Identifying subgroups of attention-deficit/hyperactivity disorder from the psychopathological and neuropsychological profiles.

The Research Domain Criteria (RDoC) advocates the dimensional approach in characterizing mental disorders. We followed RDoC to characterize children with ADHD using profiling based on the cognitive and psychopathological domains. We aimed to identify and validate ADHD subtypes with different clinical characteristics and functional impairments. We recruited 362 drug-naïve children with ADHD and 103 typically developing controls. The cluster analysis was used to identify subgroups based on the Child Behaviour Checklist (CBCL) and the Behaviour Rating Inventory of Executive Function (BRIEF). The subgroups' clinical characteristics and functional impairments were assessed using the WEISS Functional Impairment Rating Scale-Parent Report (WFIRS-P) and the Conners Parent Symptom Questionnaire (PSQ). The cluster analysis yielded four subgroups: (1) ADHD with severe impairment in psychopathology and executive functions (EF), (2) ADHD with mild executive dysfunctions and normal-level psychopathology, (3) ADHD with severe externalizing problems and (4) ADHD with severe executive dysfunctions. These subgroups showed different clinical characteristics and degrees of functional impairment. The EF impairment group displayed more serious learning problems and worse life skills than the externalizing group. The two groups with externalizing problems (i.e. the severe impairment group and the externalizing group) both exhibited higher rates of the combined subtype of ADHD and higher rates of comorbid ODD. Different subtypes of ADHD displayed different profiles of internalizing and externalizing problems and levels of executive dysfunctions. In particular, the subtype with severe impairment in EF exhibited more learning problems and worse life skills, suggesting EF is a critical target for intervention in children with ADHD.

Correlations between facial emotion processing and biochemical abnormalities in untreated adolescent patients with major depressive disorder: A proton magnetic resonance spectroscopy study.

BACKGROUND: Studies show that disturbances of the fronto-striato-thalamic-cerebellar circuit could be correlated to facial emotion processing (FEP) biases in major depressive disorder (MDD). Nevertheless, the underlying mechanism of natural metabolism-emotion relationships in adolescent MDD remains unclear. METHODS: Thirty-seven adolescent patients with MDD and 30 healthy controls completed FEP tasks using the Chinese Facial Affective Picture System (CAFPS). Proton magnetic resonance spectroscopy (1H-MRS) was also used to obtain ratios of N-acetylaspartate (NAA) /creatine (Cr) and choline (Cho) /Cr ratios in the prefrontal cortex (PFC), anterior cingulate cortex (ACC), putamen, thalamus and cerebellum. Correlations between abnormal neurometabolic ratios and FEP were also computed. RESULTS: Compared with the control group, the MDD group had significantly lower accuracy and perception intensity of happiness, and significantly higher accuracy of disgust and perception intensity of sad and fearful faces in FEP tasks. Compared to healthy controls, adolescent patients with MDD showed significantly lower NAA/Cr ratios in the left PFC, higher NAA/Cr ratios in the right thalamus, and higher Cho/Cr ratios in the right putamen, although there were no significant differences in metabolites in the ACC and cerebellum between two groups. In the MDD group, NAA/Cr ratios of the right thalamus were negatively correlated with happy reaction time and positively correlated with sad, anger, and fear intensity; Cho/Cr ratios in the right putamen were positively correlated with fear reaction time. CONCLUSIONS: Our findings suggest that FEP bias may exist in adolescents with MDD, while the impairment of FEP may be associated with abnormal metabolites in the fronto-striato-thalamic circuit.

[Intellectual characteristics of children with attention deficit hyperactivity disorder and developmental dyslexia].

OBJECTIVE: To study the intellectual characteristics of children with attention deficit hyperactivity disorder (ADHD) and developmental dyslexia (DD). METHODS: A total of 55 children with ADHD and DD (ADHD+DD group), 150 children with ADHD alone (ADHD group), and 22 children with DD alone (DD group) were enrolled as subjects. Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was used to evaluate and compare intellectual characteristics among the three groups. RESULTS: There were significant differences in the scores of full-scale intelligence quotient (FSIQ), verbal comprehension index, perceptual reasoning index, and working memory index among the three groups (P < 0.05):the ADHD+DD group had significantly lower scores of FSIQ, verbal comprehension index, perceptual reasoning index, and working memory index than the ADHD group, as well as a significantly lower FSIQ score than the DD group. A comparison of the 10 core subtests in WISC-IV showed that compared with the ADHD group, the ADHD+DD group had significantly lower scores of similarities, vocabulary, comprehension, recitation, picture concepts, matrix reasoning, and letter-number sequencing (P < 0.05). Compared with the DD group, the ADHD+DD group had significantly lower scores of vocabulary, similarities, picture concepts, matrix reasoning, and recitation (P < 0.05). CONCLUSIONS: Compared with the children with ADHD alone, the children with ADHD and DD have more severe impairment of FSIQ, verbal comprehension, perceptual reasoning, and working memory, and therefore, it is suggested to enhance the training on similarities, vocabulary, matrix reasoning, picture concepts, and recitation for children with ADHD and DD in clinical practice.

BCL-3 and ß-catenin signaling and tumor staging in colorectal cancer.

Colorectal cancer (CBC) is the third most common cancer in men and the second most common cancer in women in the world, as well as the second leading cause of death among the world's cancers. In this study, to identify the genes involved in the CRC clinical outcomes, the expression of B cell leukemia/lymphoma 3 (BCL-3) gene in patients with colorectal cancer was investigated along with serum level of ß-catenin. In this study, samples of 23 patients with colorectal cancer were prepared. mRNA was extracted and then cDNA was prepared for evaluation of PCR. Then, with specific primers for the BCL3, a semi-quantitative RT-PCR test was performed. The enzyme-linked immunosorbent assay (ELISA) was used to assess the serum level of ß-catenin. In this study, 23 men with an average age of years were included. BCL-3 expression in tumor tissue was significantly higher than its level in healthy tissue (P=0.021). BCL-3 expression at stage 0 of the tumor was significantly lower than at all other stages (P<0.05), and the comparison between the rest of the CRC stages was not significant (P>0.05). The median of serum ß-catenin levels in the patients was 32.83 (22.45, 46.09). There was no significant difference in the amount of serum ß-catenin between all 5 stages of the disease and in terms of lymph node metastasis. There were no relationships between age, BMI, smoking history, familial CRC history, and BCL-3 or ß-catenin serum levels (P>0.05). In this study, the expression of the BCL-3 gene in tumor specimens was high. It can be said that the BCL-3 gene can act as one of the genes involved in colorectal cancer, along with some genes such as ß-catenin. While BCL-3 was associated with a higher stage of CRC, ß-catenin didn't show such a relationship with CRC.

Continuous Blood Purification Ameliorates Multiple Organ Failure Through Inhibiting the Activation of the P38 MAPK Signaling Pathway in a Rat Model.

BACKGROUND/AIMS: Multiple organ failure (MOF) is a primary threat to the survival of patients with systemic inflammation. Blood purification is employed in the treatment of MOF, as an artificial kidney or artificial liver. This study focuses on the effects of continuous blood purification (CBP) on ameliorating MOF through regulating the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a rat model. METHODS: A rat model of MOF was successfully established by endotoxin injection after hemorrhagic shock resuscitation. The mRNA expressions of inducible nitric oxide synthase (iNOS) and p38 MAPK of liver, kidney, and lung tissues in each group were measured by RT-qPCR at each measuring time point. To evaluate the activation of p38 MAPK signaling pathway, protein levels of phosphorylated p38 (p-p38) MAPK and p38 MAPK was measured by western blot analysis. The serum levels of nitric oxide and TNF-α were determined. RESULTS: After CBP treatment, the levels of SGPT, SGOT, Cr, and BUN were significantly declined, while the PaO2 value was increased. Expressions of p38 MAPK mRNA, iNOS mRNA, p-p38 MAPK protein and p38 MAPK protein, and nitric oxide and TNF-α levels were markedly elevated in MOF, an effect blunted by CPB. Meanwhile, pathological sections of liver, kidney, and lung tissues after CPB treatment ameliorated swelling and inflammation. CONCLUSION: Our study proved that CBP could downregulate the p38 MAPK signaling pathway, suppress iNOS expression, reduced the serum levels of nitric oxide and TNF-α, thus ameliorate symptom of MOF.

MicroRNA-30e promotes hepatocyte proliferation and inhibits apoptosis in cecal ligation and puncture-induced sepsis through the JAK/STAT signaling pathway by binding to FOSL2.

INTRODUCTION: Hepatocyte proliferation and apoptosis are critical cellular behaviors in rat liver as a result of a liver injury. Herein, we performed this study in order to evaluate the role of miR-30e and its target Fos-Related Antigen-2 (FOSL2) in septic rats through the JAK/STAT signaling pathway. METHODS: Rat models of sepsis were induced by cecal ligation and puncture. Enzyme-linked immunosorbent assay (ELISA) was performed to access serum levels of lipopolysaccharide (LPS), inflammatory factors, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to confirm the successful establishment of the model. The hepatocytes were subject to miR-30e mimics, miR-30e inhibitors or siRNA-FOSL2. The expressions of miR-30e, FOSL2, apoptosis- and, JAK/STAT signaling pathway-related genes in liver tissues and hepatocytes were determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. MTT assay and flow cytometry were performed to evaluate hepatocyte viability and apoptosis, respectively. RESULTS: The results obtained revealed that in the septic rats, serum levels of inflammatory factors, LPS, ALT and AST, as well as the expression of FOSL2 were elevated and the JAK/STAT signaling pathway was activated, while there was a reduction in the expression of miR-30e. An initial bioinformatics prediction followed by a confirmatory dual-luciferase reporter assay determined that miR-30e targeted and negatively regulated FOSL2 expression. MiR-30e inhibited the activation of JSK2/STAT3 signaling pathway by reducing FOSL2 expression, while miR-30e enhanced hepatocyte proliferation and decreased hepatocyte cell apoptosis in septic rats. CONCLUSION: These findings indicated that miR-30e may serve as an independent therapeutic target for sepsis, due to its ability to inhibit apoptosis and induce proliferation of hepatocytes by targeted inhibition of FOSL2 through the JAK/STAT signaling pathway.

Biochemical abnormalities in basal ganglia and executive dysfunction in acute- and euthymic-episode patients with bipolar disorder: A proton magnetic resonance spectroscopy study.

BACKGROUND: Recent studies found abnormal biochemical metabolism and executive cognitive deficits in acute bipolar disorder (BD). However, the evidence concerning in euthymic BD is limited. Thus, a comparison between acute and euthymic BD is conductive to better understanding the association between cognition and the outcome of neuroimaging. This study sought to investigate the relationship between the executive function and the biochemical metabolism in acute- and euthymic-episode BD patients and delineate the prominent endophenotype of BD. METHODS: Three groups of participants were recruited in this study: 30 BD patients with an acute depressive episode, 22 euthymic BD patients, and 31 healthy controls. All participants were interviewed using the Structured Clinical Interview for DSM-IV, and underwent two-dimensional multivoxel proton magnetic resonance spectroscopy (1H-MRS) to obtain the bilateral metabolite levels in the lenticular nucleus of basal ganglia(BG). The ratios of N-acetylaspartate (NAA)/creatine (Cr) and Choline-containing compounds (Cho) /Cr ratios were calculated. Executive function was assessed by using the Wisconsin Card Sorting Test (WCST) and Trail Making Test, Part-B(TMT-B). RESULTS: The comparison of biochemical changes showed that the NAA/Cr ratios in bilateral lenticular nucleus in both acute and euthymic BD patients was significantly lower than that in healthy controls at a confidence level of p<0.05. In the comparison of executive function, both acute and euthymic BD patients showed significantly decreased numbers of categories completed, and increased numbers of total errors, perseverative and noperseverative errors, and TMT-B uptake compared to the healthy controls at a confidence level of p<0.05. There were no significant differences between the acute BD and euthymic BD groups in the biochemical metabolite ratios and executive function. We found that the NAA/Cr ratio in the left in BG in the acute -episode BD patients was positively correlated with the number of categories completed, whereas it was negatively correlated with the total errors and TMT-B uptake. There was no correlation between the NAA/Cr and Cho/Cr ratios in the bilateral BG and the scores of SWCT and TMT-B in euthymic-episode BD patients. LIMITATION: The sample size was relatively small and not all the euthymic-episode patients are the ones with an acute episode. CONCLUSIONS: Our findings suggest that biochemical abnormalities in the lenticular nucleus and the executive dysfunction may occur early in the course of BD, and persist during remission, and are the most likely markers of endophenotypes of BD. The dysfunction of the neuronal function in the lenticular nucleus may be correlated with the cold dysfunction in patients with acute BD.

Unplanned Reoperations in Neurosurgical Patients Due to Postoperative Bleeding: A Single-Center Experience and Literature Review.

The aim of this study is to investigate the incidence of unplanned reoperations from all causes due to bleeding in neurosurgical patients. The medical records of patients who received neurosurgical procedures at our hospital were retrospectively reviewed and data of patients who received reoperations were extracted and summarized. A literature review was conducted of the Medline, Cochrane, EMBASE, and Google Scholar databases up to November 2013. The main outcome measure was the rate of unplanned reoperations due to bleeding. At our hospital, 68 patients with a mean age of 41.5 ±â€Š21.5 years (range, 7 months to 76 years) received an unplanned reoperation. More than 70% of the patients were older than 18 years, 64.7% were males, and 94.1% had cranial surgery. Almost 60% of the patients received >1 blood transfusion (58.8%) after the first surgery. Of the 68 patients, 35 (51.5%) received a second operation due to bleeding. Univariate logistic regression analysis only showed that an increasing time interval between the first and second surgery was associated with a decreased chance of the reoperation being performed due to bleeding (odds ratio [OR] = 0.843, 95% confidence interval [CI]: 0.720-0.987; P = .033). Of 229 studies identified, 5 retrospective reports with a total of 1375 patients were included in the analysis. The rate of reoperations for bleeding in the 5 studies ranged from 4.2% to 31.5%. Employing measures to reduce postoperative bleeding may help reduce the rate of unplanned neurosurgical reoperations.

The antitumor immune responses induced by nanoemulsion-encapsulated MAGE1-HSP70/SEA complex protein vaccine following peroral administration route.

Previous studies have shown that there are profuse lymphatic tissues under the intestinal mucous membrane. Moreover, vaccine administered orally can elicit both mucous membrane and system immune response simultaneously, accordingly induce tumor-specific cytotoxic T lymphocyte. As a result, the oral route is constituted the preferred immune route for vaccine delivery theoretically. However, numerous vaccines especially protein/peptide vaccines remain poorly available when administered by this route. Nanoemulsion has been shown as a useful vehicle can be developed to enhance the antitumor immune response against antigens encapsulated in it and it is good for the different administration routes. Of particular interest is whether the protein vaccine following peroral route using nanoemulsion as delivery carrier can induce the same, so much as stronger antitumor immune response to following conventional ways such as subcutaneous (sc.) or not. Hence, in the present study, we encapsulated the MAGE1-HSP70 and SEA complex protein in nanoemulsion as nanovaccine NE (MHS) using magnetic ultrasound method. We then immuned C57BL/6 mice with NE (MHS), MHS alone or NE (-) via po. or sc. route and detected the cellular immunocompetence by using ELISpot assay and LDH release assay. The therapeutic and tumor challenge assay were examined then. The results showed that compared with vaccination with MHS or NE (-), the cellular immune responses against MAGE-1 could be elicited fiercely by vaccination with NE (MHS) nanoemulsion. Furthermore, encapsulating MHS in nanoemulsion could delay tumor growth and defer tumor occurrence of mice challenged with B16-MAGE-1 tumor cells. Especially, the peroral administration of NE (MHS) could induce approximately similar antitumor immune responses to the sc. administration, but the MHS unencapsulated with nanoemulsion via po. could induce significantly weaker antitumor immune responses than that via sc., suggesting nanoemulsion as a promising carrier can exert potent antitumor immunity against antigen encapsulated in it and make the tumor protein vaccine immunizing via po. route feasible and effective. It may have a broad application in tumor protein vaccine.

[Novel exploration of cathartic pharmacology induced by rhubarb].

Rhubarb is well-known for its cathartic effect, and this cathartic effect, which is closely correlated with "whter" of traditional Chinese medicine (TCM), is brought into play in colon. Recent researches about the relation between formation and effects have identified that the anthraquinone glycosides with 1,8-dio-hydroxy and without hydroxyl in the 2, 3, 6, 7 location, such as emodin, rhein, chrysophanol, et al, can bring about fairly obvious effects of "Watery Diarrhea". Aquaporins (AQPs) are expressed abundantly in colonic epithelial cells, and the abnormal expression of AQPs can lead to the less absorption of water in colon and/or the more secretion of intestinal juice, which suggest that AQPs might be one kind of the effector molecules, which some drugs playing pharmacologic actions in colon depend on. This assumption provides a novel field of vision. Is this "Watery Diarrhea" effect induced by rhubarb concerned with the location alteration or the expression change of AQPs. We deduce that the regulative effects of AQPs by rhubarb in colon might provide a new pharmacologic explation about the cathartic effect through the exploration of TCM and Chinese herbal drugs, with TCM theory and the analysis of data about efficiency and pharmacologic researches of rhubarb and the researches of AQPs. This deduction might be used to reveal why rhubarb can bring about multi-efficiency.

[Anti-tumor immune responses of nanoemulsion-encapsulated MHS vaccine].

AIM: To prepare nanoemulsion-encapsulated MAGE1-Hsp70/SEA and to evaluate its anti-tumor effects in mouse. METHODS: Nanoemulsion vaccine NE(MHS) was prepared using magnetic ultrasound methods and used to immunize C57BL/6 mice. The cellular immune responses were detected by IFN-gamma ELISPOT and LDH release assay. The tumor challenge assay was performed too. RESULTS: (1) The mean size of NE(MHS) was (20+/-5) nm. The encapsulation rate was 87% and the nanoemulsion vaccine had a good stability. (2) The frequency of MAGE-1 specific CTL and cytotoxicity of CTL to B16-MAGE-1 cells were both greatly enhanced in immunization group than those in control group (P<0.05). NE(MHS) could significantly delay the appearance of tumors and increase the percentage of tumor-free mice. CONCLUSION: The nanoemulsion had excellent physical and chemical characteristics. It could elicit MAGE-1-specific cellular immune response and anti-tumor effects against the MAGE-1-expressing tumor.

[Effect of electroacupuncture on plasma estrin and bone mineral density in ovariectomized rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on plasma estrin (E) 2 and bone mineral density (BMD) in ovariectomized (OVX) rats for studying its underlying mechanism in treating osteoporosis. METHODS: Thirty-two female SD rats were randomized into normal control, model, EA, and medication groups with 8 rats in each group. Postmenopausal osteoporosis model was established by removing the uterus under anesthesia (2% Phenobarbital, 40 mg/kg). In EA group, bilateral "Zusanli" (ST 32) and "Sanyinjiao" (SP 6) were punctured and stimulated electrically for 20 minutes with 1-3 Hz in frequency, 1 ms in duration of waves, and 0.7-1.0 mA in strength, once daily and 8 weeks altogether. Rats of medication group were drenched with 5% Nilestriol, 5 mL/week and for 8 weeks. At the end of experiments, blood samples were collected after removing the rat eyeball, and the left femoral bone tissue was taken. Serum E2 was assayed by using enzyme linked immunosorbent assay (ELISA) and BMD was measured by using double functional X-ray digital bone density meter. RESULTS: Compared with normal group, the body weight of model group was significantly bigger (P < 0.05), and that of model group was also significantly bigger than that of EA and medication groups (P < 0.11). No significant differences were found among the 4 groups before experiments and among normal control and EA groups after treatment (P > 0.05). In comparison with normal group, BMD and serum E2 of model group decreased significantly (P < 0. 01), while compared with model group, BMD and E2 of EA and medication groups increased significantly (P < 0.01, < 0.05). No significant differences were found among normal, EA and medication groups (P > 0.05). CONCLUSION: Both EA and medication can increase BMD and serum E2 in OVX rats, which may be one of the mechanisms of acupuncture in treating osteoporosis.

Calcyclin-binding protein inhibits proliferation, tumorigenicity, and invasion of gastric cancer.

Calcyclin-binding protein/Siah-1-interacting protein (CacyBP/SIP), a target protein of the S100 family, which includes S100A6, S100A1, S100A12, S100B, and S100P, has been identified as a component of a novel ubiquitinylation complex leading to beta-catenin degradation. However, the function of CacyBP/SIP in gastric cancer has not been elucidated. In the present study, we prepared CacyBP/SIP overexpressing and knockdown cell lines of gastric cancer. Forced CacyBP/SIP expression inhibited the proliferation of gastric cancer cells, suppressed tumorigenicity in vitro, and prolonged the survival time of tumor-bearing nude mice. In addition, increased CacyBP/SIP repressed the invasive potential of gastric cancer cells. Conversely, the down-regulation of CacyBP/SIP by RNA interference showed the opposite effects. Further studies showed that depressed CacyBP/SIP increased the expression of total and nuclear beta-catenin at the protein level and elevated the transcriptional activity of Tcf/LEF. Taken together, our results suggest that CacyBP/SIP may be a potential inhibitor of cell growth and invasion in the gastric cancer cell, at least in part through the effect on beta-catenin protein expression and transcriptional activation of Tcf/LEF.

[Effect of oral administration of guanxin II decoction on coronary blood flow and cardiac systolic/diastolic function in healthy males].

OBJECTIVE: To observe the effects of oral administration of guanxin II decoction (GX II) on cardiovascular function, especially on the dynamics of coronary blood flow in healthy males. METHODS: Changes of heart rate, diastolic pressure, systolic pressure, left ventricular ejection fraction (LVEF), E peak, A peak, E/A value of mitral flow, diastolic peak velocity (Vmax) and diastolic flow velocity time integrals (VTI) of left anterior descending coronary artery (LAD) in 11 healthy male subjects were measured before and after oral administration of GX II, using non-invasive echocardiogram. RESULTS: Compared with those before GX II administration, the changes after administration in heart rate, systolic pressure, diastolic pressure, LVEF, E peak, A peak and E/A value, were insignificantly different (P>0.05), but the Vmax and VTI significantly increased at 30 min, 60 min, 90 min and 120 min after GX II administration (P<0.05). CONCLUSION: To increase the coronary blood flow is possibly one of the mechanisms of GX II in treating coronary heart disease and angina pectoris.