Genetic association and drug target exploration of inflammation-related proteins with risk of major depressive disorder.

BACKGROUND: In numerous observational studies, circulating inflammation-related proteins have been linked with major depressive disorder (MDD), yet the precise causal direction of this relationship remains unclear. This study aims to investigate the potential causal link between inflammation-related proteins and the risk of developing MDD. METHODS: We utilized summary data from a genome-wide association study (GWAS) of 91 circulating inflammation-associated proteins in 14,824 individuals of European descent. Additionally, we incorporated findings from a substantial GWAS on MDD, which included 294,322 cases and 741,438 controls. Our analysis employed a two-sample bidirectional Mendelian randomization (MR) approach, with inverse variance weighting (IVW) as the primary method. We augmented this with two supplementary techniques (MR-Egger and weighted median approaches) to detect and address potential pleiotropy. Furthermore, to identify and evaluate possible drug targets, we conducted a thorough search within the Drug-Gene Interaction Database (DGIdb). RESULTS: Analysis using MR unveiled significant and causative associations between genetically determined CASP-8 (odds ratio (OR): 0.97), CD40 (OR: 0.96), IL-18 (OR: 0.98), SLAMF1 (OR: 0.97), and uPA (OR: 0.98) with MDD. Conversely, reverse MR analysis indicated causal associations between MDD and CCL19 (OR: 1.15), HGF (OR: 1.15), IL-8 (OR: 1.10), IL-18 (OR: 1.11), IL20RA (OR: 1.12), TGFA (OR: 1.12) and TNFSF14 (OR: 1.16). Notably, a significant bidirectional causal link was observed between IL-18 and MDD. Gene-drug analysis identified CD40, HGF, IL-8, IL-18, SLAMF1, and TGFA as potential therapeutic targets. CONCLUSIONS: We've pinpointed causal links between inflammation-related proteins and MDD, offering compelling and innovative evidence to enhance our understanding of the inflammatory mechanisms involved in MDD and to investigate potential targets for anti-MDD medications.

Structural characterization, anti-aging activity and mechanisms investigation in vivo of a polysaccharide from Anthriscus sylvestris.

Anthriscus sylvestris (L.) Hoffm has a long history of use for anti-aging, although the anti-aging properties of its decoction ingredients have been seldom explored. This study marks the first detailed examination of the in vivo anti-aging activity of A. sylvestris roots polysaccharide (AP). Structural analyses revealed that AP is a neutral heteropolysaccharide with an average molecular weight (Mw) of 34.17 kDa, comprising glucose, xylose, galactose, mannose, and arabinose, with a backbone primarily of 1,4-α-D-Glc and minor branching at 1,4,6-α-D-Man. Its advanced structure is characterized by stable triple-helical chains and nanoscale agglomerated spherical particles. Using a D-gal-induced aging mouse model, further investigation showed that AP boosts the activity of various antioxidant enzymes via the Nrf2/HO-1/NQO1 signaling pathway. Aging-related immune decline was also mitigated by an increase in lymphocyte production in thymus. Moreover, AP reduced inflammation and downregulated aging genes p53 and p21 in hippocampus and liver tissues, enhanced the cholinergic system, and improved liver functions and lipid metabolism. The collective impact of these mechanisms underscores the robust anti-aging properties of AP. These findings highlight the anti-aging and immunomodulatory potential of A. sylvestris polysaccharide, broadening the understanding of its active components.

Psychosocial functioning and its influencing factors in patients with depression post-remission: Implications for assessment and interventions.

BACKGROUND: Enhancing psychosocial functioning is crucial for reducing relapse in depression, but methods for monitoring and recovery are unclear. METHOD: A 1-year follow-up study assessed psychosocial functioning in 182 patients with remitted depression at baseline (T0) as well as at 1, 2, 6, 9, and 12 months post-remission (T1-T5). Using generalized estimating equations (GEE) and multiple linear regression (MLR), we analyzed the impact of changes in psychosocial functioning on relapse/recurrence risk, and assessed the influence of various factors. RESULTS: An increase in psychosocial functioning significantly lowered relapse/recurrence odds by 54.2 %, averaging a risk reduction of 3.1 %. GEE analyses indicated subjective depressive symptoms (ß = -0.315) most significantly impacted psychosocial functioning, followed by social support (ß = 0.236), positive coping (ß = 0.225), and negative automatic thoughts (ß = -0.183). Negative coping and expressed emotion exhibited non-significant effects. MLR revealed that the impact of negative automatic thoughts was most significant at initial remission, but the relative importance of residual subjective depressive symptoms, positive coping, and social support on psychosocial functioning remained stable over time. LIMITATIONS: Predetermined follow-up assessments may not fully capture psychosocial functioning at relapse/recurrence, and the inclusion of factors might not be sufficiently comprehensive. CONCLUSIONS: Recovery of psychosocial functioning significantly reduces relapse risk in post-remission patients with depression more than residual subjective depressive symptoms. The degree of influence of factors on psychosocial functioning can change with the length of remission time.

Clinical characteristics and outcome analysis of pulmonary nocardiosis in southern China: a two-center retrospective study.

BACKGROUND: Pulmonary nocardiosis (PN) is a rare and opportunistic infection. This study aimed to analyze clinical, radiological, and microbiological features, treatment and outcome of PN in southern china. METHODS: Clinical, laboratory, imaging, treatment and outcome data of PN patients at two tertiary hospitals from January 1, 2018, to January 1, 2024 were collected. Factors associated with clinical outcomes were determined by multivariate logistic regression analysis. RESULTS: 67 PN patients including 53 with clinical improvement and 14 with treatment failure were enrolled. Bronchiectasis was the most common respiratory disease in patients with PN (31.3%). The major symptoms of PN were cough (89.6%) and sputum (79.1%). Lung nodules, bronchiectasis, consolidation, pleural involvement, mass, cavity, and lymph node enlargement were the frequent computed tomography findings of PN. Among the Nocardia species detected, N. farcinica was the most common pathogen. Neutrophil-to-lymphocyte ratio (OR = 1.052, p = 0.010), concurrent bacterial infection (OR = 7.706, p = 0.016), and the use of carbapenems (OR = 9.345, p = 0.023) were independently associated with poor prognosis in patients with PN. CONCLUSIONS: This study provides important insights into the clinical features of PN in southern china. neutrophil-to-lymphocyte ratio, concurrent bacterial infection, and the use of carbapenems were independently associated with poor prognosis in patients with PN.

Continuous polyamorphic transition in high-entropy metallic glass.

Polyamorphic transition (PT) is a compelling and pivotal physical phenomenon in the field of glass and materials science. Understanding this transition is of scientific and technological significance, as it offers an important pathway for effectively tuning the structure and property of glasses. In contrast to the PT observed in conventional metallic glasses (MGs), which typically exhibit a pronounced first-order nature, herein we report a continuous PT (CPT) without first-order characteristics in high-entropy MGs (HEMGs) upon heating. This CPT behavior is featured by the continuous structural evolution at the atomic level and an increasing chemical concentration gradient with temperature, but no abrupt reduction in volume and energy. The continuous transformation is associated with the absence of local favorable structures and chemical heterogeneity caused by the high configurational entropy, which limits the distance and frequency of atomic diffusion. As a result of the CPT, numerous glass states can be generated, which provides an opportunity to understand the nature, atomic packing, formability, and properties of MGs. Moreover, this discovery highlights the implication of configurational entropy in exploring polyamorphic glasses with an identical composition but highly tunable structures and properties.

Suicidal ideation in Chinese adolescents: prevalence, risk factors, and partial mediation by family support, a cross-sectional study.

Background: Suicidal ideation is a pressing public health concern, particularly among adolescents. The objective of this study was to examine the prevalence of and factors associated with suicidal ideation in Chinese adolescents, addressing an important gap in current research. Methods: This study employed an online survey of 3443 adolescents in Lianyungang, using a cross-sectional design. The assessment included the use of the Patient Health Questionnaire-9, the seven-item Generalized Anxiety Disorder instrument, and the Perceived Social Support Scale to evaluate suicidal ideation, anxiety symptoms, and social support in adolescents, respectively. Results: In adolescents, the prevalence of suicidal ideation was 22.1%, with a significantly higher proportion among female adolescents than among males (27.9% vs 16.9%, P < 0.001). Binary regression analysis identified (OR = 1.788, 95% CI: 1.467-2.177, P < 0.001), anxiety symptoms (OR = 10.035, 95% CI: 7.441-13.534, P < 0.001), total PHQ-9 scores of mothers (OR = 1.040, 95%CI: 1.003 - 1.078, P = 0.034), total GAD-7 scores of mothers (OR = 0.958, 95%CI: 0.919 - 0.998, P = 0.039), and moderate parental relationships (OR = 2.042, 95% CI: 1.630-2.557, P < 0.001) to be risk factors for suicidal ideation; family support was a protective factor (OR = 0.888, 95% CI: 0.859-0.918, P < 0.001). Furthermore, family support partially mediates the relationship between anxiety symptoms and suicidal ideation among adolescents (9.28%). Conclusions: This study highlights high adolescent suicidal ideation rates and recommends gender-specific interventions, anxiety management, and family support for improvement in mental health status.

Efficacy of tanshinone IIA in rat models with myocardial ischemia-reperfusion injury: a systematic mini-review and meta-analysis.

Background: Myocardial ischemia-reperfusion injury (MIRI) refers to severe damage to the ischemic myocardium following the restoration of blood flow, and it is a major complication of reperfusion therapy for myocardial infarction. Notably, drugs such as metoprolol have been utilized to reduce ischemia-reperfusion injury. Tanshinone IIA is a major constituent extracted from Salvia miltiorrhiza Bunge. Recently, tanshinone IIA has been studied extensively in animal models for controlling MIRI. Therefore, we conducted a meta-analysis on the application of tanshinone IIA in rat models with MIRI to evaluate the therapeutic effects of tanshinone IIA. Methods: A comprehensive search was conducted across PubMed, Web of Science, Embase, the Cochrane Library, the China National Knowledge Infrastructure database, the Wanfang database, and the Chinese Scientific Journal Database to gather studies on tanshinone IIA intervention in rat models with MIRI.We employed SYRCLE's risk of bias tool to assess study quality. The primary outcome indicators were superoxide dismutase (SOD) and malondialdehyde (MDA). Myocardial infarction area was a secondary outcome indicator. This study was registered at PROSPERO (registration number CRD 42022344447). Results: According to the inclusion and exclusion criteria, 15 eligible studies were selected from 295 initially identified studies. In rat models with MIRI, tanshinone IIA significantly increased SOD levels while reducing MDA levels and myocardial infarction area. Moreover, the duration of myocardial ischemia influenced the effectiveness of tanshinone IIA. However, additional high-quality research studies are needed to establish the efficacy and definitive guidelines for the use of tanshinone IIA. Animal studies demonstrated that tanshinone IIA exerted a significant therapeutic effect when the ischemia duration was less than 40 minutes. Tanshinone IIA was found to be more effective when administered via intravenous, intraperitoneal, and intragastric routes at doses above 5 mg/kg. Additionally, treatment with tanshinone IIA at all stages-prior to myocardial ischemia, after ischemia but before reperfusion, prior to ischemia and after reperfusion, and after reperfusion-showed satisfactory results. Conclusions: Tanshinone IIA enhanced SOD activity and reduced MDA levels, thereby ameliorating oxidative stress damage during MIRI. Additionally, it reduced the myocardial infarction area, indicating its effectiveness in mitigating MIRI-induced damage in rats and demonstrating a myocardial protective effect. These findings contribute valuable insights for developing MIRI treatment strategies.

Career adaptability and career coping styles among Chinese medicine specialty students during the COVID-19: The mediating role of career decision-making self-efficacy.

Over the past decade, the attrition rate of Chinese medical graduates has remained high, and the COVID-19 pandemic has exacerbated this situation. Medicine specialty students are the main force of the future healthcare industry. The career choices and career confidence of those entering the healthcare industry will have a huge influence on the quality of future healthcare provision. Considering the possible emergence of public health emergencies such as COVID-19 in the future, helping students develop good career adaptability will contribute to their future career development. However, the relationship between career adaptability, career coping styles and career decision-making self-efficacy remains unclear during the COVID-19. This study aims to examine the interconnections amongst career coping styles, career adaptability and career decision-making self-efficacy among Chinese medicine specialty students and the mediating role of career decision-making self-efficacy. Questionnaire survey was conducted on 747 medicine specialty students from China. The results showed that positive coping style has a significant positive correlation with career decision-making self-efficacy, career adaptability, and their sub-dimensions. There was a partial mediating effect of career decision self-efficacy between the predictor variable positive coping style and the outcome variable career adaptability. By promoting the level of positive coping style or career decision-making self-efficacy among medicine specialty students, the career adaptability can be directly or indirectly enhanced. This survey will help to guide future medical education decisions during a similar pandemic to prevent further loss of healthcare professionals in the medical service.

Lightweight single-phase Al-based complex concentrated alloy with high specific strength.

Developing light yet strong aluminum (Al)-based alloys has been attracting unremitting efforts due to the soaring demand for energy-efficient structural materials. However, this endeavor is impeded by the limited solubility of other lighter components in Al. Here, we propose to surmount this challenge by converting multiple brittle phases into a ductile solid solution in Al-based complex concentrated alloys (CCA) by applying high pressure and temperature. We successfully develop a face-centered cubic single-phase Al-based CCA, Al55Mg35Li5Zn5, with a low density of 2.40 g/cm3 and a high specific yield strength of 344×103 N·m/kg (typically ~ 200×103 N·m/kg in conventional Al-based alloys). Our analysis reveals that formation of the single-phase CCA can be attributed to the decreased difference in atomic size and electronegativity between the solute elements and Al under high pressure, as well as the synergistic high entropy effect caused by high temperature and high pressure. The increase in strength originates mainly from high solid solution and nanoscale chemical fluctuations. Our findings could offer a viable route to explore lightweight single-phase CCAs in a vast composition-temperature-pressure space with enhanced mechanical properties.

Causal associations of obstructive sleep apnea with Chronic Respiratory Diseases: a Mendelian Randomization study.

PURPOSE: This study aimed to elucidate the causal relationship between Obstructive Sleep Apnea (OSA) and Chronic Respiratory Diseases (CRDs), employing Mendelian Randomization (MR) to overcome limitations inherent in observational studies. METHODS: Utilizing a two-sample MR approach, this study analyzed genetic variants as instrumental variables to investigate the causal link between OSA and various CRDs, including chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis, and idiopathic pulmonary fibrosis (IPF). Data were sourced from the FinnGen Consortium (OSA, n = 375,657) and UK Biobank, focusing on genome-wide associations between single-nucleotide polymorphisms (SNPs) and the diseases. Instrumental variables were selected based on strict criteria, and analyses included a random-effects inverse-variance weighted method supplemented by several sensitivity analyses. RESULTS: The study suggests a protective effect of OSA against COPD (OR = 0.819, 95% CI 0.722-0.929, P-value = 0.002), which becomes non-significant after adjusting for BMI, indicating a potential mediating role of BMI in the OSA-COPD nexus. No significant causal links were found between OSA and other CRDs (asthma, IPF, bronchiectasis) or between COPD, asthma, and OSA. CONCLUSIONS: Our findings reveal a BMI-mediated protective effect of OSA on COPD, with no causal connections identified between OSA and other CRDs. These results emphasize the complex relationship between OSA, BMI, and COPD, guiding future clinical strategies and research directions, particularly in light of the study's genetic analysis limitations.

Elevated serum IGFBP-1 levels correlate with cognitive deficits in treatment-resistant and chronic medicated schizophrenia patients.

BACKGROUND: Schizophrenia is a debilitating psychiatric disorder with diverse cognitive impairments. Insulin-like growth factor binding protein 1 (IGFBP-1), a ubiquitous negative regulator of IGF signaling, crosses the blood-brain barrier after peripheral synthesis. Given the crucial role of IGF signaling in cognitive function, we reasoned that altered serum IGFBP-1 concentrations might be associated with cognitive impairments in schizophrenia. To test this hypothesis, we examined the relationship between serum IGFBP-1 levels and cognitive performance in both medicated and treatment-resistant schizophrenia (TRS) patients. METHODS: Serum IGFBP-1 was measured in 31 TRS patients, 49 chronic medicated schizophrenia (CMS) patients, and 53 healthy controls. Clinical symptom severity was evaluated using the Positive and Negative Syndrome Scale (PANSS) and cognitive functions using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: Both TRS and CMS patients exhibited cognitive deficits compared to healthy controls (p < 0.05). Serum IGFBP-1 concentration differed significantly among groups (F=36.805, p < 0.001) and post hoc tests demonstrated significantly higher concentrations in both schizophrenia groups compared to controls (p < 0.001). Further, serum IGFBP-1 concentration was higher in the TRS group than the CMS group (p = 0.048). Correlation analysis identified a significant relationship between serum IGFBP-1 and attention in the TRS group (r = 0.411, p = 0.021), immediate memory in the CMS group (r = -0.417, p = 0.003), and RBANS total score in the CMS group (r = -0.368, p = 0.009). Multiple regression analysis adjusting for confounding factors revealed that serum IGFBP-1 was independently associated with attention in TRS patients (p = 0.016, 95 %CI. 0.002-0.015) and immediate memory in CMS patients (p = 0.022, 95 %CI-0.012 to -0.001). CONCLUSIONS: Elevated serum IGFBP-1 concentration may serve as a predictive biomarker for distinct cognitive deficits in TRS and CMS patients. Further investigations are warranted.

LINC00513 promotes colorectal cancer malignant progression by binding with IGF2BP1 to enhance the stability of connective tissue growth factor mRNA.

Aim: This study aimed to investigate the role of LINC00513 in colorectal cancer (CRC) progression.Materials & methods: Cell proliferation was evaluated using Cell Counting Kit-8. Cell migration was detected with transwell assay. RNA pull-down was applied for verifying the interactions between LINC00513, IGF2BP1 and connective tissue growth factor (CTGF).Results: LINC00513, IGF2BP1 and CTGF levels were upregulated in CRC. Knockdown of LINC00513 significantly inhibited the malignant behavior of CRC cells. LINC00513 increased CTGF mRNA stability by binding with IGF2BP1. Furthermore, overexpression of IGF2BP1 or CTGF reversed the inhibitory effect of LINC00513 shRNA on CRC progression.Conclusion: LINC00513 promoted CRC cell malignant behaviors through IGF2BP1/CTGF.

Colorectal cancer (CRC) progression seriously threatens the health of people. This study showed that LINC00513 (a long noncoding RNA), insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) and connective tissue growth factor (CTGF) were significantly upregulated in CRC tissues. Furthermore, the knockdown of LINC00513 inhibited CRC malignant progression in vitro. Mechanistically, LINC00513 increased CTGF mRNA stability in CRC cells by binding with IGF2BP1. As expect, the impact of LINC00513 downregulation on CRC cell proliferation and migration was declined by the overexpression of IGF2BP1 or CTGF. Taken together, LINC00513 upregulation promoted CRC malignant progression by regulating the IGF2BP1/CTGF axis. We believe that this study will help overcome CRC.

Efficacy, safety, and serum cytokine modulation by olopatadine hydrochloride and desloratadine citrate disodium combination therapy in urticaria.

OBJECTIVES: To assess the efficacy, safety, and impact on serum cytokines of olopatadine hydrochloride (OLP) combined with desloratadine citrate disodium (DES) in treating urticaria. METHODS: We retrospectively analyzed 114 urticaria patients treated at the Affiliated Hospital of Xinyang Vocational and Technical College from March 2020 to March 2023. The control group (55 patients) received DES, while the research group (59 patients) received OLP+DES combination therapy. We compared efficacy, safety (including epigastric pain, dry mouth, lethargy, dizziness, and fatigue), changes in serum cytokines (interleukin [IL]-2, IL-4, and interferon [IFN]-γ), symptom resolution (wheal number, wheal size, and itching degree), and 3-month recurrence rates. A univariate analysis was also conducted to identify factors influencing urticaria recurrence. RESULTS: The research group exhibited a significantly higher overall efficacy rate, lower incidence of adverse events, and reduced recurrence rates at 3 months (all P<0.05) compared to the control group. Post-treatment, the research group showed significant increases in IL-2 and IFN-γ levels and reductions in IL-4 levels, wheal number, wheal size, and itching degree (all P<0.05). Factors such as history of drinking/smoking, IL-2 levels, and treatment method were associated with urticaria recurrence (all P<0.05). CONCLUSIONS: The combination of OLP and DES is an effective and safe treatment option for urticaria, significantly improving serum cytokine profiles, alleviating symptoms, and reducing recurrence risk.

Assessing causality between obstructive sleep apnea with the dyslipidemia and osteoporosis: a Mendelian randomization study.

Purpose: This study aims to assess the causal relationship between Obstructive Sleep Apnea (OSA), dyslipidemia, and osteoporosis using Mendelian Randomization (MR) techniques. Methods: Utilizing a two-sample MR approach, the study examines the causal relationship between dyslipidemia and osteoporosis. Multivariable MR analyses were used to test the independence of the causal association of dyslipidemia with OSA. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables based on genome-wide significance, independence, and linkage disequilibrium criteria. The data were sourced from publicly available Genome-Wide Association Studies (GWAS) of OSA (n = 375,657) from the FinnGen Consortium, the Global Lipids Genetics Consortium of dyslipidemia (n = 188,577) and the UK Biobank for osteoporosis (n = 456,348). Results: The MR analysis identified a significant positive association between genetically predicted OSA and triglyceride levels (OR: 1.15, 95% CI: 1.04-1.26, p = 0.006) and a negative correlation with high-density lipoprotein cholesterol (HDL-C) (OR: 0.84, 95% CI: 0.77-0.93, p = 0.0003). Conversely, no causal relationship was found between dyslipidemia (total cholesterol, triglycerides, HDL-C, and low-density lipoprotein cholesterol) and OSA or the relationship between OSA and osteoporosis. Conclusion: The study provides evidence of a causal relationship between OSA and dyslipidemia, highlighting the need for targeted prevention and management strategies for OSA to address lipid abnormalities. The absence of a causal link with osteoporosis and in the reverse direction emphasizes the need for further research in this area.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Repetitive transcranial magnetic stimulation as a therapy for post-stroke dysphagia: An overview of systematic reviews and meta-analysis.

OBJECTIVE: Post-stroke dysphagia is a common swallowing disorder that occurs after a stroke, leading to an increased risk of aspiration pneumonia and malnutrition. There is a pressing need for effective and safe interventions for its rehabilitation. This review aims to answer two key scientific questions: (1) What is the efficacy of repetitive transcranial magnetic stimulation in the rehabilitation of post-stroke dysphagia? (2) Is repetitive transcranial magnetic stimulation a safe intervention for post-stroke dysphagia? DATA SOURCES: A comprehensive search was conducted across four electronic databases: PubMed, Cochrane Library, Web of Science, and Embase. The search aimed to identify relevant studies concerning our topic of interest and was completed on 28 May 2024. REVIEW METHODS: In accordance with the PRISMA checklist, a comprehensive search of four databases was conducted, which identified 13 relevant systematic reviews. The inclusion criteria were systematic reviews that evaluated the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. Exclusion criteria were reviews that did not focus on post-stroke dysphagia or did not evaluate repetitive transcranial magnetic stimulation as a therapeutic intervention. The quality, bias, reporting, and overall evidence quality of these reviews were assessed using validated tools, including the AMSTAR 2 tool for assessing the methodological quality of systematic reviews, the ROBIS tool for assessing the risk of bias, and the GRADE approach for evaluating the overall quality of evidence. This rigorous approach ensures that our review provides a comprehensive and reliable overview of the current state of knowledge on the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia. RESULTS: The sample sizes for the individual studies included in the systematic reviews/meta-analyses ranged from 66 to 555. The total number of participants across all studies included in the overall analyses was 752. The evidence was limited by the methodological flaws and heterogeneity of the systematic reviews. The quality of the evidence varied from high to low, with most outcomes having moderate quality. Future research should adopt more rigorous, standardized, and comprehensive designs to confirm the efficacy and safety of repetitive transcranial magnetic stimulation for post-stroke dysphagia. The main reason for downgrading the evidence quality was the small sample size and high heterogeneity of the primary studies. CONCLUSION: This overview synthesized research on repetitive transcranial magnetic stimulation for dysphagia, aiming to inform clinical and policy decisions. However, the current evidence does not conclusively establish the safety and efficacy of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The studies reviewed varied in quality, and many were of poor quality. Therefore, while some studies suggest potential benefits of repetitive transcranial magnetic stimulation, these findings should be interpreted with caution. There is a pressing need for more rigorous, high-quality research to validate the use of repetitive transcranial magnetic stimulation for post-stroke dysphagia rehabilitation. The implications of these findings for clinical practice and policy will be clearer once we have more robust, evidence-based recommendations.

Multicentre randomized clinical trial on robot-assisted versus video-assisted thoracoscopic oesophagectomy (REVATE trial).

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).

Oesophageal cancer often requires complex surgery. Recently, minimally invasive techniques like robot- and video-assisted surgery have emerged to improve outcomes. This study compared robot- and video-assisted surgery for oesophageal cancer, focusing on removing lymph nodes near a critical nerve. Patients with a specific oesophageal cancer type were assigned randomly to robot- or video-assisted surgery at three Asian hospitals. Robot-assisted surgery had a higher success rate in removing lymph nodes near the important nerve without permanent damage. It also had shorter operating times, more lymph nodes removed, and faster drain removal after surgery. In summary, for oesophageal cancer surgery, the robotic approach may provide better lymph node removal and less nerve injury than video-assisted techniques.

Decreased serum VEGF and NRG1ß1 levels in male patients with chronic schizophrenia: VEGF correlation with clinical symptoms and cognitive deficits.

BACKGROUND: Vascular endothelial growth factor (VEGF) and neuregulin1 (NRG1) are multifunctional trophic factors reported to be dysregulated in schizophrenia. However, the relationships between serum concentrations and schizophrenia symptoms have differed markedly across studies, possibly because schizophrenia is a highly heterogenous disorder. The aim of this study was to investigate the associations of serum VEGF and NRG1 with clinical symptoms and cognitive deficits specifically in male patients with chronic schizophrenia. METHODS: The study included 79 male patients with chronic schizophrenia and 79 matched healthy individuals. Serum VEGF, NRG1ß1, S100B, S100A8, and neuropilin1 were measured using the Luminex liquid suspension chip detection method, psychopathological symptom severity using the Positive and Negative Symptom Scale (PANSS), and cognitive dysfunction using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). RESULTS: Serum VEGF and NRG1ß1 concentrations were significantly lower in male chronic schizophrenic patients than healthy controls (P < 0.05), while serum S100B, S100A8, and neuropilin1 concentrations did not differ between groups (P > 0.05). Serum VEGF concentration was negatively correlated with PANSS negative subscore (beta = -0.220, t = -2.07, P = 0.042), general psychopathology subscore (beta = -0.269, t = -2.55, P = 0.013), and total score (beta = -0.234, t = -2.12, P = 0.038), and positively correlated with RBANS language score (beta = 0.218, t = 2.03, P = 0.045). Alternatively, serum NRG1ß1 concentration was not correlated with clinical symptoms or cognitive deficits (all P > 0.05). CONCLUSION: Dysregulation of VEGF and NRG1ß1 signaling may contribute to the pathogenesis of chronic schizophrenia in males. Moreover, abnormal VEGF signaling may contribute directly or through intermediary processes to neuropsychiatric and cognitive symptom expression.

Development and validation of a nomogram for suicide attempts in patients with first-episode drug-naïve major depressive disorder.

Objective: The risk of suicide can be decreased by accurately identifying high-risk suicide groups and implementing the right interventions. The aim of this study was to develop a nomogram for suicide attempts (SA) in patients with first-episode drug-naïve (FEDN) major depressive disorder (MDD). Methods: This study undertook a cross-sectional analysis of 1,718 patients diagnosed with FEDN MDD, providing comprehensive clinical data from September 2016 to December 2018. Data on anthropometric and sociodemographic factors were gathered, and the severity of depression and anxiety was evaluated using the 17-item Hamilton Depression Scale (HAMD-17) and the Hamilton Anxiety Scale (HAMA), respectively. Additionally, thyroid hormone levels, lipid profile parameters, and fasting blood glucose (FBG) were measured. Suicide attempt (SA) history was verified based on an amalgamation of medical records, patient interviews, and family interviews. Participants were randomly divided into a training group (70%, n = 1,204) and a validation group (30%, n = 514). In the training group, LASSO analysis and multivariate regression were used to identify variables associated with SA. A nomogram was then constructed using the identified risk factors to estimate the likelihood of SA within the training group. To assess the accuracy, the area under the receiver operating characteristic curve (AUC) was utilized, and calibration plots were employed to evaluate calibration. Additionally, decision curve analysis (DCA) was performed to assess the precision of the model. Finally, internal validation was carried out using the validation group. Results: A practical nomogram has been successfully constructed, incorporating HAMD, HAMA, thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and systolic blood pressure (SBP) parameters, to estimate the probability of SA in Chinese patients diagnosed with FEDN MDD. The pooled area under the ROC for SA risk in both the training and validation groups was found to be 0.802 (95% CI: 0.771 to 0.832) and 0.821 (95% CI: 0.774 to 0.868), respectively. Calibration analysis revealed a satisfactory correlation between the nomogram probabilities and the actual observed probabilities. The clinical applicability of the nomogram was confirmed through decision curve analysis. To enhance accessibility for clinicians and researchers, an online version of the nomogram can be accessed at https://doctorjunjunliu.shinyapps.io/dynnomapp/. Conclusions: We constructed and validated a nomogram for the early detection of FEDN MDD patients with a high risk of SA, thereby contributing to the implementation of effective suicide prevention programs.

The effect of ancillary ligands on hydrocarbon C-H bond functionalization by uranyl photocatalysts.

The aqueous uranyl dication has long been known to facilitate the UV light-induced decomposition of aqueous VOCs (volatile organic compounds), via the long-lived highly efficient, uranyl excited state. The lower-energy visible light excited uranyl ion is also able to cleave unactivated hydrocarbon C-H bonds, yet the development of this reactivity into controlled and catalytic C-H bond functionalization is still in its infancy, with almost all studies still focused on uranyl nitrate as the precatalyst. Here, hydrocarbon-soluble uranyl nitrate and chloride complexes supported by substituted phenanthroline (Ph2phen) ligands are compared to each other, and to the parent salts, as photocatalysts for the functionalization of cyclooctane by H atom abstraction. Analysis of the absorption and emission spectra, and emission lifetimes of Ph2phen-coordinated uranyl complexes demonstrate the utility of the ligand in light absorption in the photocatalysis, which is related to the energy and kinetic decay profile of the uranyl photoexcited state. Density functional theory computational analysis of the C-H activation steps in the reaction show how a set of dispersion forces between the hydrocarbon substrate and the Ph2phen ligand provide control over the H atom abstraction, and provide predictions of selectivity of H atom abstraction by the uranyl oxo of the ring C-H over the ethyl C-H in an ethylcyclohexane substrate.