Biomedical subjects

Zheng Chang

Publications and source records attributed to Zheng Chang.

12 recordsLinked to original sources

PubMed2026

Psychiatric and neurological predictors of early ADHD medication discontinuation across the lifespan: a multinational study.

BACKGROUND: Early discontinuation of attention-deficit/hyperactivity disorder (ADHD) medication is common and linked to worse outcomes. Identifying clinical predictors could aid personalised treatment yet evidence is inconsistent across ages and countries/regions. OBJECTIVE: Investigate psychiatric and neurological comorbidity as predictors of early ADHD medication discontinuation in new ADHD medication users across age groups, sex and countries/regions. METHODS: Using health records from eight countries/regions, we identified 1 000 411 (44% female) new ADHD medication users (2011-2020). Discontinuation was defined as a ≥180 day gap between dispensations. We examined 23 indicators of psychiatric or neurological comorbidity, severity and psychotropic medication use. Associations were estimated using Cox regression, pooled with random-effects meta-analyses and stratified by age-at-initiation and sex. FINDINGS: Discontinuation rates varied widely (children 19%-61%, adolescents 37%-68%, young adults 52-67%, adults 38%-68%). In pooled analyses, earlier discontinuation in children was predicted by intellectual disability, autism and use of psychotropic medications (HR range 1.32-1.51), while conduct/oppositional defiant disorder (CD/ODD) was protective (HR 0.83, 95% CI 0.73 to 0.94). In adolescents, no indicators remained statistically significant after multiple-testing control. In young adults, CD/ODD (HR 1.42, 95% CI 1.30 to 1.55), and in adults, schizophrenia (HR 1.25, 95% CI 1.09 to 1.44) and tic disorders (HR 1.27, 95% CI 1.11 to 1.46) predicted earlier discontinuation. Statistical heterogeneity was substantial, largely driven by US estimates. In meta-analyses excluding the USA, additional associations emerged. For example, in children, OCD and anxiety disorders predicted earlier discontinuation, while eating disorders and antidepressants/anxiolytics were protective in adults. Associations with schizophrenia, tic disorders and CD/ODD were no longer significant. Country-specific analyses showed similar association patterns, except in the USA, Hong Kong and the UK. Sex differences were limited. CONCLUSIONS: Children with neuropsychiatric comorbidity and related comedication are more likely to discontinue ADHD medication early, whereas few consistent predictors were seen from adolescence onwards. Marked cross-country variation, particularly in the USA, points to system-level influences on treatment patterns. CLINICAL IMPLICATIONS: Improving ADHD medication persistence will require consideration of healthcare context and age-specific strategies, including close monitoring for children with complex neuropsychiatric profiles, and consideration of broader factors in adolescents and adults, where clinical predictors were limited.

Humans↗

PubMed2026

Risk of subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm episode among young people: a population-based cohort study.

BACKGROUND: Self-harm in young people is associated with elevated risks for subsequent self-harm, suicide attempts and suicide, particularly during the first year. Yet the trajectory across sex, age and self-harm methods remains poorly understood. OBJECTIVE: To estimate risk for subsequent self-harm, suicide attempts and suicide following a first hospital-treated self-harm event in young people. METHODS: This study included 77 647 individuals (57.0% female) whose first hospital-treated (ie, within inpatient or outpatient specialised healthcare) self-harm episode occurred between ages 10-24 years during 1973-2019. We estimated cumulative incidence and incidence rate for subsequent self-harm, suicide attempts and suicide at 1 month, 3 months and 1 year following the initial episode. FINDINGS: Within 1 year, the cumulative incidence was 17.3% (95% CI 17.0 to17.5) for subsequent self-harm, 8.3% (8.1 to 8.5) for suicide attempt and 0.3% (0.2 to 0.3) for suicide. The highest risks occurred in the first month: 8.4% (8.2 to 8.6) for self-harm, 2.9% (2.8 to 3.0) for suicide attempt and 0.04% (0.03 to 0.05) for suicide. In the first month, the incidence rate of self-harm was 2.97 per 1000 person-days (2.90 to 3.05), falling to 0.55 (0.54 to 0.56) over the year. The suicide attempt rate declined from 0.98 (0.94 to 1.02) to 0.24 (0.24 to 0.25) and the suicide rate from 0.013 (0.009 to 0.019) to 0.007 (0.006 to 0.008). Males exhibited the highest suicide risk and females the highest attempts risk. First-month self-harm risk was greatest among males and children aged 10-12. CONCLUSIONS: The month following a self-harm episode is marked by an elevated risk of subsequent self-harm, suicide attempts and suicide, yet risk remains elevated over the full year. CLINICAL IMPLICATIONS: These findings underscore the need for both acute and sustained prevention efforts. Special attention should be given to males and children aged 10-12 presenting with self-harm of ambiguous intent, as their risk of repetition may otherwise go unrecognised.

Humans↗

PubMed2025

Associations of Genetic Liability to Six Psychiatric Disorders With Cardiometabolic Diseases.

IMPORTANCE: Individuals with psychiatric disorders have increased risk of cardiometabolic diseases (CMDs). Evaluating how psychiatric genetic liability relates to CMD may clarify mechanisms. OBJECTIVE: Identify genetic overlap between psychiatric disorders and CMDs independent of cross-disorder pleiotropy, BMI, and smoking. DESIGN SETTING AND PARTICIPANTS: Three Northern European cohorts (the Swedish Twin Registry, the Estonian Biobank, and the Norwegian Mother, Father and Child Cohort Study [MoBa]) totaling 355,159 individuals. Associations with CMDs were estimated as adjusted odds ratios (AORs) from logistic models mutually adjusted for all psychiatric PRSs and in models additionally adjusting for body mass index (BMI) and smoking. Cohort-specific AORs were pooled by inverse-variance weighting. MAIN OUTCOMES AND MEASURES: Exposures were PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorder, posttraumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Outcomes were diagnoses of CMDs (hyperlipidemia, obesity, type 2 diabetes, hypertensive diseases, arteriosclerosis, ischemic heart disease, heart failure, thromboembolic disease, cerebrovascular disease, and arrhythmias), ascertained from electronic health records. RESULTS: The MDD PRS was associated with increased risk of all CMDs across analyses (AORs ranged from 1.13 [95% CI, 1.10-1.15] for heart failure to 1.02 [95% CI, 1.00-1.05] for arrhythmias). The ADHD PRS was associated with increased risk of all CMDs (AOR ranged from 1.11 [95% CI, 1.09-1.12] for obesity to 1.02 [95% CI, 1.01-1.03] for hyperlipidemia), however associations where attenuated when adjusting for BMI and smoking (lifestyle adjusted AOR for obesity: 1.03 [95% CI, 1.02-1.05]). When not mutually adjusting for all psychiatric PRSs, anxiety disorder and PTSD PRSs were associated with all CMDs; these associations diminished after adjustment. The bipolar and schizophrenia PRSs were inversely associated with most CMDs (AOR for schizophrenia PRS and obesity, 0.93 [95% CI, 0.92-0.94]). CONCLUSIONS AND RELEVANCE: Associations between psychiatric PRSs and CMDs diverged: ADHD, MDD, anxiety disorder, and PTSD PRSs were positively associated with CMDs, whereas bipolar and schizophrenia PRSs were inversely associated. Genetic liability to MDD showed robust associations with CMDs independent of cross-disorder pleiotropy, BMI, and smoking status, whereas associations between the ADHD PRS and CMDs were largely attenuated after adjustment for BMI and smoking.

Journal Article↗

PubMed2006

Highly accelerated MRI by skipped phase encoding and edge deghosting with array coil enhancement (SPEED-ACE).

The fast MRI method of skipped phase encoding and edge deghosting (SPEED) is further developed with array coil enhancement, and thus is termed SPEED-ACE. In SPEED-ACE, k space is sparsely sampled with skipped phase encoding at every Nth step using a set of receiver coils simultaneously, similar to SENSE, leading to sensitivity-weighted images with up to N layers of overlapping aliasing ghosts. The ghosted images are edge enhanced by a differential filter to yield ghosted edge maps, in which the ghost overlapping layers are greatly reduced since the sparseness of edges reduces the chance of ghost overlapping. Typical ghosted edge maps can be adequately modeled with a double-layer structure. By using data from at least three coils through least-square-error minimization, a deghosted edge map is obtained and inverse-filtered into a final deghosted image. In this way, SPEED-ACE partially samples k space with a skip size of N by using multiple receiver coils in parallel, and obtains a fairly good deghosted image with an undersampling factor of N. SPEED-ACE is not limited to the double-layer ghost model, but can be generalized to include more layers of ghosts for more flexible and improved performance. As a new parallel imaging method, SPEED-ACE was tested using in vivo data to demonstrate the possibility of achieving undersampling factors even greater than the number of receiver coils, which is so far not achievable by other parallel imaging methods.

Algorithms↗

PubMed2005

Neural mechanisms controlling jaw-jerk reflex in the cat.

Signal substances of axon terminals presynaptic to jaw spindle Ia afferents and their ultrastructural features were examined using a combination of intra-axonal horseradish peroxidase injection and postembedding immunogold-labeling techniques in cats. A total of 35 axon terminals presynaptic to 22 horseradish peroxidase-labeled Ia boutons were examined. Of the 35 presynaptic axon terminals, 14 (40%) were immunoreactive for both gamma-aminobutyric acid and glycine, 9 (26%) for gamma-aminobutyric acid alone and 9 (26%) for glycine alone. The bouton volume, mitochondrial volume, active zone area, and apposed surface area were larger for Ia boutons than for presynaptic axon terminals, while each of the values is similar among the three types of presynaptic axon terminals. These results suggest that gamma-aminobutyric acid and glycine play an important role for modulating the jaw-jerk reflex presynaptically and that the smaller size of presynaptic axon terminals is important to prevent action potential generation from Ia afferents.

Analysis of Variance↗

PubMed2005

Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1.

The phosphoinositide 3-kinase/3-phosphoinositide-dependent kinase 1 (PDK1)/Akt signaling pathway plays a key role in cancer cell growth, survival, and tumor angiogenesis and represents a promising target for anticancer drugs. Here, we describe three potent PDK1 inhibitors, BX-795, BX-912, and BX-320 (IC(50) = 11-30 nm) and their initial biological characterization. The inhibitors blocked PDK1/Akt signaling in tumor cells and inhibited the anchorage-dependent growth of a variety of tumor cell lines in culture or induced apoptosis. A number of cancer cell lines with elevated Akt activity were >30-fold more sensitive to growth inhibition by PDK1 inhibitors in soft agar than on tissue culture plastic, consistent with the cell survival function of the PDK1/Akt signaling pathway, which is particularly important for unattached cells. BX-320 inhibited the growth of LOX melanoma tumors in the lungs of nude mice after injection of tumor cells into the tail vein. The effect of BX-320 on cancer cell growth in vitro and in vivo indicates that PDK1 inhibitors may have clinical utility as anticancer agents.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed2005

Bilateral projection of functionally characterized trigeminal oralis neurons to trigeminal motoneurons in cats.

Intracellular Neurobiotin-injections were used to label functionally identified neurons in the rostro-dorsomedial part of the trigeminal oral nucleus (Vo.r) in the cat. The labeled Vo.r neurons with the mechanoreceptive field in oral tissues innervated bilaterally either jaw-opening motoneurons or jaw-closing motoneurons. This result suggests that Vo.r neurons play an important role in sensory-motor reflexes responsible for coordination of bilaterally symmetrical jaw movements.

Animals↗

PubMed2005

Nonlinear phase correction with an extended statistical algorithm.

This paper presents a new magnetic resonance imaging (MRI) phase correction method. The linear phase correction method using autocorrelation proposed by Ahn and Cho (AC method) is extended to handle nonlinear terms, which are often important for polynomial expansion of phase variation in MRI. The polynomial coefficients are statistically determined from a cascade series of n-pixel-shift rotational differential fields (RDFs). The n-pixel-shift RDF represents local vector rotations of a complex field relative to itself after being shifted by n pixels. We have found that increasing the shift enhances the signal significantly and extends the AC method to handle higher order nonlinear phase error terms. The n-pixel-shift RDF can also be applied to improve other methods such as the weighted least squares phase unwrapping method proposed by Liang. The feasibility of the method has been demonstrated with two-dimensional (2-D) in vivo inversion-recovery MRI data.

Algorithms↗

PubMed2005

Problems created in attenuation-corrected SPECT images by artifacts in attenuation maps: a simulation study.

UNLABELLED: The importance of accurate attenuation correction, especially for imaging of the thorax region, is widely acknowledged. Appropriate compensation methods have been developed and introduced into clinical practice. Most of these methods use attenuation maps obtained using various transmission scanning systems. However, when maps are inaccurate, the correction procedure may introduce artifacts into the final images that can be difficult to identify and might inadvertently alter diagnosis and study outcome. As a result, attenuation correction is often avoided in clinical practice. Our objective was to examine issues related to the quality of attenuation maps and the effects that map artifacts may have on attenuation-corrected emission images. METHODS: The topics that are investigated include the problem of low transmission counts, cross-talk contributions from the emission isotope, truncation of the transmission data, and methods of map reconstruction and segmentation. Examples of patient studies displaying specific problems guided our investigations, but, because truth in these studies is seldom known, analytic and Monte Carlo-simulated data were used in the analysis. Attenuation maps and final emission images were visually checked for artifacts and for the presence of perfusion defects. In addition, quantitative evaluation of map uniformity, defect visibility, and size variation was performed. RESULTS: The statistical paired-sample t test showed significant (P < 0.05) improvement of relative SD for attenuation maps reconstructed with iterative methods as compared with filtered backprojection and for maps created with higher photon fluxes. When maps with artifacts were used to correct emission data, an increase in myocardial infarct size and creation of false heart defects were observed. CONCLUSION: Our study strongly recommends that at least a visual inspection of the quality of attenuation maps be performed before their use in compensation procedures. To improve image quality, remove artifacts, and increase diagnostic confidence, attenuation maps used in the correction procedure must be accurate and free of artifacts.

Algorithms↗

PubMed2005

[Study on association between gestational diabetes mellitus and sulfonylurea receptor-1 gene polymorphism].

OBJECTIVE: To investigate allelic frequency of sulfonylurea receptor-1 (SUR1) in gestational diabetes mellitus (GDM) women of Han nationality in north China in order to find out susceptible gene associated with GDM, and to assess the association between SUR1 allele and body mass index (BMI) and secretion of insulin. METHODS: Seventy cases of pregnant women were selected. It included 35 cases of pregnant women with GDM (GDM group), 35 cases of normal pregnant women (normal control group). Another 35 women patients with type 2 diabetes in the same period as T2DM group. By using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we detected the distribution of SUR1 alleles frequency in all individuals of three groups. We also examined BMI, fasting insulin (INS(0)) and 2 h insulin levels (INS(120)). RESULTS: There was significantly increased c alleles frequency of SUR1 in GDM and T2DM women compared with normal pregnancy (70.0%, 71.4% and 52.9%, P < 0.05). Also significantly increased A alleles frequency of SUR1 in GDM and T2DM women was found compared with normal pregnancy (41.4%, 44.3% and 24.3%, P < 0.05). In GDM group, women carrying cc genotype had a higher BMI [(29.2 +/- 5.6) kg/m(2)], INS(0) [(14.9 +/- 8.7) mU/L] and INS(120) [(40.2 +/- 12.1) mU/L] as compared with those in carriers of other genotypes (ct and tt) (all P < 0.05). Also they had a lower insulin sensitivity (HOMA-IR) (3.9 +/- 2.5) as compared with carriers of ct genotype. Women carrying AA genotype had a higher INS(0) as compared with carriers of other genotypes (AG and GG) [(15.4 +/- 3.2), (12.1 +/- 4.5) and (11.5 +/- 4.8) mU/L, both P < 0.05]. Logistic regression analysis showed there was relationship between SUR1 cc genotype and severity of GDM (P = 0.005, RR = 25.128). CONCLUSIONS: There are -3t-->c and A/G polymorphism of SUR1 gene in the Han nationality. Alleles c of SUR1 are significantly implicated in the susceptibility to GDM. It suggests that the defect in SUR1 gene (cc and AA) may contribute to insulin hypersecretion, which might be the cause of increased body weight and decreased insulin sensitivity and genotype cc of SUR1 is connected with severe type of GDM. It might be the predictable index of GDM conversion to type 2 diabetes.

ATP-Binding Cassette Transporters↗

PubMed2004

[The effects of culture supernatant of human GRC-1 cells transfected with PF4 cDNA on the VEGF expression and the growth of ECV304 cells].

AIM: To construct the eukaryotic expression vector pcDNA3-PF4-SS, and to detect the effects of the culture supernatant of transfected GRC-1 cells on the VEGF expression in transfected GRC-1 cells and the growth of ECV304 cells. METHODS: The eukaryotic expression vector pcDNA3-PF4-SS was constructed and identified with Bgl II/BamH I digestion. The pcDNA3-PF4-SS was transfected stably into GRC-1 cells with lipofectamine mediation. The VEGF expression in transfected GRC-1 cells was detected by immunohistochemical staining, and the effect of the culture supernatant of transfected GRC-1 cells on ECV304 cells was detected by MTT colorimetry. RESULTS: Restrictive enzyme (Bgl II/BamH I)digestion analysis showed that the recombinant expression vector pcDNA3-PF4-SS had been constructed successfully. RT-PCR detection proved that hPF4 cDNA had been transfected into GRC-1 cells. The result of immunohistochemical staining showed that the VEGF expression could be seen in the cytoplasm and on cytomembrane of GRC-1 cells transfected with pcDNA3-PF4-SS, but the expression obviously weakened as comparison with that before transfection. Cell counting and MTT colorimetry manifested that the culture supernatant of transfected GRC-1 cells could inhibit markedly growth of ECV304 cells. CONCLUSION: The eukaryotic expression vector pcDNA3-PF4-SS has been constructed successfully, and stably transfected into the GRC-1 cells. The culture supernatant of transfected GRC-1 cells has obviously inhibitory effect on the growth of ECV304 cells and the VEGF expression in the GRC-1 cells, which lays some foundation for exploring the mechanism for anti-tumor growth and developing tumor vaccine for kidney neoplasms.

Carcinoma, Renal Cell↗

PubMed2003

Modulation of the electrophoretic mobility of the linker for activation of T cells (LAT) by the calcineurin inhibitors CsA and FK506: LAT is a potential substrate for PKC and calcineurin signaling pathways.

The linker for activation of T cells (LAT) is essential for T cell activation. Cyclosporin A (CsA) and FK506, inhibitors of T cell proliferation, have been very useful for preventing autoimmune and inflammatory disease and graft rejection. However, both compounds are associated with side effects. We show that TCR ligation in the presence of FK506 or CsA induced rapid modifications in LAT that modulate the electrophoretic mobility of the molecule in SDS-PAGE. Calcineurin, a target for CsA and FK506, dephosphorylated LAT in vitro and restored its electrophoretic mobility. Stimulating T cells with the protein kinase C (PKC) activator PMA induced a shift in the mobility of LAT, whereas inhibitors of PKC blocked the effect of PMA. Thus, manipulating calcineurin or PKC activation alters the electrophoretic mobility of LAT. These results shed light on the molecular actions of CsA and FK506 in T cells and implicate LAT in mediating the drugs' actions.

Adaptor Proteins, Signal Transducing↗