliferation rates in vitro . These results suggest that DISC1 promotes NSCLC growth, likely through GSK3β/β-catenin signaling, and that DISC1 may function as an oncogene and novel anti-NSCLC therapeutic target.

Citrin deficiency initially presents as neonatal intrahepatic cholestasis (NICCD) and often resolves within first year of infancy. Failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD) has been recently proposed as a novel post-NICCD phenotype and its clinical features are still being established. Herein, we encountered a 2-year-old girl who was hospitalized for intermittent fever lasting 10 days. Besides pneumonia, we observed an NICCD-like phenotype with the presence of liver dysfunction, dyslipidemia, aminoacidemia, organic academia, and extremely high levels of alpha-fetoprotein (AFP). Genetic testing confirmed the diagnosis of citrin deficiency and, liver histology revealed she had already developed cirrhosis. Although, improvement of biochemical parameters and liver histology were observed after treatment that included dietary restrictions and symptomatic treatments, AFP levels remained elevated (>400 ng/ml) during a 3-year follow-up period. Moreover, liver magnetic resonance imaging (MRI) examination performed on the patient at age 5 revealed the development of multiple liver nodules with diffusion restriction on diffusion-weighted imaging (DWI). These observations highly indicate the possibility of hepatocellular carcinoma (HCC). Thus, this case reveals that an NICCD-like phenotype complicated with cirrhosis can exist during FTTDCD stage without any prior signs. It also emphasizes the necessity of monitoring AFP levels during follow-up for citrin deficiency patients with persistently high AFP level after treatment as FTTDCD may progress to HCC. Individualized treatment strategy for patients with FTTDCD also need to be explored.

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of psychiatric disorders, and studies have shown BDNF aberrations in major psychiatric diseases including schizophrenia (SCZ) and major depressive disorder (MDD). However, data from clinical studies were inconsistent. In this study, we recruited 34 patients with MDD, 77 patients with SCZ and 65 healthy control (HC) subjects to clarify the circulating BDNF levels in MDD and SCZ patients, and to assess whether serum BDNF levels were associated with the disease severity. Our results showed that serum BDNF levels were significantly decreased in the patients with SCZ (Mean difference = -4.517, 95%CI of difference = -7.854 to -1.180, p 0.01) and MDD (Mean difference = -5.699, 95%CI of difference = -9.892 to -1.506, p 0.01) when compared with HC subjects. Sub-group analyses suggested that BDNF levels were significantly reduced in the female SCZ (Mean difference = -5.700, 95%CI of difference = -10.21 to -1.189, p 0.01) and MDD (Mean difference = -5.840, 95%CI of difference = -10.66 to -1.019, p 0.05) patients, but not in male patients. Further analyses indicated that serum BDNF levels were not correlated with disease severity of MDD and SCZ. In addition, the transcriptional expression of TrkB was significantly down-regulated in the blood of MDD patients, but not in SCZ patients. However, there was no significant correlation between BDNF concentrations and TrkB mRNA levels. Taken together, our results revealed differential changes of BDNF-TrkB signaling in MDD and SCZ patients, therefore contributed to a better understanding of MDD and SCZ pathophysiology.

Approximately 20% of Graves' disease (GD) patients may result eventually in hypothyroidism in their natural course. Uterus globulin-associated protein 1 (UGRP1) was associated with GD in our previous study. Here we investigated the role of UGRP1 in the development of autoimmune thyroid disease (AITD). The results showed that UGRP1 was expressed in the thyrocytes of most Hashimoto's thyroiditis (HT) patients and a proportion of GD patients (293 HT and 198 GD). The pathologic features of UGRP1-positive thyrocytes resembled "Hurthle cells", and were surrounded by infiltrated leukocytes. The positivity rate of TPOAb in UGRP1-positive GD patients was much higher than that in -negative GD patients. Moreover, UGRP1 was co-expressed with Fas and HLA-DR in the thyrocytes of AITD patients. We also found IL-1β but not Th1 or Th2 cytokines was able to upregulate the expression of UGRP1. Our findings indicated that UGRP1 may be a novel marker in thyrocytes to predict GD patients who develop hypothyroidism.

Background Low bone mineral density (BMD) and left ventricular (LV) diastolic function are associated with heart failure. However, little is known about the association between BMD and LV diastolic function. Hypothesis BMD is independently related to LV diastolic function in women. Methods We conducted a cross-sectional study of 432 women. Brachial-ankle pulse wave velocity (baPWV) and BMD measurements were performed. LV diastolic function and structure were assessed by echocardiographic examination. Results BaPWV and the percentage of LV diastolic dysfunction increased with progressive bone loss. Moreover, partial correlation analysis demonstrated that BMD at spine L2–4 and at femoral neck were correlated with baPWV and LV diastolic function parameters after adjusting covariates. Multivariate logistic regression analysis revealed that osteoporosis was independently associated with LV diastolic dysfunction in women. Conclusions Osteoporosis is independently associated with LV diastolic dysfunction in women. A prospective study is needed to elucidate the effects of BMD on cardiac function in women.

Hypertension (HTN) and osteoporosis are associated with the development and progress of atherosclerosis. However, little research has been conducted to examine the relationship between arterial stiffness and bone mineral density (BMD) in men with HTN. This cross‐sectional study recruited 355 men with HTN and 353 control patients without HTN. Brachial‐ankle pulse wave velocity (baPWV) and BMD measurements were performed. BMD was decreased and baPWV was elevated in patients with HTN compared with control patients (femoral neck [FN] BMD in the HTN and control groups were 0.662±0.195 g/cm(2) and 0.713±0.204 g/cm(2), respectively [P=.001], and baPWV in the HTN and control groups were 1403.3±156.8 cm/s and 1354.8±136.0 cm/s, respectively [P

Oxidative stress has been suggested to be involved in schizophrenia, but studies have demonstrated inconsistent results on oxidative stress marker level/activity in patients with schizophrenia. In order to clarify the circulating oxidative stress marker level/activity in patients with schizophrenia, this study recruited 80 schizophrenia patients (40 first-episode, drug-free and 40 chronically medicated patients) and 80 controls to analyze serum activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC), and levels of lipid peroxidation marker malondialdehyde (MDA) in schizophrenia patients, and whether they associate with the severity of the disease. We showed that only serum GSH-Px activity was significantly reduced in unmedicated patients with schizophrenia when compared with control subjects, whereas the other three analyzed oxidative stress markers did not show significant differences between cases and controls. Moreover, our results demonstrated that chronic medication increased GSH-Px activity and MDA levels in patients with schizophrenia, but reduced SOD activity in the patients. We also found that short-term antipsychotic treatments on the patients with schizophrenia reduced the SOD activity. Correlation analyses indicated that the oxidative stress marker activity/level is not significantly associated with the severity of schizophrenia, except that SOD level correlated with PANSS positive score significantly. Taken together, the data from the present study suggested that the dysfunctions of oxidative stress markers in patients with schizophrenia were mainly caused by antipsychotics, emphasizing increased oxidative stress as a potential side effect of antipsychotics on the patients.

Adipokines such as leptin play important roles in the regulation of energy metabolism, particularly in the control of appetite. Here, we describe a hormone, mimecan, which is abundantly expressed in adipose tissue. Mimecan was observed to inhibit food intake and reduce body weight in mice. Intraperitoneal injection of a mimecan-maltose binding protein (-MBP) complex inhibited food intake in C57BL/6J mice, which was attenuated by pretreatment with polyclonal antibody against mimecan. Notably, mimecan-MBP also induced anorexia in Ay/a and db/db mice. Furthermore, the expression of interleukin (IL)-1β and IL-6 was up-regulated in the hypothalamus by mimecan-MBP, as well as in N9 microglia cells by recombinant mouse mimecan. Taken together, the results suggest that mimecan is a satiety hormone in adipose tissue, and that mimecan inhibits food intake independently of leptin signaling by inducing IL-1β and IL-6 expression in the hypothalamus.

Objectives To investigate whether ureteroscopy (URS) before radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUCs) has an impact on oncological outcomes. Patients and Methods We performed a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described URS performed on patients with UTUC and conducted a standard meta-analysis on survival outcomes. Results Our meta-analysis included eight eligible studies containing 3975 patients. The results were as follows: cancer-specific survival (CSS; hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59-0.99; P = 0.04), overall survival (OS; HR 0.76, 95% CI 0.48-1.21; P = 0.24), recurrence-free survival (RFS; HR 0.89, 95% CI 0.69-1.14; P = 0.37), metastasis-free survival (MFS; HR 1.06, 95% CI 0.82-1.36; P = 0.66), and intravesical recurrence-free survival (IRFS; HR 1.51, 95% CI 1.29-1.77; P l 0.001). When excluding previous bladder tumour history, the result for IRFS was a HR of 1.81 (95% CI 1.53-2.13; P l 0.001). Conclusions This meta-analysis indicated that URS before RNU did not have a negative impact on CSS, OS, RFS, or MFS in patients with UTUC. However, patients were at higher risk of intravesical recurrence after RNU when they had undergone URS before RNU. Further studies are needed to assess the effects of post-URS intravesical chemotherapy on intravesical recurrence.

Importance Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified:DCHS2on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85;P = 1.24 × 10−8) andC11orf67on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74;P = 2.80 × 10−7). One previously reported specific locus was confirmed on 17q24.3 nearKCNJ2(rs312729: OR, 2.08; 95% CI, 1.83-2.38;P = 8.02 × 10−29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16;P = 7.05 × 10−6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.

Objective To investigate the clinical significance of preoperative aspects and dimensions used for anatomic (PADUA) and radius exophytic/endophytic nearness anterior/posterior location (RENAL) scoring systems for renal neoplasms in patients undergoing laparoscopic partial nephrectomy. Methods A retrospective analysis was carried out on clinical data of 245 Chinese patients with renal neoplasms undergoing laparoscopic partial nephrectomy from June 2008 to June 2012. The perioperative complications and variables, as well as PADUA and RENAL score, were compared. Results The PADUA and RENAL scoring systems were significantly associated with percent change in estimated glomerular filtration rate (P = 0.032 and P = 0.026 respectively), whereas the RENAL scoring system was also significantly associated with warm ischemia time (P = 0.032). On multivariate analysis, both scores were able to predict percent change in estimated glomerular filtration rate (PADUA, P = 0.011; RENAL, P = 0.028). There were no significant associations between the two scoring systems assessed and the occurrence of complications or tumor stage. The correlation between PADUA classification and RENAL nephrometry score was significant (P

Objectives Poor nutritional status is associated with osteoporosis (OP) in postmenopausal women. Moreover, recent studies documented that prealbumin is the best and most widely used parameter to monitor nutrition intervention and is a sensitive predictor of short-term outcome compared with albumin. Therefore, the aim of this study was to examine the association of prealbumin levels with bone mineral density (BMD) in patients with OP. Methods This cross-sectional study recruited 664 women. Prealbumin levels and BMD at femoral neck and lumbar spine were measured. Multiple linear regression analysis was performed to assess the correlation between prealbumin and BMD. Results Results of this study found that prealbumin levels dropped gradually as BMD decreased. Furthermore, partial correlation analysis revealed that prealbumin was correlated with BMD after adjusting for confounders. Multiple linear regression analysis showed that prealbumin is a significant factor for reduced BMD in women (for BMD at spine L2–4, β = 0.186, P P Conclusion Prealbumin was significantly correlated with BMD after adjusting for traditional cardiovascular risk factors. Further prospective research is warranted to further enhance our understanding of the important role of prealbumin in OP.

Osteoporosis (OP) has been associated with cardiovascular disease. More specifically, osteoporosis was found to be an independent predictor of cardiovascular mortality. Recent studies revealed that platelets play a critical role in bone remodeling. Mean platelet volume (MPV) is an early marker of platelet activation, which is involved in the pathophysiology of coronary heart disease. However, little research has been conducted to investigate the relationship between MPV and OP. In this cross-sectional study, we investigated the relationship between platelet count, MPV, and bone mineral density (BMD) in 410 subjects in the geriatric department of the Second Affiliated Hospital, Harbin, China. Different biochemical parameters, platelet count, and MPV were determined, and bone mineral density (BMD) (g/cm(2)) was measured in the osteoporosis, osteopenia, and normal BMD groups. Mean age, systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), and MPV increased gradually, and body mass index (BMI), decreased as BMD decreased. A negative correlation was present between MPV and the lumbar spine (L2-L4) and femoral neck BMD after adjusting other risk factors. Univariate analysis and multivariate analysis showed that MPV was significantly associated with lumbar spine L2-L4 BMD and femoral neck BMD (β = -0.285, P 0.001 for lumbar spine L2-L4 BMD; β = -0.207, P 0.001 for femoral neck BMD in multivariate model). The findings show that MPV is negatively correlated with BMD. Further studies on the involvement of MPV in osteoporosis may contribute to the evaluation of thrombotic risk in elderly patients with osteoporosis.

Various vascular risk factors such as smoking, obesity, and diabetes mellitus are associated with hyper- viscosity and lumbar disc herniation (LDH). However, the changes of viscosity in LDH have not been examined. AIMS: The present study was to elucidate 1) the rheological parameter levels in patients with LDH, 2) the risk factors that were related to rheological parameters. METHODS: Our study evaluated the rheological parameters in 307 cases with LDH and in 307 control subjects. Multiple linear regression analysis was conducted to assess the significant factors for whole blood viscosity (WBV) at low shear rate. RESULTS: LDH patients had markedly lower physical activity and significantly higher WBV 3 s -1 compared with non-LDH subjects (p < 0.001). Moreover, WBV (3 s -1 ) tended to increase as physical activity decreased. Multiple linear regression analysis revealed that reduced physical activity was a significant factor contributing to elevated WBV (3 s -1 ). CONCLUSIONS: WBV (3 s -1 ) is elevated in patients with LDH. In addition, reduced physical activity is a significant factor for WBV (3 s -1 ). Further studies are warranted to determine the role of WBV (3 s -1 ) in LDH.

The relationship between single nucleotide polymorphism (SNP) of interleukin-17 (IL-17A), transforming growth factor β (TGF-β), as well as its receptor (TGFR-β2) and susceptibility to intracerebral hemorrhage in patients with brain arteriovenous malformation (BAVM) was investigated in the present study. A total of 53 patients with BAVM and 120 healthy controls were recruited, all of whom were Han Chinese from South China. There were no statistically significant differences in the IL-17A-197 guanine/adenine (G/A) or TGF-β1-509 cytosine/thymine (C/T) genotypes or gene frequencies between BAVM patients and controls (p>0.05), but the gene frequency of the TGFR-β2-875 A/G genotype in patients with BAVM was significantly higher (p

Systemic inflammation may be a common mechanism for the development of osteoporosis (OP) and atherosclerosis. Elevated arterial stiffness is an index of subclinical atherosclerosis. Recent studies found that neutrophil/lymphocyte ratio (NLR), is a useful marker of cardiovascular disease and a more powerful predictor than any other leukocyte subtypes. However, little research has been conducted to investigate the relationship between NLR and arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV).In this cross-sectional study, we examined the relationship between NLR and baPWV in 512 subjects.Compared to the control subjects, NLR and baPWV increased in patients with OP. Partial correlation analysis revealed that there was a significant correlation between NLR and baPWV after adjusting for confounding factors in OP. Multivariate linear regression analysis showed that NLR was a significant factor for increased baPWV in patients with OP (β=0.249, p0.001). However, there was no association between NLR and baPWV in control subjects.NLR and baPWV are elevated in OP. Moreover, NLR is independently associated with baPWV. Further studies are warranted to investigate whether anti-inflammatory treatment could improve arterial stiffness in postmenopausal women with OP.

Alzheimer's disease (AD) is a progressive neurological disorder that primarily affects memory, and its prevalence is rising. Increasing evidence suggests that dysfunction of the blood-brain barrier (BBB) may be involved in AD and other neurodegenerative diseases. Herein, we report that the permeability of the BBB is increased and that AD-like alterations are present in Slit-2 overexpressing transgenic mice. We found that behavioral change and the corresponding molecular diagnostic markers of AD, such as hippocampal neuron apoptosis, amyloid-β (Aβ) protein deposition, and acetylcholinesterase expression, were increased in the Slit-2 transgenic mice. Moreover, the endothelial cells were dysfunctional, the size of the lateral ventricle cavity increased, and the permeability of the BBB increased. Additionally, there was an increased serum level of glutamate indicating that the BBB is related to AD. Finally, histopathological analysis of other organs in the Slit-2 overexpressing mice did not show any marked abnormalities. These findings demonstrate that Slit2 overexpression may be responsible for AD-like alterations and the increased BBB permeability in these mice. Our study provides a potential novel mechanism for the development of AD.

Mimecan mRNA was present in a limited number of mouse and human tissues, however, abundant mimecan mRNA was observed in the lung tissue. Therefore, we hypothesize that mimecan could serve as a biomarker for differentiating various histological types of lung cancers. In humans, the mimecan mRNA was found most abundant in ovary and less abundant in lung by using Northern blot analysis. Moreover, the mimecan was expressed strongly in the epithelial cells of the bronchial wall and weaker in the epithelial cells of the alveolar sacs by in situ hybridization and immunohistochemical analysis. Furthermore, the mimecan immunoreactivity was found in 103 (97.2%) of 106 non-small cell lung cancers (NSCLCs). Nevertheless, a large majority of small cell lung cancers (SCLCs) (50/56, 89.3%) showed negative immunoreactivity to mimecan polyclonal antibody. A significant difference of mimecan immunoreactivity was found between NSCLC and SCLC (P

Although circulating ghrelin levels correlate inversely with adiposity at baseline, little is known about the effect of percent visceral adipose tissue value (PVATV) on ghrelin expression and secretion in response to fasting. Our study demonstrated that ghrelin increased with 24-h fasting in rats with the lowest PVATV (less than 6%), after 3 days in rats with intermediate PVATV (6–9%) and 5 days in rats with the highest PVATV (greater than 9%). Ghrelin mRNA in the stomach was increased after 3 days in low-PVATV (5.8±0.9%) rats but not in high-PVATV (14±1.6%) rats. Therefore, both ghrelin secretion and mRNA were delayed in response to fasting in rats with increased visceral fat. In rats matched for PVATV, but with different body weights, the fasting induced similar levels of increased ghrelin while in rats with different PVATV ghrelin secretion was different in response to fasting, even when body weights were matched in two groups. These data suggested that the initial PVATV, not lean mass, was related to the pattern of plasma ghrelin in response to fasting in rats.

The present study was to investigate the therapeutic efficacy of the magnetic arsenic trioxide (ATO) nanoparticles against osteosarcoma in vivo tumor models. ATO was incorporated in the magnetic nanoparticles and encapsulated by poly lactic acid. Human MG-63 osteosarcoma cells were injected subcutaneously into the nude mice. After 15 days, the mice were randomly assigned to the four groups (n=6 mice): group 1: control, saline only (10 mL kg(-1) day(-1), intravenously (i.v.)); group 2: ATO alone (5 mg kg(-1) day(-1), i.v.); group 3: magnetic ATO nanoparticles at a dose equivalent to 50% of the ATO alone, with an external magnetic field on the tumor; group 4: CDDP, cisplatin (5 mg kg(-1) day(-1), i.v.). The mice were sacrificed after 21 days. In vitro release profiles showed that ATO was released rapidly from the nanoparticles. The magnetic ATO evaluation indicated that the magnetic nanoparticles might localize under the magnet in vivo. The tumor volume examination showed that the treatment with magnetic ATO nanoparticles achieved the similar inhibition effect on osteosarcoma as that of CDDP or ATO alone. Electron microscopic features typical of apoptosis were identified in the tumor tissue with the three-drug treatment. This "magnetic ATO targeting" offers an opportunity to treat osteosarcoma with a lower dose.

C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. The aim of the present study is to investigate the effects of CRP on the production of adiponectin in 3T3-L1 adipocytes. Northern and western blot analysis revealed that CRP treatment inhibited adiponectin mRNA expression and secretion in a dose- and time-dependent manner. Co-incubation of adipocytes with rosiglitazone and CRP decreased induction of adiponectin gene expression by rosiglitazone. However, luciferase reporter assays did not show that CRP affected the activity of ~2.1 kb adiponectin gene promoter, which was increased by rosiglitazone alone. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by LY294002 partially reversed inhibition of adiponectin gene expression by CRP. These results collectively suggest that CRP suppresses adiponectin gene expression partially through the PI-3 kinase pathway, and that decreased production of adiponectin might represent a mechanism by which CRP regulates insulin sensitivity.

Background To compare the efficacy of sorafenib and sunitinib with regard to overall survival (OS) and progression free survival (PFS) in Chinese patients with metastatic renal cell carcinoma (mRCC). Methods A multicenter, retrospective study was performed to elucidate the relationship between clinical variables and prognosis comparing sorafenib and sunitinib as first-line treatment agents in Chinese patients with mRCC. Between September 2006 and December 2014, 845 patients received either sorafenib (400 mg bid; n = 483) or sunitinib (50 mg q.d; n = 362). The primary end point was OS and PFS. Results The percentage of patients with low and moderate risk according to Memorial Sloan-Kettering Cancer Centre (MSKCC) score was significantly higher in sunitinib group, and that with high risk was significantly higher in sorafenib group (15.1 vs. 5.2%; p