Association of subclinical hypothyroidism with metabolic syndrome and its components among outpatients with first-episode drug-naïve major depressive disorder: a large-scale cross-sectional study.

Both metabolic syndrome (MetS) and subclinical hypothyroidism (SCH) are prevalent in major depressive disorder (MDD) patients. However, their relationship in this population remains unknown. The study assessed the association between SCH and MetS in 1706 first-episode drug-naïve (FEDN) MDD patients. We also compared the relationship between MetS and clinical symptoms in patients with and without comorbid SCH. The Positive and Negative Syndrome Scale positive subscale, the Hamilton Anxiety Rating Scale, and the Hamilton Depression Rating Scale were used to detect clinical symptoms. Serum levels of free triiodothyronine, free thyroxine, thyroid stimulating hormone (TSH), anti-thyroglobulin, thyroid peroxidases antibody, cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose were measured. The Area Under the Curve (AUC) was used to test the performance of serum TSH in identifying MetS patients. The prevalence of MetS and SCH was 34.5% (n = 585) and 61% (n = 1034), respectively. The presence of SCH increased the risk of MetS, hyperglycemia, hypertension, obesity, and low HDL-C by 4.91, 3.51, 3.54, 2.02, and 2.34 times, respectively. Serum TSH had a nice ability to distinguish MetS patients from non-MetS patients (AUC value = 0.77). MetS and its components exhibited a positive association with clinical profiles only in SCH patients, but not in non-SCH patients. Taken together, our study suggested SCH was closely related to MetS and might play a vital role in the relationship between MetS and clinical symptoms. Regular thyroid function checks might help early detect MetS.

Employing Bayesian analysis to establish a cut-off point and assess stigma prevalence in substance use disorder: a comprehensive study of the Chinese version of the Substance Use Stigma Mechanism Scale.

PURPOSE: In China, individuals with substance use disorders (SUD) face severe stigma, but reliable stigma assessment tool is lacking. Therefore, this study aimed to validate the Chinese version of the Substance Use Stigma Mechanism Scale (SU-SMS-C) and set its cut-off point. METHODS: We recruited 1005 individuals with SUDs from Chinese rehabilitation centers. These participants completed a battery of questionnaires that included the SU-SMS-C, The Multidimensional Scale of Perceived Social Support (MSPSS), Center for Epidemiologic Studies Depression Scale (CES-D), General Self-Efficacy Scale (GSES), and Perceived Devaluation and Discrimination (PDD). Confirmatory factor analysis was used to assess the construct validity of the scale. Additionally, the Naive Bayes classifier was used to establish the cut-off point for the SU-SMS-C. We additionally explored the correlation between patient demographic characteristics and stigma. RESULTS: A confirmatory factor analysis was utilized, revealing a second-order five-factor model. Based on the Naive Bayes classifier, the area under the receiver operating characteristic (AUCROC) of 0.746, the cut-off point for the SU-SMS-C was established at 44.5. The prevalence of stigma observed in the study population was 49.05%. Significant disparities were observed in the distribution of stigma across genders, with males experiencing more pronounced stigma than females. Moreover, patients consuming different primary substances reported diverse levels of stigma. Notably, those primarily using heroin endured a higher degree of stigma than users of other substances. CONCLUSION: The study is the first to identify a cut-off point for the SU-SMS-C by Naive Bayes classifier, bridging a major gap in stigma measurement research. SU-SMS-C may help treat and manage SUDs by reducing stigma.

Efficacy and Safety of Fillers for the Treatment of Nasolabial Folds: A Network meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Nasolabial fold formation is increasingly becoming a cause of concern for many people. However, no network meta-analysis has compared the efficacy of different fillers in treating nasolabial folds. This network meta-analysis simultaneously compared the efficacy and safety of various fillers. METHODS: We included randomized controlled trials (RCTs) that used fillers to treat nasolabial folds. We extracted data of Wrinkle Severity Rating Scale (WSRS), Global Esthetic Improvement Scale (GAIS, investigator) scores, GAIS scores (self-reported) and adverse events. RESULTS: We included 13 RCTs. WSRS scores at 6 months were higher in patients receiving HA than those receiving poly (L-lactic acid) (mean difference [MD] 0.630, 95% confidence interval [CI] 0.275, 0.985) but significantly lower in patients receiving HA than in those receiving bovine collagen (MD - 0.580, 95% CI - 0.777, - 0.383) and porcine collagen (MD - 0.525, 95% CI - 0.790, - 0.260). Regarding adverse events, HA was significantly less likely to cause nodule formation compared with bovine collagen (RR 0.593, 95% CI 0.438, 0.803). CONCLUSION: HA is a safe filler for correcting nasolabial folds, and poly (L-lactic acid) showed potential in treating nasolabial folds. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Association between white matter microstructure and cognitive function in patients with methamphetamine use disorder.

Methamphetamine use disorder (MUD) has been associated with broad neurocognitive impairments. While the cognitive impairments of MUD have been demonstrated, the neuropathological underpinnings remain inadequately understood. To date, the published human diffusion tensor imaging (DTI) studies involving the correlation between diffusion parameters and neurocognitive function in MUD are limited. Hence, the present study aimed to examine the association between cognitive performance and white matter microstructure in patients with MUD. Forty-five patients with MUD and 43 healthy controls (HCs) completed their demographic information collection, cognitive assessments, and DTI imaging. DTI images were preprocessed to extract fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of various fiber tracts. Univariate tests were used to examine group differences in cognitive assessments and DTI metrics. Linear regression was used to examine the relationship between these two metrics. The results revealed that patients with MUD had lower subset scores of the MATRICS Consensus Cognitive Battery (MCCB), which reflects five cognitive domains: processing speed, attention, verbal learning, visual learning, problem-solving. Patients with MUD also had significantly higher AD, MD, and RD values of the left superior longitudinal fasciculus than HCs. Furthermore, the RD value of the left superior longitudinal fasciculus was a significant predictor of processing speed and problem-solving ability, as shown by the digit-symbol coding test and NAB-Mazes scores, respectively. Findings extended our understanding of white matter microstructure that is related to neurocognitive deficits in MUD and provided potential targets for the prevention and treatment of this chronic disorder.

Effectiveness and Safety of Vortioxetine for the Treatment of Major Depressive Disorder in the Real World: A Systematic Review and Meta-Analysis.

INTRODUCTION: Major depressive disorder (MDD) is a highly prevalent and burdensome condition. This study aims to evaluate the effectiveness, tolerability, and safety of vortioxetine in treating MDD based on real-world data. METHODS: A systematic search of 8 electronic databases was performed from inception until October 2022 to identify real-world studies, excluding randomized controlled trials. We conducted subgroup, meta-regression, sensitivity analyses, publication bias, and quality assessments using the random-effects model. The effects were summarized by rates or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: Of the 870 records identified, 11 studies (3139 participants) and 10 case reports or series were eligible for inclusion. Vortioxetine significantly relieved depression symptoms as assessed by both patients (SMD = 2.25, 95% CI = 1.60-2.89) and physicians (SMD = 3.73, 95% CI = 2.78-4.69). Cognitive function (SMD =1.86, 95% CI = 1.11-2.62) and functional disability (SMD =1.71, 95% CI = 1.14-2.29) were similarly markedly improved. Subgroup and meta-regression analyses showed that geographic location and medication regimen (whether combined with other antidepressants) were crucial factors influencing effectiveness (in terms of depression severity and cognitive function), potentially contributing to significant heterogeneity. The estimated response and remission rates were 66.4% (95% CI = 51.2%-81.5%) and 58.0% (95% CI = 48.9%-67.1%), respectively. Vortioxetine was well tolerated, with a pooled dropout rate of 3.5% (95% CI = 1.8%-5.8%), and the most common adverse event was nausea, with an estimated rate of 8.9% (95% CI = 3.8%-15.8%). LIMITATIONS: The study has some limitations, including significant heterogeneity and limited evidence for some outcomes. CONCLUSIONS: Vortioxetine is effective, well tolerated, and safe for treating MDD in clinical practice, with significant improvements observed in depressive severity, cognitive function, and functioning. Future studies should directly compare vortioxetine with other antidepressants in real-world settings to further evaluate its clinical utility.

Gender differences in alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period (October 20, 2020-April 5, 2021) in China.

BACKGROUND: This study aimed to assess the prevalence and the gender-specific risk factors of alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period in China. METHOD: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to identify respondents with alcohol abuse/dependence. A questionnaire on basic demographics and mental distresses (learning burnout, depression symptoms, anxiety symptoms, excessive daytime sleepiness, and history of mental disorders) was used. The logistic regression model was used to explore the associations between the above characteristics and alcohol abuse/dependence. RESULTS: A total of 3,412 medical undergraduates were included in the analysis. Males showed a higher prevalence of alcohol abuse/dependence than females (16.6% vs 7.4%, p < 0.001). Alcohol abuse/dependence was associated with learning burnout (OR: 2.168, p < 0.001) and having a partner (OR: 1.788 p = 0.001) among female medical undergraduates. Among male medical undergraduates, excessive daytime sleepiness (OR: 1.788 p = 0.001) and older age (OR: 1.788, p = 0.001) were independently associated with alcohol abuse/dependence. CONCLUSION: Alcohol abuse/dependence was common among medical undergraduates during the post-COVID­19 pandemic period. Substantial gender differences in the prevalence and risk factors of alcohol abuse/dependence were found among medical undergraduates in this study, which highlighted the need for timely gender-specific screening and interventions. However, the cross-sectional design adopted in this study has limited the examination of causality, thus further longitudinal studies are warranted.

Relationships Between Impulsivity, Methamphetamine use Disorder and Gambling Disorder.

Methamphetamine use disorder (MAUD) and gambling disorder (GD) frequently co-occur. Individuals with both conditions are typically more difficult to treat than those with either disorder alone. This study aimed to investigate the co-occurrence and clinical characteristics of people with MAUD and GD. Between March 2018 and August 2020, 350 men with methamphetamine use entering a compulsory drug rehabilitation center in Changsha, Hunan Province received semi-structured interviews. Participants completed the Barratt Impulsiveness Scale-11 and provided information on childhood upbringings and drug use characteristics. Independent sample t-tests compared differences between individuals with MAUD and with and without co-occurring GD. Dichotomous logistic regression was used to statistically predict co-occurring GD. The prevalence of GD was 45.1%. Most individuals (39.1% overall) had post-onset methamphetamine use (PoMAU-GD). The number of MAUD symptoms, history of gambling by family members, age of first sexual activity, and non-planning impulsivity statistically predicted PoMAU-GD, jointly explaining 24.0% of the total variance. The regression model fit well (HLχ2 = 5.503, p = 0.70), in which the specificity was 0.80, the sensitivity was 0.64, and the area under the curve was 0.79 (95%CI: 0.75-0.84). This study clarifies the prevalence of and potential risk factors for GD among individuals engaging in compulsory MAUD treatment in China. The high prevalence and associated clinical features of GD in the MAUD group highlight the importance of screening for GD in this population and intervening accordingly.

Inter-relationships of insomnia and psychiatric symptoms with suicidal ideation among patients with chronic schizophrenia: A network perspective.

BACKGROUND: Insomnia is common in patients with schizophrenia, which contributes to worsening psychiatric symptoms and suicidality. We aimed to assess the inter-relationships of insomnia and psychopathology with suicidal ideation (SI) among 1407 Chinese patients with chronic schizophrenia via the network approach. METHOD: We used Positive and Negative Syndrome Scale, Insomnia Severity Index, and Beck Scale for Suicidal Ideation to assess psychiatric symptoms, insomnia, and SI, respectively. Lifetime suicidal attempts (SA) were collected. RESULTS: (1) The incidence of insomnia, lifetime SI, lifetime SA, and current SI was 13.5% (n = 190), 22.8% (n = 321), 13.5% (n = 190), and 9.7% (n = 136), respectively. (2) Patients with insomnia had worse clinical symptoms and higher suicidal risk. (3) Daytime dysfunction, sleep-related distress, conceptual disorganization, delusions, anxiety, and poor rapport were the core symptoms, while late sleep onset and sleep dissatisfaction emerged as bridge symptoms connecting insomnia and psychopathology. (4) Depressive mood, hallucinations, poor impulse control, guilty feelings, insomnia-related impaired quality of life, and sleep dissatisfaction were directly associated with SI. CONCLUSION: Our findings called for formal assessment of insomnia in patients with schizophrenia, which should cover both nocturnal and daytime insomnia symptoms. Targeted interventions for key symptoms may help reduce insomnia, psychiatric symptoms, and SI in patients with schizophrenia.

Altered spontaneous neurological activity in methamphetamine use disorders and its association with cognitive function.

BACKGROUND: Methamphetamine (MA) is a widely used and detrimental drug, yet the precise mechanisms by which MA affects cognitive function remain unclear. This study aims to investigate the relationship between cognitive function and brain functional imaging in individuals with MA use disorder (MUD). METHODS: This study involved 45 patients diagnosed with MUD and 43 healthy controls (HC). Cognitive function assessment utilized the MATRICS Consensus Cognitive Battery, and functional data were acquired using a 3.0 Tesla magnetic resonance imaging scanner. RESULTS: The MUD group exhibited lower regional homogeneity (ReHo) values in the bilateral postcentral, the left superior temporal, and the left lingual regions compared to the HC group. Additionally, the MUD group displayed higher amplitude of low-frequency fluctuation (ALFF) values in the bilateral fusiform and the left putamen compared to the HC group, along with lower ALFF values in the bilateral postcentral cortices and the left middle cingulate cortex compared to the HC group (all p < 0.05, with false discovery rate corrected). Linear regression analysis revealed a positive correlation between the ReHo value in the right postcentral cortex and the neuropsychology assessment battery-mazes test (p = 0.014). Furthermore, the ALFF value in the left putamen showed negative correlations with the scores of the digit-symbol coding test (p = 0.027), continuous performance test (p = 0.037), and battery-mazes test (p = 0.024). CONCLUSION: Patients with MUD exhibit altered brain spontaneous neurological activities, and the intensity of spontaneous neurological activity in the left putamen is strongly associated with cognitive function.

Ten circumstances and solutions for finding the sample mean and standard deviation for meta-analysis.

A common problem in meta-analyses is the unavailability of mean and standard deviation (SD). Unfortunately, only having values of the median, interquartile range (IQR), or range cannot be directly utilized for meta-analysis. Although some estimation and conversion methods have been proposed in the past two decades, there were no published and user-friendly tools developed based on multiple scenarios of missing SD. Therefore, this study aimed to provide a collection of possible circumstances of missing sample means or SD with solutions for teaching and research. A total of 10 common circumstances of missing SD or mean could have available statistics of p value, t value, z score, confidence interval, standard error, median, IQR, and range. Teachers and investigators can use relevant formulas for finding the sample mean and SD according to the available circumstance. Due to the complicated computations, our team provides a free available spreadsheet. With ever-evolving statistical methods, some formulas may be further improved in the future; therefore, it is recommended to involve statisticians in evidence-based practice or systematic reviews.

P2X7R Mediates the Synergistic Effect of ATP and MSU Crystals to Induce Acute Gouty Arthritis.

Activation of the nod-like receptor protein 3 (NLRP3) inflammasome by monosodium urate (MSU) crystals has been identified as the molecular basis for the acute inflammatory response in gouty arthritis. However, MSU crystals alone are not sufficient to induce acute gouty arthritis (AGA). Adenosine triphosphate (ATP) is an endogenous signaling molecule involved in the NLRP3 inflammasome activation. We aimed to explore the role of ATP in MSU crystal-induced AGA development. In peripheral blood mononuclear cell-derived macrophages obtained from gout patients, we observed a synergistic effect of ATP on MSU crystal-induced IL-1ß release. Furthermore, in a rat model of spontaneous gout, we demonstrated that a synergistic effect of ATP and MSU crystals, but not MSU crystals alone, is essential for triggering AGA. Mechanistically, this synergistic effect is achieved through the purinergic receptor P2X7 (P2X7R). Blockade of P2X7R prevented AGA induction in rats after local injection of MSU crystals, and carrying the mutant hP2X7R gene contributed to the inhibition of NLRP3 inflammasome activation induced by costimulation of MSU crystals and ATP in vitro. Taken together, these results support the synergistic effect of ATP on MSU crystal-induced NLRP3 inflammasome activation facilitating inflammatory episodes in AGA. In this process, P2X7R plays a key regulatory role, suggesting targeting P2X7R to be an attractive therapeutic strategy for the treatment of AGA.

Effectiveness and Safety of Energy-Based Devices for Acne Scars: A Network Meta-Analysis of Randomized Controlled Trials.

Background: Acne vulgaris is an inflammatory disease of the pilosebaceous unit in teenagers. Acne-induced inflammation leads to acne scarring. Scholars have discussed acne scar treatments; however, energy-based devices with satisfactory outcomes remain unidentified. Objective: To measure quartile grading scale and visual analog scale (VAS) to study the difference between energy-based devices. Methods: We included randomized controlled trials that evaluated patients with acne scars. The primary outcomes were the quartile grading scale and VAS scores. We used Confidence in Network Meta-Analysis to evaluate indirectness, imprecision, heterogeneity, and incoherence. Results: A total of 26 studies met the inclusion criteria. The quartile grading scale results revealed that ablative fractional laser was significantly more effective than nonablative fractional laser (standard mean difference [SMD]: 0.516, confidence interval [95% CI]: 0.281-0.750) and radiofrequency treatment (SMD: 0.941, 95% CI: 0.540-1.342). Moreover, nonablative fractional laser was significantly more effective than radiofrequency treatment (SMD: 0.426, 95% CI: 0.049-0.802). No significant difference in VAS score was found among the devices. Conclusion: Ablative fractional laser is an effective treatment for acne scars although it is associated with more pain.

Depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia by inhibiting the EGFR-Stat3/Akt pathway.

Homeostasis of the skin barrier is essential for maintaining normal skin function. Gasdermin A (GSDMA) is highly expressed in the skin and is associated with many skin diseases, such as melanoma and psoriasis. In mice, GSDMA is encoded by three gene homologues, namely Gsdma1, Gsdma2, and Gsdma3. Although Gsdma3 gain-of-function mutations cause hair loss and skin inflammation, Gsdma3-deficient mice show no phenotypes in skin or hair structures. To explore the physiological function of GSDMA, we generated conventional Gsdma1/2/3 knockout (KO) mice. We found that Gsdma1/2/3 KO mice showed significantly decreased epidermal hyperplasia and inflammation induced by phorbol 12-myristate 13-acetate (PMA). Furthermore, we found that the alleviation of epidermal hyperplasia depends on Gsdma1/2/3 expressed specifically in keratinocytes. Mechanistically, Gsdma1/2/3 depletion downregulated epidermal growth factor receptor (EGFR) ligands, leading to decreased EGFR-Stat3/Akt signalling. These results demonstrate that depletion of Gsdma1/2/3 alleviates PMA-induced epidermal hyperplasia partially by inhibiting the EGFR-Stat3/Akt pathway.

Metabolic characteristics, prevalence of anxiety and its influencing factors in first-episode and drug-naïve major depressive disorder patients with impaired fasting glucose.

BACKGROUND: Both major depressive disorder (MDD) and impaired fasting glucose (IFG) are associated with metabolic abnormalities and anxiety, but few studies have investigated the relationship between abnormal metabolism and anxiety in first-episode and drug-naïve (FEDN) MDD patients with IFG. This study investigated the psychological status, metabolic properties, the prevalence and influencing factors of anxiety symptoms in the FEDN MDD patients with IFG. METHODS: A total of 1718 FEDN MDD outpatients were recruited. Sociodemographic and suicide data were collected for each participant. The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Rating Scale (HAMA) were used to assess patients' clinical symptoms. Fasting blood glucose, lipids, body mass index (BMI), and thyroid function-related indicators were also measured. RESULTS: FEDN MDD patients with IFG (IFG group) had higher psychotic symptoms, suicide attempts, HAMD score, and HAMA score than FEDN MDD patients without IFG (NIFG group). There were also significant differences in blood lipids, BMI, and thyroid function indicators between the two groups. The prevalence of anxiety symptoms in the IFG group was 20.9 %, which was significantly higher than that in the NIFG group (10.4 %). Furthermore, anxiety symptoms were significantly associated with female, marital status, psychotic symptoms, suicide attempts, and low high-density lipoprotein (HDL-C). CONCLUSION: FEDN MDD patients with anxiety who have IFG are more likely to have problems with thyroid function, lipid metabolism, psychotic symptoms and suicide attempts, especially in female patients. Prevention of these problems should be enhanced when treating such patients.

Association between thyroid hormones and comorbid psychotic symptoms in patients with first-episode and drug-naïve major depressive disorder.

Thyroid dysfunction is common in major depressive disorder (MDD) patients; however, its relationship with psychotic depression (PD) remains unclear. We aimed to assess thyroid hormones in 1718 first episode drug naïve (FEND) MDD patients and to determine their association with PD. The positive subscale of the Positive and Negative Symptom Scale (PANSS-P), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD) were used to detect clinical symptoms. The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), and thyroid peroxidases antibody (TPOAb) were assessed. The logistic regression model was conducted to determine risk factors for PD, and the Area Under the Curve (AUC) was used to test the performance of this model. 171 (10%) patients were identified as having PD. Serum levels of TSH, TgAb, and TPOAb displayed small-to-moderate associations with PANSS-P. HAMA score, HAMD score, and TSH levels were independently associated with PD. The regression model had excellent power to distinguish PD patients from non-PD patients with an AUC value of 0.93. Our study suggests TSH levels and severity of depression and anxiety symptoms were independent risk factors for PD. Regular thyroid function tests may help early detect PD.

Stigmatizing attitudes toward mental illness among caregivers of patients with mental disorders in China.

Objective: This study aimed to investigate stigmatizing attitudes toward depression, schizophrenia, and general anxiety disorder (GAD) among caregivers of patients with mental disorders in China. Methods: A cross-sectional study was conducted among 607 caregivers in China, using vignettes that described three mental illnesses. Data on the caregivers' attitudes and other people's attitudes toward individuals with mental disorders and their willingness to come in contact with people with mental disorders were collected. Results: In the three vignettes, caregivers agreed that positive outcomes outnumbered negative outcomes. The top two statements endorsing the stigma were "the person could snap out of the problem" and "people with this problem are dangerous." In the section for perceived stigma, caregivers in the GAD vignette agreed that most people believed this problem is not a real medical illness, compared to schizophrenia. The rates of the statement endorsing unpredictability were significantly different in the schizophrenia (57.2%) and depression (45.5%) vignette, in comparison to the GAD (45.6%) vignette. For personal stigma, the caregivers tended to avoid people described in the depression vignette more often than in the GAD vignette. The caregivers were most unwilling to let the person described in the vignettes marry into their family, especially in the schizophrenia vignette. Conclusion: Despite the stigma and desire for social distance associated with schizophrenia, depression, and GAD, caregivers often expect positive outcomes. Actions should be taken to improve caregivers' knowledge about mental health and reduce the stigma.

The prevalence and risk factors of mental problems in medical students during COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the global prevalence and risk factors of mental problems (i.e., depression, anxiety, stress, sleep disorder, posttraumatic stress disorder (PTSD), burnout, psychological distress, and suicidal ideation) among medical students during the COVID-19 pandemic. METHOD: We searched PubMed, Embase, Web of Science, psycARTICLES, PsycINFO, CNKI, and Wan Fang for studies on the prevalence of mental problems among medical students from January 1, 2020, to April 1, 2022. The pooled prevalence was calculated by random-effect models. We performed a narrative review to identify the risk factors. RESULTS: The meta-analysis included 201 studies (N = 198,000). The prevalence of depression (41 %, 95 % CI, 37-45 %,), anxiety (38 %,95 % CI, 34 %-42 %), stress (34 %, 95 % CI, 27 %-42 %), sleep disorder (52 %, 95 % CI, 44 %-60 %), psychological distress (58 %, 95 % CI, 51 %-65 %), PTSD (34 %, 95 % CI, 22 %-46 %), suicidal ideation (15 %, 95 % CI, 11 %-18 %) and burnout (38 %, 95 % CI, 25 %-50 %) was high. The major risk factors were being female, being junior or preclinical students, exposure to COVID-19, academic stress, psychiatric or physical disorders history, economic trouble, fear of education impairment, online learning trouble, fear of infection, loneliness, low physical activity, low social support, problematic internet or smartphone use, and young age. LIMITATIONS: Most studies were cross-sectional. Few studies provided a reasonable response rate, suggesting potential selection bias. CONCLUSIONS: The study demonstrated a high prevalence and risk factors for mental problems during COVID-19, calling for mental health services. Our findings are valuable for college and health authorities to identify high-risk students and provide targeted intervention.

The functional change of the P2X7R containing the Ala348 to Thr polymorphism is associated with the pathogenesis of gout.

Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the functional changes of P2X7R single nucleotide polymorphisms (SNPs) on the effects of ATP-P2X7R-IL-1ß signaling pathway and uric acid remained unknown. We aimed to investigate the association between the functional change of P2X7R containing the Ala348 to Thr polymorphisms (rs1718119) and the pathogenesis of gout. First, 270 gout patients and 70 hyperuricemic patients (without gout attack history in recent 5 years) were recruited for genotyping. In addition, the changes of ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, and the effects on P2X7R-NLRP3-IL-1ß pathway activation were explored in P2RX7 overexpression THP-1 cells. The risk allele for gout was A at rs1718119, and the AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala348 to Thr mutants increased P2X7-dependent ethidium+ bromide uptake, upregulated IL-1ß and NLRP3 levels as compared to the wild-type. We suggest that genetic polymorphisms of P2X7R containing the Ala348 to Thr are associated with the increased risk of gout, showing an enhanced gain-of-function effect on the development of this disease.

The prevalence and clinical correlates of anxiety in Chinese patients with first-episode and drug-naïve major depressive disorder at different ages of onset.

BACKGROUND: Major depressive disorder (MDD) with comorbid anxiety is very common and is associated with worse clinical outcomes. MDD patients at different ages of onset may have different clinical features and associated factors. The aim of this study was to investigate the prevalence of anxiety and related factors in MDD patients at different ages of onset. METHODS: A total of 1718 first-episode and drug-naïve (FEDN) MDD patients were recruited. The cutoff point for early-adulthood onset (EAO) and mid-adulthood onset (MAO) was the first depressive episode before or after age 45 years. Clinical features (depressive, anxiety and psychiatric symptoms) and some metabolic parameters were collected. RESULTS: There was no significant difference in the prevalence of anxiety between EAO patients (50.7 %) and MAO patients (55.7 %). For EAO patients, regression analysis showed that TSH levels, TgAb levels, and TC levels were significantly associated with anxiety. For MAO patients, regression analysis showed that anxiety was associated with HDL-c levels and impaired glucose metabolism. Furthermore, suicide attempts, psychotic symptoms, and depression severity were correlated with anxiety in both groups. LIMITATIONS: Our cross-sectional study cannot explain the causal relationship between anxiety and related factors in MDD patients at different ages of onset. CONCLUSIONS: This study revealed that the clinical characteristics and factors associated with anxiety in MDD patients differed according to age of onset, and therefore age of onset needs to be considered while treating anxiety.

Effects of Multiple High-Dose Methamphetamine Administration on Enteric Dopaminergic Neurons and Intestinal Motility in the Rat Model.

Several studies have identified the effects of methamphetamine (MA) on central dopaminergic neurons, but its effects on enteric dopaminergic neurons (EDNs) are unclear. The aim of this study was to investigate the effects of MA on EDNs and intestinal motility. Male Sprague-Dawley rats were randomly divided into MA group and saline group. The MA group received the multiple high-dose MA treatment paradigm, while the controls received the same saline treatment. After enteric motility was assessed, different intestinal segments (i.e., duodenum, jejunum, ileum, and colon) were taken for histopathological, molecular biological, and immunological analysis. The EDNs were assessed by measuring the expression of two dopaminergic neuronal markers, dopamine transporter (DAT) and tyrosine hydroxylase (TH), at the transcriptional and protein levels. We also used c-Fos protein, a marker of neural activity, to detect the activation of EDNs. MA resulted in a significant reduction in TH and DAT mRNA expression as well as in the number of EDNs in the duodenum and jejunum (p < 0.05). MA caused a dramatic increase in c-Fos expression of EDNs in the ileum (p < 0.001). The positional variability of MA effects on EDNs paralleled the positional variability of its effect on intestinal motility, as evidenced by the marked inhibitory effect of MA on small intestinal motility (p < 0.0001). This study found significant effects of MA on EDNs with locational variability, which might be relevant to locational variability in the potential effects of MA on intestinal functions, such as motility.