Screening anabolic androgenic steroids in human urine: an application of the state-of-the-art gas chromatography-Orbitrap high-resolution mass spectrometry.

Over the past few decades, anabolic androgenic steroids (AASs) have been abused in and out of competition for their performance-enhancing and muscle-building properties. Traditionally, AASs were commonly detected using gas chromatography-mass spectrometry in the initial testing procedure for doping control purposes. Gas chromatography-Orbitrap high-resolution mass spectrometry (GC-Orbitrap-HRMS) is a new technology that has many advantages in comparison with GC-MS (e.g., a maximum resolving power of 240,000 (FWHM at m/z 200), excellent sub-ppm mass accuracy, and retrospective data analysis after data acquisition). Anti-doping practitioners are encouraged to take full advantage of the updated techniques of chromatography-mass spectrometry to develop sensitive, specific, and rapid screening methods for AASs. A new method for screening a wide range of AASs in human urine using GC-Orbitrap-HRMS was developed and validated. The method can qualitatively determine 70 anabolic androgenic steroids according to the minimum required performance limit of the World Anti-Doping Agency. Moreover, the validated method was successfully applied to detect six metabolites in urine after the oral administration of metandienone, and their excretion curves in vivo were studied. Metandienone M6 (17ß-hydroxymethyl-17α-methyl-18-nor-androst-1,4,13-trien-3-one) has been identified as a long-term urinary metabolite which can be detected up to 7 weeks, thus providing a longer detection window compared with previous studies. This study provides a rationale for GC-Orbitrap-HRMS in drug metabolism and non-targeted screening.

Systematic investigation of cerebellar functional alterations and their association with surgical outcomes in patients with degenerative cervical myelopathy: a resting-state fMRI study.

OBJECTIVE: The aim of this study was to systematically investigate the changes in cerebellar neural activity and cerebellar-cortical functional connectivity (FC) in patients with degenerative cervical myelopathy (DCM) using resting-state functional magnetic resonance imaging (fMRI). METHODS: In this study, we collected clinical data and resting-state fMRI data from 54 DCM patients and 50 healthy controls (HCs). We analyzed voxel-wise regional fMRI metrics, including amplitude of low frequency fluctuation (ALFF), fractional ALFF, regional homogeneity, functional connectivity density, and voxel-mirrored homotopic connectivity. In analysis 1, we examined the differences in regional fMRI metrics within the cerebellum between the DCM patient group and the healthy control group, as well as their correlation with preoperative neurological status and prognosis. In analysis 2, we investigated cerebellar-cortical functional connectivity differences between the two groups and their correlation with preoperative neurological status and prognosis. Lastly, in analysis 3, we explored the internetwork connectivity between the 'cerebellar-SMN' (sensorimotor network) system, examined the between-group differences, and investigated its correlation with preoperative neurological status and prognosis. RESULTS: (1) Relative to HCs, DCM patients exhibited functional alterations in wide-spread cerebellar regions; (2) DCM patients exhibited altered cerebellar-cortical FC which was associated with the preoperative neurological status and prognosis; (3) DCM patients exhibited altered internetwork connectivity between 'cerebellar-SMN' system which was associated with duration of symptom. CONCLUSION: Wide-spread cerebellar functional alterations occur in DCM pathogenesis and the deficits in cerebellar-SMN functional connectivity may be beneficial in future studies for predicting surgical outcomes in patients with DCM.

Maladaptive cognitive regulation moderates the mediating role of emotion dysregulation on the association between psychosocial factors and non-suicidal self-injury in depression.

Introduction: Non-suicidal self-injury (NSSI) is highly prevalent in depression, and is associated with psychosocial factors, emotion dysregulation, and strategies of cognitive emotion regulation. However, the internal combination and interactions of these risk factors in depression remain unclear. Methods: Data from 122 patients with depression, including 56 with NSSI and 66 without NSSI, were analyzed. Self-rating scales were used to assess psychosocial factors, emotion dysregulation, and cognitive regulation strategies. Sparse partial least squares discriminant analysis (sPLS-DA) was employed to explore internal combinations in each profile. A moderated mediation model was applied to examine their interactional relationship. Results: The results identified an NSSI-related psychosocial profile characterized by high neuroticism, childhood trauma, poor family functioning, and low psychological resilience. Emotion dysregulation, including high levels of alexithymia, anhedonia, and emotion regulation difficulties, mediated the association between this psychosocial profile and NSSI. The mediated effect was further moderated by maladaptive cognitive regulation strategies. Limitations: Lack of sufficient information on NSSI frequency and severity. Relatively small sample size for discussing the impact of gender and age of depressive patients with NSSI. Conclusion: These findings hold important implications for the prevention, treatment, and rehabilitation of NSSI.

High-risk group and functional subtypes of non-suicidal self-injury in young adults with mental disorders.

Background: Identifying high-risk groups of non-suicidal self-injury (NSSI) with multiple risk factors and different functional subtypes contribute to implementing person-centered interventions. Methods: We investigated NSSI profiles among a sample of 258 psychiatric inpatients aged 18-25 years. All participants completed well-validated measures of internal personal and external environmental characteristics. One-hundred and ninety patients reported a lifetime history of NSSI and completed an additional NSSI assessment. A k-means cluster analysis was conducted to extract characteristics of risk factors and functional subtypes. Independent sample t-test, analysis of variance and χ 2 test were used to test the difference of demographic statistical factors, risk factors and functional scores among groups with different frequency of NSSI. Results: The clustering of risk factors analyses supported 4-clusters. The proportion of repeat NSSI patients was the highest (67.1%) in the group with unfavorable personal and unfavorable environmental characteristics. Functional subtype clustering analyses supported 5-clusters. Among patients with repeated NSSI, those with depression were mainly accompanied by the "Sensation Seeking" subtype (39.7%), bipolar disorder mainly supported the "Anti-suicide" subtype (37.9%), and eating disorders were mostly "Social Influence" subtype (33.3%). There was an interaction between functional subtypes and mental disorders. Limitations: All participants were in treatment in a psychiatric service and the results may not be generalizable to a community sample. The data included retrospective self-report which may be inaccurate due to recall bias. Conclusion: It is necessary to identify high-risk groups of NSSI who with unfavorable personal and environmental characteristics and clinical interventions need to consider the heterogeneity of patients' functional subtypes of NSSI.

Derivatization-Enhanced Analysis of Glucocorticoids for Structural Characterization by Gas Chromatography-Orbitrap High-Resolution Mass Spectrometry.

Glucocorticoids are classified in section S9 of the Prohibited List of the World Anti-Doping Agency, due to a potential risk to improving physical performance and causing harm to the health of athletes. Based on the similar physiological actions of glucocorticoids, both differentiating known glucocorticoids and identifying unknown glucocorticoids are important for doping control. Gas chromatography coupled with mass spectrometry plays an important role in structural characterization because of abundant structural diagnostic ions produced by electron ionization. It also provides a chance to study the fragmentation patterns. Thus, an enhanced derivatization procedure was optimized to produce trimethylsilylated glucocorticoids and structural diagnostic ions of nineteen trimethylsilylated glucocorticoids were obtained by gas chromatography-orbitrap high-resolution mass spectrometry. In our study, glucocorticoids were classified as: 3-keto-4-ene, 1,4-diene-3-keto, 3α-hydroxy with saturated A-ring, 21-hydroxy-20-keto and halo substituent glucocorticoids based on their structural difference. Structural diagnostic ions that contributed to structural characterization were specifically presented and the fragment patterns were demonstrated according to the above categories. This study not only gave new insights into the structural characterization of these glucocorticoids but also provided evidence for tracing unknown glucocorticoids or chemically modified molecules.

Brain connectivity markers in degenerative cervical myelopathy patients with depression for predicting the prognosis following decompression surgery.

Objective: To determine if brain functional connectivity (FC) is associated with the prognosis in depressed degenerative cervical myelopathy patients (DCM) and to investigate the possible brain functional mechanism. Methods: Resting-state fMRI scans and peripheral blood cell counts from 33 depressed DCM patients, 33 age and gender-matched DCM patients without depression were analyzed. All patients were evaluated using Japanese Orthopedic Association score before and 6 weeks after decompression surgery. JOA recovery rate was calculated to assess the functional recovery for DCM patients. For each participant, seed-based functional connectivity maps based on sub-regions centered on the striatum were computed and compared between groups. Pearson correlations were performed to explore the relationships between clinical measures and brain alterations in depressed DCM patients. To further investigate the relationships between brain alterations and clinical measures in depressed DCM patients, mediation analyses were performed. Flow cytometry was also performed on the three of the 33 depressed DCM patients, and the results were analyzed. Results: In comparison to patients without depression, DCM patients exhibited lower FC between the dorsal caudate (dC) and the inferior frontal operculum, which is located in the dorsal lateral prefrontal cortex (dlPFC). In depressed DCM patients, the altered dC-dlPFC FC was associated with inflammation as determined by the neutrophils/lymphocyte's ratio and prognosis. Furthermore, the mediation analysis demonstrated that the dC-dlPFC FC mediated the effect of inflammation on prognosis. The outcomes of our three cases followed a similar pattern to these findings. Conclusion: In conclusion, our findings imply that inflammation slowed the functional recovery in depressed DCM patients through the striatal-frontal FC pathway.

Quantification of urinary steroids by supported liquid extraction with GC-MS/MS: Unravelling cyclic fluctuations of steroid profiling in regular menstrual cycle.

A method for simultaneous quantification of urinary steroids has been developed using supported liquid extraction technique in combination with gas chromatography-triple quadruple tandem mass spectrometry. The supported liquid extraction technique could enrich low-concentration analytes by reducing matrix interference, hence the technique offered better extraction efficiency compared to conventional preparation methods. The method was shown to be linear (r2 > 0.99) in the range of concentrations for all steroids with accuracy ranging from 88.0% to 115.6%. The intra- and inter-day precision, expressed as relative standard deviation, were both below 11.9%. The lower limits of quantification were between 1 and 50 ng·mL-1, and the limits of detection were between 0.5 and 2.5 ng·mL-1, which were suitable for the detection of steroids. The validated method was subsequently applied for analyzing urinary steroid profiling in regular menstrual cycle. The cyclic fluctuations and positive correlations between the steroids in different phases were observed. The results indicated that the proposed method was an effective tool for revealing hormonal fluctuations during menstrual cycle in complex biological samples.

High-definition transcranial direct current stimulation facilitates emotional face processing in individuals with high autistic traits: A sham-controlled study.

The deficit in emotional face processing is a critical impairment for individuals with high autistic traits. The temporalparietal junction(TPJ) is considered to be closely related to emotional face processing. The aim of this study was to examine the effect of highdefinition transcranial direct current stimulation (HD-tDCS) over the right temporal-parietal junction (rTPJ) on facial emotion processing of individuals with high autistic traits using eye-tracking technology. Twenty-nine participants with high autistic traits completed an eyetracking task (including happy, fearful and neutral faces) before and after five consecutive days of stimulation (anodal or sham). Results showed that anodal HD-tDCS significantly increased fixation time and fixation count in the mouth area, but this effect was not found after the sham stimulation. Moreover, this increased effect of mouth recognition with anodal rTPJ HD-tDCS was shown in both happy and fearful faces, but no remarkable difference was found in neutral faces. These findings suggest that right TPJ anodal HD-tDCS can facilitate emotional face processing in individuals with high autistic traits.