Exosomes in esophageal cancer: Promising nanocarriers in cancer progression, diagnosis, prognosis, and therapy.

Esophageal cancer (EC) is one of the most fatal cancers all over the world. Sensitive detection modalities for early-stage EC and efficient treatment methods are urgently needed for the improvement of the prognosis of EC. Exosomes are small vesicles for intercellular communication, mediating many biological responses including cancer progression, which are not only promising biomarkers for diagnosis and prognosis but also therapeutic tools for EC. This review provides an overview of the relationships between exosomes and EC progression, as well as the application of exosomes in the diagnosis, prognosis, and treatment of EC. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Panax ginseng extract prevents UVB-induced skin photodamage by modulating VMP1-mediated ER stress.

BACKGROUND: The endoplasmic reticulum (ER) stress is a crucial toxic signaling event triggered by chronic exposure to Ultraviolet B radiation (UVB), which significantly exacerbate photodamage responses in the irradiated skin. Therefore, the identification of agents capable of inhibiting ER stress could serve as a promising therapeutic strategy for addressing the unmet clinical needs in the treatment of UVB-induced photodamage. METHODS: A UVB-irradiated mouse model was used and topical administration of Panax ginseng extract was carried out for a duration of 9 weeks. Vitamin E was used as a positive control. After 9 weeks of administration, the skin appearance, epidermal hyperplasia, infiltration of inflammatory cells, apoptosis, and collagen content were measured. The keratinocytes were irradiated with 6 mJ/cm2 UVB to establish an in vitro model. The levels of ER stress and apoptosis were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. RESULTS: Among the 14 extracts derived from 13 distinct plant species that were screened, Panax ginseng, Prunus mume, and Camellia japonica showed inhibitory effect on UVB-induced ER stress. Notably, Panax ginseng effectively inhibits collagen degradation and apoptosis in both irradiated keratinocytes and Balb/C mice skin. Furthermore, the silencing of VMP1 significantly impeded the cellular protective effect of Panax ginseng extract on UVB-irradiated keratinocytes, indicating that Panax ginseng exerts its protective effects through targeted promotion of VMP1. CONCLUSION: Our data suggest that Panax ginseng extract possess a therapeutical effect on UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.

Childhood trauma, resilience, psychopathology and social functioning in schizophrenia: A network analysis.

The affective pathway to psychosis implicates affective symptoms and neuroticism as mediating steps between childhood trauma and symptoms of schizophrenia. Prior research seldom examined the interplay between childhood trauma, resilience, personality, social functioning and symptoms in schizophrenia patients. This study recruited 290 schizophrenia patients, and constructed a regularized partial correlation network of childhood trauma, resilience, big-five personality traits, symptoms and social functioning. We further applied flow diagram and shortest path analysis to clarify how different childhood trauma types would contribute to and reach different symptoms. In the network, emotional and physical abuse showed the highest expected influence, and resilience showed the highest strength. In flow diagrams, all nodes together contributed two-thirds of variance of social functioning (which had highest predictability). Among childhood trauma types, emotional abuse contributed most to positive symptoms; physical neglect contributed most to negative, depressive and disorganized symptoms. Childhood abuse reached positive symptoms via neuroticism and depressive symptoms, yet it reached negative symptoms via physical neglect and social functioning. Childhood neglect reached positive symptoms via resilience, conscientiousness, neuroticism and depressive symptoms, yet it reached negative symptoms via social functioning. Our findings support that different childhood trauma types contribute to different symptoms, and interacts with resilience, personality and social functioning.

A Transdiagnostic Network Analysis of Childhood Trauma and Psychopathology.

BACKGROUND AND HYPOTHESIS: Psychiatric comorbidities suggest that symptoms overlap across different diagnoses; the transdiagnostic network approach is valuable for studying psychopathology. Childhood trauma is a common transdiagnostic risk factor for psychiatric disorders, but the complex relationship between childhood trauma and psychopathology has seldom been investigated using a large cross-sectional transdiagnostic sample. STUDY DESIGN: This study recruited 869 patients with different diagnoses, including 418 schizophrenia, 215 bipolar disorder, and 236 major depressive disorder. Participants completed psychiatric interviews and self-report questionnaires. We constructed dimension- and item-level Least Absolute Shrinkage and Selection Operator-based (LASSO) networks to explore the relationship between childhood trauma, psychopathology, and duration of illness. Moreover, we constructed directed acyclic graphs (DAGs) to tentatively clarify the potential directions of associations among these variables. Network Comparison Tests (NCTs) were conducted for different diagnostic groups and gender-stratified groups. STUDY RESULTS: The transdiagnostic LASSO networks showed that different types of childhood trauma exerted distinct impacts on various psychopathological dimensions. Emotional abuse was linked to depressive symptoms, physical abuse to excited symptoms, sexual abuse to positive and disorganized symptoms, emotional neglect to depressive symptoms and motivation and pleasure (MAP) deficits factor of negative symptoms, and physical neglect to MAP factor. The DAG findings generally concurred with the LASSO network. The NCT showed comparable networks. CONCLUSIONS: Our findings suggest that childhood trauma is significantly associated with the development of psychopathology across different diagnostic groups. The affective pathway model suggests that early identification and tailored interventions would be needed for people with a history of childhood trauma.

Patient-reported outcomes in lung cancer surgery: A narrative review.

Lung cancer is a leading cause of cancer-related mortality worldwide, profoundly affecting patients' quality of life. Patient-reported outcomes (PROs) provide essential insights from the patients' perspective, a crucial aspect often overlooked by traditional clinical outcomes. This review synthesizes research on the role of PROs in lung cancer surgery to enhance patient care and outcomes. We conducted a comprehensive literature search across PubMed, Scopus, and Web of Science up to March 2024, using terms such as "lung cancer," "Patient Reported Outcome," "lobectomy," "segmentectomy," and "lung surgery." The criteria included original studies on lung cancer patients who underwent surgical treatment and reported on PROs. After screening and removing duplicates, reviews, non-English articles, and irrelevant studies, 36 research articles were selected, supported by an additional 53 publications, totaling 89 references. The findings highlight the utility of PROs in assessing post-surgical outcomes, informing clinical decisions, and facilitating patient-centered care. However, challenges in standardization, patient burden, and integration into clinical workflows remain, underscoring the need for further research and methodological refinement. PROs are indispensable for understanding the quality-of-life post-surgery and enhancing communication and decision-making in clinical practice. Their integration into routine care is vital for a holistic approach to lung cancer treatment, promising significant improvements in patient outcomes and quality of care.

Differential manifestations of anhedonia in people with social anhedonia and subsyndromal depression.

Empirical findings suggested that anhedonia, a reduced capability to access pleasure and a core symptom in both schizophrenia and the major depressive disorder, can be present in people with high levels of social anhedonia and people with subsyndromal depression. Few studies have adopted a multidimensional framework to investigate anhedonia in these subclinical samples. We recruited 35 participants with high social anhedonia (SA), 53 participants with subsyndromal depression (SD), 20 participants with co-occurrence of both traits (CO), and 47 participants with low levels of both traits (CN) to complete a self-report questionnaire capturing the pleasure experience, and the Monetary Incentives Delay (MID) Task and the Social Incentives Delay (SID) Task capturing the motivation of reward. Results indicated that people with SA, SD and CO exhibited lower abstract anticipatory pleasure compared to CN. Moreover, people with SD and CO exhibited specific impairment in response to social incentives. Together, our findings characterized the multidimensional features of anhedonia performances of subclinical samples with SA, SD and CO, which may contribute to the formulation of early identification of at-risk groups.

Analysis of surgical complexity and short-term prognostic indicators in NSCLC patients: neoadjuvant targeted therapy versus neoadjuvant chemoimmunotherapy.

Background: Neoadjuvant therapy improves survival benefits in patients with locally advanced non-small cell lung cancer but increases tissue density, presenting challenges for surgeons. Objectives: To compare the differences in surgical complexity and short-term prognostic outcomes between neoadjuvant targeted therapy (NTT) and neoadjuvant chemoimmunotherapy (NCI). Design/methods: This study enrolled 106 patients underwent curative surgery after neoadjuvant therapy between January 2020 and December 2023 at the National Cancer Center of China. Differences in surgical complexity and short-term prognostic outcomes between the two neoadjuvant therapy cohorts were evaluated. The pathological indicators such as pathological response rate and lymph node upstaging/downstaging were then analyzed. Results: In total, 33 patients underwent NTT and 73 underwent NCI preoperatively. Patients who received NTT showed a higher minimally invasive surgery rate (84.8% versus 53.4%, p < 0.01), shorter operative time (144 versus 184 min, p < 0.01), lower conversion rate (3.3% versus 17.8%, p = 0.03), less postoperative drainage (day 3: 140 versus 200 mL, p = 0.03), and lower incidence of postoperative complications including arrhythmias (6.1% versus 26%, p = 0.02). The pathological response rate in the NTT and NCI groups was 70% and 75%, respectively, with the latter group showing a higher complete pathological response rate. The two groups had no significant differences in major pathological response and lymph node pathological response rate. Conclusion: Patients who received NTT presented fewer surgical challenges for surgeons and had better surgical outcomes than those who received NCI therapy, with comparable pathological response rates between the two cohorts. Accordingly, NTT is the preferred induction regimen for patients harboring mutation status.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis: A network meta-analysis.

BACKGROUND: Currently, traditional Chinese medicine (TCM) formulas are commonly being used as adjunctive therapy for ulcerative colitis in China. Network meta-analysis, a quantitative and comprehensive analytical method, can systematically compare the effects of different adjunctive treatment options for ulcerative colitis, providing scientific evidence for clinical decision-making. AIM: To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis (UC) in clinical practice through a network meta-analysis. METHODS: Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1, 2022. Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard. The methodological quality of the studies was assessed using ReviewManager (RevMan) 5.4, and a funnel plot was constructed to test for publication bias. ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures. RESULTS: A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study. The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients. Adjuvant treatment with Baitouweng decoction (BTWT) showed a significant effect [mean difference = 36.22, 95% confidence interval (CI): 7.63 to 65.76]. For the reduction of tumor necrosis factor in patients with UC, adjunctive therapy with BTWT (mean difference = -9.55, 95%CI: -17.89 to -1.41), Shenlingbaizhu powder [SLBZS; odds ratio (OR) = 0.19, 95%CI: 0.08 to 0.39], and Shaoyao decoction (OR = -23.02, 95%CI: -33.64 to -13.14) was effective. Shaoyao decoction was more effective than BTWT (OR = 0.12, 95%CI: 0.03 to 0.39), SLBZS (OR = 0.19, 95%CI: 0.08 to 0. 39), and Xi Lei powder (OR = 0.34, 95%CI: 0.13 to 0.81) in reducing tumor necrosis factor and the recurrence rate of UC. CONCLUSION: TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Identification of TFRC as a biomarker for pulmonary arterial hypertension based on bioinformatics and experimental verification.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there is a paucity of studies that reflect the available biomarkers from separate gene expression profiles in PAH. METHODS: The GSE131793 and GSE113439 datasets were combined for subsequent analyses, and batch effects were removed. Bioinformatic analysis was then performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis were then used to further filter the hub genes. Functional enrichment analysis of the intersection genes was performed using Gene Ontology (GO), Disease Ontology (DO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA). The expression level and diagnostic value of hub gene expression in pulmonary arterial hypertension (PAH) patients were also analyzed in the validation datasets GSE53408 and GSE22356. In addition, target gene expression was validated in the lungs of a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model and in the serum of PAH patients. RESULTS: A total of 914 differentially expressed genes (DEGs) were identified, with 722 upregulated and 192 downregulated genes. The key module relevant to PAH was selected using WGCNA. By combining the DEGs and the key module of WGCNA, 807 genes were selected. Furthermore, protein-protein interaction (PPI) network analysis identified HSP90AA1, CD8A, HIF1A, CXCL8, EPRS1, POLR2B, TFRC, and PTGS2 as hub genes. The GSE53408 and GSE22356 datasets were used to evaluate the expression of TFRC, which also showed robust diagnostic value. According to GSEA enrichment analysis, PAH-relevant biological functions and pathways were enriched in patients with high TFRC levels. Furthermore, TFRC expression was found to be upregulated in the lung tissues of our experimental PH rat model compared to those of the controls, and the same conclusion was reached in the serum of the PAH patients. CONCLUSIONS: According to our bioinformatics analysis, the observed increase of TFRC in the lung tissue of human PAH patients, as indicated by transcriptomic data, is consistent with the alterations observed in PAH patients and rodent models. These data suggest that TFRC may serve as a potential biomarker for PAH.

Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.

The impact of renaming schizophrenia on destigmatization: The Asian experience.

The term "schizophrenia" can indeed carry stigmatizing connotations. Proposals to rename schizophrenia have emerged as a potential strategy to alleviate this stigma, but the impact of such a change is not yet fully understood. In several Asian countries that have adopted a new name for schizophrenia, there is evidence that renaming is associated with improved attitudes towards individuals with schizophrenia and an increased willingness to disclose diagnoses. However, the portrayal of schizophrenia in the media seems unaffected by these name changes. In other countries where "schizophrenia" is still the standard term, alternative names have been suggested, but research on their effectiveness in reducing stigma shows mixed results. Mental health professionals frequently support a name change, recognizing the term's negative implications. However, it is crucial to recognize that a mere semantic revision, devoid of substantial conceptual alterations, may only offer a temporary decrease in stigma. Thus, renaming schizophrenia, coupled with a re-conceptualization of the disorder, may be a constructive step toward reducing its stigmatization.

Catechol compounds as dual-targeting agents for fish protection against Ichthyophthirius multifiliis infections.

Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.

Unraveling Halogen Role in Two-Step Solution Growth of Organic-Inorganic Hybrid Mixed-Halide Perovskites: Guidelines of Fabricating Single-Phase Perovskites with Predictable Stoichiometry.

The challenge faced in optoelectronic applications of halide perovskites is their degradation. Minimizing material imperfections is critical to averting cascade degradation processes. Identifying causes of such imperfections is, however, hindered by mystified growth processes and is particularly urgent for mixed-halide perovskites because of inhomogeneity in growth and phase segregation under stresses. To unravel two-step solution growth of MAPbBr x I3-x , we monitored the evolution of Br composition and found that the construction of perovskite lattice is contributed by iodine from PbI2 substrate and Br from MABr solution with a 1:1 ratio rather than a 2:1 ratio originally thought. Kinetic analysis based on a derived three-stage model extracted activation energies of perovskite construction and anion exchange. This model is applicable to the growth of PbI2 reacting with a mixed solution of MABr and MAI. Two guidelines of fabricating single-phase MAPbBr x I3-x with predictable stoichiometry thus developed help strategizing protocols to reproducibly fabricate mixed-halide perovskite films tailored to specific optoelectronic applications.

Current treatment of biliary Sphincter of Oddi Dysfunction.

The sphincter of Oddi is a delicate neuromuscular structure located at the junction of the biliary-pancreatic system and the duodenum. Sphincter of Oddi Dysfunction (SOD) can result in various clinical manifestations, including biliary-type pain and recurrent idiopathic pancreatitis. The management of SOD has been challenging. With the publication of the landmark Evaluating Predictors and Interventions in Sphincter of Oddi Dysfunction (EPISOD) trial and the Rome IV consensus, our clinical practice in the treatment of SOD has changed significantly in recent years. Currently, the management of type II SOD remains controversial and there is a lack of non-invasive therapy options, particularly for patients not responding to endoscopic treatment. In this mini review, we aimed to discuss the current knowledge on the treatment of biliary SOD.

Proteome-Wide Multicenter Mendelian Randomization Analysis to Identify Novel Therapeutic Targets for Lung Cancer.

INTRODUCTION: Lung cancer (LC) remains a leading cause of cancer mortality worldwide, underscoring the urgent need for novel therapeutic targets. The integration of Mendelian randomization (MR) with proteomic data presents a novel approach to identifying potential targets for LC treatment. METHODS: This study utilized a proteome-wide MR analysis, leveraging publicly available data from genome-wide association studies (GWAS) and protein quantitative trait loci (pQTL) studies. We analyzed genetic association data for LC from the TRICL-ILCCO Consortium and proteomic data from the Decode cohort. The MR framework was employed to estimate the causal effects of specific proteins on LC risk, supplemented by external validation, co-localization analyses, and exploration of protein-protein interaction (PPI) networks. RESULTS: Our analysis identified five proteins (TFPI, ICAM5, SFTPB, COL6A3, EPHB1) with significant associations to LC risk. External validation confirmed the potential therapeutic relevance of ICAM5 and SFTPB. Co-localization analyses and PPI network exploration provided further insights into the biological pathways involved and their potential mechanistic roles in LC pathogenesis. CONCLUSION: The study highlights the power of integrating genomic and proteomic data through MR analysis to uncover novel therapeutic targets for lung cancer. The identified proteins, particularly ICAM5 and SFTPB, offer promising directions for future research and development of targeted therapies, demonstrating the potential to advance personalized medicine in lung cancer treatment.

Determining cut-off values and predictors for the Snaith-Hamilton Pleasure Scale: comparison between clinical and school settings.

BACKGROUND: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. AIMS: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. METHOD: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. RESULTS: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. CONCLUSIONS: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Distribution and Severity of Cervical Intraepithelial Neoplasia in Women With Different Human Papillomavirus: An Analysis From Liaoning Province of Northeastern China.

OBJECTIVE: Persistent infection with high-risk human papillomavirus (HPV) is a key contributor to cervical intraepithelial neoplasia (CIN), but the relation between high-risk HPV genotypes and the location of CIN lesions remains unclear. The aims of this study were to investigate the most frequent biopsy site of CIN lesions in women with different HPV infection and to analyze the biopsy times, CIN frequency, and the clustering of CIN frequency based on 12-o'clock sites and cervical quadrant locations. MATERIALS AND METHOD: We conducted a retrospective study of HPV detection and genotyping at the virology department of our hospital. Colposcopy exams were performed by specialists according to a standardized protocol, and all visually abnormal areas were further biopsied. Pearson chi-squared tests and cluster analyses were implemented to analyze the data. RESULTS: Among 1,381 women enrolled in this study, 933 cases infected with HPV. HPV16, HPV58, and HPV18 were the most common genotypes. The most frequent biopsy site was the 6 o'clock position. The highest frequency of high-grade CIN findings in single-genotype HPV groups was the 6 o'clock position and that for multiple-genotype HPV group was the 12 o'clock location. All CIN clusters were found in the 6 and 12 o'clock biopsy sites, except in the HPV18 group. Quadrant 2 and 4 were clustered in most groups. CONCLUSIONS: The 6 and 12 o'clock sites in cervical quadrant 2 and 4 should be targeted during cervical biopsy procedures. These findings can provide clinicians with specific recommendations on the optimal site for CIN biopsy when considering the HPV genotype.