Ulinastatin inhibits the metastasis of nasopharyngeal carcinoma by involving uPA/uPAR signaling.

Distant metastasis is the primary reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we investigated the effect of ulinastatin (UTI) on NPC metastasis and its underlying mechanism. Highly-metastatic NPC cell lines S18 and 58F were treated with UTI and the effect on cell proliferation, migration, and invasion were determined by MTS and Transwell assays. S18 cells with luciferase-expressing (S18-1C3) were injected into the left hind footpad of nude mice to establish a model of spontaneous metastasis from the footpad to popliteal lymph node (LN). The luciferase messenger RNA (mRNA) was measured by quantitative polymerase chain reaction (qPCR), and the metastasis inhibition rate was calculated. Key molecular members of the UTI-related uPA, uPAR, and JAT/STAT3 signaling pathways were detected by qPCR and immunoblotting. UTI suppressed the migration and infiltration of S18 and 5-8F cells and suppressed the metastasis of S18 cells in vivo without affecting cell proliferation. uPAR expression decreased from 24 to 48 h after UTI treatment. The antimetastatic effect of UTI is partly due to the suppression of uPA and uPAR. UTI partially suppresses NPC metastasis by downregulating the expression of uPA and uPAR.

PBRM1 deficiency oncogenic addiction is associated with activated AKT-mTOR signalling and aerobic glycolysis in clear cell renal cell carcinoma cells.

The PBRM1 (PB1) gene which encodes the specific subunit BAF180 of the PBAF SWI/SNF complex, is highly mutated (~ 40%) in clear cell renal cell carcinoma (ccRCC). However, its functions and impact on cell signalling are still not fully understood. Aerobic glycolysis, also known as the 'Warburg Effect', is a hallmark of cancer, whether PB1 is involved in this metabolic shift in clear cell renal cell carcinoma remains unclear. Here, with established stable knockdown PB1 cell lines, we performed functional assays to access the effects on 786-O and SN12C cells. Based on the RNA-seq data, we selected some genes encoding key glycolytic enzymes, including PFKP, ENO1, PKM and LDHA, and examined the expression levels. The AKT-mTOR signalling pathway activity and expression of HIF1α were also analysed. Our data demonstrate that PB1 deficiency promotes the proliferation, migration, Xenograft growth of 786-O and SN12C cells. Notably, knockdown of PB1 activates AKT-mTOR signalling and increases the expression of key glycolytic enzymes at both mRNA and protein levels. Furthermore, we provide evidence that deficient PB1 and hypoxic conditions exert a synergistic effect on HIF 1α expression and lactate production. Thus, our study provides novel insights into the roles of tumour suppressor PB1 and suggests that the AKT-mTOR signalling pathway, as well as glycolysis, is a potential drug target for ccRCC patients with deficient PB1.

Evaluation of nuclear PGAM2 value in hepatocellular carcinoma prognosis.

Phosphoglycerate mutase (PGAM) is a critical enzyme in glycolysis. PGAM2 is abundant in several types of tissues and malignant tumours. However, there is limited information regarding their clinicopathological significance in dysplastic nodules and hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of PGAM2 as a new biomarker for HCC. The PGAM2 expression level was evaluated by immunohistochemistry in liver cirrhosis (n = 10), low-grade dysplastic nodules (n = 15), high-grade dysplastic nodules (n = 15) and HCCs (n = 20) and 178 pairs of HCC and adjacent peritumoral liver tissues. We selected X-tile software for counting cut-point based on the outcomes for prognosis analysis, and used Kaplan-Meier analysis and Cox regression analysis can assess the prognosis of clinicopathologic parameters. Nuclear PGAM2 was significantly overexpressed in peritumoral liver tissues compared with HCC tissues (P = 0.0010). Kaplan-Meier analyses of 178 HCC samples revealed that nuclear PGAM2's high expression level, but not cytoplasmic PGAM2, was significantly related to good overall survival rate (OS). In addition, univariate and multivariate Cox analyses indicated nuclear PGAM2 expression could be regarded as valuable predictors for OS in HCC. PGAM2 was highly expressed in HCC tissues than liver cirrhosis tissues, and nuclear PGAM2's high expression might demonstrate HCC patients have poor postoperative results. Thus, nuclear PGAM2 can be regarded as valuable predictors for OS in HCC patients after surgery.

Post-hepatectomy liver failure prediction and prevention: Development of a nomogram containing postoperative anticoagulants as a risk factor.

INTRODUCTION AND OBJECTIVES: Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients' risk of developing PHLF. PATIENTS AND METHODS: A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index. RESULTS: Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711. CONCLUSION: Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.

[Study on urine biomarkers in 1,3-butadiene exposed workers].

OBJECTIVE: To discuss the urine biomarkers in 1,3-butadiene exposed workers, and to provide basement for establishing biological limit value. METHODS: 44 BD exposed workers as exposure group and 25 BD non-exposed people as control group including 12 workers in boiler workshop in the same factory and 13 people in one public institute, we collected their in-end-of shift urine, then detected urine BD-derived mercapturic metabolites [3,4-dihydroxybutyl mercapturic acid (DHBMA),1- and 2-monohydroxy-3-butenyl mercapturic acid (MHBMA)] concentrations using UPLC-MS/MS method. Meanwhile, we detected air BD concentration with GC-FID in the workplace, and compared their relationship. RESULTS: lgDHBMA and lg (MHBMA + DHBMA) levels in exposed group (lgDHBMA: 2.51 ± 0.44) µg/L, lg [MHBMA + DHBMA: (2.68 ± 0.27) µg/L] were higher than which in control group (lgDHBMA: (2.20 ± 0.25) µg/L, lg(MHBMA + DHBMA: (2.49 ± 0.34) µg/L), and the differences were significant (P < 0.01). Urine DHBMA was obviously influenced by air BD concentrations (r = 0.539, P = 0.001). The equation of Multiple Regression Analysis was y = 2.417 + 0.520x (x represents air BD dose, and represents urinary DHBMA level). Adjusted R(2) of this model was 0.262. Urinary MHBMA was not affected by smoking, alcohol and years of works. CONCLUSION: Urine metabolite DHBMA in BD-exposed workers might be major biological exposure indice.

[Effects of CUMS on excitatory/inhibitory balance of hippocampal and prefrontal cortex pyramidal neurons in anxiety-like mice].

Objective: To explore the changes in the excitatory/inhibitory (E/I) balance of pyramidal neurons in prefrontal cortex and hippocampus in mice with anxiety disorder induced by chronic unpredictable mild stress (CUMS). Methods: Twenty-four C57/BL6 male mice were randomly divided into control group (CTRL) and model group (CUMS), with 12 mice in each group. The mice in CUMS group were subjected to 21 days of stress, including restraint for 1 h, reversed day/night cycle for 24 h, forced warm water bath for 5 min, water/food deprivation for 24 h, housing in wet sawdust for 18 h, shaking the cage for 30 min, noise for 1 h, and social stress for 10 min. CTRL group mice were fed normally. Anxiety-related behavioral tests and whole-cell recording tests were performed after modeling. Results: Compared with CTRL group, the time of spent in the central arena of CUMS group was reduced significantly in open field test (P＜0.01), the time and number of entering the open arms were decreased significantly in elevated plus maze test (P＜0.01), and the time of staying in the closed arms was increased significantly in CUMS group (P＜0.01). The sEPSC frequency, capacitance and E/I ratio of dlPFC, mPFC and vCA1 pyramidal neurons of mice in CUMS group were increased significantly (P＜0.01), while sEPSC amplitude, sIPSC frequency, amplitude and capacitance were not significantly changed (P＞0.05). The frequency, amplitude, capacitance and E/I ratio of sEPSC and sIPSC of dCA1 pyramidal neurons were not significantly changed (P＞0.05). Conclusion: The anxiety-like behavior of CUMS-induced mice may be the result of the participation of multiple brain regions, which is mainly related to the increase of the excitability of pyramidal neurons in dlPFC, mPFC and vCA1 brain regions, but seems to have little relationship with dCA1 brain regions.

Sex difference in lipid levels in first-diagnosed drug-naïve depression patients: A case-control and 12-weeks follow-up study.

AIM: Patients with depression have a high prevalence of developing dyslipidemia. In this study, we aim to investigate the difference of serum lipids, including total cholesterol (TCH), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), between the depressed patients and healthy controls. Sex differences in lipids and their psychological correlations were also included. METHODS: The study included 56 healthy controls (males/females = 26/30) and 110 first-diagnosed drug-naïve outpatients (males/females = 35/75). A total of 42 patients (males/females = 14/28) were followed for 3 months. RESULTS: A significant difference was found in TCH and LDL-C among healthy control and patients. Interestingly, female patients with first-diagnosed, drug-naïve depression had lower atherogenic indices than male patients. After 3 months of antidepressants therapy, female patients exhibited detrimental changes in serum lipids, namely increased TG and atherogenic index. Moreover, correlation analysis showed significant correlations between changes of depression inventory (HAMD and BDI) score and serum lipids (TCH, HDL-C) in depressed patients. CONCLUSION: We found that dyslipidemia was more common in female patients with depression during therapy with antidepressants. Moreover, the altered serum lipids and atherogenic index might be a hallmark of female patients. Further investigation of sex differences in lipid metabolism of depression is warranted.

Weighted Gene Coexpression Network Analysis Reveals Essential Genes and Pathways in Bipolar Disorder.

Bipolar disorder (BD) is a major and highly heritable mental illness with severe psychosocial impairment, but its etiology and pathogenesis remains unclear. This study aimed to identify the essential pathways and genes involved in BD using weighted gene coexpression network analysis (WGCNA), a bioinformatic method studying the relationships between genes and phenotypes. Using two available BD gene expression datasets (GSE5388, GSE5389), we constructed a gene coexpression network and identified modules related to BD. The analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways were performed to explore functional enrichment of the candidate modules. A protein-protein interaction (PPI) network was further constructed to identify the potential hub genes. Ten coexpression modules were identified from the top 5,000 genes in 77 samples and three modules were significantly associated with BD, which were involved in several biological processes (e.g., the actin filament-based process) and pathways (e.g., MAPK signaling). Four genes (NOTCH1, POMC, NGF, and DRD2) were identified as candidate hub genes by PPI analysis and CytoHubba. Finally, we carried out validation analyses in a separate dataset, GSE12649, and verified NOTCH1 as a hub gene and the involvement of several biological processes such as actin filament-based process and axon development. Taken together, our findings revealed several candidate pathways and genes (NOTCH1) in the pathogenesis of BD and call for further investigation for their potential research values in BD diagnosis and treatment.

Meta-analysis dataset comparing orthodontic mini-implants and conventional anchorage reinforcement for maximum orthodontic anchorage.

The present article describes data from systematic review and meta-analysis investigating the efficacy and safety outcomes comparing mini-implants (MIs) and conventional anchorage reinforcement in patients with maximum dentoalveolar protrusion. All relevant RCTs and non-RCTs published up to 2018 were collected from PubMed, Embase and Cochrane database. Thirteen studies assessing the effect of mini-implants were included, of which 4 were randomized controlled trials (RCTs) and 9 observational studies. The efficacy parameters include mesiodistal movements of molars and incisors and vertical movements of molars and incisors. Whereas, the safety parameters were angular and linear measurement of soft tissue change. Subgroup analysis data was provided in terms of patients average age (<18 years and ≥18 years) at the initiation of treatment. This dataset is suitable for research purpose in the field of orthodontics and also helps dental doctors to determine their treatment preferences in the choice of anchorage reinforcement.

Increased frontal gray matter volume in individuals with prodromal psychosis.

BACKGROUND: Brain anatomical deficits associated with cognitive dysfunction have been reported in patients with schizophrenia. However, it remains unknown whether such anatomical deficits exist in individuals with prodromal psychosis. The present study is designed to investigate anatomical deficits in prodromal individuals and their associations with clinical/cognitive features. METHODS: Seventy-four prodromal individuals and seventy-six healthy controls were scanned using structural magnetic resonance imaging. Support vector machines were applied to test whether anatomical deficits might be used to discriminate prodromal individuals from healthy controls. RESULTS: Prodromal individuals showed significantly increased gray matter volume (GMV) in the right inferior frontal gyrus (IFG) and right rectus gyrus relative to healthy controls. No correlations were observed between increased GMV and clinical/cognitive characteristics. The combination of increased GMV in the right rectus gyrus and right IFG showed a sensitivity of 74.32%, a specificity of 67.11%, and an accuracy of 70.67% in differentiating prodromal individuals from healthy controls. CONCLUSION: Our results provide evidence of increased frontal GMV in prodromal individuals. A combination of GMV values in the two frontal brain areas may serve as potential markers to discriminate prodromal individuals from healthy controls. The results thus highlight the importance of the frontal regions in the pathophysiology of psychosis.

Metformin addition attenuates olanzapine-induced weight gain in drug-naive first-episode schizophrenia patients: a double-blind, placebo-controlled study.

OBJECTIVE: The purpose of this study was to assess the efficacy of metformin in preventing olanzapine-induced weight gain. METHOD: Forty patients with schizophrenia were randomly assigned to treatment for 12 weeks with olanzapine, 15 mg/day, plus metformin, 750 mg/day (N=20), or olanzapine, 15 mg/day, plus placebo (N=20). This investigation was conducted in a double-blind fashion. Planned assessments included body weight, body mass index, proportion of patients who gained more than 7% of their baseline weight at the end of the 12-week treatment, waist circumference, waist-to-hip ratio, fasting glucose and insulin, insulin resistance index, and scores on the Scale for the Assessment of Positive Symptoms (SAPS) and Scale for the Assessment of Negative Symptoms (SANS). RESULTS: Of the 40 patients who were randomly assigned, 37 (92.5%) completed treatments. The weight, body mass index, waist circumference, and waist-to-hip ratio levels increased less in the olanzapine plus metformin group relative to the olanzapine plus placebo group during the 12-week follow-up period. The insulin and insulin resistance index values of the olanzapine plus placebo group increased significantly at weeks 8 and 12. In contrast, the insulin and insulin resistance index levels of the olanzapine plus metformin group remained unchanged. Significantly fewer patients in the olanzapine plus metformin group relative to patients in the olanzapine plus placebo group increased their baseline weight by more than 7%, which was the cutoff for clinically meaningful weight gain. There was a significant decrease in SAPS and SANS scores within each group from baseline to week 12, with no between-group differences. Metformin was tolerated well by all patients. CONCLUSIONS: Metformin was effective and safe in attenuating olanzapine-induced weight gain and insulin resistance in drug-naive first-episode schizophrenia patients. Patients displayed good adherence to this type of preventive intervention.

Lifestyle intervention and metformin for treatment of antipsychotic-induced weight gain: a randomized controlled trial.

CONTEXT: Weight gain, a common adverse effect of antipsychotic medications, is associated with medical comorbidities in psychiatric patients. OBJECTIVE: To test the efficacy of lifestyle intervention and metformin alone and in combination for antipsychotic-induced weight gain and abnormalities in insulin sensitivity. DESIGN, SETTING, AND PATIENTS: A randomized controlled trial (October 2004-December 2006) involving 128 adult patients with schizophrenia in the Mental Health Institute of the Second Xiangya Hospital, Central South University, China. Participants who gained more than 10% of their predrug weight were assigned to 1 of 4 treatment groups. INTERVENTIONS: Patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 mg/d of metformin alone, 750 mg/d of metformin and lifestyle intervention, or lifestyle intervention only. MAIN OUTCOME MEASURES: Body mass index, waist circumference, insulin levels, and insulin resistance index. RESULTS: All 128 first-episode schizophrenia patients maintained relatively stable psychiatric improvement. The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8 (95% confidence interval [CI], 1.3-2.3), insulin resistance index of 3.6 (95% CI, 2.7-4.5), and waist circumference of 2.0 cm (95% CI, 1.5-2.4 cm). The metformin-alone group had mean decreases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 3.5 (95% CI, 2.7-4.4), and waist circumference of 1.3 cm (95% CI, 1.1-1.5 cm). The lifestyle-plus-placebo group had mean decreases in BMI of 0.5 (95% CI, 0.3-0.8) and insulin resistance index of 1.0 (95% CI, 0.5-1.5). However, the placebo group had mean increases in BMI of 1.2 (95% CI, 0.9-1.5), insulin resistance index of 0.4 (95% CI, 0.1-0.7), and waist circumference of 2.2 cm (95% CI, 1.7-2.8 cm). The lifestyle-plus-metformin treatment was significantly superior to metformin alone and to lifestyle plus placebo for weight, BMI, and waist circumference reduction. CONCLUSIONS: Lifestyle intervention and metformin alone and in combination demonstrated efficacy for antipsychotic-induced weight gain. Lifestyle intervention plus metformin showed the best effect on weight loss. Metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone. Trial Registration clinicaltrials.gov Identifier: NCT00451399.

[Association of HTR2C-759C/T and -697G/C polymorphisms with antipsychotic agent-induced weight gain].

OBJECTIVE: To determine whether antipsychotic agent-induced weight gain was associated with 5-hydroxytryptamine 2C receptor (HTR2C) gene-759C/T and -697G/C polymorphisms. METHODS: A case-matching controlled study was done. Eighty-five patients who had gained more than 7% of their pre-drug body weight served as a study group, and 85 patients who had gained less than 7% of their pre-drug body weight served as a control group. The control group were matched with the study group in the kinds of antipsychotic agents and the course of antipsychotic treatment. The ligation diction reaction technique was used to analyse the frequencies of HTR2C gene-759C/T and -697G/C polymorphisms. RESULTS: The study group were more likely to be hemizygous for the -759C (for male) and the -759CC genotype (for female) than the control group. The study group were more likely to be hemizygous for the -697G (for male) and the -697CG/GG genotype (for female) (all P<0.05) than the control group. CONCLUSION: The -759C/T and -697G/C polymorphisms of the promoter region of HTR2C gene may be associated with antipsychotic agent-induced weight gain.

[Anatomical study of human lumbar spine innervation].

OBJECTIVE: To explore the detailed innervation of the lumbar spine of humans. METHODS: Six adult cadavers fixed in a solution containing 10% formalin were investigated under a stereomicroscope. The lumbar spine, together with the abdominal aorta, inferior vena cava and psoas muscle, was extracted. The dissection was focused on various patterns of rami communicantes (RC), including superficial oblique rami (SOR) and deep transverse rami (DTR), and their relationship to the psoas major muscle, the minute nerve supply of the anterior and posterior longitudinal ligaments, vertebral bodies and the intervertebral discs. RESULTS: Two types of RC were observed: SOR and DTR. SOR ran obliquely between the superficial heads of the psoas major muscle, connecting the sympathetic trunk and T12-L2 spinal nerves non-segmentally. DTR, running along the lumbar arteries and veins, were distributed segmentally, close to the vertebral bodies. On the anterior aspect of the lumbar spine, the anterior longitudinal ligaments received branches from the sympathetic trunk and splanchnic nerves non-segmentally. On the lateral side of the lumbar spine, the vertebral bodies and the intervertebral discs received branches from the DTR and ventral rami segmentally, branches from the sympathetic trunk, and, in the upper lumbar region, SOR non-segmentally. Within the vertebral canal, the posterior aspect of the intervertebral discs and the posterior longitudinal ligaments received the sinu-vertebral nerves originating from DTR. CONCLUSION: Exist two different types of innervation in the lumbar vertebrae: one originating directly from the spinal nerve segmentally, and one reaching the vertebral body and intervertebral disc via the sympathetic nerves non-segmentally. Therefore, sympathetic nerves are involved in the innervation of the spinal column and intervertebral disc and are likely involved in discogenic low back pain.

Dalbergioidin (DAL) protects MC3T3-E1 osteoblastic cells against H2O2-induced cell damage through activation of the PI3K/AKT/SMAD1 pathway.

Reactive oxygen species (ROS) is a pivotal pathogenic factor in the development of osteoporosis. Dalbergioidin (DAL) can be isolated from Uraria crinite, an edible herb used as a natural food for childhood skeletal dysplasia. Recent research has implicated DAL as having an antiosteoporosis effect, although the mechanism of this is unclear. We used an effective oxidative stress model, induced by hydrogen peroxide (H2O2) in osteoblastic MC3T3-E1 cells, to investigate the protective effects of DAL in osteoporosis and the underlying molecular mechanisms. The results indicated that treatment with DAL maintained redox balance, reduced MC3T3-E1 cell apoptosis, improved alkaline phosphatase activity, and elevated the osteogenic-related protein expression of Runx2, Osterix, and BMP2 against oxidative damage induced by H2O2. The potential molecular mechanism involved in the protective effect of DAL against H2O2-induced cell death in MC3T3-E1 cells may lie in the activation of the PI3K/AKT/SMAD1 cell signal pathway. Taken together, the results indicated that the potential protective effects of DAL against osteoporosis were linked to a reduction in oxidative damage, suggesting that DAL may be useful in bone metabolism diseases, particularly osteoporosis.

Identifying cancer-related genes in nasopharyngeal carcinoma cell lines using DNA and mRNA expression profiling analyses.

The goals of this study were to evaluate the potential of detecting cryptic amplification and deletion of cancer-related genes using array-based comparative genomic hybridization (CGH), and to identify candidate cancer genes by combined parallel analyses of copy number and gene expression profiles in nasopharyngeal carcinoma (NPC) cell lines. We established global DNA copy number and mRNA expression profiles on human NPC cell lines using a high-density cDNA microarray. The DNA copy number alterations detected by array CGH were compared to the DNA copy number variations identified by metaphase CGH. A cryptic amplification at 3q26 was detected by array CGH, which was not found by metaphase CGH. By amplicon mapping and parallel analyses of DNA copy number and mRNA expression levels, we identified several candidates which could be important mediators in tumor formation or progression. Taken together, the combination of copy number and gene expression profiling using cDNA microarrays provides an improved strategy for gene discovery in human cancer.

[Expression of HIF-1α in the genioglossus associated with induced bilateral intermittent nasal obstruction in young rats].

PURPOSE: To investigate the expression of HIF-1α in the genioglossus associated with induced bilateral intermittent nasal obstruction in young rats. METHODS: Thirty 4-week-old SD rats were employed and equally divided into 3 groups. In group A, both nostrils were occluded by nose plugs. In group B, the right nostril was occluded. In group C, no obstruction of the nose was performed as control group. The obstruction time was from 8 am to 12 am everyday, and the period was 21 d and 55 d. The genioglossus was taken for HE, and immunohistochemical staining was used to detect the expression of HIF-1α. The data was analyzed with SPSS 13.0 software package. RESULTS: The rats were sacrificed at the 21th day and 55th day, respectively. The expression of HIF-1α in group A was significantly higher than that in group B and group C, and became stronger with the increasing of obstruction time. CONCLUSIONS: Oral breathing caused by bilateral intermittent nasal obstruction in young rats results in overexpression of HIF-1α in the genioglossus. Supported by Research Fund and Experimental Animal Fund of Science and Technology Committee of Shanghai Municipality (11140902001).

Potential mechanisms of atypical antipsychotic-induced hypertriglyceridemia.

RATIONALE AND BACKGROUND: The development of atypical antipsychotic (AAP) drugs has brought about dramatic improvement in the function of many patients with schizophrenia and related mental disorders. However, prescription of AAPs is frequently associated with the emergence of weight gain, hypertriglyceridemia, and other metabolic disturbances. Although the mechanisms involved in AAP-induced hypertriglyceridemia remain to be fully elucidated, several studies have proposed that this side effect may be associated with weight gain and obesity. Recently, special emphasis has been placed on the evidence indicating a direct effect of AAPs on triglyceride metabolism. OBJECTIVES: In this review, we highlight recent findings discussing the potential mechanisms by which AAPs may contribute to hypertriglyceridemia. In addition, we summarize the adjunctive pharmacologic treatments for AAP-associated dyslipidemia. CONCLUSIONS: There is evidence that AAPs may cause hypertriglyceridemia through several possible mechanisms: (1) a direct effect on triglyceride metabolism either by stimulation of hepatic triglyceride production and secretion or by inhibition of lipoprotein lipase-mediated triglyceride hydrolysis and (2) an indirect mechanism associated with obesity and insulin resistance. The practical applications of this manuscript provide new insights for the future investigation of AAPs.

Reversal alterations of amplitude of low-frequency fluctuations in early and late onset, first-episode, drug-naive depression.

BACKGROUND: It is unclear how patients with early onset depression (EOD) and late onset depression (LOD) differ at the neural level. Using amplitude of low-frequency fluctuations (ALFF) approach, we are to test the hypothesis of the different abnormal neural activities between patients with EOD and LOD. METHODS: Fifteen patients with EOD, 15 patients with LOD, 15 young healthy subjects (HS) and 15 old HS were enrolled in the study. ALFF approach was employed to analyze the images. RESULTS: ANOVA analysis revealed widespread differences in ALFF values among the four groups throughout frontal, parietal, temporal, occipital cortex, cerebellum and limbic regions. Compared to LOD group, EOD group had higher ALFF in bilateral precuneus, superior medial frontal gyrus and superior frontal gyrus, and lower ALFF in left brainstem and left superior temporal gyrus. Compared to young HS, lower ALFF in left superior/inferior temporal gyrus, left lingual gyrus and right middle occipital gyrus and higher ALFF in left medial frontal gyrus and bilateral superior frontal gyrus were seen in the EOD group; in contrast, in the LOD group, lower ALFF in bilateral superior frontal gyrus and higher ALFF in left superior temporal gyrus were observed. Further ROC analysis suggested that the mean ALFF values in the bilateral superior frontal gyrus and left superior temporal gyrus could serve as markers to separate patients with EOD from individuals with LOD. CONCLUSIONS: Patients with EOD and LOD exhibit reversal pattern of abnormal ALFF in bilateral superior frontal gyrus and left superior temporal gyrus.