Disease Duration Affects the Clinical Phenotype of Primary Sjögren Syndrome: A Medical Records Review Study of 952 Cases.

OBJECTIVES: To investigate the impact of disease duration on clinical phenotypes in Chinese patients with primary Sjögren syndrome (pSS) and examine the correlation between clinical phenotypes and onset age, age at diagnosis, and disease duration. METHODS: Data from 952 patients diagnosed with pSS in China between January 2013 and March 2022 were analyzed based on medical records. Patients were categorized into 3 groups based on disease duration: short (<5 years), moderate (≥5 and <10 years), and long (≥10 years) group. Clinical characteristics were compared among the 3 groups, and pSS patients with a long disease duration were compared with the other patients after matching age at diagnosis and age at onset. RESULTS: Among the patients, 20.4% had a disease duration over 10 years. After matching for age at onset and age at diagnosis, pSS patients with a long disease duration exhibited a significantly higher prevalence of dry mouth ( p <0.001), dry eyes ( p <0.001), fatigue ( p <0.001), arthralgia ( p <0.001), and dental caries ( p <0.001) and higher rates of anti-Sjögren syndrome A ( p < 0.05), anti-Ro52 ( p < 0.05), and anti-SSB ( p < 0.05) positivity than their control groups, with prevalence increasing with disease duration ( ptrend < 0.001). However, no differences were noted in the prevalence of interstitial lung disease and leukopenia between different disease duration groups after matching for age at onset, although differences were shown when matching for age at diagnosis. CONCLUSION: Longer disease duration in pSS patients correlates with increased prevalence of sicca symptoms, fatigue, and arthralgia and higher positivity of autoantibodies associated with pSS. However, the prevalence of interstitial lung disease and leukopenia did not correlate with disease duration after matching for age at onset.

Sex Difference in Primary Sjögren Syndrome: A Medical Records Review Study.

OBJECTIVES: The aim of this study was to study clinical and biological differences between men and women with primary Sjögren syndrome (pSS) in China and perform a literature review to confirm if the clinical phenotypes are affected by sex in patients with pSS. METHODS: Data from 961 patients with pSS treated at a tertiary hospital in China between January 2013 and March 2022 were analyzed based on medical records. Clinical characteristics, including disease manifestations and serological parameters of the disease, were compared between men and women with pSS using the Mann-Whitney U test and χ 2 test. RESULTS: This study included 140 (14.6%) men and 821 (85.4%) women with pSS. Women with pSS demonstrated a higher prevalence of dry mouth, dry eyes, arthralgia, and dental caries ( p < 0.05); higher erythrocyte sedimentation rate and immunoglobulin M levels ( p < 0.05); higher prevalence of leukopenia, neutropenia, anemia, low complement 3, and low complement 4 ( p < 0.05); and higher titers of antinuclear antibody, anti-Sjögren syndrome A, anti-Ro52, and rheumatoid factor positivity ( p < 0.05) than men, whereas men with pSS had a higher prevalence of parotid enlargement and interstitial lung disease ( p < 0.05). CONCLUSIONS: Women with pSS are associated with more dryness, cytopenia, hypocomplementemia, and autoantibody positivity. Although men with pSS probably have lighter sicca symptoms and lower immunoactivity and serologic responses, regular monitoring of interstitial lung disease in men is vital.

Knowledge mapping of biological disease-modifying anti-rheumatic drugs for axial spondyloarthritis: a bibliometric study.

Various biological disease-modifying anti-rheumatic drugs (bDMARDs) have been applied for treating axial spondyloarthritis (axSpA). However, there is a glaring absence of a bibliometric analysis on bDMARDs against axSpA. Articles related to use of bDMARDs in treating axSpA published from 2004 to 2022 were searched from the Web of Science Core Collection. VOS viewer 1.6.18 and CiteSpace 6.1.R2 were used to analyze and visualize the quantity and citations of publications, as well as to identify "research hotspots" and trends in this field. BibExcel version 1.0.0 and gCLUTO version 1.0 were used to build matrices for bi-clustering analysis. A total of 2546 articles referring to bDMARDs for treatment of axSpA were included in this bibliometric analysis. Overall, the number of publications has been increasing steadily annually. The USA (23.21%, 591 publications) ranked first with the largest output of papers, followed by Germany, and the Netherlands. Rheumazentrum Ruhrgebiet ranked first as the most frequent publisher (119 articles). Annals of the Rheumatic Diseases published the most documents (6.76%, 172 publications) in this field. The predominant hotspots have been "tuberculosis," "IL-17," and "quality of life" in the field until 2020. Since 2015, "biosimilar pharmaceuticals" has retained the popularity. Current research hotspots are "spinal radiographic progression," Janus kinase (JAK) inhibitors, and adverse events (AEs). Machine learning has become popular gradually. Globally, there has been a steady increase in the number of studies on bDMARDs use against axSpA. JAK inhibitors, spinal radiographic progression, biosimilar pharmaceuticals, and AEs are current research hotspots. Machine learning is emerging research hotspots and trends in this field.

Efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia: A meta-analysis of randomized sham-controlled trials.

Theta-burst stimulation is a non-invasive brain stimulation technique that was introduced as a potential augmentation treatment for patients with schizophrenia. The purpose of this meta-analysis was to investigate the therapeutic efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia. Following the PRISMA guidelines, the MEDLINE, Embase, Cochrane, Scopus, Web of Science, and CNKI databases were searched for relevant studies from database inception to 9 January 2022. Change in symptom severity among patients with schizophrenia was the primary outcome, and changes in cognitive function and safety profiles, including the discontinuation rate and adverse events, were secondary outcomes. In total, 13 double-blind randomized sham-controlled trials with 524 patients were included. Intermittent theta-burst stimulation adjunct to antipsychotics was associated with significantly improved psychopathology in patients with schizophrenia, particularly for negative symptoms and general psychopathology but not for positive symptoms or cognitive function. The stimulation parameters influenced the effectiveness of intermittent theta-burst stimulation. A more favorable effect was observed in patients who received theta-burst stimulation at the left dorsolateral prefrontal cortex, with ≥1800 pulses per day, for ≥20 sessions, and using an inactive sham coil as a placebo comparison in the study. The intermittent theta-burst stimulation is well tolerated and safe in patients with schizophrenia. Intermittent theta-burst stimulation adjunct to antipsychotics treatment is associated with significant improvement in negative symptoms and favorable tolerability in patients with schizophrenia. This meta-analysis may provide insights into the use of intermittent theta-burst stimulation as an additional treatment to alleviate the negative symptoms of schizophrenia.

Developing a Sensitive Platform to Measure 5-Methyltetrahydrofolate in Subjects with MTHFR and PON1 Gene Polymorphisms.

Inadequate levels of 5-methyltetrahydrofolate (5-MTHF) and the T variant of MTHFR C677T have been suggested to be associated with an increased risk of developing mental illness, whereas the PON1 SNP variant provides a protective role. However, reports validating the methodology for plasma 5-MTHF levels in schizophrenia patients are limited. A sensitive LC−MS/MS system using an amide column and calibration curve was determined by dialyzed human plasma, and applied to schizophrenia patients and healthy controls in Taiwan, and the differences between the subgroups were discussed. This analysis system meets regulation criteria, and the lower limit of quantification for 5-MTHF levels was 4 nM from 200 µL plasma, within 7 min. The mean plasma 5-MTHF levels in schizophrenia patients (n = 34; 11.70 ± 10.37 nM) were lower than those in the healthy controls (n = 42; 22.67 ± 11.12 nM) significantly (p < 0.01). 5-MTHF concentrations were significantly lower in male carriers than in female carriers (18.30 ± 10.37 nM vs. 24.83 ± 11.01 nM, p < 0.05), especially in subjects who were MTHFR CT/PON1 Q allele carriers. In conclusion, this quantitative system, which employed sensitive and simple processing methods, was successfully applied, and identified that schizophrenic patients had significantly lower levels of 5-MTHF. Lower plasma 5-MTHF concentrations were observed in male subjects.

Crosstalk between Schizophrenia and Metabolic Syndrome: The Role of Oxytocinergic Dysfunction.

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.

Correction notice to "Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model".

[This corrects the article DOI: 10.1177/1758835920922034.].

Subgrouping time-dependent prescribing patterns of first-onset major depressive episodes by psychotropics dissection.

BACKGROUND: Subgrouping patients with major depressive disorder is a promising solution for the issue of heterogeneity. However, the link between available subtypes and distinct pathological mechanisms is weak and yields disappointing results in clinical application. AIM: To develop a novel approach for classification of patients with time-dependent prescription patterns at first onset in real-world settings. METHODS: Drug-naive patients experiencing their first major depressive episode (n = 105) participated in this study. Psychotropic agents prescribed in the first 24 mo following disease onset were recorded monthly and categorized as antidepressants, augmentation agents, and hypnosedatives. Monthly cumulative doses of agents in each category were converted into relevant equivalents. Four parameters were used to summarize the time-dependent prescription patterns for each psychotropic load: Stability, amount, frequency, and the time trend of monthly prescriptions. A K-means cluster analysis was used to derive subgroups of participants based on these input parameters of psychotropic agents across 24 mo. Clinical validity of the resulting data-driven clusters was compared using relevant severity indicators. RESULTS: Four distinct clusters were derived from K-means analysis, which matches experts' consent: "Short-term antidepressants use", "long-term antidepressants use", "long-term antidepressants and sedatives use", and "long-term antidepressants, sedatives, and augmentation use". At the first 2 years of disease course, the four clusters differed on the number of antidepressants used at adequate dosage and duration, frequency of outpatient service use, and number of psychiatric admissions. After the first 2 years following disease onset, depression severity was differed in the four subgroups. CONCLUSION: Our findings suggested a new approach to optimize the subgrouping of patients with major depressive disorder, which may assist future etiological and treatment response studies.

The Relationships Between Hyperprolactinemia, Metabolic Disturbance, and Sexual Dysfunction in Patients With Schizophrenia Under Olanzapine Treatment.

The aim of the study was to assess the relationship between prolactin levels and sexual dysfunction in patients with schizophrenia who use olanzapine medication. The potential risk factors of hyperprolactinemia and sexual dysfunction were also investigated. Patients with schizophrenia undergoing olanzapine monotherapy were invited to participate in this cross-sectional study. The Arizona Sexual Experiences Scale (ASEX) and the Positive and Negative Syndrome Scale were used to evaluate subjective sexual dysfunction and psychopathology, respectively. Levels of prolactin and metabolic parameters were also measured. In total, 279 participants with schizophrenia were recruited. The overall incidences of hyperprolactinemia, sexual dysfunction, and metabolic syndrome were 51.6, 53.8, and 43.7%, respectively. Higher ASEX scores, higher insulin levels, female sex, and younger age were associated with hyperprolactinemia. Prolactin level was significantly correlated with ASEX score. Elevated prolactin levels, concomitant antidepressant, increased insulin resistance, longer illness duration, and female sex were associated with sexual dysfunction. Female participants recorded higher levels of sexual dysfunction than their male counterparts did, whereas male participants had comparatively lower prolactin levels and lower rates of spousal partnership. Hyperprolactinemia, metabolic syndrome, and sexual dysfunction are prevalent in patients with schizophrenia treated with olanzapine. Clinicians should maintain awareness of these problems and monitor them regularly with their patients.

Visualizing Patterns of Medication Switching Among Major Depressive Patients with Various Stability and Difficulty to Treatments.

INTRODUCTION: Efforts have been made in assessing efficacy and tolerability to various antidepressants, but understanding personalized chances of stability to medication switching sequence is still inconclusive. This study aimed to identify naturalistic switching patterns of medication in stratifying MDD patients. METHODS: MDD patients were stratified based on treatment difficulty evaluated with the "Treatment Resistance to Antidepressants Evaluation Scale for Unipolar Depression" (TRADES). The duration of the time of diagnoses until the final switch to another class of antidepressants was used as prediction of unstable to drug therapy. ROC analysis was used to determine the cutoff values. A continuous temporal events function from the visual analytic tool was employed to perform patterns of switching between distinct pharmacological class such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). RESULTS: TRADES scores of 4.5 and not-switching times of 12.5 months were used as cutoff values to divide patients into four subgroups: stable/easy-to-treat (SE), unstable/easy-to-treat (UE), stable/difficult-to-treat (SD) and unstable/difficult-to-treat (UD). A total of 80% and 76.9% of patients initially treated with the SSRIs paroxetine or fluoxetine, respectively, were predicted to be stable to drug therapy. Approximately 70%, 44.8% and 41.4% of patients initially treated with the SNRIs fluvoxamine, sertraline and venlafaxine, respectively, were predicted to be UD, and 60% of patients using duloxetine were predicted to be stable to drug therapy. Analysis of the switching phenomenon showed that SSRIs were the first prescribed medications and mostly taken by the stable subgroups, and SNRIs were the preferentially chosen switching alternative. Medication switching patterns in unstable MDD patients are discussed. CONCLUSION: Paroxetine, fluoxetine and duloxetine users were mostly stable among MDD patients in Taiwan with various stability and difficulty to treatments. Although responsiveness to specific medication sequence is likely required for clinical application, the results provide a baseline for such studies.

Efficacy of N-methyl-D-aspartate receptor modulator augmentation in schizophrenia: A meta-analysis of randomised, placebo-controlled trials.

BACKGROUND: Dysfunction of the N-methyl-D-aspartate glutamate receptor is involved in the putative pathology of schizophrenia. There is growing interest in the potential of N-methyl-D-aspartate receptor modulators to improve the symptoms of schizophrenia, but the evidence for the use of glutamatergic agents for augmenting schizophrenia remains inconclusive. AIMS: We conducted a meta-analysis to test the efficacy and safety of N-methyl-D-aspartate receptor modulator supplements in patients with schizophrenia. METHODS: Following a systemic search in MEDLINE, Embase, Cochrane and Scopus, 40 double-blinded, randomised, placebo-controlled trials involving 4937 patients with schizophrenia were included in this meta-analysis. The change in the severity of symptoms among patients with schizophrenia was defined as the primary outcome, whereas the safety profiles of the intervention, including the discontinuation rate and adverse events, were defined as secondary outcomes. RESULTS: When added to antipsychotic treatments, N-methyl-D-aspartate receptor modulators improved multiple schizophrenia symptoms, particularly negative symptoms, and had satisfactory side effects and safety profile. Among the seven glutamatergic agents analysed, glycine, D-serine and sarcosine had better treatment profiles than other agents, and NMDA receptor co-agonists, as a group, provided a reduction in schizophrenia symptoms compared to antipsychotic treatments without supplementation. Augmentation with N-methyl-D-aspartate receptor modulators was only effective among patients treated with antipsychotics other than clozapine. CONCLUSIONS: The results indicate that N-methyl-D-aspartate receptor modulators, particularly with glycine, D-serine and sarcosine, are more beneficial than the placebo in treating schizophrenia, and the effects extended to both positive and negative symptoms, when augmented with antipsychotics other than clozapine.

Increased infiltration of regulatory T cells in hepatocellular carcinoma of patients with hepatitis B virus pre-S2 mutant.

Hepatocellular carcinoma (HCC) is a frequent and deadly human cancer worldwide that is intimately associated with chronic hepatitis B virus (HBV) infection. Pre-S2 mutant is a HBV oncoprotein that plays important roles in HCC development and is linked to poor prognosis in HCC patients. However, the profiles of tumor-infiltrating lymphocytes in HCC tissues of pre-S2 mutant-positive patients remain unknown. In this study, we performed fluorescent immunohistochemistry staining to detect the infiltration of 'anti-tumor' cytotoxic T lymphocytes (CTLs) and 'pro-tumor' regulatory T cells (Tregs) in pre-S2 mutant-positive and -negative HCC patients. We showed that pre-S2 mutant-positive patients had a significantly higher infiltration of CD4+CD25+ cells and forkhead box P3 (Foxp3)-expressing cells but similar CTLs and lower granzyme B-expressing cells in HCC tissues compared with pre-S2 mutant-negative patients. Moreover, the percentage of pre-S2 plus pre-S1 + pre-S2 deletion (pre-S2 mutant) was positively correlated with the density of CD4+CD25+ cells and Foxp3-expressing cells but negatively with granzyme B-expressing cells in HCC tissues. Considering that increased intratumoral Tregs have been shown to promote tumor immune evasion, our data may provide new insights into the pathogenesis of HBV pre-S2 mutant-induced HCC and suggest that therapeutics targeting Tregs may be a promising strategy for treating pre-S2 mutant-positive high-risk patient population.

Increased Expression of Programmed Death Ligand 1 in Hepatocellular Carcinoma of Patients with Hepatitis B Virus Pre-S2 Mutant.

PURPOSE: Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), a leading cause of cancer-related death worldwide. The HCC patients who harbor HBV pre-S2 mutant, an oncoprotein that plays key roles in HCC development, have been closely associated with a worse prognosis after curative surgical resection, suggesting an urgent need for alternative therapeutic options to improve their survival. In this study, we aimed to evaluate the expression profiles of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), two of the most well-studied immune checkpoint molecules that promote tumor immune evasion, in tumor of the pre-S2 mutant-positive/high HCC patients. METHODS: We classified 40 HBV-related HCC patients into the pre-S2-positive/high and -negative/low groups by a next-generation sequencing-based approach. The fluorescent immunohistochemistry staining was performed to detect the expression of PD-1 and PD-L1 in HCC tissues of patients. RESULTS: We showed that patients with either deletion spanning pre-S2 gene segment or high percentage of pre-S2 plus pre-S1+pre-S2 deletion (the pre-S2 mutant-positive/high group) exhibited a significantly higher density of PD-L1-positive cells in HCC tissues than those without. Moreover, the percentage of pre-S2 plus pre-S1+pre-S2 deletion displayed a high positive correlation with the density of PD-L1-positive cells in HCC tissues. CONCLUSION: The increased expression of PD-L1 in tumor tissues of the pre-S2 mutant-positive HCC patients suggest that pre-S2 mutant may play a potential role in dysregulation of tumor immune microenvironment in the progression of HBV-related HCC, implicating for the development of future therapeutic strategies.

Phosphoproteomics and Bioinformatics Analyses Reveal Key Roles of GSK-3 and AKAP4 in Mouse Sperm Capacitation.

Protein phosphorylation can induce signal transduction to change sperm motility patterns during sperm capacitation. However, changes in the phosphorylation of sperm proteins in mice are still incompletely understood. Here, capacitation-related phosphorylation in mouse sperms were firstly investigated by label-free quantitative (LFQ) phosphoproteomics coupled with bioinformatics analysis using ingenuity pathway analysis (IPA) methods such as canonical pathway, upstream regulator, and network analysis. Among 1632 phosphopeptides identified at serine, threonine, and tyrosine residues, 1050 novel phosphosites, corresponding to 402 proteins, were reported. Gene heatmaps for IPA canonical pathways showed a novel role for GSK-3 in GP6 signaling pathways associated with capacitation for 60 min. At the same time, the reduction of the abundant isoform-specific GSK-3α expression was shown by western blot (WB) while the LFQ pY of this isoform slightly decreased and then increased. The combined results from WB and LFQ methods explain the less inhibitory phosphorylation of GSK-3α during capacitation and also support the predicted increases in its activity. In addition, pAKAP4 increased at the Y156 site but decreased at the Y811 site in a capacitated state, even though IPA network analysis and WB analysis for overall pAKAP revealed upregulated trends. The potential roles of GSK-3 and AKAP4 in fertility are discussed.

Combination therapy with dendritic cell vaccine and programmed death ligand 1 immune checkpoint inhibitor for hepatocellular carcinoma in an orthotopic mouse model.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most common and lethal human cancers worldwide. Despite remarkable advances in treatment, high mortality in HCC patients remains a big challenge. To develop novel therapeutic strategies for HCC is thus urgently needed to improve patient survival. Dendritic cells (DC)-based vaccines can induce tumor-specific immunity and have emerged as a promising approach for treating HCC patients; however, its effectiveness needs to be improved. Recently, blockade of programmed death ligand 1 (PD-L1) immune checkpoint pathway has been shown to enhance anti-tumor immune responses and exhibited great potential in HCC therapy. METHODS: In this study, we generated DC vaccine by pulsing the C57BL/6J mouse bone marrow-derived DC with mouse hepatoma Hep-55.1C cell lysate. We developed a therapeutic strategy combining DC vaccine and PD-L1 inhibitor for HCC and evaluated its efficacy in an orthotopic HCC mouse model in which Hep-55.1C cells were directly injected into left liver lobe of C57BL/6J mouse. RESULTS: Compared with a control group of mice, groups of mice treated with DC vaccine or PD-L1 inhibitor had significantly improved overall survival, reduced tumor volume, and increased tumor cell apoptosis. Remarkably, combination treatment with DC vaccine and PD-L1 inhibitor led to considerably longer overall survival, smaller tumor volume, and higher tumor cell apoptosis of mice than either treatment alone in a dose-dependent manner through inducing a stronger anti-tumor cytotoxic T cell response. CONCLUSION: Our data suggested that combination therapy with DC vaccine and PD-L1 inhibitor might have great promise as a novel treatment strategy for HCC.

Quantifying the level of difficulty to treat major depressive disorder with antidepressants: Treatment Resistance to Antidepressants Evaluation Scale.

BACKGROUND: The present study aimed to develop a new scale to evaluate the level of difficulty in treating major depressive disorder with antidepressants based on the lifetime treatment profile. METHODS: In addition to evaluating the difficulty of treatment with antidepressants (A subscale), the Treatment Resistance to Antidepressants Evaluation Scale (TRADES) is comprised of a subscale to account for the attributes that compromise the efficacy of treatment (B subscale). One hundred and six participants aged 18 to 65 years with remitted major depressive disorder were enrolled. Eligible cases were those with at least 2 years from disease onset until the scoring date of the TRADES (the index date), with a complete treatment record. Various psychosocial and clinical features, such as neuroticism, harm avoidance, and utilization of psychiatric services, were used to validate the TRADES. RESULTS: The mean duration of the course before and after the index date were 5.5 ± 3.5 and 3.1 ± 1.7 years, respectively. In a multiple regression analysis, the final total scores of the TRADES independently correlated with higher levels of neuroticism and harm avoidance. Total scores were also associated with a higher utilization of psychiatric outpatient and admission services before the index date. Furthermore, it is thought that total scores could predict a higher number of visits to psychiatric outpatient, emergency, and admission services following the index date. CONCLUSIONS: The TRADES has acceptable validity and could help to quantify the level of treatment difficulty with antidepressants in major depressive disorder.

Relationship between metabolic syndrome and acylated/desacylated ghrelin ratio in patients with schizophrenia under olanzapine medication.

BACKGROUND: Ghrelin is a peptide hormone that mediates glucose homeostasis and lipid metabolism. Acylated ghrelin (AG) and desacylated ghrelin (DAG) are the two main forms of ghrelin, which have opposing roles in energy homeostasis. The AG/DAG ratio has been proposed to be associated with metabolic syndrome (MetS) in the general population. This study compared the relationships between MetS and ghrelin parameters in patients with schizophrenia. METHODS: Patients diagnosed with schizophrenia and under olanzapine monotherapy were recruited. Fasting blood samples were collected for the analyses of metabolic and ghrelin parameters. The serum levels of total ghrelin and AG were measured by enzyme-linked immunosorbent assay kits. DAG level was calculated by subtracting the AG level from the total ghrelin level. RESULTS: We recruited 151 subjects with schizophrenia, and classified them into those with MetS (n = 41) and those without MetS (n = 110). Subjects with MetS had a significantly higher AG/DAG ratio, as well as lower total ghrelin and DAG levels. There were no sex differences in ghrelin parameters. The AG/DAG ratio was significantly and positively correlated with weight, body mass index, waist circumference, insulin level, homeostasis model assessment of insulin resistance and number of MetS components. Multiple linear regression analysis indicated that the number of MetS components remained significantly associated with the AG/DAG ratio. CONCLUSIONS: Our results revealed that lower AG/DAG ratios were associated with better metabolic profiles in olanzapine-treated patients with schizophrenia. These observations suggest that the balance between AG and DAG plays a crucial role in the metabolic homeostasis among patients with schizophrenia.

Constructing a bilingual website with validated database for Herb and Western medicine interactions using Ginseng, Ginkgo and Dong Quai as examples.

BACKGROUND: Concerns have been raised regarding the efficacy and safety resulting from the potential interactions of herbs with Western medications due to the use of both herbs and Western medicine by the general public. Information obtained from the web must be critically evaluated prior to its use in making decisions. DESCRIPTION: This study aimed to construct an herb-drug interaction (HDI) website (https://drug-herb-interaction.netlify.com) with a critically reviewed database. Node.js was used to store the database by running JavaScript. Vue.js is a front-end framework used for web interface development. A total of 135 sets of information related to the interactions of ginseng, ginkgo and dong quai with Western medicine from the literature identified in Medline were collected, followed by critical reviews to prepare nineteen items of information for each HDI monograph. A total of 80 sets of validated HDIs met all criteria and were further assessed at the individual reliability level (likely, possible, and unevaluable) and labeled with the "interaction" item. This query system of the website can be operated in both the Chinese and English languages to obtain all monographs on HDIs in the database, including bilingual interaction data. The database of HDI monographs can be updated by simply uploading a new version of the information Excel file. The designed "smart search" module, in addition to the "single search", is convenient for requesting multiple searches. Among the "likely" interactions (n = 26), 50% show negative HDIs. Ten of these can increase the effect of the Western drug, and the others (n = 3) imply that the HDI can be beneficial. CONCLUSIONS: The current study provides a website platform and 80 sets of validated bilingual HDIs involving ginseng, ginkgo and dong quai in an online database. A search of HDI monographs related to these three herbs can be performed with this bilingual, easy-to-use query website, which is feasible for professionals and the general public. The identified reliability level for each HDI may assist readers' decisions regarding whether taking Western medications concomitant with one of three herbal medicinal foods is safe or whether caution is required due to potentially serious outcomes.

Chemopreventive Effect of Phytosomal Curcumin on Hepatitis B Virus-Related Hepatocellular Carcinoma in A Transgenic Mouse Model.

Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), a leading cause of cancer mortality worldwide. Hepatitis B X protein (HBx) and pre-S2 mutant have been proposed as the two most important HBV oncoproteins that play key roles in HCC pathogenesis. Curcumin is a botanical constituent displaying potent anti-inflammatory and anti-cancer properties without toxic side effects. Phytosomal formulation of curcumin has been shown to exhibit enhanced bioavailability, improved pharmacokinetics, and excellent efficacy against many human diseases. However, effectiveness of phytosomal curcumin for HCC treatment remains to be clarified. In this study, we evaluated chemopreventive effect of phytosomal curcumin on HBV-related HCC by using a transgenic mouse model specifically expressing both HBx and pre-S2 mutant in liver. Compared with unformulated curcumin, phytosomal curcumin exhibited significantly greater effects on suppression of HCC formation, improvement of liver histopathology, decrease of lipid accumulation and leukocyte infiltration, and reduction of total tumor volume in transgenic mice. Moreover, phytosomal curcumin exerted considerably stronger effects on activation of anti-inflammatory PPARγ as well as inhibition of pro-inflammatory NF-κB than unformulated curcumin. Furthermore, phytosomal curcumin showed a comparable effect on suppression of oncogenic mTOR activation to unformulated curcumin. Our data demonstrated that phytosomal curcumin has promise for HCC chemoprevention in patients with chronic HBV infection.

The Association Between the Sedative Loads and Clinical Severity Indicators in the First-Onset Major Depressive Disorder.

Background: High sedative use in a major depressive episode may imply specific clinical features. This study aims to examine the correlation between sedative use and clinical severity indicators in the initial treatment phase of first-onset major depressive disorder. Methods: A study cohort in the first episode of major depressive disorder was used to conduct pharmacological dissection. All participants had at least a 2-year follow-up period with a complete treatment record. The defined daily dose of antidepressants and augmentation agents were calculated as the antidepressant load and augmentation load, respectively. Sedative use, which was calculated as the equivalent dosage of lorazepam, were defined as the sedative load. These psychotropic loads were measured monthly and the averaged psychotropic loads for each day were obtained. Results: A total of 106 individuals (75.5% female) were included. The mean duration of disease course in participants was 5.5 ± 3.5 years. In the multiple regression analysis, after controlling for other classes of psychotropics and comorbid anxiety disorders, the sedative load independently correlated with higher number of antidepressants used, higher number of antidepressant used with an adequate dose and duration, more psychiatric emergency and outpatient visits within 2 years of disease onset. Conclusion: High loading of sedatives correlated with several indicators of clinical severity in major depressive disorder. The sedative load may be used as a specifier to identify subgroups in patients with major depressive disorder.