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Abstract Objectives This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice. Methods We recruited 60 patients (aged 40–89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann–Whitney U test, the chi-square test (χ2), or Fisher’s exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables. Results Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p 0.05). Conclusion Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.

BackgroundPeople who undergo sphincter-preserving surgery have high rates of anorectal functional disturbances, known as low anterior resection syndrome (LARS). LARS negatively affects patients’ quality of life (QoL) and increases their need for self-management behaviors. Therefore, approaches to enhance self-management behavior and QoL are vital. ObjectiveThis study aims to assess the effectiveness of a remote digital management intervention designed to enhance the QoL and self-management behavior of patients with LARS. MethodsFrom July 2022 to May 2023, we conducted a single-blinded randomized controlled trial and recruited 120 patients with LARS in a tertiary hospital in Hefei, China. All patients were randomly assigned to the intervention group (using the “e-bowel safety” applet and monthly motivational interviewing) or the control group (usual care and an information booklet). Our team provided a 3-month intervention and followed up with all patients for an additional 3 months. The primary outcome was patient QoL measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. The secondary outcomes were evaluated using the Bowel Symptoms Self-Management Behaviors Questionnaire, LARS score, and Perceived Social Support Scale. Data collection occurred at study enrollment, the end of the 3-month intervention, and the 3-month follow-up. Generalized estimating equations were used to analyze changes in all outcome variables. ResultsIn the end, 111 patients completed the study. In the intervention group, 5 patients withdrew; 4 patients withdrew in the control group. Patients in the intervention group had significantly larger improvements in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 total score (mean difference 11.51; 95% CI 10.68-12.35; Cohen d=1.73) and Bowel Symptoms Self-Management Behaviors Questionnaire total score (mean difference 8.80; 95% CI 8.28-9.32; Cohen d=1.94) than those in the control group. This improvement effect remained stable at 3-month follow-up (mean difference 14.47; 95% CI 13.65-15.30; Cohen d=1.58 and mean difference 8.85; 95% CI 8.25-9.42; Cohen d=2.23). The LARS score total score had significantly larger decreases after intervention (mean difference –3.28; 95% CI –4.03 to –2.54; Cohen d=–0.39) and at 3-month follow-up (mean difference –6.69; 95% CI –7.45 to –5.93; Cohen d=–0.69). The Perceived Social Support Scale total score had significantly larger improvements after intervention (mean difference 0.47; 95% CI 0.22-0.71; Cohen d=1.81). ConclusionsOur preliminary findings suggest that the mobile health–based remote interaction management intervention significantly enhanced the self-management behaviors and QoL of patients with LARS, and the effect was sustained. Mobile health–based remote interventions become an effective method to improve health outcomes for many patients with LARS. Trial RegistrationChinese Clinical Trial Registry ChiCTR2200061317; https://tinyurl.com/tmmvpq3

Abstract Aim This study aims to translate the English version of the ‘caring ability of family caregivers of patients with cancer scale (CAFCPCS)’ into Chinese and validate its psychometric properties in the family caregivers of elderly patients with cancer. Design A methodological study. Methods Based on the Brislin translation model, the original scale will be translated and back‐translated, the Delphi expert consultation method will be adopted for cross‐cultural adaptation, and the pilot will be carried out in 20–30 family caregivers of elderly patients with cancer. Then, a dual‐centre prospective study will be conducted by recruiting 371–542 family caregivers of elderly patients with cancer to validate the psychometric properties of the Chinese version of CAFCPCS. Results The scale's content validity will be evaluated using the Delphi expert inquiry method, and the face validity will be evaluated using a pre‐experiment. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) will be used to assess structural validity, while internal consistency reliability and split‐half reliability will be used to assess reliability. Patient or Public Contribution Public involvement is of great significance for this study. Participants will be used in a pre‐test to give feedback on whether the contents of the clinical pilot version of CAFCPCS after expert consultation can reflect real problems and whether the sentences can be well understood. Based on their opinions, the research group will further refine the scale.

Abstract Early detection of bipolar depression (BPD) and major depressive disorder (MDD) has been challenging due to the lack of reliable and easily measurable biological markers. This study aimed to investigate the accuracy of discriminating patients with mood disorders from healthy controls based on task state skin potential characteristics and their correlation with individual indicators of oxidative stress. A total of 77 patients with BPD, 53 patients with MDD, and 79 healthy controls were recruited. A custom-made device, previously shown to be sufficiently accurate, was used to collect skin potential data during six emotion-inducing tasks involving video, pictorial, or textual stimuli. Blood indicators reflecting individual levels of oxidative stress were collected. A discriminant model based on the support vector machine (SVM) algorithm was constructed for discriminant analysis. MDD and BPD patients were found to have abnormal skin potential characteristics on most tasks. The accuracy of the SVM model built with SP features to discriminate MDD patients from healthy controls was 78% (sensitivity 78%, specificity 82%). The SVM model gave an accuracy of 59% (sensitivity 59%, specificity 79%) in classifying BPD patients, MDD patients, and healthy controls into three groups. Significant correlations were also found between oxidative stress indicators in the blood of patients and certain SP features. Patients with depression and bipolar depression have abnormalities in task-state skin potential that partially reflect the pathological mechanism of the illness, and the abnormalities are potential biological markers of affective disorders.

Assessing changes in human attention states via noninvasive physiological signals poses a significant challenge. Research has often associated the migration of mitochondrial superoxide radicals with electrical skin signals and physiological state. This study proposes a novel method to identify meaningful features for discerning variations in attention states by examining skin potential (SP) signals from specific features. This research project began with gathering SP signals. Next, Wavelet Packet Transform (WPT) and other approaches are applied to conduct an energy analysis across various frequency bands, which allows for the extraction of time- and frequency-domain features from the SP signals, and the potential of these features to differentiate human attention states is then examined via regression-based classifiers. Feature selection refinement is accomplished through statistical tests and Linear Support Vector Machines (SVM) with Recursive Feature Elimination (RFE). The focus is on the discriminative power of a selected set of primary features to distinguish human attention states. The designed experiment revealed significant variations in SP signal features when the subjects experienced shifts in their attention states. These features encompass measures such as first- and second-order derivative sequences, wavelet energy, wavelet coefficient, and power spectral density in different frequency bands. The core significance of this research lies in its focus on the feature selection of the SP signal, which yields a set of highly impactful features contributing to the distinction of attention states. This study underscores the potential of classifier models to effectively distinguish attention states, particularly through the examination of critical features, such as the wavelet energy of SP signals within certain frequency bands. These features may be relevant to several psychological mechanisms that reinforce the relationship between physiological signals and cognitive state. The insights derived from this investigation deepen the comprehension of human attention states and set the groundwork for more granular future explorations of SP signals.

Summary: Background: Antipsychotics and mood stabilisers are gathering attention for the disturbance of metabolism. This network meta-analysis aims to evaluate and rank the metabolic effects of the commonly used antipsychotics and mood stabilisers in treating bipolar disorder (BD). Methods: Registries including PubMed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar were searched before February 15th, 2024, for randomised controlled trials (RCTs) applying antipsychotics or mood stabilisers for BD treatment. The observed outcomes were twelve metabolic indicators. The data were extracted by two reviewers independently, and confirmed by another four reviewers and a corresponding author. The above six reviewers all participated in data analyses. Data extraction was based on PRISMA guidelines, and quality assessment was conducted according to the Cochrane Handbook. Use a random effects model for data pooling. The PROSPERO registration number is CRD42023466669. Findings: Together, 5421 records were identified, and 41 publications with 11,678 complete-trial participants were confirmed eligible. After eliminating possible sensitivity, risperidone ranked 1st in elevating fasting serum glucose (SUCRA = 90.7%) and serum insulin (SUCRA = 96.6%). Lurasidone was most likely to elevate HbA1c (SUCRA = 82.1%). Olanzapine ranked 1st in elevating serum TC (SUCRA = 93.3%), TG (SUCRA = 89.6%), and LDL (SUCRA = 94.7%). Lamotrigine ranked 1st in reducing HDL (SUCRA = 82.6%). Amisulpride ranked 1st in elevating body weight (SUCRA = 100.0%). For subgroup analyses, quetiapine is more likely to affect indicators of glucose metabolism among male adult patients with bipolar mania, while long-term lurasidone tended to affect glucose metabolism among female patients with bipolar depression. Among patients under 18, divalproex tended to affect glucose metabolism, with lithium affecting lipid metabolism. In addition, most observed antipsychotics performed higher response and remission rates than placebo, and displayed a similar dropout rate with placebo, while no between-group significance of rate was observed among mood stabilisers. Interpretation: Our findings suggest that overall, antipsychotics are effective in treating BD, while they are also more likely to disturb metabolism than mood stabilisers. Attention should be paid to individual applicability in clinical practice. The results put forward evidence-based information and clinical inspiration for drug compatibility and further research of the BD mechanism. Funding: The National Key Research and Development Program of China (2023YFC2506200), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (No. JNL-2023001B).

ObjectivesThis clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia.MethodsIn this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed.ResultsA total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p

BackgroundSchizophrenia (SCZ) is a heritable disorder with a polygenic architecture, and the gut microbiota seems to be involved in its development and outcome. In this study, we investigate the interplay between genetic risk and gut microbial markers.MethodsWe included 159 first-episode, drug-naïve SCZ patients and 86 healthy controls. The microbial composition of feces was characterized using the 16S rRNA sequencing platform, and five microbial α-diversity indices were estimated [Shannon, Simpson, Chao1, the Abundance-based Eoverage Estimator (ACE), and a phylogenetic diversity-based estimate (PD)]. Polygenic risk scores (PRS) for SCZ were constructed using data from large-scale genome-wide association studies. Effects of microbial α-diversity, microbial abundance, and PRS on SCZ were evaluated via generalized linear models.ResultsWe confirmed that PRS was associated with SCZ (OR = 2.08, p = 1.22×10−5) and that scores on the Shannon (OR = 0.29, p = 1.15×10−8) and Simpson (OR = 0.29, p = 1.25×10−8) indices were inversely associated with SCZ risk. We found significant interactions (p

We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.

Abstract Background Major depressive disorder (MDD) is a prevalent mental health condition characterized by recurrent episodes in a substantial proportion of patients. The number of previous episodes is one of the most crucial predictors of depression recurrence. However, the underlying neural mechanisms remain unclear. To date, there have been limited neuroimaging studies investigating morphological changes of the brainstem in patients with first-episode MDD (FMDD) and recurrent MDD (RMDD). This study aimed to examine volumetric changes of individual brainstem regions in relation to the number of previous episodes and disease duration. Method A total of 111 individuals including 36 FMDD, 25 RMDD, and 50 healthy controls (HCs) underwent T1-weighted structural magnetic resonance imaging scans. A Bayesian segmentation algorithm was used to analyze the volume of each brainstem region, including the medulla oblongata, pons, midbrain, and superior cerebellar peduncle (SCP), as well as the whole brainstem volume. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. Partial correlation analyses were further conducted to identify associations between regional volumes and clinical features. Results The ANOVA revealed significant brainstem volumetric differences among three groups in the pons, midbrain, SCP, and the whole brainstem (F = 3.996 ~ 5.886, adjusted p = 0.015 ~ 0.028). As compared with HCs, both groups of MDD patients showed decreased volumes in the pons as well as the entire brainstem (p = 0.002 ~ 0.034), however, only the FMDD group demonstrated a significantly reduced volume in the midbrain (p = 0.003). Specifically, the RMDD group exhibited significantly decreased SCP volume when comparing to both FMDD (p = 0.021) group and HCs (p = 0.008). Correlation analyses revealed that the SCP volumes were negatively associated with the number of depressive episodes (r=-0.36, p

Abstract Background Testicular volume in neonates is a potential indicator of testicular development during the fetal period, particularly the masculinization programming window. Reliable measurements of testicular volume provide an opportunity for early detection of testicular abnormalities. This study aimed to assess the testicular volume in neonates and evaluate its relationship with gestational week and birth weight in Hainan Province, China. Methods Data on 458 neonates who underwent ultrasonography examinations at our institution from 2018 to 2022 were collected. The neonates were categorized by gestational week, birth weight, and presence of cryptorchidism. We evaluated the testicular volume among different groups and its relationship to gestational week and birth weight. Results There was no significant difference between the right and left testicular volume in neonates without cryptorchidism. However, a significant difference was observed between normal birth weight and low birth weight neonates in terms of testicular volume. Similarly, there was a significant difference between premature and full-term neonates in testicular volume. Bilateral testicular volume showed positive and significant correlations with gestational week and birth weight. Additionally, a significant difference was noted in testicular volume between the affected side in neonates with cryptorchidism and the same side in normal birth weight full-term neonates. Conclusions We established the normal range of testicular volume for neonates in Hainan Province and demonstrated that testicular volume is positively correlated with both birth weight and gestational week. Cryptorchidism also affects testicular volume during the neonatal period, likely due to reduced androgenic exposure in utero, particularly during the masculinization programming window. The findings of this study have significant implications for assessing testis development during fetal development.

Abstract Background Previous neuroimaging findings have demonstrated the association between anhedonia and the hippocampus. However, few studies have focused on the structural changes in the hippocampus in major depressive disorder (MDD) patients with anhedonia. Meanwhile, considering that multiple and functionally specialized subfields of the hippocampus have their own signatures, the present study aimed to investigate the volumetric alterations of the hippocampus as well as its subfields in MDD patients with and without anhedonia. Methods A total of 113 subjects, including 30 MDD patients with anhedonia, 40 MDD patients without anhedonia, and 43 healthy controls (HCs), were recruited in the study. All participants underwent high-resolution brain magnetic resonance imaging (MRI) scans, and the automated hippocampal substructure module in FreeSurfer 6.0 was used to evaluate the volumes of hippocampal subfields. We compared the volumetric differences in hippocampal subfields among the three groups by analysis of variance (ANOVA, post hoc Bonferroni), and partial correlation was used to explore the association between hippocampal subregion volumes and clinical characteristics. Results ANOVA showed significant volumetric differences in the hippocampal subfields among the three groups in the left hippocampus head, mainly in the cornu ammonis (CA) 1, granule cell layer of the dentate gyrus (GC-ML-DG), and molecular layer (ML). Compared with HCs, both groups of MDD patients showed significantly smaller volumes in the whole left hippocampus head. Interestingly, further exploration revealed that only MDD patients with anhedonia had significantly reduced volumes in the left CA1, GC-ML-DG and ML when compared with HCs. No significant difference was found in the volumes of the hippocampal subfields between MDD patients without anhedonia and HCs, either the two groups of MDD patients. However, no association between hippocampal subfield volumes and clinical characteristics was found in either the subset of patients with anhedonia or in the patient group as a whole. Conclusions These preliminary findings suggest that MDD patients with anhedonia exhibit unique atrophy of the hippocampus and that subfield abnormalities in the left CA1 and DG might be associated with anhedonia in MDD.

Individuals with bipolar disorder (BD) have a greater suicide risk than the general population. In this study, we employed latent profile analysis (LPA) to explore whether Chinese individuals with different phases of BD differed at the levels of suicidal ideation. We recruited 517 patients. Depressive symptoms were measured using the 24-item Hamilton Depression Rating Scale (HAMD-24), and manic symptoms were evaluated using the Young Mania Rating Scale (YMRS). The extent of suicidal thoughts was determined through the Beck Scale for Suicide Ideation (BSSI). The scores of HAMD and YMRS were used to perform LPA. LPA categorized participants into three classes: one exhibiting severe depressive and mild manic symptomatology, another showing severe depressive and severe manic symptomatology, and the third one displaying severe depressive and intermediate manic symptomatology. Suicidal ideation levels were found to be remarkably elevated across all three classes. Additionally, the three classes showed no significant differences in terms of suicidal ideation. Our research confirms the link between depressive symptoms and suicide, independent of the manic symptoms. These findings carry meaning as they provide insight into the suicide risk profiles within different phases of BD.

Recently, supercritical CO2 (S-CO2) has been extensively applied for the recovery of waste heat from flue gas. Although various cycle configurations have been proposed, existing studies predominantly focus on the steady analysis and optimization of different S-CO2 structures under design conditions, and there is a noticeable deficiency in off-design research, especially for the innovative S-CO2 cycles. Thus, in this work aimed at the proposed novel S-CO2 power cycle, off-design characteristics and corresponding control strategies are investigated for the waste heat recovery. Based on the design parameters of the S-CO2 cycle, structural dimensions of printed circuit heat exchangers (PCHEs) and shell-and-tube heat exchangers are determined, and design values of turbines and compressors are specified. On this basis, off-design models for these key components are formulated. By manipulating variables such as cooling water inlet temperature, cooling water mass flow rate, flue gas inlet temperature and flue gas mass flow rate, cycle performances of the system are analyzed under off-design conditions. The simulation results show that when the inlet temperature and the mass flow rate of cooling water vary separately, the thermal efficiency both can reach the maximum value of 28.43% at the design point. For the changes in heat source parameters, the optimum point is slightly deviated from the design condition. Amidst the fluctuations in flue gas inlet temperature, the thermal efficiency optimizes to a peak of 28.56% at 530 °C. In the case of variation in the flue gas mass flow rate, the highest thermal efficiency 28.75% can be obtained. Furthermore, to maintain the efficient and stable operation of the S-CO2 power cycle, the corresponding control strategy of the cooling water mass flow rate is proposed for the cooling water inlet temperature variation. Generally, when the inlet temperature of cooling water increases from 23 °C to 27 °C, the cooling water mass flow should increase from 82.3% to 132.7% of the design value to keep the system running as much as possible at design conditions.

Abstract A more effective and better-tolerated site for repetitive transcranial magnetic stimulation (rTMS) for treating cognitive dysfunction in patients with bipolar disorder (BD) is needed. The primary visual cortex (V1) may represent a suitable site. To investigate the use of the V1, which is functionally linked to the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), as a potential site for improving cognitive function in BD. Seed-based functional connectivity (FC) analysis was used to locate targets in the V1 that had significant FC with the DLPFC and ACC. Subjects were randomly assigned to 4 groups, namely, the DLPFC active-sham rTMS (A1), DLPFC sham-active rTMS (A2), ACC active-sham rTMS (B1), and ACC sham-active rTMS groups (B2). The intervention included the rTMS treatment once daily, with five treatments a week for four weeks. The A1 and B1 groups received 10 days of active rTMS treatment followed by 10 days of sham rTMS treatment. The A2 and B2 groups received the opposite. The primary outcomes were changes in the scores of five tests in the THINC-integrated tool (THINC-it) at week 2 (W2) and week 4 (W4). The secondary outcomes were changes in the FC between the DLPFC/ACC and the whole brain at W2 and W4. Of the original 93 patients with BD recruited, 86 were finally included, and 73 finished the trial. Significant interactions between time and intervention type (Active/Sham) were observed in the scores of the accuracy of the Symbol Check in the THINC-it tests at baseline (W0) and W2 in groups B1 and B2 (F = 4.736, p = 0.037) using a repeated-measures analysis of covariance approach. Group B1 scored higher in the accuracy of Symbol Check at W2 compared with W0 (p

Abstract Autoimmune diseases (AID) cause inflammatory changes in the peripheral blood, which might be a predisposing factor for the development of comorbid bipolar disorder (BD). The levels of peripheral inflammatory indicators and cytokines may also serve as potential biomarkers for predicting BD susceptibility and the efficacy of antipsychotics in patients with AID. Herein, we present the case of a 43-year-old female who has suffered from AID for over 16 years and was recently diagnosed with “bipolar and related disorder due to another medical condition”.

Abstract Background To explore the gut microbiota characteristics in depressed patients with bipolar disorder (BD) as well as the connection between the gut microbiota and inflammatory markers. Methods Totally 72 depressed BD patients and 16 healthy controls (HCs) were enrolled in the study. Blood and feces samples were taken from each subject. With the help of 16S-ribosomal RNA gene sequencing, the characteristics of the gut microbiota in each participant were examined. Correlation analysis was then utilized to assess the relationship between the gut microbiota and clinical parameters. Results We found the taxonomic composition of the gut microbiota, but not its diversity, was significantly different in BD patients compared to HCs. We found the abundance of Bacilli, Lactobacillales and genus Veillonella were higher in BD patients than in HCs, while genus Dorea was more abundant in HCs. Additionally, correlation analysis showed that the bacterial genera’ abundance in BD patients was strongly correlated with the severity of depression and inflammatory markers. Conclusions According to these results, the gut microbiota characteristics were changed in depressed BD patients, which may have been associated with the severity of depression and the inflammatory pathways.

ABSTRACT The emerging infectious agent Elizabethkingia meningoseptica is associated with life-threatening infections in immunocompromised individuals. However, there are limited data on its geographic distribution, phylogenetic evolution, pathogenesis, and transmission. In this study, we comprehensively analyze and compare the genomic features, evolutionary history, emergence date, and transmission networks of global E. meningoseptica. Geographical distribution reveals the presence of the emerging bacteria in Asia, Europe, and North America, three continents with similar latitudes. Phylogenetic analyses show no relationship between the strain’s evolutionary history and its location, origin, or source, despite the presence of genetic diversity. Analysis of the emergence timeline suggests that America is the most likely source of E. meningoseptica with the common ancestor of this pathogen dating back 90 years. Putative transmission networks indicate that E. meningoseptica bacteria can spread within the same hospital and even across borders. Minor variations in resistance genotypes and virulence genes are observed, supporting existing evidence of inherent resistance and pathogenicity in E. meningoseptica. Additionally, minocycline and doxycycline demonstrate potent antimicrobial activity against this pathogen, making them promising candidates for treating E. meningoseptica infections. Our research highlights the potential for severe nosocomial outbreaks caused by E. meningoseptica with horizontal transmission occurring between countries worldwide. To prevent future outbreak infections, increased genomic surveillance of global E. meningoseptica populations is necessary. IMPORTANCE Elizabethkingia meningoseptica is an emerging infectious agent associated with life-threatening infections in immunocompromised individuals. However, there are limited data available on the genomic features of E. meningoseptica. This study aims to characterize the geographical distribution, phylogenetic evolution, pathogenesis, and transmission of this bacterium. A systematic analysis of the E. meningoseptica genome revealed that a common ancestor of this bacterium existed 90 years ago. The evolutionary history showed no significant relationship with the sample source, origin, or region, despite the presence of genetic diversity. Whole genome sequencing data also demonstrated that E. meningoseptica bacteria possess inherent resistance and pathogenicity, enabling them to spread within the same hospital and even across borders. This study highlights the potential for E. meningoseptica to cause severe nosocomial outbreaks and horizontal transmission between countries worldwide. The available evidence is crucial for the development of evidence-based public health policies to prevent global outbreaks caused by emerging pathogens.

With the acceleration of the mining process, the goaf has become one of the main sources of danger in underground mines, seriously threatening the safe production of mines. To make an accurate prediction of the risk level of the goaf quickly, this paper optimizes the features of the goaf by correlation analysis and feature importance and constructs a combination of feature parameters for the risk level prediction of the goaf to solve the problem of redundancy of evaluation indexes. Multiple machine learning algorithms are applied to 121 sets of goaf data respectively, and the optimal algorithm and the best combination of feature parameters are obtained by evaluating the mining area with multiple indicators such as accuracy and kappa coefficient. The best combination of features parameters are ground-water, goaf layout, volume of goaf, goaf volume, span-height ratio, and mining disturbance, and the optimal algorithm is Extra Tree (ET), which needles the goaf risk level prediction problem with the accuracy of 94%. This model can be used to solve the problem of how to quickly and accurately predict the risk level of the goaf.

Elizabethkingia anophelis is an emerging species and has increasingly been reported to cause life-threatening infections and even outbreaks in humans. Nevertheless, there is little data regarding the E. anophelis geographical distribution, phylogenetic structure, and transmission across the globe, especially in Asia. We utilize whole-genome sequencing (WGS) data to define a global population framework, phylogenetic structure, geographical distribution, and transmission evaluation of E. anophelis pathogens. The geographical distribution diagram revealed the emerging pathogenic bacteria already distributed in various countries worldwide, especially in the USA and China. Strikingly, phylogenetic analysis showed a part of our China original E. anophelis shared the same ancestor with the USA outbreak strain, which implies the possibility of localized outbreaks and global spread. These closer related strains also contained ICEEaI, which might insert into a disrupted DNA repair mutY gene and made the strain more liable to mutation and outbreak infection. BEAST analysis showed that the most recent common ancestor for ICEEaI E. anophelis was dated twelve years ago, and China might be the most likely recent source of this bacteria. Our study sheds light on the potential possibility of E. anophelis causing the large-scale outbreak and rapid global dissemination. Continued genomic surveillance of the dynamics of E. anophelis populations will generate further knowledge for optimizing future prevent global outbreak infections.

Abstract Objective Anhedonia is a core feature of major depressive disorder (MDD), and as a subtype of depression, MDD with anhedonia may have exceptional neurobiological mechanisms. However, the neuropathology of anhedonia in MDD remains unclear. Thus, this study aimed to investigate the brain functional differences between MDD with and without anhedonia. Methods A total of 62 individuals including 22 MDD patients with anhedonia, 20 MDD patients without anhedonia, and 20 healthy controls (HCs) were recruited for this study. All participants underwent 3.0-T functional magnetic resonance imaging scan. Voxel-mirrored homotopic connectivity (VMHC) was employed to quantitatively describe bilateral functional connectivity. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. Results The ANOVA revealed significant VMHC differences among three groups in the bilateral middle temporal gyrus (MTG), superior frontal gyrus (SFG), and inferior parietal lobule (IPL) (F = 10.47 ~ 15.09, p

Summary: Epigenetic alterations are especially important in necrotizing enterocolitis (NEC). Here, we reported that histone deacetylase 8 (HDAC8) plays a previously unknown role in modulating arginine metabolism via acetylation of histone 3 lysine 9 (acetyl-H3K9) regulation during the pathogenesis of NEC. We found that HDAC8 was upregulated in humans and mice intestinal samples with NEC, while selective inhibition of HDAC8 expression ameliorated NEC. HDAC8 regulates enzymes involved in the metabolic conversion of proline to arginine (PRODH, PRODH2, OAT, and OTC) and arginine to ornithine (ARG1). The results showed that H3K9ac signal in the PRODH/PRODH2 promoter region was mediated by HDAC8. Additionally, the decreased concentration of butyric acid was strongly correlated with elevated HDAC8 levels and circulating arginine, which may result from an unbalanced Firmicutes/Bacteroidetes ratio. These results reveal previously underappreciated roles of microbial metabolites and HDAC8 to coordinate the arginine metabolism during NEC development.

As a safe neuromodulation therapy, rTMS is applied to treat a variety of psychiatric and neurological disorders. Additionally, both aripiprazole and sodium valproate are effective in the treatment of rapid cycling bipolar disorder. This case reports a female patient with a 17-year history of bipolar disorder who developed rapid-circulation bipolar disorder 5 years prior to presentation. After combined treatment with rTMS, aripiprazole, and sodium valproate, the patient’s mood remained stable and she was able to live and work normally.

Abstract The pathophysiology of major depressive disorder (MDD) remains obscure. Recently, the microbiota-gut-brain (MGB) axis’s role in MDD has an increasing attention. However, the specific mechanism of the multi-level effects of gut microbiota on host metabolism, immunity, and brain structure is unclear. Multi-omics approaches based on the analysis of different body fluids and tissues using a variety of analytical platforms have the potential to provide a deeper understanding of MGB axis disorders. Therefore, the data of metagenomics, metabolomic, inflammatory factors, and MRI scanning are collected from the two groups including 24 drug-naïve MDD patients and 26 healthy controls (HCs). Then, the correlation analysis is performed in all omics. The results confirmed that there are many markedly altered differences, such as elevated Actinobacteria abundance, plasma IL-1β concentration, lipid, vitamin, and carbohydrate metabolism disorder, and diminished grey matter volume (GMV) of inferior frontal gyrus (IFG) in the MDD patients. Notably, three kinds of discriminative bacteria, Ruminococcus bromii, Lactococcus chungangensis, and Streptococcus gallolyticus have an extensive correlation with metabolome, immunology, GMV, and clinical symptoms. All three microbiota are closely related to IL-1β and lipids (as an example, phosphoethanolamine (PEA)). Besides, Lactococcus chungangensis is negatively related to the GMV of left IFG. Overall, this study demonstrate that the effects of gut microbiome exert in MDD is multifactorial.

Introduction Low anterior resection syndrome (LARS) involves bowel dysfunction after sphincter-preserving surgery for rectal resection that significantly impacts patients’ quality of life (QoL). The improvement of LARS largely depends on patient self-management behaviour; however, insufficient information about supportive care and weak awareness of self-management lead to poor self-management behaviour. Motivational interviewing (MIs) explore and change patients’ ambivalence during the conversation, thereby changing and maintaining healthy behaviours to enhance effective participation. In recent years, mobile health has been widely used in clinical practice, providing continuous information support and remote interaction. However, current online information on LARS is suboptimal, websites are highly variable, important content is often lacking and the material is too complex for patients. Therefore, this study will evaluate the impacts of a remote LARS interaction management intervention based on a WeChat applet (‘e-bowel safety’) and MIs on patients with LARS.Methods and analysis This study will be a single-blind, two-arm randomised controlled trial involving patients with LARS in three tertiary grade A general hospitals who will be randomised into two groups. The intervention group will use the ‘e-bowel safety’ applet and the intervention team will conduct a monthly MI about syndrome management. The control group will receive an information booklet that contains the same information as that provided in the ‘e-bowel safety’ informational module. The intervention will last for 3 months, followed by 3 months of follow-up. The primary outcome will be global QoL; the secondary outcomes will include bowel function, social support, self-management measured at the baseline, 3 months and 6 months for three times and patients’ thinkings at the end of the intervention (at 3 months).Ethics and dissemination Ethics approval was granted by the Clinical Medical Research Ethics Committee of the First Affiliated Hospital of Anhui Medical University (PJ2022-07-53).Trial registration number Chinese Clinical Trial Registry (ChiCTR2200061317).

BackgroundAnhedonia, as the core endophenotype of major depressive disorder (MDD), is closely related to poor prognosis, but the mechanism of this feature remains to be understood. The aim of this study was to investigate the inflammatory factors and brain structural alterations in MDD patients with anhedonia and evaluate the relationship between these factors.MethodsWe assessed the plasma levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MDD patients with anhedonia (n = 22), MDD patients without anhedonia (n = 20), and age- and sex-matched healthy controls (HCs, n = 20) by enzyme-linked immunosorbent assay kits. All participants underwent high-resolution brain magnetic resonance imaging (MRI) scans, and voxel-based morphometry (VBM) was used to evaluate their gray matter volume (GMV). We compared inflammatory factors and GMV among the three groups and explored their relationships in MDD patients with anhedonia.ResultsCompared with those of HCs, plasma levels of IL-1β were increased in patients with MDD independent of anhedonia features, while plasma levels of IL-6 were elevated in MDD patients with anhedonia only. Meanwhile, MDD patients with anhedonia exhibited reduced GMV in the left striatal structures compared to MDD patients without anhedonia and HCs. Moreover, a significant association was observed between increased plasma levels of IL-6 and decreased GMV of the left putamen in MDD patients with anhedonia.ConclusionsThe present research outcomes suggest that anhedonia is associated with increased plasma levels of IL-6 and decreased GMV in the left striatal structures. In addition, this study demonstrates that GMV loss in the left putamen is related to increased plasma levels of IL-6 in MDD with anhedonia, which provides further insights into the possible mechanisms of anhedonia.

Abstract Preclinical studies have shown that the gut microbiota can play a role in schizophrenia (SCH) pathogenesis via the gut-brain axis. However, its role in the antipsychotic treatment response is unclear. Here, we present a 24-week follow-up study to identify gut microbial biomarkers for SCH diagnosis and treatment response, using a sample of 107 first-episode, drug-naïve SCH patients, and 107 healthy controls (HCs). We collected biological samples at baseline (all participants) and follow-up time points after risperidone treatment (SCH patients). Treatment response was assessed using the Positive and Negative Symptoms Scale total (PANSS-T) score. False discovery rate was used to correct for multiple testing. We found that SCH patients showed lower α-diversity (the Shannon and Simpson’s indices) compared to HCs at baseline (p = 1.21 × 10−9, 1.23 × 10−8, respectively). We also found a significant difference in β-diversity between SCH patients and HCs (p = 0.001). At baseline, using microbes that showed different abundance between patients and controls as predictors, a prediction model can distinguish patients from HCs with an area under the curve (AUC) of 0.867. In SCH patients, after 24 weeks of risperidone treatment, we observed an increase of α-diversity toward the basal level of HCs. At the genus level, we observed decreased abundance of Lachnoclostridium (p = 0.019) and increased abundance Romboutsia (p = 0.067). Moreover, the treatment response in SCH patients was significantly associated with the basal levels of Lachnoclostridium and Romboutsia (p = 0.005 and 0.006, respectively). Our results suggest that SCH patients may present characteristic microbiota, and certain microbiota biomarkers may predict treatment response in this patient population.

The aim of this study was to develop a brief version of cognitive assessment test for evaluating the efficacy of treatments targeting cognitive impairments in Chinese schizophrenia patients, to examine its reliability, and establish normative data. Stratified according to age, gender, and educational level, healthy adult subjects were recruited from fifteen institutions in seven administrative regions of China and 723 valid samples were obtained, of which 50 were retested. Generalized Linear Models were conducted to analyze the effects of age, sex, and education. There was no significant difference between genders, while significant effects were demonstrated respectively among age and education on the normative data of C-BCT. The Cronbach α of C-BCT is 0.75, and the test-retest reliability (ICC) ranged from 0.62 to 0.76. Normative data of C-BCT were generated by gender, age and education, and the effects of these demographic factors were analyzed. It revealed good internal consistency and test-retest reliability of C-BCT.

Elizabethkingia anophelis has recently gained global attention and is emerging as a cause of life-threatening nosocomial infections. The present study aimed to investigate the association between antimicrobial resistance and the ability to form biofilm among E. anophelis isolated from hospitalized patients in China. Over 10 years, a total of 197 non-duplicate E. anophelis strains were collected. Antibiotic susceptibility was determined by the standard agar dilution method as a reference assay according to the Clinical and Laboratory Standards Institute. The biofilm formation ability was assessed using a culture microtiter plate method, which was determined using a crystal violet assay. Culture plate results were cross-checked by scanning electron microscopy imaging analysis. Among the 197 isolates, all were multidrug-resistant, and 20 were extensively drug-resistant. Clinical E. anophelis showed high resistance to current antibiotics, and 99% of the isolates were resistant to at least seven antibiotics. The resistance rate for aztreonam, ceftazidime, imipenem, meropenem, trimethoprim-sulfamethoxazole, cefepime, and tetracycline was high as 100%, 99%, 99%, 99%, 99%, 95%, and 90%, respectively. However, the isolates exhibited the highest susceptibility to minocycline (100%), doxycycline (96%), and rifampin (94%). The biofilm formation results revealed that all strains could form biofilm. Among them, the proportions of strong, medium, and weak biofilm-forming strains were 41%, 42%, and 17%, respectively. Furthermore, the strains forming strong or moderate biofilm presented a statistically significant higher resistance than the weak formers (p < 0.05), especially for piperacillin, piperacillin-tazobactam, cefepime, amikacin, and ciprofloxacin. Although E. anophelis was notoriously resistant to large antibiotics, minocycline, doxycycline, and rifampin showed potent activity against this pathogen. The data in the present report revealed a positive association between biofilm formation and antibiotic resistance, which will provide a foundation for improved therapeutic strategies against E. anophelis infections in the future.

BackgroundOrexins are polypeptides regulating appetite, sleep-wake cycle, and cognition functions, which are commonly disrupted in patients with schizophrenia. Patients with schizophrenia show a decreased connectivity between the prefrontal cortex and midline-anterior thalamus, and orexin can directly activate the axon terminal of cells within the prefrontal cortex and selectively depolarize neurons in the midline intralaminar nuclei of the thalamus. To address the relationship between orexin and schizophrenia, this study performed a meta-analysis on the alteration of plasma orexin-A levels in patients with schizophrenia.MethodWe searched eligible studies in PubMed, Embase, Cochrane, and China National Knowledge Infrastructure (CNKI) from 1998 to September 3, 2021. A total of 8 case-control studies were included in the meta-analyses, providing data on 597 patients with schizophrenia and 370 healthy controls. The Stata version 16.0 software was used to calculate the Hedges's adjusted g with 95% confidence intervals (CI).ResultsThe plasma orexin-A levels were not altered in subjects with schizophrenia (n = 597) when compared to healthy controls (n = 370). Subgroup analyses of gender (male and female vs. only male), country (China vs. other countries), medication (medication vs. non-medication), and the measurement of plasma orexin-A (Enzyme-linked immunosorbent assay vs. radioimmunoassay) revealed heterogeneity ranging from 30.15 to 98.15%, but none showed a significant alteration of plasma orexin-A levels in patients with schizophrenia. Heterogeneity was lower in the other countries and radioimmunoassay subgroup, while other subgroups remained to be highly heterogeneous. No significant evidence of publication bias was found either in Begg's test or the Egger's test.ConclusionThe present meta-analysis indicated that patients with schizophrenia did not show abnormal plasma levels of orexin-A.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021283455, identifier: CRD42021283455.

Summary: Background: Non-suicidal self-injury (NSSI) in adolescents is a significant mental health problem around the world. Here, we performed a meta-analysis to systematically delineate the risk factors for NSSI. Method: We searched Medline, Embase, Web of Science and Cochrane for relevant articles and abstracts published prior to 12 November 2021. Pooled odds ratios (ORs) and 95% confident intervals (CIs) were used to assess various risk factors, and publication bias was assessed by Egger's test, the trim and fill method and meta-regression. This study is registered with PROSPERO, CRD42021265885. Results: A total of 25 articles were eventually included in the analysis. Eighty risk factors were identified and classified into 7 categories: mental disorders (ORs, 1·89; 95% CI, 1·60–2·24), bullying (ORs, 1·98; 95% CI, 1·32–2·95), low health literacy (ORs, 2·20; 95% CI, 1·63–2·96), problem behaviours (ORs, 2·36; 95% CI, 2·00–2·77), adverse childhood experiences (ORs, 2·49; 95% CI, 1·85–3.34), physical symptoms (ORs, 2·85; 95% CI, 1·36–5·97) and the female gender (ORs, 2·89; 95% CI, 2·43–3·43). The range of heterogeneity (I2) was from 20·3% to 99·2%. Conclusion: This meta-analysis found that mental disorders, low health literacy, adverse childhood experiences, bullying, problem behaviours, the female gender and physical symptoms appear to be risk factors for NSSI. Funding: NSFC grant (81,822,017), National Key R&D Program of China (2020YFA0113600), Natural Science Foundation of Zhejiang Province, China (No. LY19H090015), Shenzhen-Hong Kong Institute of Brain Science - Shenzhen Fundamental Research Institutions (NYKFKT20190020), Shanghai Municipal Education Commission - Gaofeng Clinical Medicine Grant Support (20,181,715), Social Science Foundation of China (BIAl80167).

BackgroundMetanephric adenoma is an extremely rare renal neoplasm, especially in pediatrics. Chemotherapy combined with surgery in metanephric adenoma has not been reported.MethodsWe describe a case of metanephric adenoma in a child less than 2 years old, which were treated by chemotherapy combined with surgery.ResultsNephron sparing surgery was performed after regular chemotherapy, and the pathological result was metanephric adenoma.ConclusionPediatric metanephric adenoma is extremely rare; the clinical manifestations and imaging examinations lack specificity. Nephron sparing surgery is recommended as the preferred treatment for metanephric adenoma. Long-term follow-up and more in-depth molecular genetic research are still needed to determine the benign or malignant of metanephric adenoma and whether chemotherapy drugs have an effect on it.

We propose a cascaded neural network (NN) to simultaneously identify the modulation formats and monitor the optical-signal-to-noise ratio (OSNR). In the second-level network, it is a single deep NN (DNN) rather than multiple sub-networks, which makes the architecture more compact and can save the resource for real implementation. However, since the data set is constituted from all modulation formats, the universality can be guaranteed but not for the accuracy and the complexity. To accelerate the estimation process and improve the accuracy, we introduce the transfer learning (TL) and reconstruct the data set with a part from all of the modulation formats for universality and another part from a specific modulation format for TL to pursue higher accuracy. In the experiment, we compare the proposed cascaded single neural network (CSNN) with or without TL, cascaded multiple neural networks (CMNN) and adaptive multi-task learning (MTL) for MFI and OSNR monitoring. In the first-level NN, all of the three schemes can achieve the accuracy of MFI as 100%. In the second-level NN, the CSNN with TL (TL-CSNN) can significantly improve the training speed and decline the RMSE of 0.19 dB compared with CSNN without TL. The TL-CSNN also has faster convergence speed and is more stable compared with CMNN and adaptive MTL.

Effective pharmacotherapy of bipolar depression with mixed features defined by DSM-5 remains unclear in clinical treatment guidelines. Quetiapine (QTP) and valproate have potential treatment utility but are often inadequate as monotherapy. Meanwhile, the efficacy of combination therapies of QTP plus valproate or lithium have yet to be verified. Hence, we conducted a randomized controlled pilot study to evaluate the efficacy of QTP monotherapy in patients with bipolar depression with mixed features defined by DSM-5 and compared the combination therapy of QTP plus valproate (QTP + V) versus QTP plus lithium (QTP + L) for those patients who responded insufficiently to QTP monotherapy. Data was analyzed according to the intent-to-treat population. Generalized linear mixed model was performed by using “nlme” package in R software. A total 56 patients were enrolled, among which, 35 patients responded to QTP alone, and 11 and 10 patients were randomly assigned to QTP + V and QTP + L group, respectively. Nearly 60% enrolled patients responded to QTP monotherapy at the first two weeks treatment. No statistically significant difference in efficacy between QTP + V and QTP + L was observed. In conclusion, QTP monotherapy appeared to be efficacious in patients with bipolar depression with mixed features, and for those who responded insufficiently to QTP, combining with either valproate or lithium appeared to have positive effects.

Sustainable resource utilization of tailings is a long-term challenge. Therefore, a novel waste-based binder is proposed in this study to stabilize/solidify gold mine tailings (GMTs). This binder is composed of fly ash (FA), ground blast furnace slag (GBFS), and metakaolin (MK) activated with mixed calcium carbide residue (CCR) as well as pure reagent grade chemical, sodium hydroxide (SH, NaOH), and plaster gypsum (PG, CaSO4·2H2O). The mechanical properties and hydration of stabilized tailings with curing period were investigated. Tests included triaxial compression test and nitrogen adsorption to evaluate the strength of the stabilized tailings and microstructure. The results show that the addition of the waste-based binder yields significant improvement in shear strength. Strain softening occurred for all cured samples, and a local shear band can be observed in all failed stabilized samples. Based on the relationship between strength and curing period, it can be speculated that the hydration reaction of the sample ends after around 40 days of curing. A bimodal pore-size distribution was observed in all solidified/stabilized samples. FTIR and 27Al MAS-NMR were used to analyze hydration products. The strength improvement of stabilized tailings was mainly attributed to the formation of ettringite and C–S–H gels after various polymerization reactions. These new hydrates bind tailings particles and fill the pores to form a more stable structure, which supplied superior mechanical properties. This paper can provide a theoretical basis for exploring the application of the industrial waste-based binder to modify the mechanical properties of gold tailings.

Dam safety is considerably affected by seepage, and uplift pressure is a key indicator of dam seepage. Thus, making accurate predictions of uplift pressure trends can improve dam hazard forecasting. In this study, a convolutional neural network, (CNN)-gated recurrent neural network, (GRU)-based uplift pressure prediction model was developed, which included the CNN model’s feature extractability and the GRU model’s learnability for time series correlation data. Then, the model performance was verified using a dam as an example. The results showed that the mean absolute errors (MAEs) of the CNN-GRU model were 0.1554, 0.0398, 0.2306, and 0.1827, and the root mean square errors (RMSEs) were 0.1903, 0.0548, 0.2916, and 0.2127. The prediction performance was better than that of the particle swarm optimization–back propagation (PSO-BP), artificial bee colony optimization–support vector machines (ABC-SVM), GRU, long short-term memory network (LSTM), and CNN-LSTM models. The method improves the utilization rate of dam safety monitoring results and has engineering utility for safe dam operations.

Bipolar disorder (BD) is one of the major psychiatric disorders that is characterized by recurrent episodes of depression and mania (or hypomania), leading to seriously adverse outcomes with unclear pathogenesis. There is an underlying relationship between bacterial communities residing in the gut and brain function, which together form the gut-brain axis (GBA). Recent studies have shown that changes in the gut microbiota have been observed in a large number of BD patients, so the axis may play a role in the pathogenesis of BD. This review summarizes briefly the relationship between the GBA and brain function, the composition and changes of gut microbiota in patients with BD, and further explores the potential role of GBA-related pathway in the pathogenesis of BD as well as the limitations in this field at present in order to provide new ideas for the future etiology research and drug development.

As the biggest rigid constraint for high-quality economic and social development, how to improve the carrying capacity of water resources, realize the stable and coordinated development of water resources-ecological environment-economic and social integrated system, and provide water resources guarantee for regional transformation and upgrading development is a major issue in the current social development. This paper firstly selects the minimum loss of water resources allocation as the objective function for mathematical modelling, chooses the particle swarm algorithm as the objective algorithm, and proposes a particle swarm algorithm based on the standard particle swarm algorithm with improved adaptive decreasing inertia weights. It is a time-varying process for the inertia weights and acceleration factors of the standard particle swarm algorithm so that they change nonlinearly with the continuous advancement of the iterative optimization seeking process, thus improving the convergence accuracy and speed of the algorithm and reducing the risk of falling into local optimum solutions at a later stage. Finally, based on the actual installation of the current water distribution reactive power compensation device, the shunt distributor set is selected as the reactive power compensation device, sensitivity analysis is applied to the load nodes for sensitivity calculation, and the nodes requiring compensation are connected to the shunt distributor set for flexible and optimal configuration. The stronger local search capability of the inertia weight adaptive decreasing algorithm is utilized in the generation process of new particles to perform a local search operation for particles, which avoids premature convergence and improves the search performance of the algorithm. To realize the rational allocation of water resources, a multiobjective receiving area water resources optimization allocation model with maximum water supply benefit, minimum regional water shortage, and minimum pollutant emission is established.

Abstract. The current epidemic situation of coronavirus disease 2019 (COVID-19) still remains severe. As the National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital of the Zhejiang University School of Medicine is the primary medical care center for COVID-19 in Zhejiang Province. Based on the present expert consensus carried out by the National Health Commission and National Administration of Traditional Chinese Medicine, our team summarized and established an effective treatment strategy centered on “Four-Anti and Two-Balance” for clinical practice. The “Four-Anti and Two-Balance” strategy includes antivirus, anti-shock, anti-hypoxemia, and anti-secondary infection, and maintaining of water, electrolyte and acid/base balance and microecological balance. Simultaneously, an integrated multidisciplinary personalized treatment is recommended to improve therapeutic effects. The importance of early viral detection, dynamic monitoring of inflammatory indexes, and chest radiographs has been emphasized in clinical decision-making. Sputum was observed with the highest positive rate by reverse transcription-polymerase chain reaction (RT-PRC). Viral nucleic acids could be detected in 10% of the patients’ blood samples at the acute phase and 50% of patients had positive RT-PCR results in their feces. We also isolated live viral strains from feces, indicating potential infectiousness of feces. Dynamic cytokine detection was necessary to timely identify cytokine storms and for the application of the artificial liver blood purification system. The “Four-Anti and Two-Balance” strategy effectively increased cure rates and reduced mortality. Early antiviral treatment alleviated disease severity and prevented illness progression. We found that lopinavir/ritonavir combined with abidol showed antiviral effects against COVID-19. Shock and hypoxemia were usually caused by cytokine storms. The artificial liver blood purification system was able to rapidly remove inflammatory mediators and block the cytokine storm. Moreover, it also contributed to the balance of fluids, electrolytes, and acids/bases and thus improved treatment efficacy during critical illness. For cases of severe illness, early and also short periods of moderate glucocorticoid administration was supported. Patients with an oxygenation index below 200 mm Hg were transferred to the intensive care unit. Conservative oxygen therapy was preferred and noninvasive ventilation (NIV) was not recommended. Patients with mechanical ventilation were strictly supervised with cluster ventilator-associated pneumonia prevention strategies. Antimicrobial prophylaxis was prescribed rationally and was not recommended, except for patients with a long course of disease, repeated fever, and elevated procalcitonin, similarly secondary fungal infections were of concern. Some patients with COVID-19 showed intestinal microbial dysbiosis with decreased genus such as Lactobacillus and Bifidobacterium. Nutritional and gastrointestinal function should; therefore, be assessed for all patients. Nutritional support and application of prebiotics or probiotics were suggested to regulate the balance of intestinal microbiota and reduce the risk of secondary infections due to bacterial translocation. Anxiety and fear were common in patients with COVID-19. Therefore, we established a dynamic assessment and warning for psychological crises. We also integrated Chinese medicine in the treatment to promote rehabilitation. We optimized nursing processes for severe patients to promote their rehabilitation. Since viral clearance patterns after severe acute respiratory syndrome coronavirus 2 infections remained unclear, 2 weeks quarantine for discharged patients was required, and a regular following-up was also needed. These Zhejiang experiences and suggestions have been implemented in our center and achieved good results. However, since COVID-19 was a newly emerging disease, more work is warranted to further improve strategies of prevention, diagnosis, and treatment for COVID-19.

Tetratricopeptide repeat and ankyrin repeat containing 1 (TRANK1) is a robust risk gene of bipolar disorder (BD). However, little is known on the role of TRANK1 in the pathogenesis of BD and whether the gut microbiota is capable of regulating TRANK1 expression. In this study, we first investigated the serum mRNA level of TRANK1 in medication-free patients with a depressive episode of BD, then a mice model was constructed by fecal microbiota transplantation (FMT) to explore the effects of gut microbiota on brain TRANK1 expression and neuroinflammation, which was further verified by in vitro Lipopolysaccharide (LPS) treatment in BV-2 microglial cells and neurons. 22 patients with a depressive episode and 28 healthy individuals were recruited. Serum level of TRANK1 mRNA was higher in depressed patients than that of healthy controls. Mice harboring ‘BD microbiota’ following FMT presented depression-like phenotype. mRNA levels of inflammatory cytokines and TRANK1 were elevated in mice hippocampus and prefrontal cortex. In vitro, LPS treatment activated the secretion of pro-inflammatory factors in BV-2 cells, which was capable of upregulating the neuronal expression of TRANK1 mRNA. Moreover, primary cortical neurons transfected with plasmid Cytomegalovirus DNA (pcDNA3.1(+)) vector encoding human TRANK1 showed decreased dendritic spine density. Together, these findings add new evidence to the microbiota-gut-brain regulation in BD, indicating that microbiota is possibly involved in the neuropathogenesis of BD by modulating the expression of TRANK1.

Background: Herein, we validate the psychometric properties of the Chinese version of the THINC-integrated tool (THINC-it) as a screening tool for cognitive deficits in patients with major depressive disorder. The primary aim of this study is to determine whether cognitive deficits as detected by the THINC-it tool in adults with major depressive disorder (MDD) are associated with workplace productivity and/or psychosocial function.Methods: Subjects aged 18–65 (n = 91) with MDD were evaluated and compared to age-, sex- and education- matched healthy controls (n = 95). Symptoms of cognitive dysfunction, workplace productivity, and psychosocial function were measured using the THINC-it tool, Hamilton Depression Scale (HAMD), Sheehan Disability Scale (SDS), The Work Productivity and Activity Impairment questionnaire- Specific Health Problem (WPAI-SHP).Results: There were significant differences in THINC-it scores (p < 0.01), the average of HAMD total score (p < 0.01) and all aspects of SDS (p < 0.01) between two groups. There were significant differences in the four aspects of WPAI between the two groups in the employed status (p

Nanoparticle-based drug delivery systems, which can overcome the challenges associated with poor aqueous solubility and other harmful side effects of drugs, display potent applications in cataract treatment. Herein, we designed a nanosystem of gold nanoparticles containing resveratrol (RGNPs) as an anti-aging agent to delay cataracts. The spherical RGNPs had a superior ability to inhibit hydrogen peroxide-mediated oxidative stress damage, including reactive oxygen species (ROS) production, malondialdehyde (MDA) generation, and glutathione (GSH) consumption in the lens epithelial cells. Additionally, the present data showed that RGNPs could delay cellular senescence induced by oxidative stress by decreasing the protein levels of p16 and p21, reducing the ratio of BAX/BCL-2 and the senescence-associated secretory phenotype (SASP) in vitro. Moreover, the RGNPs could also clearly relieve sodium selenite-induced lens opacity in a rat cataract model. Our data indicated that cell senescence was reduced and cataracts were delayed upon treatment with RGNPs through activating the Sirt1/Nrf2 signaling pathway. Our findings suggested that RGNPs could serve as an anti-aging ingredient, highlighting their potential to delay cataract development.

The clinical efficacy of lurasidone and quetiapine, two commonly prescribed atypical antipsychotics for bipolar depression, has been inadequately studied in young patients. In this randomized and controlled study, we aimed to compare the effects of these two drugs on cognitive function, emotional status, and metabolic profiles in children and adolescents with bipolar depression. We recruited young participants (aged 10–17 years old) with a DSM-5 diagnosis of bipolar disorder during a depressive episode, who were then randomly assigned to two groups and treated with flexible doses of lurasidone (60 to 120 mg/day) or quetiapine (300 to 600 mg/day) for consecutive 8 weeks, respectively. All the participants were clinically evaluated on cognitive function using the THINC-it instrument at baseline and week 8, and emotional status was assessed at baseline and the end of week 2, 4, and 8. Additionally, the changes in weight and serum metabolic profiles (triglyceride, cholesterol, and fasting blood glucose) during the trial were also analyzed. In results, a total of 71 patients were randomly assigned to the lurasidone group (n = 35) or the quetiapine group (n = 36), of which 31 patients completed the whole treatment course. After an 8-week follow-up, participants in the lurasidone group showed better performance in the Symbol Check Reaction and Accuracy Tests, when compared to those in the quetiapine group. No inter-group difference was observed in the depression scores, response rate, or remission rate throughout the trial. In addition, there was no significant difference in serum metabolic profiles between the lurasidone group and the quetiapine group, including triglyceride level, cholesterol level, and fasting blood glucose level. However, the quetiapine group presented a more apparent change in body weight than the lurasidone group. In conclusion, the present study provided preliminary evidence that quetiapine and lurasidone had an equivalent anti-depressive effect, and lurasidone appeared to be superior to quetiapine in improving the cognitive function of young patients with bipolar depression.

This study reports an experimental investigation on the impact behavior of elliptical concrete-filled steel tubular (CFT) columns subjected to lateral loading. A total of five CFT columns, including one circular cross-section and four elliptical cross-sections, were tested using a horizontal-impact-testing system. The influences of the impact velocity, the impact times, and the cross-section geometry on the dynamic response of the elliptical CFT columns were analyzed. The experimental results have shown that the specimens withstood the global displacements without the buckling of the steel tubes. The strain rates of the steel tubes in this paper were small. The impact velocity had significant influences on the impact load-time histories and energy absorption. Meanwhile, the impact times had little influence on the impact force and displacement at the same impact velocity. Circular CFT columns have the highest ductility and impact-energy-absorption capacity. Based on the finite element analysis software ABAQUS, the finite element models of the elliptical CFT columns under impact loads were established. The simulation results were in good agreement with the experimental results. Finally, the mechanical mechanism of the elliptical CFT columns under lateral impact was analyzed by the finite element model.

Background: The emergence of coronavirus disease 2019 (COVID-19) has created a severe mental health problem for international students living in China. Despite the little information on the psychological impact on international students, we aimed to assess the psychological outcomes and associated factors among international students currently living in China during the COVID-19 pandemic.Methods: An online cross-sectional survey was conducted from May 28, 2020 to June 12, 2020 on 402 full-time international students across 26 provinces in China. The frequency of symptoms of depression, anxiety, stress, insomnia, psychological distress, loneliness, and fear was assessed with the English versions of the Depression Anxiety Stress Scale (DASS-21), Insomnia Severity Index (ISI), Kessler Psychological Distress Scale (K6), University of California, Los Angeles, Loneliness Scale (UCLA-LS), and Fear of COVID-19 scale (FCV-19S) scales, respectively.Results: The prevalence of symptoms of depression (73.4%), anxiety (76.6%), stress (58.5%), insomnia (77.6%), psychological distress (71.4%), loneliness (62.4%), and fear (73.1%) among international students during the COVID-19 pandemic was shown. The prevalence of moderate to extremely severe symptoms of all psychological outcomes was significantly associated with 26–30-year-old students, students who lived with roommates, and students who stayed in China shorter than 2 years. Participants in the central region reported significantly moderate to extremely severe symptom levels of all the psychological outcomes except fear symptoms. Univariate analysis indicated that a significant association of all psychological outcomes was found among 26–30-year-old students and students who stayed in China shorter than 2 years. Multivariate analysis showed that Engineering, Business, Social Sciences and Law, and Language students were significantly associated with the symptoms of depression, anxiety, insomnia, and fear. Participants staying in China for shorter than 2 years were associated with a higher risk of all psychological outcomes except psychological distress and loneliness symptoms.Conclusions: We found a higher prevalence of psychological outcomes and risk factors among international students during the COVID-19 pandemic. We immediately appealed to university authorities, mental health professionals, and government officials to provide mental health interventions and strategies for their international students, particularly young, central region students, living with roommates, different study backgrounds, and short time staying during the pandemic.

Background: Butyric acid, a major short-chain fatty acid (SCFA), has an important role in the microbiota–gut–brain axis and brain function. This study investigated the role of butyric acid in treatment response in drug-naïve first episode schizophrenia.Methods: The study recruited 56 Chinese Han schizophrenia inpatients with normal body weight and 35 healthy controls. Serum levels of butyric acid were measured using Gas Chromatography-Mass Spectrometer (GC-MS) analysis at baseline (for all participants) and 24 weeks after risperidone treatment (for patients). Clinical symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) for patients at both time points.Results: At baseline, there was no significant difference in serum levels of butyric acid between patients and healthy controls (p = 0.206). However, there was a significant increase in serum levels of butyric acid in schizophrenia patients after 24-week risperidone treatment (p = 0.030). The PANSS total and subscale scores were decreased significantly after 24-week risperidone treatment (p's < 0.001). There were positive associations between baseline serum levels of butyric acid and the reduction ratio of the PANSS total and subscale scores after controlling for age, sex, education, and duration of illness (p's < 0.05). Further, there was a positive association between the increase in serum levels of butyric acid and the reduction of the PANSS positive symptoms subscale scores (r = 0.38, p = 0.019) after controlling for potential confounding factors.Conclusions: Increased serum levels of butyric acid might be associated with a favorable treatment response in drug-naïve, first episode schizophrenia. The clinical implications of our findings were discussed.