Real-world evidence from a retrospective study on suicide during depression: clinical characteristics, treatment patterns and disease burden.

BACKGROUND: Suicide stands as both a primary symptom and the direst outcome of major depressive disorder (MDD). The scarcity of effective treatment strategies makes managing MDD patients with suicide especially challenging. Hence, it is crucial to investigate disease characteristics and efficacious therapeutic strategies for these patients, drawing insights from disease databases and real-world data. METHODS: In this retrospective study, MDD patients hospitalized between January 2013 and December 2020 were investigated using Electronic Health Records (EHR) data from Beijing Anding Hospital. The study enrolled 4138 MDD patients with suicidal ideation or behavior (MDS) and 3848 without (MDNS). Demographic data, clinical attributes, treatment approaches, disease burden, and re-hospitalization within one year of discharge were extracted and compared. RESULTS: Patients in the MDS group were predominantly younger and female, exhibiting a higher prevalence of alcohol consumption, experiencing frequent life stress events, and having an earlier onset age. Re-hospitalizations within six months post-discharge in the MDS group were significantly higher than in the MDNS group (11.36% vs. 8.91%, p < 0.001). Moreover, a more considerable fraction of MDS patients underwent combined electroconvulsive therapy treatment (56.72% vs. 43.71%, p < 0.001). Approximately 38% of patients in both groups were prescribed two or more therapeutic regimes, and over 90% used antidepressants, either alone or combined. Selective serotonin reuptake inhibitors (SSRIs) were the predominant choice in both groups. Furthermore, antidepressants were often prescribed with antipsychotics or mood stabilizers. When medication alterations were necessary, the favoured options involved combination with antipsychotics or transitioning to alternative antidepressants. Yet, in the MDS group, following these initial modifications, the addition of mood stabilizers tended to be the more prioritized alternative. CONCLUSIONS: MDD patients with suicidal ideation or behaviour displayed distinctive demographic and clinical features. They exhibited intricate treatment patterns, a pronounced burden of illness, and an increased likelihood of relapse.

Inhibition of Wnt/ß-catenin signaling by monensin in cervical cancer.

The challenging clinical outcomes associated with advanced cervical cancer underscore the need for a novel therapeutic approach. Monensin, a polyether antibiotic, has recently emerged as a promising candidate with anti-cancer properties. In line with these ongoing efforts, our study presents compelling evidence of monensin's potent efficacy in cervical cancer. Monensin exerts a pronounced inhibitory impact on proliferation and anchorage-independent growth. Additionally, monensin significantly inhibited cervical cancer growth in vivo without causing any discernible toxicity in mice. Mechanism studies show that monensin's anti-cervical cancer activity can be attributed to its capacity to inhibit the Wnt/ß-catenin pathway, rather than inducing oxidative stress. Monensin effectively reduces both the levels and activity of ß-catenin, and we identify Akt, rather than CK1, as the key player involved in monensin-mediated Wnt/ß-catenin inhibition. Rescue studies using Wnt activator and ß-catenin-overexpressing cells confirmed that ß-catenin inhibition is the mechanism of monensin's action. As expected, cervical cancer cells exhibiting heightened Wnt/ß-catenin activity display increased sensitivity to monensin treatment. In conclusion, our findings provide pre-clinical evidence that supports further exploration of monensin's potential for repurposing in cervical cancer therapy, particularly for patients exhibiting aberrant Wnt/ß-catenin activation.

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study.

BACKGROUND: Bipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral hormones profiles could differentiate the manic and depressive mood episodes in BD. In this study, we investigated the changes of various hormones and inflammatory markers across distinct mood episodes of BD in a large clinical study to provide mood episode-specific peripheral biomarkers for BD. METHODS: A total of 8332 BD patients (n = 2679 depressive episode; n = 5653 manic episode) were included. All patients were in acute state of mood episodes and need hospitalization. A panel of blood tests were performed for levels of sex hormones (serum levels of testosterone, estradiol, and progesterone), stress hormones (adrenocorticotropic hormone and cortisol), and an inflammation marker (C-reactive protein, CRP). A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes. RESULTS: In overall comparison between mood episodes, the BD patients expressed higher levels of testosterone, estradiol, progesterone, and CRP (P < 0.001) and lower adrenocorticotropic hormone (ACTH) level (P < 0.001) during manic episode. The episode-specific changes of testosterone, ACTH, and CRP levels remained between the two groups (P < 0.001) after correction for the confounding factors including age, sex, BMI, occupation, marital status, tobacco use, alcohol consumption, psychotic symptoms, and age at onset. Furthermore, we found a sex- and age-specific impact of combined biomarkers in mood episodes in male BD patients aged ≥ 45 years (AUC = 0.70, 95% CI, 0.634-0.747), not in females. CONCLUSIONS: While both hormone and inflammatory change is independently associated with mood episodes, we found that the combination of sex hormones, stress hormones and CRP could be more effective to differentiate the manic and depressive episode. The biological signatures of mood episodes in BD patients may be sex- and age-specific. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.

Discharge readiness after remimazolam versus propofol for colonoscopy: A randomised, double-blind trial.

BACKGROUND: Remimazolam is an ultrashort-acting benzodiazepine that is potentially a practical option for procedural sedation in colonoscopy. OBJECTIVE: To test the hypothesis that remimazolam could provide a noninferior discharge time to propofol for ambulatory colonoscopy. DESIGN: A prospective, randomised, double-blind, noninferiority clinical trial. SETTING: Ambulatory endoscopy centre. PATIENTS: A total of 132 adult participants undergoing ambulatory colonoscopy were enrolled. INTERVENTIONS: Participants were randomly assigned in a 1 : 1 ratio to receive propofol or remimazolam for sedation. MAIN OUTCOME MEASURES: The primary outcome was discharge time after a colonoscopy, assessed using the Modified Postanaesthetic Discharge Scoring System scale. Secondary outcomes included induction time, emergence time, the extent of recovery upon arrival in the postanaethesia care unit, fatigue, endoscopist and patient satisfaction and adverse events. RESULTS: The median discharge time was 24 min in the remimazolam group versus 21 min in the propofol group, with a difference of 2 min [95% confidence interval (CI), 0 to 4 min], meeting the criteria for noninferiority. Injection pain occurred in 11 of 66 (17%) participants receiving remimazolam versus 32 of 66 (49%) participants receiving propofol ( P  < 0.001); hypotension occurrence was 20% versus 47%, ( P  < 0.001), respectively, and bradycardia 6% versus 20%, ( P  = 0.019), respectively. Compared with propofol, the patient satisfaction score was higher in the remimazolam group ( P  < 0.001). CONCLUSION: For sedation in ambulatory colonoscopy, compared with propofol, remimazolam provides a noninferior discharge time. Furthermore, remimazolam is associated with less injection pain, lower risks of hypotension and bradycardia, and improved patient satisfaction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2100048678.

TRAF3 plays a role in lupus nephritis by regulating Th17 cell and Treg cell balance as well as NF-κB signaling pathway in mice.

Lupus nephritis (LN) occurs with inflammatory lesion in patients suffering from systemic lupus erythematosus (SLE). Tumor necrosis factor (TNF) receptor associated factor 3 (TRAF3) is an important mediator in inflammation. To explore the roles of TRAF3 in LN, the LN mouse model was firstly established with intraperitoneal (i.p.) injection of pristine. Our results found that the amount of urinary protein was increased evidently at day 28, and renal damage occurred in the LN mouse model, but the TRAF3 knockdown reduced the urinary protein and alleviated the inflammatory lesion. The proinflammatory cytokines TNF-α, IL-1ß, IL-17a, IFN-γ and IgM, IgG antibody were enriched, but there was little amount of IL-10 in the LN mouse model. Moreover, the amount of CD40+ B cells, CD4+ T cells sub-type, Th17 cells were abundant, and the proteins TRAF3, TRAF2, NF-κBp52, IKKα, ICAM1 in the kidney were highly expressed in the LN mouse model. However, TRAF3 knockdown enhanced the production of IL-10 and reduced the amount of pro-inflammatory cytokines, immunoglobulin, and the protein expressions of TRAF3, TRAF2, NF-κBp52, IKKα, ICAM1. In conclusion, TRAF3 plays a role in LN by regulating Th17 cell and Treg cell balance as well as NF-κB signaling pathway in mice.

Interactions between dietary fiber and ferulic acid change the aggregation of glutenin, gliadin and glutenin macropolymer in wheat flour system.

BACKGROUND: Glutenin macropolymer (GMP), glutenin and gliadin proteins are important indicators of the baking quality of dough. This study investigated the impacts of wheat bran and a mixture of ferulic acid (FA) and dietary fiber (DF) on the constitution of gluten proteins. Addition of wheat bran (100 and 150 g kg-1 ) into gluten decreased the gliadin/glutenin ratio, while the addition of different amounts of FA + DF (C1 group: 20 g kg-1 FA and 60 g kg-1 DF; C2 group: 30 g kg-1 FA and 90 g kg-1 DF) had the opposite effect. RESULTS: The GMP contents of wheat bran groups (B1 group: 100 g kg-1 ; B2 group: 150 g kg-1 ) were similar to that of the control group, and disulfide bond contents were increased. However, both GMP and disulfide bond contents of FA + DF groups significantly decreased. The GMP gel properties and microstructures were destroyed after addition of wheat bran and FA + DF. The wheat bran and FA + DF additives induced different effects on the thermal properties and secondary structures of glutenin, gliadin and GMP. CONCLUSIONS: The results suggest that the interaction mechanism of bran fractions and gluten proteins is not only related to the physicochemical properties of the additives, but also to interactions between the additives and the components of gluten protein. © 2020 Society of Chemical Industry.

Driving forces of impervious surface in a world metropolitan area, Shanghai: threshold and scale effect.

Shanghai is one of the largest metropolitan areas in the world, during the rapid urbanization of the past decades, impervious surface expanded dramatically and became a main factor influencing surface water quality. Thus, exploring the driving forces of impervious surface has great implications in such metropolitan area. In this study, an impervious surface coefficient method (ISC) was used to measure the percentage of total impervious area (PTIA) of Shanghai; regression analysis was conducted to define the relationship between PTIA and three socio-economic factors, population density, unit area gross domestic product, and unit area industrial output at the city and district scale. Results showed that the industrial land use generated the highest ISC value, followed by high-density residential. Strong correlations were showed between PTIA and socio-economic indicators, in which population density was the most significant. Threshold effect was presented that when population density was higher than 15000 per/km2, this relationship would become less significant and PTIA remained stable. Similar effects were found when unit area gross domestic product exceeded 125 million yuan/km2. Scale effect was also discussed that the relationship was more significant at city scale than district. An improved understanding of the threshold effect and scale effect will help guide future urban planning and design new urban ecosystem policies.

Isoprenylcysteine carboxylmethyltransferase regulates ovarian cancer cell response to chemotherapy and Ras activation.

Inhibition of isoprenylcysteine carboxylmethyltransferase (Icmt), which catalyzes the final step of oncoproteins' prenylation, targets growth and survival of various cancers. In this work, we systematically studied the expression, functions and molecular signaling of Icmt in ovarian cancer. We show that the upregulation of Icmt expression is a common feature in patients with epithelial ovarian cancer regardless of age and disease stage. In line with the observations in ovarian cancer patients, a panel of epithelial ovarian cancer cell lines also demonstrates the significant increase on Icmt transcript and protein levels than normal ovarian epithelial cells. In addition, ovarian cancer cell lines with higher Icmt levels are more resistant to chemotherapeutic agents. We further show that Icmt inhibition by siRNA or inhibitor cysmethynil suppresses growth and induces apoptosis in ovarian cancer cells. Importantly, Icmt inhibition significantly augments chemotherapeutic agent's efficacy in vitro and in vivo, demonstrating the translational potential of Icmt inhibition in ovarian cancer. Mechanistically, we show that Ras activation is a critical effector of Icmt in ovarian cancer cells. Using cell culturing system, mouse model and patient samples, our work is the first to demonstrate the essential roles of Icmt in ovarian cancer via Ras signaling, particularly on its response to chemotherapy. Our findings suggest that Icmt inhibition is a promising therapeutic strategy to overcome chemoresistance in ovarian cancer, in particular, those patients with high Icmt expression.

Fine mapping identifies CsGCN5 encoding a histone acetyltransferase as putative candidate gene for tendril-less1 mutation (td-1) in cucumber.

KEY MESSAGE: Next-generation sequencing-aided map-based cloning delimited the cucumber tendril - less1 ( td - 1 ) locus into a 190.7-kb region in chromosome 6 harboring a putative, novel-function candidate gene encoding a histone acetyltransferase ( CsGCN5 ). The tendril initiated from the lateral meristem is an important and characteristic organ for the species in the Cucurbitaceae family including cucumber (Cucumis sativus L.). While the tendril has its evolutionary significance, it also poses a nuisance in cucumber cultivation under protected environments in which tendril-less cucumber has its advantages. From an EMS mutagenesis population, we identified a tendril-less mutant B007, which was controlled by a recessive gene td-1. Through next-generation sequencing-aided map-based cloning, we show CsGCN5 (Cucumis sativus GENERAL CONTROL NONDEREPRESSIBLE 5), a cucumber gene for a histone acetyltransferase as the most possible candidate for td-1. A non-synonymous SNP in the first exon of CsGCN5 resulted in an amino-acid substitution from Asp (D) in the wild type to Asn (N) in the tendril-less mutant. The candidacy of CsGCN5 was further confirmed by multiple lines of evidence in both biparental and natural cucumber populations. Non-significant expression of CsGCN5 in multiple organs was found between the wild type and the mutant. CsGCN5 exhibited strong expression in the tendril of wild-type plants suggesting its important roles in growth and development of plant tendrils. The identification and characterization of the td-1 mutant from the present study provided a useful tool in understanding the molecular mechanisms of tendril organogenesis and investigation of novel functions of the histone acetyltransferase in cucumber.

Observations on the expression of human papillomavirus major capsid protein in HeLa cells.

BACKGROUND: The goal of this study was to identify the nature of the inclusion bodies that have been found in HeLa cells (cervical cancer immortal cell line) by electron microscope and to determine whether the major capsid protein (L1) of human papillomavirus (HPV) can be expressed in HPV-positive uterine cervix cancer cells. METHODS: HPV L1 protein expression in HeLa cells was detected with anti-HPV L1 multivalent mice monoclonal antibody and rabbit polyclonal anti-HPV L1 antibody by ELISA, light microscope immunohistochemistry, electron microscope immunocytochemistry and Western blotting assays. Reverse transcriptional PCR (RT-PCR) was performed to detect the transcription of L1 mRNA in HeLa cells. The immortalized human keratinocyte HeCat was used as the negative control. RESULTS: HPV L1 proteins reacted positively in the lysate of HeLa cells by ELISA assays. HRP labeled light microscope immunohistochemistry assay showed that there was a strong HPV L1 positive reaction in HeLa cells. Under the electron microscope, irregular shaped inclusion bodies, assembled by many small and uniform granules, had been observed in the cytoplasm of some HeLa cells. These granules could be labeled by the colloidal gold carried by HPV L1 antibody. The Western blotting assay showed that there was a L1 reaction strap at 80-85 kDa in the HeLa cell lysates, hence demonstrating the existence of HPV18 L1 in HeLa cells. RT-PCR assay showed that the L1 mRNA was transcribed in HeLa cells. CONCLUSIONS: The inclusion bodies found in the cytoplasm of HeLa cells are composed of HPV18 L1 protein. Since HeLa cell line is a type of cervical cancer cells, this implies that HeLa cells have the ability to express HPV L1 proteins.

Modular probe integrating with quantum dots based versatile platform for sensitive and label-free biomarker detection.

Multiplexed analysis of biomarkers in a single sample tube is essential for accurate diagnosis and therapy of diseases. However, the existing detection platforms suffer from many drawbacks, such as low specificity, limited applicable sceneries, and complicated operation. Hence, it is highly important to develop a versatile biomarker detection platform that can be used for disease diagnosis and pathophysiological research. In this study, we provide a versatile method for detecting biomarkers using dual-loop probes and quantum dots (QDs). This approach utilizes a dual-loop probe that consists of a recognition module for identifying specific targets, a template recognition module for initiating subsequent chain replacement cycles, and a signal module for facilitating the fixation of QDs on the 96-well plate. The lower limit of detection for miRNA-21 is determined to be at the aM level. Furthermore, this design may be easily expanded to simultaneously detect several targets, such as miRNA and C-reactive protein. The experimental results demonstrated the successful construction of the versatile biomarkers detection platform, and indicated that the sensitive and versatile platform has significant potential in the areas of bio-sensing, clinical diagnostics, and environmental sample analysis.

Sociodemographic, clinical and treatment characteristics of current rapid-cycling bipolar disorder: a multicenter Chinese study.

BACKGROUND: Rapid cycling bipolar disorder (RCBD), characterized by four or more episodes per year, is a complex subtype of bipolar disorder (BD) with poorly understood characteristics. METHOD: This multicenter, observational, longitudinal cohort study enrolled 520 BD patients across seven psychiatric institutions in China from January 2013 to January 2014. Participants were divided into RCBD and non-RCBD (NRCBD) groups based on the frequency of mood episodes in the preceding year. Data collection utilized a standardized form, supplemented by a medical record review, focusing on sociodemographic, clinical, and treatment characteristics. Statistical analysis involved independent samples t-tests, Kruskal-Wallis H tests, Chi-square or Fisher's exact tests, with Bonferroni correction applied to account for multiple comparisons, and multivariable logistic regression to identify characteristics associated with RCBD. RESULTS: Among the BD cohort, 9.4% were identified as current RCBD. Compared to NRCBD, RCBD patients had a shorter duration from the first psychiatric consultation to the diagnosis of BD, a reduced duration of their longest period of euthymia, a lower proportion of lifetime hospitalization history due to BD, and less use of electroconvulsive therapy (ECT) within the last 12 months. Additionally, they presented higher baseline scores on the Mood Disorder Questionnaire (MDQ) and the Brief 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). However, after applying the Bonferroni correction, these differences were not statistically significant. Multivariable logistic regression analysis identified three factors that were independently associated with RCBD: time from first psychiatric consultation to BD diagnosis (Odds Ratio [OR] = 0.512, P = 0.0416), lifetime hospitalization history due to BD (OR = 0.516, P = 0.0476), and ECT treatment within the past 12 months (OR = 0.293, P = 0.0472). CONCLUSION: This study revealed that the duration from first psychiatric consultation to BD diagnosis, lifetime hospitalization history due to BD, and ECT treatment in the past year were associated with RCBD. Recognizing these factors could contribute to enhance the early identification and clinical outcomes of RCBD. Trial Registration Number Registry ClinicalTrials.gov NCT01770704. Date of Registration: First posted on January 18, 2013.

Bifunctional 3D POM-based coordination polymers for improved pseudocapacitance and catalytic oxidation performance.

Developing novel high-efficiency supercapacitors as energy storage devices to solve the energy crisis is of vital significance. Meanwhile, designing highly active and selective oxidation catalysts for various sulfides is desirable but still a big challenge. To work out these problems, three novel 3D POM-based coordination polymers (POMCPs), formulated as [{Ag6(pytz)4}{SiMo12O40}] (1), [{Cu3(pytz)4}{SiMo12O40}]·5.5H2O (2) and [{Cu6(pytz)6}{SiMo12O40}]·2H2O (3) (pytz = 4-(5-(4-pyridyl)-1H-tetrazole)), are successfully prepared via a one-step synthetic strategy by changing different temperatures under hydrothermal or solvothermal conditions. In compounds 1 and 2, {SiMo12}, as 9-capped and 2-capped polyoxoanions, are engaged among the 2D Ag/Cu-organic sheets to generate the novel 3D POM-based coordination polymers. In addition, 1D Cu-organic chains are combined with 3-capped {SiMo12} polyoxoanions to construct 2D POM-based coordination polymers in 3. To our delight, as electrode materials for supercapacitors, the three compounds exhibit excellent specific capacitances of 261.76 F g-1, 248.82 F g-1 and 156.47 F g-1 at 0.5 A g-1, respectively. Besides, they can effectively and selectively catalyze the oxidation of various sulfides to sulfoxides.

Waste milk humification product can be used as a slow release nano-fertilizer.

The demand for milk has increased globally, accompanied by an increase in waste milk. Here, we provide an artificial humification technology to recycle waste milk into an agricultural nano-fertilizer. We use KOH-activated persulfate to convert waste milk into fulvic-like acid and humic-like acid. We mix the product with attapulgite to obtain a slow-release nano fulvic-like acid fertilizer. We apply this nano-fertilizer to chickweeds growing in pots, resulting in improved yield and root elongation. These results indicate that waste milk could be recycled for agricultural purposes, however, this nano-fertilizer needs to be tested further in field experiments.

Implementation effect of China's green finance pilot policy based on synthetic control method: a green innovation perspective.

In order to develop green finance and realize the coordinated development of the environment and economy, China established green finance reform and innovation pilot zones in 2017. Green innovation has problems such as low financing utilization rate and lack of market competitiveness. The green finance pilot policies (GFPP) based on government management provide solutions to these problems. It is of great significance to measure and provide feedback on the implementation effect of GFPP in China for policy-making and green development. This article focuses on the influence of the construction of GFPP by using the five pilot zones as the study area and constructs the green innovation level indicator. Based on the synthetic control method, it chooses provinces that do not carry out the pilot policy as a control group. After that, assign weights to the control region to fit a synthetic control group with resembling characteristics to simulate the five pilot provinces without implementing the policy. Then, compare it with its current policy effect and highlight the policy implementation effect on green innovation. The placebo test and robustness test were conducted to prove the reliability of the conclusions. The results show that since the implementation of GFPP, the level of green innovation in the five pilot cities has shown an overall rising trend. Furthermore, we found that the balance of credit and investment in science and technology has a negative moderating effect on the implementation of GFPP, while the per capita GDP has a significant positive moderating effect.

[The expression of autophagy-related proteins in peripheral blood mononuclear cells of patients with lupus nephritis is upregulated and related to kidney damage].

Objective To identify the relationship between nephritis activity, autophagy and inflammation in patients with SLE. Methods Western blot analysis was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3) and P62 in peripheral blood mononuclear cells (PBMCs) of SLE patients with lupus nephritis and non-lupus nephritis patients. Tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) in the serum of SLE patients were determined by ELISA. The correlation between LC3II/LC3I ratio and SLE disease activity score (SLEDAI), urinary protein, TNF-α and IFN-γ levels was analyzed by Pearson method. Results The expression of LC3 was increased and P62 was decreased in SLE patients. TNF-α and IFN-γ were increased in the serum of SLE patients. LC3II/LC3I ratio was positively correlated with SLEDAI (r=0.4560), 24 hour urine protein (r=0.3753), IFN-γ (r=0.5685), but had no correlation with TNF-α (r=0.04 683). Conclusion Autophagy is found in PBMCs of SLE, and the autophagy is correlated with renal damage and inflammation in patients with lupus nephritis.

Agomelatine in the treatment of anhedonia, somatic symptoms, and sexual dysfunction in major depressive disorder.

Objective: This study evaluated the treatment outcomes of agomelatine on anhedonic state, anxiety/somatic symptoms, and sexual function in Chinese patients with major depressive disorder (MDD). Method: In total, 93 adult patients with MDD were enrolled, and 68 of them were included in a prospective, open-label, multicenter clinical study. All patients received agomelatine monotherapy during a 9-week treatment phase. The effectiveness of the treatment was reflected by the improvement of anhedonia and somatic symptoms based on the 17-item Hamilton Depression Rating Scale (HAMD-17). In addition, the Arizona Sexual Dysfunction Scale (ASEX), Sheehan Disability Scale (SDS), and Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) were administered to all participants at baseline and at the 3-, 6-, and 9-week follow-ups. Results: After 9 weeks of treatment with agomelatine, the response and remission rates were 73.5% and 39.7%, respectively. Somatic symptoms significantly improved at week 9 (p < 0.001), and significant effects were also observed on the HAMD anhedonia items (p < 0.001). The patients exhibited lower levels of disease severity (the SDS score dropped from 15.52 ± 4.7 to 7.09 ± 5.62 at week 9; the ASEX score dropped from 21.89 ± 4.06 to 16.19 ± 4.79, p < 0.001) and higher levels of QOL (the Q-LES-Q-SF score dropped from 41.02 ± 5.99 to 50.49 ± 8.57, p < 0.001) during the follow-up. Furthermore, treatment with agomelatine improved depressive symptoms without causing serious adverse events. Conclusion: These analyses indicate that agomelatine is a treatment option for improving anhedonic status, anxiety/somatic symptoms, and sexual dysfunction in MDD patients.

A multicenter, randomized, double-blind, duloxetine-controlled, non-inferiority trial of desvenlafaxine succinate extended-release in patients with major depressive disorder.

BACKGROUND: Desvenlafaxine and duloxetine are selective serotonin and norepinephrine reuptake inhibitors. Their efficacy has not been directly compared using statistical hypotheses. This study evaluated the non-inferiority of desvenlafaxine extended-release (XL) to duloxetine in patients with major depressive disorder (MDD). METHODS: In this study, 420 adult patients with moderate-to-severe MDD were enrolled and randomly assigned (1:1) to receive 50 mg (once daily [QD]) of desvenlafaxine XL (n = 212) or 60 mg QD of duloxetine (n = 208). The primary endpoint was evaluated using a non-inferiority comparison based on the change from baseline to 8 weeks in the 17-item Hamilton Depression Rating Scale (HAMD17) total score. Secondary endpoints and safety were evaluated. RESULTS: Least-squares mean change in HAM-D17 total score from baseline to 8 weeks was -15.3 (95% confidence interval [CI]: -17.73, -12.89) in the desvenlafaxine XL group and - 15.9 (95% CI, -18.44, -13.39) in the duloxetine group. The least-squares mean difference was 0.6 (95% CI: -0.48, 1.69), and the upper boundary of 95% CI was less than the non-inferiority margin (2.2). No significant between-treatment differences were found in most secondary efficacy endpoints. The incidence of the most common treatment-emergent adverse events (TEAEs) was lower for desvenlafaxine XL than for duloxetine for nausea (27.2% versus 48.8%) and dizziness (18.0% versus 28.8%). LIMITATIONS: A short-term non-inferiority study without a placebo arm. CONCLUSIONS: This study demonstrated that desvenlafaxine XL 50 mg QD was non-inferior to duloxetine 60 mg QD in efficacy in patients with MDD. Desvenlafaxine had a lower incidence of TEAEs than duloxetine did.

Efficacy of systemic lidocaine in postoperative delirium in elderly patients undergoing laparoscopic colorectal surgery: study protocol for a multicentre, prospective, double-blind, randomised, parallel-group, superiority, placebo-controlled trial.

INTRODUCTION: Systemic lidocaine may reduce pain intensity and accelerate postoperative recovery. However, the efficacy of systemic lidocaine in cognitive function has not been established. This study protocol is designed to clarify the effectiveness of lidocaine in postoperative delirium (POD) in elderly patients scheduled for elective laparoscopic colorectal surgery. METHODS AND ANALYSIS: This is a prospective, multicentre, randomised, double-blind, parallel-group, placebo-controlled trial. One thousand and twenty elderly patients will be randomly allocated in a ratio of 1:1 to receive either systemic lidocaine (a bolus of 1.5 mg/kg, followed by an infusion of 1.5 mg/kg/hour until the end of the surgery) or identical volumes and rates of 0.9% saline. The primary outcome measure is the prevalence of POD during the first 5 postoperative days. Secondary outcomes include emergence agitation, the area under the curve of the Numeric Rating Scale pain scores over 48 hours, postoperative 48-hour cumulative opioid consumption, postoperative nausea and vomiting (PONV), recovery of bowel function, quality of recovery, and patient satisfaction with postoperative analgesia. ETHICS AND DISSEMINATION: The Ethical Committee of the Fujian Provincial Hospital approved the study protocol (ref: K2021-06-018). Other participating subcentres must also obtain ethics committee approval before the start of the study. We will obtain written informed consent from each patient before they are randomised. This study will be presented at scientific conferences and submitted to international journals. TRIAL REGISTRATION NUMBER: ChiCTR2100050314.

A machine learning model for predicting patients with major depressive disorder: A study based on transcriptomic data.

Background: Identifying new biomarkers of major depressive disorder (MDD) would be of great significance for its early diagnosis and treatment. Herein, we constructed a diagnostic model of MDD using machine learning methods. Methods: The GSE98793 and GSE19738 datasets were obtained from the Gene Expression Omnibus database, and the limma R package was used to analyze differentially expressed genes (DEGs) in MDD patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to identify potential molecular functions and pathways. A protein-protein interaction network (PPI) was constructed, and hub genes were predicted. Random forest (RF) and artificial neural network (ANN) machine-learning algorithms were used to select variables and construct a robust diagnostic model. Results: A total of 721 DEGs were identified in peripheral blood samples of patients with MDD. GO and KEGG analyses revealed that the DEGs were mainly enriched in cytokines, defense responses to viruses, responses to biotic stimuli, immune effector processes, responses to external biotic stimuli, and immune systems. A PPI network was constructed, and CytoHubba plugins were used to screen hub genes. Furthermore, a robust diagnostic model was established using a RF and ANN algorithm with an area under the curve of 0.757 for the training model and 0.685 for the test cohort. Conclusion: We analyzed potential driver genes in patients with MDD and built a potential diagnostic model as an adjunct tool to assist psychiatrists in the clinical diagnosis and treatment of MDD.