Background: Bipolar disorder (BD) is characterized by persistent cognitive deficits. These deficits contribute to functional impairment and often respond poorly to pharmacotherapy. Although deep transcranial magnetic stimulation (dTMS) has demonstrated antidepressant efficacy, there is limited knowledge about its cognitive effects and comprehensive clinical performance in BD. In this study, we assessed the cognitive outcomes, clinical efficacy, and safety of H1-coil dTMS in BD patients. Methods: In this randomized, double-blind, sham-controlled trial, 100 inpatients with BD received 4 weeks of active or sham H1-coil dTMS. The MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) Consensus Cognitive Battery (MCCB) was used to investigate the cognitive function, and the 17-item Hamilton Depression Rating Scale (HDRS-17) was used to assess depressive symptoms from baseline to week 4. Results: Both groups, active and sham dTMS, showed significant cognitive improvements across most domains (p < 0.05), with no statistically significant between-group differences (all p > 0.05). At the endpoint, the active dTMS group showed statistically significantly lower HDRS-17 scores and a higher response rate than the sham group (mean difference = 2.94, 95% CI [0.10, 5.78], p = 0.04); 50% vs. 24%; OR = 3.17, 95% CI [1.35, 7.44], p = 0.007). All treatments demonstrated a favorable safety profile, with only mild and transient adverse effects. Conclusions: In patients with BD, active dTMS was well-tolerated and was associated with a higher response rate and statistically significant (albeit modest) lower depressive symptom scores compared to sham stimulation, without inducing cognitive adverse effects. However, no specific cognitive benefit beyond its antidepressant effect was established. Overall, these results indicate that dTMS has potential as an adjunctive treatment option for bipolar depression, particularly when medications are limited or poorly tolerated. Clinical Trial Registration: NCT06524505. Registered 23 July, 2024, https://clinicaltrials.gov/study/NCT06524505.

Objective The literature on large-scale studies of Chinese patients with adolescent-onset bipolar disorder (adolescent-onset BD) was limited. Based on the analysis of the National Bipolar Mania Pathway Survey (BIPAS) Phase II data, we examined the demographic and clinical characteristics of adults with adolescent-onset BD. Methods Among 899 participants diagnosed with BD from 20 mental health services, demographics and clinical data were collected at screening. Comparisons were made using chi-square (or Fisher's exact) tests and ANOVA. Multivariate logistic regression identified independent factors for adolescent-onset BD, and a CHAID decision tree analysis (SPSS) was constructed to detect risk factors. Results In the sample, 360 (40%) had adolescent-onset BD and 539 (60%) adult-onset BD. Significant differences between the two groups were observed in current age, number of episodes, years of education, gender, age of onset, education level, marital status, occupation, comorbid chronic physical illness, and first episode type. Stratified analysis also revealed significant differences between adolescent-onset BD I and BD II. Multivariate logistic regression identified younger onset age, more frequent episodes, lower education level, marital status, occupation, first episode type, and prior hospitalization as independent factors for adolescent-onset BD. The decision tree model selected current age as the first splitting variable, followed by occupation and marital status as the second, and years of education and prior hospitalization as the third. Conclusions Adolescent-onset BD exhibits distinct demographic and clinical features compared to adult-onset BD. Early recognition and tailored treatment strategies may improve prognosis and outcomes in this population.

IntroductionUnderstanding geographic inequalities in psychotropic medication dispensing is important for improving health equity and informing place‐based pharmaceutical management. This study characterized the spatiotemporal distribution of methylphenidate hydrochloride extended‐release tablet dispensing in Jiangsu Province, China, from 2019 to 2023 and examined its socioeconomic and education‐related correlates.MethodsAnnual county‐level dispensed tablet volumes were analyzed using Getis–Ord Gi* hot‐spot analysis, standard deviational ellipses, and weighted‐centroid analysis. Prefecture‐level contextual correlates were examined using annual Lasso models interpreted with SHAP.ResultsThe proportion of county‐level units with zero recorded dispensing decreased from approximately 52%–36%, while the proportion with annual volumes exceeding 20,000 tablets increased from 7% to 20%. Southern Jiangsu consistently exhibited higher dispensing volumes than Northern Jiangsu, with Central Jiangsu generally occupying an intermediate position. Getis–Ord Gi* identified localized high‐value concentrations mainly in Southern and parts of Central Jiangsu. The standard deviational ellipse area increased by 23.1%, while the weighted centroid remained in south‐central Jiangsu. Within the annual Lasso models, predictive importance was allocated mainly to economic‐demographic indicators in 2019–2020 and more strongly to education‐related indicators in 2021–2023.DiscussionThe findings support geographically differentiated monitoring of medication access, dispensing patterns, and prescribing quality.

The present study provides a comprehensive introduction to the features of histone tails, including their length, subtypes, nomenclature, biological functions, and regulation, and systematically reviews their roles in psychiatric disorders. A literature search was conducted, covering over 200 common histone modifications and the top 20 common psychiatric disorders. The results indicate that 26 histone tail modifications are positively associated with ten psychiatric disorders, with most located at H3 and H4 tails, and only one at the H2AX tail. All modifications occur at lysines (K), except for two at arginine (R) or serine (S). The top five modifications associated with psychiatric disorders are H3K9ac, H3K4me3, H3K27ac, H3K9me2, and γH2AX. The majority of the studies (92%) report substance use disorders, Alzheimer's disease, major depressive disorder, schizophrenia, and autism spectrum disorders as the top five psychiatric disorders associated with histone tail modifications. In conclusion, histone tail modifications play crucial roles in various psychiatric disorders, and targeting them and associated epigenetic regulators may offer potential therapeutic strategies for treating psychiatric disorders by providing new insights into the molecular mechanisms underlying abnormal gene expression.

This study aims to conduct a real-world analysis of blinatumomab-associated neurological adverse events (NAEs) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) to comprehensively elucidate its safety profile. A retrospective analysis was conducted in children with B-ALL who were treated at hematology medical ward of our institution from January 2024 to December 2025. Document the occurrence of all NAEs during the dosing cycle of blinatumomab, including the time of occurrence, cycle of appearance, severity, management, and outcome. There were 13 individuals with an average age of 10.08 ± 4.23 years experienced a total of 18 NAEs among all the 60 B-ALL patients. These NAEs primarily manifest as headache, dizziness, tremor, delirium, status epilepticus, and cerebral herniation. Most NAEs occur during the first cycle of medication (77.78

The human brain is a dynamic neural system with time-varying functional connectivity (FC) strengths between brain regions. Evidence indicates that adolescents with major depressive disorder (MDD) exhibit decreased average FC strength in cognitive tasks. Nevertheless, research focused on dynamic FC analysis in this population remains limited. This study aims to identify cognitive task-related dynamic FC features as valuable biomarkers to characterize clinical symptoms in adolescents with MDD. A total of 83 adolescents with MDD and 78 age/sex-matched healthy controls (HCs) were recruited. We utilized functional near-infrared spectroscopy (fNIRS) to record brain functional data from participants while they performed the verbal fluency task (VFT). An analytical framework for fNIRS data was proposed, in which the average FC strength values over the entire VFT duration and the principal components (PCs) of dynamic (time-varying) FC strength values were extracted as static and dynamic FC features, respectively. A random forest model was built to distinguish adolescents with MDD from HCs. Statistical analyses of the FC features were conducted to identify between-group differences, as well as their relationships with clinical symptoms in adolescents with MDD. The random forest model achieved an accuracy of 86.32

A rapid isocratic LC-MS/MS method for quantifying busulfan in human plasma was developed and validated. Plasma samples were processed by protein precipitation with acetonitrile using busulfan-d8 as internal standard. Separation...

Background:Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a life-threatening syndrome, the condition can deteriorate rapidly, and the 90-day mortality rate is high. Due to the rapid changes in the clinical course, early and accurate risk stratification is crucial for timely decision-making and resource allocation in the ICU. This study has developed and verified a machine learning framework that integrates the C-reactive protein-albumin-lymphocyte (CALLY) index to predict the 90-day mortality rate of HBV-ACLF patients. Methods:We conducted a retrospective single-center study on 471 patients with HBV-ACLF who met the 2018 Chinese liver failure diagnosis criteria and were hospitalized in the Western Theater General Hospital from 2015 to 2023. We randomly divide the constructed data set into training set (n = 329) and internal verification set (n = 142) according to the ratio of 7:3. In addition, we performed temporal external validation using a later cohort of 46 patients with HBV-ACLF admitted between 2024 and 2025. Six machine-learning algorithms including logistic regression, support vector machine, K-nearest neighbors, Extra Trees, XGBoost, and LightGBM, were trained to develop predictive models. SHAP was applied to assess feature importance and model interpretability. Results:Among the evaluated algorithms, the LightGBM model showed the strongest overall discriminative performance, with AUCs of 0.940 (95% CI, 0.916-0.964) in the training set, 0.825 (95% CI, 0.757-0.894) in the internal validation set, and 0.804 (95% CI, 0.669-0.939) in the external validation set. SHAP analysis identified international normalized ratio (INR) as the strongest predictor of mortality, followed by the CALLY index, log-transformed total bilirubin (TBIL), age, and creatinine. The CALLY-based model significantly improved risk stratification compared with the Model for End-Stage Liver Disease (MELD) score, as demonstrated by a continuous net reclassification index of 0.6223 and an integrated discrimination improvement of 0.0937. To facilitate clinical implementation, a user-friendly online tool was created to predict mortality rates. Conclusions:Our machine-learning framework integrating the CALLY index provides a high-precision and transparent decision-support tool for predicting 90-day mortality with HBV-ACLF patients. By quantifying the immune-nutritional-inflammatory axis, this approach may facilitate earlier risk stratification and personalized interventions, potentially improving survival in high-risk patients.

Objective:This study aimed to explore the impacts of social cognition and interaction training (SCIT) on serum brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) levels, and psychosocial function in first-episode, drug-naïve (FEDN) major depressive disorder (MDD) patients. Methods:In this 8-week randomized controlled trial (RCT), 45 MDD patients were assigned to SCIT group and 39 to cognitive behavioral therapy (CBT) group. The 17-item Hamilton Rating Scale (HDRS-17) and the Functioning Assessment Short Test (FAST) were performed to measure depressive symptoms and functional impairment severity, respectively. We also collected blood samples for serum BDNF/GDNF level detection. Results:Compared to CBT, SCIT demonstrated significantly greater improvements in total FAST scores (F (1,82) = 109.21, p < 0.001, η p 2   =   0.57 ); especially in occupational (F (1,82) = 16.69, p < 0.001, η p 2 = 0.17 ); cognitive (F (1,82) = 103.51, p < 0.001, η p 2 = 0.56 ), and interpersonal relationship domains (F (1,82) =65.07, p < 0.001, η p 2 = 0.44 ). Changes in serum GDNF levels were positively associated with changes in autonomy (r (40) = 0.32, 95% CI = [0.02, 0.57], p = 0.038), and financial domains (r (40) = 0.44, 95% CI = [0.15, 0.65], p = 0.004) in SCIT group. Conclusion:Improvements in social function through SCIT can be effectively generalized to MDD patients. Moreover, improved GDNF levels were associated with improvements in specific aspects of social functioning post-SCIT.

Adolescent unipolar and bipolar depression share many overlapping symptoms, frequently resulting in diagnostic delays and inappropriate treatment. The Rapid Mood Screener (RMS) is a brief and practical tool designed for the preliminary screening of bipolar disorder. This study aimed to evaluate the reliability, validity, and diagnostic utility of the Chinese version (RMS-C) in adolescents experiencing depressive episodes. A total of 167 patients aged 13-18 years were recruited, including 68 with major depressive disorder (MDD) and 99 with bipolar disorder (BD). Participants completed the RMS-C, the Mood Disorder Questionnaire (MDQ), and the Hypomania Checklist-32 (HCL-32) at baseline and at 2-, 4-, and 8-week follow-ups. The RMS-C demonstrated satisfactory reliability, with test-retest intraclass correlation coefficients (ICCs) ranging from 0.71 to 0.79, and a two-factor model supported good structural validity (CFI = 0.92). Using a cutoff score of 4, the RMS-C achieved AUCs of 0.81 for BD, 0.78 for BD-I, 0.82 for BD-II, and 0.83 for BD-II with anxious distress, outperforming both the MDQ and HCL-32. These findings suggest that the RMS-C is a reliable and efficient screening tool for the rapid identification of bipolar depression in adolescents and holds strong promise for clinical application in outpatient settings.

ObjectivesSERINC2 has been associated with alcoholism, bipolar disorder and autism, but the comparability and specificity issues of the findings remain unaddressed. The present study aimed to comprehensively analyze various neuropsychiatric disorders pinpoint the most reliable conditions predisposed by SERINC2.MethodsA total of 2,187 imputed SNPs across SERINC2 were examined in 1,167,439 subjects from 72 independent cohorts with 18 different neuropsychiatric disorders. SNP-disease associations were tested and then meta-analyzed, followed by FDR correction, to identify significant disease-risk SNPs. Finally, functional studies on the differential SERINC2 mRNA expression in brains and the potential regulatory effects of disease-risk alleles on SERINC2 mRNA expression, gray matter volumes (GMVs) of subcortical structures, cortical surface area (SA) and average thickness (TH) were conducted.ResultsIn European descent, alcoholism was most significantly associated with SERINC2 variants (245 SNPs with 5.5×10-8≤p ≤ 0.049 and 4.9×10-5≤q ≤ 0.034) that were largely shared across cocaine dependence, marijuana dependence, nicotine dependence, polysubstance dependence, schizophrenia, OCD, and autism (8.2×10-8≤p ≤ 0.050 and 1.9×10-5≤q ≤ 0.049); in Chinese population, bipolar disorder was also significantly associated with SERINC2 variants (10 SNPs: 1.3×10-4≤p ≤ 4.7×10-4 and 0.025≤q ≤ 0.031). Furthermore, the disease-risk alleles had highly similar regulatory effects on mRNA expression (8.1×10-7≤p ≤ 0.046), subcortical GMVs (7.0×10-4≤p ≤ 0.048) and cortical TH and SA (1.3×10-3≤p ≤ 0.050) in brains across alcoholism, schizophrenia, OCD and autism. The bipolar disorder-risk alleles had these regulatory effects but with different effect patterns. Finally, SERINC2 mRNA was differentially expressed in several brain regions between alcoholism or schizophrenia and controls.ConclusionSERINC2 is primarily linked to substance use disorders, schizophrenia, OCD, autism and bipolar disorder, not only statistically but also biologically.

Purpose: We aimed to verify the impact of functional remediation (FR) on serum brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) levels, to explore the biomechanism of FR intervention in patients with euthymic bipolar disorder (BD). Patients and Methods: This is a randomized controlled, 12-week intervention study with participants randomized into the FR group (n=39) and the treatment as usual group (TAU, n=42) at the 11 ratio. 17-Hamilton Depression Rating Scale-17 (HDRS-17), Young Mania Rating Scale (YMRS), and Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) were used to assess affective symptoms and cognitive functioning both at baseline and week 12, respectively. Meanwhile, we collected blood samples (10 milliliters) from all participants for determination of serum BDNF/ TrkB levels both at baseline and week 12. After baseline assessment, all participants received FR or TAU treatments, respectively. Results: Our results showed significant decreasing in HDRS-17 and YMRS scores, increasing in serum BDNF and TrkB levels in both groups over 12 weeks (all p's< 0.05). There were no group differences in the HDRS-17 and YMRS scores (all p's> 0.05), but the FR group showed greater increasing in serum BDNF and TrkB levels than those in the TAU group (all p's< 0.05). In terms of cognition, the change in serum BDNF levels was negatively correlated with changes in Mazes test, and the improved TrKB levels were associated with improved Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) in the FR group (all p's< 0.05). Conclusion: The changes in serum BDNF and TrkB levels may be implicated in the mechanisms underlying FR intervention in euthymic patients with BD. Limitation: A longer follow-up period than 12 weeks and set up healthy controls may make the results more convincing, and the sample size of this study is still insufficient.

BACKGROUND:Major depressive disorder (MDD) is associated with disrupted brain structural integration. Morphometric similarity offers a means to capture the coordinated patterns of various structural features. However, it remains unknown whether MDD-related changes can be detected in cortical morphometric similarity through the Morphometric Inverse Divergence (MIND) network. Additionally, the role of brain connectivity in shaping these alterations, and their links to neuroreceptors and gene expression, have yet to be investigated. METHODS:Using the T1-weighted MRI data from 71 patients with first-episode, treatment-naïve MDD and 69 healthy controls, we constructed the MIND network for all participants. We then performed between-group comparisons to investigate abnormalities in the network and spatial relationships between the observed patterns of MIND disruption and the patterns of neuroreceptors were estimated. Network-based spreading was utilized to explore the abnormalities constrained by brain connectivity based on structural, functional, and transcriptional connectome architecture and to further identify potential epicenters of MDD. In addition, partial least squares regression was conducted to examine the associations of gene expression profiles with MIND changes in MDD. RESULTS:Patients with MDD showed significantly increased MIND in regions associated with sensation and cognition compared with healthy controls, with this altered pattern being influenced by a combination of transcriptional and structural connectivity, and potential epicenters of MDD were identified in the frontal, parietal, and paracentral cortices. Furthermore, the cortical map of case-control differences in MIND was spatially correlated with the cannabinoid CB1 receptor and the brain-wide expression of a weighted combination of genes. These genes were enriched for neurobiologically relevant pathways and preferentially expressed in different cell classes and cortical layers. CONCLUSION:These results highlight the abnormal pattern of morphometric similarity observed in MDD, shedding light on the complex interplay between disrupted macroscale coordinated morphology and microscale molecular organization in MDD.

OBJECTIVE:We collected maintenance treatment medication information from Chinese multicenter bipolar disorder patients, exploring the characteristics of medication use and related factors. We analyzed medication guideline adherence and compared trends in medication use with a study from 2014. METHODS:323 patients receiving maintenance therapy for bipolar disorder across 20 hospitals have been recruited. Their prescription information was collected to compare with the recommended drug protocols outlined by CANMAT to assess consistency. Additionally, descriptive statistics were conducted to document the quantities and percentages of different classes of medications used. Regression analysis was employed to explore factors influencing medication choices. RESULT:The rate of medication inconsistency in this study was 12.38 %, characterized by inappropriate use of antidepressants and mood stabilizers. The rate of using additional drugs was 67.80 %, with antipsychotics being the most common adjunctive treatment in the Bipolar I group and antidepressants in the Bipolar II group. Factors influencing the occurrence of adjunctive therapy included previous hospitalization, most recent episode type, and gender. The rate of polypharmacy was 47.10 %, with previous hospitalization and most recent episode type being the main influencing factors. CONCLUSION:There has been a noticeable improvement in guideline concordance in medication use compared to 2014; however, improper use of antidepressants remains a significant clinical issue. The increasing prevalence of adjunctive medication use underscores the need for more personalized medication recommendations in clinical guidelines.

Da ChaiHu decoction (DCHD) is used in Chinese medicine to treat pancreatic cancer (PC), but its exact mechanism is not known. The aim of this study was to investigate the main active ingredients and specific mechanisms of DCHD against PC. Firstly, the active ingredients and targets of DCHD and PC-related targets were searched from the TCMSP, DrugBank, NCBI and GeneCards databases, respectively. The intersected targets of both were then taken to construct a PPI network using STRING, and this network was visualized by Cytoscape 3.8.2. GO and KEGG enrichment analyses of the intersected targets were performed using R 4.2.1 "clusterProfiler", "enrichplot", and "ggplot2" packages. Molecular docking was performed utilizing MOE software to detect the binding capacity between compounds and targets. Cell proliferation, apoptosis, invasion and migration were examined through a CCK8 kit, Muse® Cell Analyzer, transwell and wound healing experiment, respectively. The expression levels of five core targets were assessed by RT-qPCR in PANC-1 cells treated with stigmasterol. Molecular dynamic simulations analysis was conducted to analyze the binding affinities and modes of interaction between molecules and stigmasterol using the GROMACS 5.1.4 program package. In this study, 141 common targets of DCHD and PC were obtained. GO-MF items indicated that DCHD exerts its effects on PC primarily by influencing the binding activity of DNA-binding transcription factors. The KEGG analysis revealed that these genes were implicated in various signaling pathways, including the IL-17 signaling pathway and the PI3K/Akt signaling pathway. Stigmasterol was chosen as the final ingredient for subsequent investigation due to its derivation from herb (Da ChaiHu), its encompassment of more common targets, and the scarcity of existing research on its role in PC. The results of molecular docking and Molecular dynamic simulations analysis showed that stigmasterol had good binding activity with BCL2, and ICAM1. In vitro experiments suggested that stigmasterol could effectively inhibit the proliferation, invasion and migration of PANC-1 cells, and promote cell apoptosis. Moreover, stigmasterol treatment led to the reduced expression of AKT1, HIF1A, BCL2, IL1B, and ICAM1. This study is the first to reveal the main active components and potential mechanisms of DCHD against PC, which provides a theoretical basis for studying the role of DCHD in the treatment of PC. Especially, the anti-PC mechanism of active compound stigmasterol might be associated with inhibiting proliferation, invasion and migration and accelerating apoptosis. Furthermore, five targets (AKT1, HIF1A, BCL2, IL1B, and ICAM1) were identified as key targets of stigmasterol, and the mRNA expressions of these genes were down-regulated by stigmasterol through in vitro experiments.

Purpose:Major depressive disorder (MDD) is associated with worse cognitive functioning. We aim to examine the association between baseline cognitive functioning and the reduction rate in HDRS-17 total scores and to highlight the predictors of the reduction rate in HDRS-17 total scores in MDD with first-episode, drug-naïve (FED) patients.Patients and Methods:Ninety FED patients were recruited consecutively and evaluated using the 17-item Hamilton Depression Rating Scale (HDRS-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Functioning Assessment Short Test (FAST) and the MATRICS Consensus Cognitive Battery (MCCB) at baseline and again at week 8.Results:Eighty-four FED patients completed the study. Comparison showed that response group had significantly higher T scores in TMT-A, BACS-SC, WMS-III, BVMT-R, MSCEI and CPT-IP, but showed significantly lower scores in FAST total scores including autonomy, occupational functioning, cognitive functioning, interpersonal relationship than non- response group (all p's< 0.05). Partial correlation analysis also found that the reduction rate in HDRS-17 total scores could be negatively associated with autonomy, cognitive functioning and interpersonal relationship domains as well as total FAST scores, also was further positively associated with T-scores of BACS-SC, CPT-IP and MSCEI in MCCB, even when accounting for potential confounders. Furthermore, the levels of cognitive function domain, autonomy domain in FAST, and BACS-SC, CPT-IP in MCCB may predict the reduction rate in HDRS-17 total scores in FED patients (all p's< 0.05).Conclusion:Our findings underscore significant correlations between baseline functioning and the reduction rate in HDRS-17 total scores in FED patients. Moreover, better baseline cognitive function, autonomy, speed of processing and attention/vigilance are more likely to predict patients' response to antidepressant treatment, indicating pre-treatment better cognitive functioning may be predictors to treatment response in FED.

目的 探索惊恐障碍患者儿茶酚胺-O-甲基转移酶(catechol-O-methyltransferase,COMT)基因多态性(rs4680、rs740603)与艾司酞普兰疗效的关系.方法 纳入惊恐障碍患者69例,正常对照78名.患者组使用艾司西酞普兰固定剂量10 mg/d连续治疗8周,分别在基线及第2、4、8周使用汉密尔顿焦虑量表(Hamilton anxiety scale,HAMA)评估焦虑症状.采用基质辅助激光解吸飞行时间质谱(MALDI-TOF-MS)对所有被试COMT基因rs4680、rs740603位点进行基因分型.结果 患者组与对照组两位点基因型和等位基因分布无统计学差异(P>0.05).患者治疗第8周时,rs4680的G/G基因型患者HAMA减分率(72.52％±11.38％)大于A/G基因型患者(60.70％±16.25％),差异有统计学意义(P<0.05).在第2、8周时rs4680不同基因型患者焦虑症状治疗有效率差异有统计学意义(P<0.05).rs740603不同基因型患者HAMA减分率无统计学差异(P>0.05).结论 COMT基因多态性在艾司西酞普兰对惊恐障碍焦虑症状改善中可能有作用.

Objective:To compare the recovery effect of continuous infusion of dexmedetomidine combined with oxycodone or sufentanil in the anesthesia intensive care unit (AICU) in elderly patients after thoracoscopic radical surgery for lung cancer.Methods:Using the method of prospective study, 80 elderly lung cancer patients underwent selective thoracoscopic radical surgery under general anesthesia in Nanjing First Hospital from February 2021 to May 2022 were selected. The patients were divided into dexmedetomidine combined with sufentanil group (S group) and dexmedetomidine combined with oxycodone group (Q group) by random digits table method with 40 cases each group. On the basis of routine monitoring and treatment after operation, the patients in Q group were continuously injected with oxycodone 0.03 mg/(kg·h) and dexmedetomidine 0.4 μg/(kg·h) through analgesia pump, the patients in S group were continuously injected with sufentanil 0.03 mg/(kg·h) and dexmedetomidine 0.4 μg/(kg·h) through analgesia pump. The wake-up time, extubation time, awakening quality (Aldrete score and bucking score) and comfort level (Bruggrmann comfort scale score, BCS score) after entering the AICU were record; the sedation score (Ramsay score) and pain relief score (numerical rating scale score, NRS score) and hemodynamic changes (mean arterial pressure and heart rate) 3, 5, 7, 10 and 14 h after entering the AICU were record; the level of serum inflammatory factors, including tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) immediately, 5 h and 14 h after entering the AICU; press times of analgesia pump, adverse events, bleeding volume of drainage tube during AICU and overall satisfaction score when leaving the AICU were record.Results:The bucking score in Q group was significantly lower than that in S group: (1.02 ± 0.77) scores vs. (1.88 ± 0.34) scores, the Aldrete score and BCS score were significantly higher than those in S group: (8.93 ± 0.25) scores vs. (5.97 ± 0.32) scores and (3.03 ± 0.32) scores vs. (0.93 ± 0.52) scores, and there were statistical differences ( P<0.01); there were no statistical difference in wake-up time and extubation time between two groups ( P>0.05). There were no statistical difference Ramassy score, NRS score 3 and 5 h after entering the AICU, mean arterial pressure and heart rate between two groups ( P>0.05); the Ramassy score 7, 10 and 14 h after entering the AICU in Q group was significantly lower than that in S group, the NRS score, mean arterial pressure and heart rate were significantly lower than those in S group, and there were statistical differences ( P<0.01). There were no statistical differences in TNF-α, IL-6 and CRP immediately after entering the AICU between two groups ( P>0.05); the TNF-α, IL-6 and CRP 5 and 14 h after entering the AICU in Q group were significantly lower than those in S group, and there were statistical difference ( P<0.01). The press times of analgesia pump, bleeding volume of drainage tube and the incidences of nausea vomiting, respiratory depression, lethargy, restlessness, fever and lung infection in Q group were significantly lower than those in S group: (4.63 ± 1.10) times vs. (18.80 ± 1.54) times, (129.67 ± 4.14) ml vs. (164.00 ± 8.14) ml, 10.0% (4/40) vs. 52.5% (21/40), 2.5% (1/40) vs. 25.0% (10/40), 7.5% (3/40) vs. 47.5% (19/40), 0 vs. 20.0% (8/40), 2.5% (1/40) vs. 22.5% (9/40) and 2.5% (1/40) vs. 20.0% (8/40), and there were statistical differences ( P<0.01 or <0.05); there was no severe hypotension, severe bradycardia and delirium in both groups. The overall satisfaction score in Q group was significantly higher than that in S group: (3.53 ± 0.63) scores vs. (2.70 ± 0.65) scores, and there was statistical difference ( P<0.01). Conclusions:Continuous micro-pump infusion of dexmedetomidine combined with oxycodone in AICU elderly patients with lung cancer after thoracoscopic radical surgery can significantly improve the quality of recovery and comfort during extubation, without affecting the extubation time, and can effectively reduce the degree of pain, stress and inflammatory reaction in the early recovery period, and reduce the incidence of adverse events after surgery.

Objectives Numerous genome-wide association studies have identified CACNA1C as one of the top risk genes for schizophrenia. As a necessary post-genome-wide association study (GWAS) follow-up, here, we focused on this risk gene, carefully investigated its novel risk variants for schizophrenia, and explored their potential functions. Methods We analyzed four independent samples (including three European and one African-American) comprising 5648 cases and 6936 healthy subjects to identify replicable single nucleotide polymorphism-schizophrenia associations. The potential regulatory effects of schizophrenia-risk alleles on CACNA1C mRNA expression in 16 brain regions (n = 348), gray matter volumes (GMVs) of five subcortical structures (n = 34 431), and surface areas and thickness of 34 cortical regions (n = 36 936) were also examined. Results A novel 17-variant block across introns 36-45 of CACNA1C was significantly associated with schizophrenia in the same effect direction across at least two independent samples (1.8 x 10(-4) <= P <= 0.049). Most risk variants within this block showed significant associations with CACNA1C mRNA expression (1.6 x 10(-3) <= P <= 0.050), GMVs of subcortical structures (0.016 <= P <= 0.048), cortical surface areas (0.010 <= P <= 0.050), and thickness (0.004 <= P <= 0.050) in multiple brain regions. Conclusion We have identified a novel and functional risk variant block at CACNA1C for schizophrenia, providing further evidence for the important role of this gene in the pathogenesis of schizophrenia. Psychiatr Genet 33: 182-190 Copyright (c) 2023 Wolters Kluwer Health, Inc. All rights reserved.