JPT2 in subclinical hypothyroidism-related miscarriage as a transcription co-factor: involvement of LEPR/STAT3 activation.

BACKGROUND AND PURPOSE: Subclinical hypothyroidism (SCH) has been identified to be associated with implantation failure, in which the dysfunction of trophoblast cells is involved. In this study, the transcriptomics of aborted placenta from SCH rats were analyzed. Jupiter microtubule-associated homolog 2 (JPT2) was downregulated in the aborted placenta. This study aims to investigate its role in SCH-associated miscarriage. METHODS: Spontaneous abortion was observed in SCH rats generated by thyroidectomy combined with levothyroxine administration. The transcriptomics analysis was performed using aborted placenta. Afterward, the effects of JPT2 on trophoblast cells were explored using gain-and loss-of-function experiments. RESULTS: Transcriptomics analysis showed 1286 downregulated genes and 2300 upregulated genes in the aborted placenta, and JPT2 was significantly downregulated in the aborted placenta from SCH rats. Afterward, gain-and loss-of-function experiments exhibited that overexpression of JPT2 promoted the proliferation, migration, invasion, spheroid formation of HTR-8/SVneo trophoblast cells and their attachment to endometrial stromal cells, while these biological behaviors were suppressed by JPT2 knockdown. Furthermore, JPT2 accelerated the transcription of leptin receptor (LEPR), and activated signal transducer and activator of transcription 3 (STAT3) signal in a transcription factor AP-2γ-dependent manner. In addition, silencing of LEPR abolished the role of JPT2. CONCLUSION: Our results revealed that JPT2, which was downregulated in the aborted placenta from SCH rats, promoted proliferation, migration, invasion, spheroid formation, and attachment of trophoblast cells via regulating LEPR/STAT3 axis as a transcription co-factor. It is indicated that low expression of JPT2 may contribute to the abortion in individuals with SCH.

Potential ultrasonic anatomical markers of obstructive sleep apnoea-hypopnoea syndrome.

AIM: To investigate the potential value of ultrasonography in evaluating the pathophysiology of obstructive sleep apnoea-hypopnoea syndrome (OSAHS) by assessing the correlation of critical ultrasonic anatomical characteristics of the oropharynx with the severity of OSAHS. MATERIALS AND METHODS: One hundred and seventy-one patients with suspected OSAHS underwent oropharyngeal sonographic examination and overnight polysomnography. Ultrasonic measurement was compared with the apnoea-hypopnoea index (AHI) and other parameters. An ordinal logistic regression model was used to identify potential ultrasonic anatomical markers for OSAHS. RESULTS: The AHI was significantly correlated with lingual height (r=0.40, p<0.01), maximal width of the tongue (r=0.35, p<0.01), and distance from the symphysis of the mandible to the hyoid bone (M-HB) (r=0.24, p<0.01). A positive relationship between Friedman tongue position (FTP) grades and lingual height (r=0.24, p<0.01), between FTP grades and maximal width of the tongue (r=0.23, p<0.01), and between FTP grades and width of tongue base (TB; r=0.17, p<0.05) was found. Multivariate models adjusted for sex, age, and body mass index (BMI) revealed that lingual height (95% confidence interval [CI]: 1.04-1.24; p=0.004) is independently associated with a higher risk for the severity of OSAHS. CONCLUSIONS: Ultrasonography may be a potential imaging method for providing additional useful information about the correlation between ultrasound findings and the severity of OSAHS. Lingual height could be considered an ultrasonic anatomical marker for determining the severity of OSAHS patients independent of age, sex, and BMI.

Molecular characterization of insulin-like peptides in the brown planthopper, Nilaparvata lugens (Hemiptera: Delphacidae).

Insulin-like peptides (ILPs) including insulin, insulin-like growth factor (IGF) and relaxin are evolutionarily conserved hormones in metazoans, and they are involved in diverse physiological processes. The migratory brown planthopper (BPH), Nilaparvata lugens, encodes four ILP genes (Nlilp1, Nlilp2, Nlilp3 and Nlilp4) but their physiological roles are largely unknown. Sequence analysis showed that NlILP1 contained a relaxin-specific G protein-coupled receptor-binding motif and a variant motif of cysteine residues, and NlILP2 and NlILP4 resembled vertebrate IGFs. RNA interference (RNAi)-mediated gene silencing showed that depletion of each of Nlilp1, 2 and 3 significantly delayed the developmental duration of nymphs, and this effect could be exacerbated by double or triple gene depletion. Depletion of Nlilp1, Nlilp2 or Nlilp3 induces the accumulation of glucose, trehalose and glycogen, which is contradictory to depletion of the insulin receptor (NlInR1) in the BPH. Depletion of Nlilp1 significantly enhanced starvation resistance in both females and males although its extent was smaller than NlInR1 depletion. A parental RNAi assay showed that depletion of each of Nlilp1-4 dramatically impaired female fecundity. These findings indicate that NlILP1-4 have redundant and distinct roles in physiological processes in the BPH, thereby enhancing our understanding of the contribution of each NlILP to the ecological success of this species in natural habitats.

A splicing-regulatory polymorphism in DRD2 disrupts ZRANB2 binding, impairs cognitive functioning and increases risk for schizophrenia in six Han Chinese samples.

The rs1076560 polymorphism of DRD2 (encoding dopamine receptor D2) is associated with alternative splicing and cognitive functioning; however, a mechanistic relationship to schizophrenia has not been shown. Here, we demonstrate that rs1076560(T) imparts a small but reliable risk for schizophrenia in a sample of 616 affected families and five independent replication samples totaling 4017 affected and 4704 unaffected individuals (odds ratio=1.1; P=0.004). rs1076560(T) was associated with impaired verbal fluency and comprehension in schizophrenia but improved performance among healthy comparison subjects. rs1076560(T) also associated with lower D2 short isoform expression in postmortem brain. rs1076560(T) disrupted a binding site for the splicing factor ZRANB2, diminished binding affinity between DRD2 pre-mRNA and ZRANB2 and abolished the ability of ZRANB2 to modulate short:long isoform-expression ratios of DRD2 minigenes in cell culture. Collectively, this work implicates rs1076560(T) as one possible risk factor for schizophrenia in the Han Chinese population, and suggests molecular mechanisms by which it may exert such influence.

Peptic Ulcer Disease in Living Liver Donors: A Longitudinal Population-Based Study.

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003-2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non-LD comparison cohort comprised age- and sex-matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74-fold higher in the LD cohort than in the non-LD cohort (2.14 vs. 1.48 per 1000 person-years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non-LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45-2.09). The incidence of PUD increased with age; the risk of PUD was 2.53-fold higher in patients aged ≥35 years (95% CI 2.14-2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64-5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.

Functional and mutational analyses of an omega-class glutathione S-transferase (GSTO2) that is required for reducing oxidative damage in Apis cerana cerana.

Glutathione S-transferases perform a variety of vital functions, particularly in reducing oxidative damage. Here, we investigated the expression patterns of Apis cerana cerana omega-class glutathione S-transferase 2 (AccGSTO2) under various stresses and explored its connection with antioxidant defences. We found that AccGSTO2 knockdown by RNA interference triggered increased mortality in Ap. cerana cerana, and immunohistochemistry revealed significantly decreased AccGSTO2 expression, particularly in the midgut and fat body. Further analyses indicated that AccGSTO2 knockdown resulted in decreases in catalase and glutathione reductase activities, ascorbate content and the ratio of reduced to oxidized glutathione, and increases in H2 O2 , malondialdehyde and carbonyl contents. We also analysed the transcripts of other antioxidant genes and found that many genes were down-regulated in the AccGSTO2 knockdown samples, revealing that AccGSTO2 may be indispensable for attaining a normal lifespan by enhancing cellular oxidative resistance. In addition, the roles of cysteine residues in AccGSTO2 were explored using site-directed mutagenesis. Mutants of Cys(28) and Cys(124) significantly affected the enzyme and antioxidant activities of AccGSTO2, which may be attributed to the changes in the spatial structures of mutants as determined by homology modelling. In summary, these observations provide novel insight into the structural and functional characteristics of GSTOs.

Ropivacaine- and bupivacaine-induced death of rabbit annulus fibrosus cells in vitro: involvement of the mitochondrial apoptotic pathway.

OBJECTIVE: The purposes of this study were to assess whether local anesthetics (LAs), such as ropivacaine and bupivacaine, could induce apoptosis of rabbit annulus fibrosus (AF) cells in vitro and further to explore the possible underlying mechanism. METHODS: Rabbit AF cells at second passage were treated with saline solution and various concentrations of LAs. Apoptosis of AF cells were examined by cell counting kit-8 (CCK-8), Annexin V assays, Hoechst 33342 staining, and Caspase-3, -9 activity assays. The expression of apoptosis-related markers was detected by real-time PCR (RT-PCR) and Western Blot. The JC-1 staining was used to evaluate the change of mitochondrial membrane potential (MMP). Moreover, the levels of reactive oxygen species (ROS) were determined with fluorescent probe DCFH-DA. RESULTS: The results of flow cytometry indicated that LAs could induce apoptosis of rabbit AF cells in a dose-dependent manner. Apoptosis was confirmed by cell morphology, condensed nuclei and activation of Caspase-3 and -9. In addition, the molecular data showed that LAs could significantly up-regulate the expression of Bax, accompanied by a significant down-regulation of Bcl-2 expression. Furthermore, we also observed that LAs resulted in alteration of MMP and accumulation of intracellular ROS in AF cells. Blockade of ROS production by N-acetyl-l-cysteine (NAC) inhibited LAs-induced apoptosis. CONCLUSIONS: These findings suggest that LAs in clinically relevant concentrations could induce apoptosis of rabbit AF cells in vitro, and the mitochondrial pathway was, at least in part, involved in the LAs-mediated apoptosis. Further investigations focusing on the potential cytotoxicity of LAs on IVD cells are needed.

Increased risk of cardiovascular events in end-stage renal disease patients with osteoporosis: a nationwide population-based cohort study.

SUMMARY: We investigated the cardiovascular disease risk and mortality in end-stage renal disease (ESRD) patients. A total of 12,535 patients with ESRD undergoing incident dialysis were enrolled, 4,153 (33.13 %) of whom had osteoporosis. The osteoporosis group was associated with a significantly higher risk of coronary artery disease, congestive heart failure, stroke, and mortality. INTRODUCTION: In this study, we aimed to investigate the risk of cardiovascular disease and mortality in a sample of end-stage renal disease patients with osteoporosis. METHODS: We conducted this retrospective cohort study of incident dialysis patients with and without osteoporosis to evaluate the risk of overall mortality and cardiovascular complications including stroke, coronary heart disease, and congestive heart failure between the two groups. A total of 12,535 patients with ESRD undergoing incident dialysis were enrolled, 4,153 (33.13 %) of whom had osteoporosis, from the National Health Insurance Research Database of Taiwan for the years 1998 through 2011. The osteoporosis group had more comorbidities than the group without osteoporosis including hypertension, hyperlipidemia, mental disorders, and hepatitis C infection. RESULTS: After adjusting for age, gender, and related comorbidities, the osteoporosis group was associated with a significantly higher risk of coronary artery disease (hazard ratio (HR)=1.32, 95 % confidence interval (CI)=1.20-1.45) which was significant in both genders (women, HR=1.35, 95% CI=1.20-1.50; men HR=1.27, 95% CI=1.06-1.52) and all age groups (≤49 years HR=1.41, 95% CI=1.16-1.70; >49 years HR=1.30, 95% CI=1.16-1.45). Similar results were observed for the outcomes of congestive heart failure, stroke, and mortality. CONCLUSIONS: The results showed that osteoporosis was significantly associated with the subsequent risk of cardiovascular events in patients with ESRD. When encountering patients with ESRD and osteoporosis, physicians should be alert to the subsequent cardiovascular risk in incident dialysis patients to prevent the subsequent occurrence of these adverse events.

Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma.

BACKGROUND & AIMS: Subtle inter-patient genetic variation and environmental factors combine to determine disease progression in non-alcoholic fatty liver disease (NAFLD). Carriage of the PNPLA3 rs738409 c.444C >G minor allele (encoding the I148M variant) has been robustly associated with advanced NAFLD. Although most hepatocellular carcinoma (HCC) is related to chronic viral hepatitis or alcoholic liver disease, the incidence of NAFLD-related HCC is increasing. We examined whether rs738409 C >G was associated with HCC-risk in patients with NAFLD. METHODS: PNPLA3 rs738409 genotype was determined by allelic discrimination in 100 European Caucasians with NAFLD-related HCC and 275 controls with histologically characterised NAFLD. RESULTS: Genotype frequencies were significantly different between NAFLD-HCC cases (CC=28, CG=43, GG=29) and NAFLD-controls (CC=125, CG=117, GG=33) (p=0.0001). In multivariate analysis adjusted for age, gender, diabetes, BMI, and presence of cirrhosis, carriage of each copy of the rs738409 minor (G) allele conferred an additive risk for HCC (adjusted OR 2.26 [95% CI 1.23-4.14], p=0.0082), with GG homozygotes exhibiting a 5-fold [1.47-17.29], p=0.01 increased risk over CC. When compared to the UK general population (1958 British Birth Cohort, n=1476), the risk-effect was more pronounced (GC vs. CC: unadjusted OR 2.52 [1.55-4.10], p=0.0002; GG vs. CC: OR 12.19 [6.89-21.58], p<0.0001). CONCLUSIONS: Carriage of the PNPLA3 rs738409 C >G polymorphism is not only associated with greater risk of progressive steatohepatitis and fibrosis but also of HCC. If validated, these findings suggest that PNPLA3 genotyping has the potential to contribute to multi-factorial patient-risk stratification, identifying those to whom HCC surveillance may be targeted.

Association of interleukin-6 and CD4+ T cells and two-week prognosis of patients with COVID-19: a predictive role.

OBJECTIVE: The aim of this study was to determine the association of inflammation and immune responses with the outcomes of patients at various stages, and to develop risk stratification for improving clinical practice and reducing mortality. PATIENTS AND METHODS: We included 77 patients with primary outcomes of either death or survival. Demographics, clinical features, comorbidities, and laboratory tests were compared. Linear, logistic, and Cox regression analyses were performed to determine prognostic factors. RESULTS: The average age was 59 years (35-87 years). There were 12 moderate cases (16.2%), 42 severe cases (54.5%), and 23 critical cases (29.9%); and 41 were male (53.2%). Until March 20, 68 cases were discharged (88.3%), and nine critically ill males (11.7%) died. Interleukin-6 (IL-6) levels on the 1st day were compared with IL-6 values on the 14th day in the severe and the critically ill surviving patients (F=4.90, p=0.034, ß=0.35, 95% CI: 0.00-0.10), and predicted death in the critically ill patients (p=0.028, ß=0.05, OR: 1.05, 95% CI: 1.01-1.10). CD4+ T-cell counts at admission decreased the hazard ratio of death (p=0.039, ß=-0.01, hazard ratio=0.99, 95% CI: 0.98-1.00, and median survival time 13.5 days). CONCLUSIONS: The present study demonstrated that IL-6 levels and CD4+ T-cell count at admission played key roles of predictors in the prognosis, especially for critically ill patients. High levels of IL-6 and impaired CD4+t cells are seen in severe and critically ill patients with COVID-19.

Allergen detection and logistic multifactor analysis of allergic rhinitis.

OBJECTIVE: This study aims to investigate the allergens in children with allergic rhinitis (AR) and AR-related influencing factors. PATIENTS AND METHODS: The clinical data of 230 children with AR admitted to our hospital from June 2020 to June 2021 were retrospectively analyzed and included in the observation group. The clinical data of 230 healthy children during the same time period were included as the control group. All children had been tested for allergens using serum allergens, and the clinical data were collected by telephone questionnaires. Univariate and multivariate logistic regression were used to analyze the risk factors affecting AR. RESULTS: A total of 230 children with AR was included in this study, and some of them had two or more allergens. The proportion of house dust mite was the highest among the inhaled allergens, about 75.22%. Shrimp accounted for the highest proportion of food allergens, about 40.87%. Compared with the control group, the proportion of floating population, home heating, allergy history, asthma and other general information in the observation group was higher. At the same time, the proportion of environmental factors such as second-hand smoke, number of residents (≤ 3), daily ventilation and cleaning (no), domestic animals, domestic plants, decoration within 2 years, and living environment (rural) in the observation group was higher. In addition, the proportion of family factors such as delivery mode (cesarean section), family history of allergic rhinitis, parents' education level (middle school and above) in the observation group was higher (p < 0.05). Univariate logistic regression analysis showed that allergic history, asthma, second-hand smoke, floating population, number of residents, domestic animals, decoration within 2 years, delivery mode, and family history of allergic rhinitis were the risk factors affecting the incidence of AR in children (p < 0.05), and daily window ventilation and cleaning were the protective factors (p < 0.05). The multivariate logistic regression analysis showed that asthma, second-hand smoke, floating population, decoration within 2 years, family history of allergic rhinitis and domestic animals were independent risk factors for the occurrence of AR (p < 0.05), and daily ventilation and cleaning were protective factors for the occurrence of AR in children (p < 0.05). CONCLUSIONS: The proportion of house dust mite in inhalation allergens and shrimp in food allergens were the highest in AR children. The incidence of AR was closely related to asthma, second-hand smoke, floating population, decoration within 2 years, family history of AR and domestic animals, etc. Targeted measures could effectively prevent the occurrence and recurrence of AR. At the same time, daily ventilation and cleaning were the protective factors which could reduce the incidence and occurrence of AR in children.

Outcomes of elderly patients with traumatic brain injury associated with the pre-injury antithrombotic prophylaxis type - A systematic review and meta-analysis.

OBJECTIVE: Our review aims at comparing the morbidity and mortality-related risks associated with the pre-injury administration of VK-antagonists or DOACs in elderly patients with TBI. MATERIALS AND METHODS: We performed a systematic search of the academic literature across five databases (Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE), following PRISMA guidelines. We conducted a random-effect meta-analysis to compare the influence of pre-injury VK-antagonists or DOACs administration on the overall intensive care unit and hospital stays of patients with TBI. We also evaluated the overall risks associated with VK-antagonists and with DOACs for intracranial hemorrhage progression, surgical intervention, and overall mortality in patients with TBI. RESULTS: From 973 studies, we found 11 eligible with 4,991 patients with traumatic brain injury (mean age, 77.82 ± 6.76 years). Our meta-analysis revealed insignificantly higher odds of surgical intervention (OR=1.72) and mortality (OR=1.07) associated with VK-antagonists administration than with DOACs administration. Similarly, we found that the intensive care unit (Hedge's g, 0.13) and hospital (g, 0.26) stays were insignificantly longer for individuals on VK-antagonists than for those on DOAC. Moreover, we observed insignificantly higher intracranial hemorrhage progression risks (OR=1.22) for individuals receiving DOACs than for those receiving VK-antagonists. CONCLUSIONS: This study provides evidence on the morbidity and mortality-related outcomes associated with the pre-injury administration of VK-antagonists or DOACs in patients with TBI. We found no significant differences between VK-antagonists and DOACs on the overall morbidity (hospital and intensive care unit stays, intracranial hemorrhage, and surgical intervention frequency) and mortality outcomes in elderly patients with TBI.

Effect of tirofiban in treating patients with progressive ischemic stroke.

OBJECTIVE: Our aim is to investigate the efficacy and safety of tirofiban in the treatment of patients experiencing progressive ischemic stroke (PIS). PATIENTS AND METHODS: A retrospective analysis was performed on the clinical data of 150 patients with ischemic stroke admitted to our hospital from May 2018 to December 2019. All the patients were divided into two groups according to different treatment methods. In Control group, conventional comprehensive treatment and antiplatelet therapy with aspirin + clopidogrel were conducted, while tirofiban was administered in Tirofiban group in addition to the treatments in Control group. Neurological deficits were scored by means of the National Institutes of Health Stroke Scale (NIHSS) at the time of progression and 30 d after treatment, and the modified Rankin Scale (mRS) and Activity of Daily Living (ADL) scale were employed to assess prognosis at 90 d after treatment. Thereafter, the platelet aggregation rate, platelet adhesion rate, plateletcrit (PCT), platelet distribution width (PDW), and platelet inhibition rate were measured before and after treatment. Finally, the patients were followed up, and the occurrence of hemorrhage events during treatment and within 90 d after discharge was recorded. RESULTS: After treatment, all the patients had significantly lower NIHSS and mRS scores and a dramatically higher Barthel index (BI) than those before treatment (p<0.001). At 90 d after treatment, Tirofiban group exhibited significantly higher BI (p<0.001) and lower mRS score than Control group (p=0.011). In addition, at 14 d after treatment, the clinical efficacy was assessed for all the patients. It was found that the overall response rate in Tirofiban group was substantially higher than that in Control group [82.7% (62/75) vs. 64.0% (48/75), p=0.009]. At 7 d after treatment, the PCT and adenosine diphosphate (ADP) platelet inhibition rate in Tirofiban group were markedly higher than those in Control group (p=0.006, p<0.001), and Tirofiban group had remarkably lower measured values of platelet aggregation rate, platelet adhesion rate and PDW than Control group (p=0.007, p=0.021, p<0.001). After treatment, the levels of serum IL-6 and hs-CRP declined notably in the two groups of patients, and the differences in their levels at 2 and 14 d after treatment between the two groups were statistically significant (p<0.05). During treatment and within 90 d after discharge, both groups of patients had no cerebral hemorrhage, gastrointestinal hemorrhage, and severe hemorrhage adverse events requiring blood transfusion, but they experienced subcutaneous ecchymosis, epistaxis, gingival hemorrhage, and hemorrhage around the infarct, which were improved after symptomatic treatment. Moreover, the occurrence rate of hemorrhage in Tirofiban group was higher than that in Control group, showing no statistically significant difference (p>0.05). CONCLUSIONS: Tirofiban combined with conventional basic treatment can greatly improve neurological deficits and disease outcomes, alleviate platelet adhesion, and reduce platelet activation without increasing the risk of hemorrhage in PIS patients.

Changes of brain-derived neurotrophic factors in rats with generalized anxiety disorder before and after treatment.

OBJECTIVE:   The aim of the current study was to investigate the association between brain-derived neurotrophic factor (BDNF) and generalized anxiety disorder (GAD). MATERIALS AND METHODS: A total of sixty male adult Wistar rats with similar body weight and age were randomly divided into 3 groups the blank control group (CON, n=20), the saline control group (SAL, n=20), and the combined medication group (Deanxit +fluoxetine, DF, n=20), then rats in group SAL and group DF were prepared for model of anxiety disorder for 14 days. The body weight, center-retention time (CRT) and square-crossover number per unit time (SCN) were compared during modeling to define the anxiety of rats on day 1, day 7 and day 14; the BDNF mRNA in brain were detected by RT-PCR and the protein of BDNF in brain were detected by immunohistochemistry before and after intervention. The body weight, CRT and SCN in group SAL and DF after modeling were decreased with time compared with CON (p<0.05). The rats were taken euthanasia after 14 days, the BDNF mRNA showed significant decrease in SAL group (0.58±0.07) compared with group CON (2.87±0.23), while in DF group (1.76±0.21), the BDNF mRNA were higher than SAL group but lower than CON (p<0.05); the BDNF positive cells in group CON was highest (90%), then was group DF (75%) and group SAL was the lowest (35%). RESULTS: The changes in the indexes of the rats among different groups before and after modeling showed that after modeling, the body weights of the rats in group SAL and group DF were lower than group CON, the CRT decreased, and the SCN increased. The differences were statistically significant (p < 0.05), indicating that the combined medication (Qilixin + fluoxetine) can improve anxiety symptoms (body weight, CRT, and SCN). CONCLUSIONS: Anti-anxiety drugs (Deanxit+fluoxetine) can improve anxiety symptoms of rats and increase the expressions of BDNF mRNA and protein in rat brain cells. Anxiolytic drugs (Deanxit+fluoxetine) may achieve the treatment of anxiety disorders through improving the 5-HT nervous system and the expressions of BDNF mRNA and protein. BDNF can be used as a biochemical indicator for the diagnosis and efficacy evaluation of GAD.

LINC00261 regulates EBF1 to suppress malignant progression of thyroid cancer.

OBJECTIVE: We aimed to explore the role of LINC00261 in thyroid cancer (TC) and the potential regulatory mechanism. PATIENTS AND METHODS: 40 cases of tumor tissues and adjacent tissues of TC patients were collected, and the expressions of LINC00261 and EBF1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the relationship between LINC00261 and the clinical pathological indicators and prognosis of TC patients were analyzed. Next, LINC00261 overexpression and knockdown cell models were constructed in TC cell lines BPH5-16 and K1, respectively. Cell counting kit-8 (CCK-8) and transwell migration were used to detect the impact of LINC00261 overexpression or silencing on cell proliferative and migration ability. The bioinformatics website was used to screen the possible target gene of LINC00261. RESULTS: qRT-PCR analysis showed that LINC00261 level was markedly reduced in TC tumor tissues, as well as corresponding cell lines. Retrospective analysis showed that low expression of LINC00261 was in positive correlation with the pathological stage, lymphatic and distant metastasis in patients with TC, meanwhile, the expression of LINC00261 was also in positive correlation with overall survival rate of TC patients. Bioinformatics analysis suggested that LINC00261 could target EBF1. Luciferase reporter gene experiment and qRT-PCR analysis suggested that LINC00261 could target EBF1 and that their expressions showed a negative correlation in TC tumor tissues and cells. Cell functional experiments confirmed that LINC00261 can inhibit the proliferative and migration ability of TC cells. Subsequently, the recovery experiment also suggested that silencing EBF1 could reverse the promotion effect of LINC00261 knockdown on the proliferative and migration ability of TC cells; while EBF1 overexpression could reverse the inhibition of LINC00261 on the proliferative and migration ability of TC cells. CONCLUSIONS: LINC00261 was markedly downregulated in TC tissues and cells. In addition, the level of LINC00261 was closely related to lymph node and distant metastasis, as well as the prognosis in TC patients. Moreover, LINC00261 could negatively regulate EBF1, thereby promoting the malignant progression of TC.

Subcutaneous oxyntomodulin analogue administration reduces body weight in lean and obese rodents.

OBJECTIVE: To determine the efficacy of a long-acting oxyntomodulin (OXM) analogue, OXM6421, in inhibiting food intake and decreasing body weight in lean and diet-induced obese (DIO) rodents. RESEARCH DESIGN AND METHODS: The glucagon-like peptide-1 (GLP-1) receptor binding affinity and efficacy, sensitivity to enzymatic degradation in vitro and persistence in the circulation after peripheral administration were investigated for OXM6421 and compared with native OXM. The chronic effect of OXM6421 on food intake, body weight and energy expenditure was examined in lean rats, and its anti-obesity potential was evaluated in DIO mice. RESULTS: OXM6421 showed enhanced GLP-1 receptor binding affinity and cyclic adenosine monophosphate (cAMP) stimulation, and higher resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase (NEP) compared with native OXM. OXM6421 persisted longer in the circulation than OXM after peripheral administration. Acute administration of OXM6421 potently inhibited food intake in lean rodents, with cumulative effects lasting up to 24 h. In lean rats, daily subcutaneous (s.c.) administration of OXM6421 caused greater weight loss than the pair-fed animals, and a higher rate of oxygen consumption than both the pair-fed and the saline controls. In DIO mice, continuous s.c. infusion of OXM6421 resulted in a significant weight loss, accompanied by an improvement in glucose homeostasis and an increase in circulating adiponectin levels. Once-daily s.c. administration of OXM6421 for 21 days caused sustained weight loss in DIO mice. CONCLUSION: OXM6421 induces negative energy balance in both lean and obese rodents, suggesting that long-acting OXM analogues may represent a potential therapy for obesity.

Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance.

OBJECTIVE: The hypothalamic control of energy balance is regulated by a complex network of neuropeptide-releasing neurons. Although the effect of these neuropeptides on individual aspects of energy homoeostasis has been studied, the coordinated response of these effects has not been comprehensively investigated. We have simultaneously monitored a number of metabolic parameters following intracerebroventricular (ICV) administration of 1 and 3 nmol of neuropeptides with established roles in the regulation of feeding, activity and metabolism. Ad libitum- fed rats received the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin-A. Overnight-food-deprived rats received an ICV injection of the anorectic peptides alpha-melanocyte-stimulating hormone (MSH), corticotrophin-releasing factor (CRF) or neuromedin U (NMU). RESULTS: Our results reveal the temporal sequence of the effects of these neuropeptides on both energy intake and expenditure, highlighting key differences in their function as mediators of energy balance. NPY and AgRP increased feeding and decreased oxygen consumption, with the effects of AgRP being more prolonged. In contrast, orexin-A increased both feeding and oxygen consumption, consistent with an observed increase in activity. The potent anorexigenic effects of CRF were accompanied by a prolonged increase in activity, whereas NMU injection resulted in significant but short-lasting inhibition of food intake, ambulatory activity and oxygen consumption. alpha-MSH injection resulted in significant increases in both ambulatory activity and oxygen consumption, and reduced food intake following administration of 3 nmol of the peptide. CONCLUSION: We have for the first time, simultaneously measured several metabolic parameters following hypothalamic administration of a number of neuropeptides within the same experimental system. This work has shown the interrelated effects of these neuropeotides on activity, energy expenditure and food intake, thus facilitating comparison between the different hypothalamic systems.

The relationship between chronic hepatitis B infection and bone mineral, metabolism in peritoneal dialysis patients.

OBJECTIVE: Abnormality of bone mineral metabolism is a common complication in chronic liver disease and/or chronic renal disease patients. We designed this study to evaluate the relationship between chronic hepatitis B infection and bone mineral metabolism in peritoneal dialysis patients. PATIENTS AND METHODS: Serum calcium[adj], phosphorus, calcium and phosphorus product (Ca x P), along with intact parathyroid hormone (iPTH) levels were compared in peritoneal dialysis patients with and without chronic hepatitis B infection. RESULTS: A total of 220 patients (142 female, 78 male) with a mean age of 56.30 +/- 14.28 (range 19 - 86) years old were recruited, 23 showed chronic hepatitis B infection and 197 showed none. No statistically significant difference in serum calcium[adj] levels (9.90 +/- 0.85 mg/dl vs. 10.08 +/- 0.80 mg/dl, p = 0.354), phosphorus levels (5.26 +/- 1.58 mg/dl vs. 5.21 +/- 1.35 mg/dl, p = 0.879) and calcium and phosphorus product (Ca x P) (52.23 +/- 17.54 mg(2)/dl(2) vs. 52.42 +/- 14.16 mg(2)/dl(2), p = 0.960) between groups with and without chronic hepatitis B infection was observed. Serum iPTH levels were significantly lower in chronic hepatitis B patients (median 143 pg/ml, range 3.42 - 889) than in the control group (median 235 pg/ml, range 3 - 2381) (p = 0.035). As analyzed by multi-variable linear regression, chronic hepatitis B was a predictor of lower serum iPTH levels (beta = -0.271; p = 0.030) after adjustments for age, gender, serum calcium and phosphorus levels and diabetes. CONCLUSION: No significant difference in serum calcium[adj]), phosphorus and calcium and phosphorus product (Ca x P) levels appeared between peritoneal dialysis patients with and without chronic hepatitis B infection. Serum iPTH levels proved to be definitely lower in chronic hepatitis B infection patients.

C-reactive protein predicts ischaemic stroke in haemodialysis patients.

Dialysis patients have a higher incidence of cerebrovascular events compared with the general population. However, the value of C-reactive protein (CRP) in predicting stroke in chronic haemodialysis patients is unknown. The aim of this study was to determine the association between serum CRP levels and ischaemic stoke in chronic haemodialysis patients. We retrospectively reviewed 391 chronic haemodialysis patients between November 2001 and November 2004. Patients who developed acute ischaemic stroke within 36-month were recorded. Patients who had lacunar infarction discovered accidentally during brain computed tomography or magnetic resonance imaging scans were recorded for subgroup analysis. The relation of predialysis serum CRP levels, measured via the nephelometric method, to the development of acute ischaemic stroke was analysed using Kaplan-Meier analysis. Factors related to lacunar infarctions were analysed by multivariate logistic regression. Of the 391 patients, 21 developed acute stroke and 24 had lacunar infarction. Kaplan-Meier analysis showed that patients with a serum CRP > 0.8 mg/dl were at risk of developing acute infarction (p = 0.002). In the Cox regression model adjusted for age, cardiovascular disease, hypertension and diabetes, patients with serum CRP > 0.8 mg/dl are at risk of developing acute ischaemic stroke (p = 0.03). In multivariate logistic regression with adjusted for age, hypertension and diabetes, serum CRP levels significantly associated with lacunar infarction (p = 0.05). Serum CRP levels, independent of cardiovascular disease, age, hypertension and diabetes, are associated with the development of acute ischaemic stroke and lacunar infarct in chronic haemodialysis patients.

Intravenous iron attenuates postvaccination anti-HBsAg titres after quadruple hepatitis B vaccination in dialysis patients with erythropoietin therapy.

BACKGROUND: Anaemia in patients with end-stage renal disease (ESRD) is commonly treated with recombinant human erythropoietin (rHuEPO), often in combination with an adjuvant iron supplement. There is much evidence that rHuEPO can influence the immune response by its effect on lymphocytes. Also, iron catalyses the formation of radicals and increases the risk of major infections by negatively affecting the immune system. The relationship between antibodies to hepatitis B surface antigen (anti-HBsAg) responsiveness after hepatitis B vaccination and rHuEPO/adjuvant iron supplementation has not been reported before. AIM: To determine the effects of subcutaneous erythropoietin and intravenous (i.v.) iron therapy on the responsiveness of anti-HBsAg after quadruple hepatitis B vaccination among ESRD patients. METHODS: Retrospective medical records were reviewed in a hospital with a tertiary teaching facility. Eighty-three ESRD patients, including 51 who underwent haemodialysis and 32 who underwent peritoneal dialysis therapy, received a quadruple recombinant hepatitis B vaccine. We investigated anti-HBsAg titres in those patients who either received rHuEPO alone (n = 50) or rHuEPO in combination with i.v. iron (n = 33). RESULTS: We found that the postvaccination anti-HBsAg titre was significantly lower in the rHuEPO plus i.v. iron group when compared with the group with rHuEPO alone (p < 0.05). The increment of anti-HBsAg between the initial month and the seventh month was positively correlated with therapeutic rHuEPO dosages in the group with rHuEPO alone (r = 0.303, p = 0.033). This relationship was not present in the rHuEPO with i.v. iron group (r = -0.289, p = 0.229). CONCLUSIONS: The levels of anti-HBsAg after hepatitis B vaccination are positively correlated with the dose of rHuEPO treatment during the vaccinated period among ESRD patients without i.v. iron supplementation. Also, i.v. iron negatively impacts the responsiveness of anti-HBsAg titre after hepatitis B vaccination in ESRD patients who have undergone rHuEPO therapy.