This study aimed to examine the relationship between affective lability, pre-sleep social-media engagement, and suicide-attempt vulnerability among adolescents. This cross-sectional study included 159 adolescents aged 10-17 years, of whom 66 had a suicide-attempt history, and 93 controls. Affective lability was measured using the Children's Affective Lability Scale, and pre-sleep social-media engagement was assessed with two investigator-developed items on duration of social-media use and difficulty disengaging before sleep. Mann-Whitney U tests and binary logistic regression models adjusted for age, sex, and sexual-minority status were used to identify group differences and predictors of suicide-attempt history. Adolescents with a suicide-attempt history showed higher affective lability (median = 36.5 vs. 12) and greater pre-sleep social-media engagement, reflected in both longer time spent on social media before sleep (median = 60 vs. 30 min, p = .016) and greater difficulty disengaging at bedtime (median = 5 vs. 4, p = .004). In regression analyses adjusting for age, sex, and sexual-minority status, both affective lability (OR = 1.05, 95% CI [1.03-1.08], p < .001) and pre-sleep social-media engagement (OR = 1.71, 95% CI [1.06-2.76], p = .029) independently predicted suicide-attempt history. Sexual-minority status further elevated risk (OR = 9.33, 95% CI [3.95-22.01], p < .001). The full model demonstrated strong discrimination (AUC = 0.861, 95% CI [0.802-0.920]) and good calibration. Findings indicate that affective lability and pre-sleep social-media engagement each uniquely predict suicide-attempt vulnerability among adolescents, underscoring their relevance as potential markers of suicide risk.
Suicide is a complex and multidimensional public health problem that affects hundreds of thousands of people worldwide every year. This study was conducted to evaluate traumatic experiences and coping strategies from the perspective of individuals with repeated suicide attempts. Using a phenomenological design from qualitative research methods, this study was conducted with 18 individuals with repeated suicide attempts. Criterion sampling method, one of the purposeful sampling methods, was used in the study. Interviews continued until data saturation was achieved. All interviews were recorded with a voice recorder and then transcribed. The research data were analyzed using Colaizzi's phenomenological method, and the research was conducted and reported in accordance with the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist. Three main themes (traumatic life events, psychological trauma and affect, coping strategies) and nine sub-themes (abuse, neglect, family dynamics, social problems, feelings of worthlessness and emptiness, anger and inner conflict, hopelessness and burnout, functional pathways, and hopeful steps) were obtained. This study highlights the multidimensional nature of suicidal behavior by revealing that repeated suicide attempts are closely related to traumatic events experienced by individuals, intense emotional processes, and the coping strategies they use.
This study investigated the relationship between hematological inflammatory parameters and suicidal behavior by examining their levels before and at the time of referral, exploring their potential use as early indicators in assessing suicide risk. Our sample consisted of 454 individuals who visited the emergency department due to suicidal behavior and 451 control individuals of similar age and gender. Routine hematological parameters(neutrophils, monocytes, lymphocytes, platelets) and indices calculated from these values, such as NLR, MLR, PLR, SII, and SIRI, were evaluated both in the period prior to the year of presentation and at the time of presentation. Clinical characteristics and inflammatory parameters were analyzed for suicide attempts and completed suicides. Logistic regression analyses were performed to assess between-group differences, individual changes over time, and factors predicting suicidal behavior. In our study, inflammatory parameters were significantly elevated in the suicide behavior group(p<0.001). MLR and SIRI levels showed the strongest association with suicide attempts. Logistic regression analysis revealed that high MLR levels prior to admission increased the risk of suicide attempts by 25 times(OR = 25.2), while high monocyte levels at admission increased this risk by 8 times(OR = 7.7). Suicide-related mortality was associated with male gender, the presence of additional physical illnesses, and the absence of psychiatric evaluation. High MLR(OR = 12.202, p=0.007) and monocyte(OR = 13.113, p< 0.001) levels at the time of admission significantly predicted mortality. Our findings support the presence of chronic low-grade inflammation in suicidal behavior and indicate that these parameters have the potential to be used as accessible and low-cost biomarkers in the assessment of suicide risk.
To evaluate the efficacy of a modified pressure-reducing fixation protective nasal strip in preventing device-related pressure injuries and improving nursing outcomes in patients undergoing high-flow nasal cannula (HFNC) therapy. This study included 60 patients receiving HFNC therapy from January 2024 to September 2024. Participants were randomly divided into an observation group (n = 30), which used the modified decompression fixation protective nasal strip, and a control group (n = 30), which underwent standard care with hydrocolloid dressing protection. The study compared general demographic data, the interval between fixation strap changes, frequency of catheter position adjustments, skin management effectiveness (Braden score), number of ineffective oxygenation attempts, incidence of adverse events, and patient comfort scores. The 2groups were comparable in baseline characteristics (p > 0.05). The observation group showed longer intervals between fixation strap changes, fewer catheter position adjustments, fewer ineffective oxygenation attempts, and a lower incidence of adverse events relative to the control group (p < 0.05). Furthermore, the observation group had significantly higher Braden scores and comfort levels than those in the control group (p < 0.05). The modified pressure-reducing fixation protective nasal strip is effective in reducing device-related complications and enhancing patient comfort during HFNC therapy.
Suicide is a critical global public health issue, with millions experiencing suicidal ideation (SI) each year. Global estimates suggest that the lifetime prevalence of SI ranges between 9% and 12% worldwide, underscoring the scale of this public health concern. Online platforms, such as Reddit, provide spaces where individuals express suicidal thoughts and seek peer support. While prior computational research has leveraged machine learning and natural language analysis to detect SI, much of it lacks grounding in psychological theory, limiting interpretability and intervention design. This study applied the Interpersonal Theory of Suicide (IPTS) to understand the underlying psychosocial mechanisms driving high-risk suicidal intent in online spaces, analyze linguistic expressions of SI, and assess the role of artificial intelligence (AI) systems in providing supportive responses. We analyzed 59,607 posts from Reddit's r/SuicideWatch community. Posts were categorized into 4 SI dimensions (ie, loneliness, lack of reciprocal love, self-hate, and liability) and 3 IPTS-based risk factors (ie, thwarted belongingness, perceived burdensomeness, and acquired capability for suicide). High-risk posts were operationalized based on the language markers of suicidal planning, attempts, and explicit intent. We further conducted psycholinguistic and content analyses of supportive responses and evaluated AI chatbot-generated replies for structural coherence and empathy. High-risk SI posts contained frequent references to planning and attempts, methods and tools, and expressions of weakness and pain, patterns that are consistent with theoretical expectations regarding the progression of suicidal capability. Supportive peer responses varied significantly across SI stages (P<.001), with deeper empathy and self-disclosure emerging in replies to high-risk posts. Compared with online community responses, AI-generated replies showed higher semantic similarity (Cohen d=0.20) and linguistic style accommodation (Cohen d=0.08), but substantially lower diversity (Cohen d=-0.31); empathy differences were minimal in the most context-rich prompting condition. Expert evaluators further noted that AI responses often lacked contextual personalization and emotional depth. Grounding computational analysis in IPTS provides richer theoretical insight into SI expressed online. While AI-based systems can enhance the structural and linguistic quality of supportive messages, they currently lack the nuanced empathy and contextual awareness needed for effective mental health support. These findings highlight the need for theory-driven, human-AI collaborative frameworks in suicide prevention research and interventions.
Embryo aneuploidy increases substantially with maternal age, contributing to implantation failure and miscarriage. Conventional morphological assessment cannot determine euploidy. Non-invasive preimplantation genetic testing (ni-PGT) evaluates cell-free DNA in spent embryo culture medium, potentially improving embryo selection without trophectoderm biopsy. Robust evidence of clinical benefit in women aged 35-42 years remains limited. This is a multicentre, open-label, parallel-group randomised controlled trial conducted in three centres in China. Infertile women aged 35-42 years undergoing their first intracytoplasmic sperm injection cycle and having ≥2 good-quality days 5-6 blastocysts (Gardner grade ≥4BC,defined as an expansion grade of at least 4, with an inner cell mass grade of B or better and a trophectoderm grade of C or better) will be randomised 1:1 to ni-PGT-guided embryo selection or conventional morphology-based selection. Randomisation will be stratified by study centre using variable permuted block sizes of 4 and 6 and implemented through a unified centralised randomisation system. After a multicentre set-up period for investigator training and harmonisation of spent culture-medium sampling procedures, during which no participant was enrolled or randomised, recruitment and randomisation commenced on 14 February 2025 at the lead site; additional sites started recruitment after local ethics approval and site initiation. A freeze-all strategy will be applied; frozen-thawed single blastocyst transfer will start from the second menstrual cycle after oocyte retrieval.For the primary endpoint, embryo transfers using embryos from the index retrieval cycle that occur within 12 months after randomisation and within the first three frozen-thawed single embryo transfer attempts will contribute to the cumulative outcome, whichever occurs first. Clinical care will not be restricted beyond this prespecified analysis range. The primary outcome is the cumulative ongoing pregnancy rate within 12 months after randomisation, defined as the proportion of participants achieving at least one ongoing pregnancy (clinical pregnancy continuing to ≥12 weeks' gestation) following a qualifying embryo transfer within the prespecified analysis range. Key secondary outcomes include early miscarriage rate (<12 weeks) in the first transfer cycle, biochemical and clinical pregnancy, time to live birth, number of transfers to live birth, pregnancy/perinatal complications, neonatal birth weight and congenital anomalies. The primary analysis will follow the intention-to-treat principle, comparing groups using relative risks with 95% CIs. A total of 354 participants (177 per group) will be recruited. The trial will be conducted according to the Declaration of Helsinki. Ethics approval has been obtained from all participating centres before participant recruitment at each site. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publication and conference presentations. ChiCTR2400088283.
Percutaneous mitral commissurotomy (PMC) remains the standard therapy for rheumatic mitral stenosis, although decreasing disease prevalence in developed countries has reduced operator familiarity. Advancing the Inoue balloon across the mitral valve continues to pose a technically demanding step that may extend procedures or result in unsuccessful attempts. We describe 2 cases of severe mitral stenosis successfully treated with PMC using a zero-exchange-wire technique. Transseptal puncture was performed under transesophageal echocardiography guidance using the VersaCross radiofrequency system. The same preshaped 0.035-inch radiofrequency wire was advanced across the mitral valve into the left ventricle, guided by the steerable sheath. The Inoue balloon was then slenderized and delivered over the wire after septal dilatation. Sequential inflations were performed over the wire, achieving optimal results. In summary, we describe a modified over-the-wire technique for PMC that most structuralists are familiar with, using dedicated Inoue balloons, obviating the need for wire exchange, with shorter procedural time and no safety concerns.
Preoperative percutaneous transhepatic portal vein embolization is used to induce future liver remnant hypertrophy before major hepatectomy in perihilar cholangiocarcinoma. We report a patient who developed peritoneal nodules along the suspected transhepatic puncture route after right-sided percutaneous transhepatic portal vein embolization. Histopathology showed adenocarcinoma consistent with the primary tumor. The spatial distribution and timing were considered more suggestive of tract-related seeding from bile leakage rather than hematogenous spread. This rare but serious complication warrants preventive strategies, including careful route planning, strict avoidance of bile contamination, minimization of puncture attempts, and secure tract closure.
Drosophila models have proven invaluable for studying skeletal and cardiac muscle diseases. While permeabilized indirect flight muscle (IFM) and jump muscle fibers from Drosophila yield insightful mechanical data, these preparations cannot resolve the kinetics of activation and relaxation because calcium diffusion into the fiber core is rate-limited at this scale. In contrast, myofibrils have a diameter of only 1-3 μm, making them ideal for measuring physiologically relevant activation and relaxation rates. However, previous attempts using IFMs failed to produce myofibrils that generated measurable active force, likely due to the muscle's inherently low force output. Therefore, instead of using IFMs as the source, we developed a method to isolate myofibrils from the Drosophila jump muscle. By applying brief, low-amplitude sonication to permeabilized jump muscles, we isolated myofibrils that produced 19.8 ± 10.5 mN/mm2 net active tension, the first active force measurements from an insect myofibril, with an activation rate of 8.2 ± 4.0 s-1. Jump muscle myofibrils exhibited the typical biphasic relaxation seen in vertebrates: an initial slow, linear phase lasting 76 ± 2 ms, followed by a fast exponential decay with a rate constant of 19.7 ± 9.6 s-1. We also characterized myofibrils from jump muscles transgenically expressing a Drosophila larval body wall myosin isoform (EMB), which we previously reported displays slower actin-binding and detachment kinetics. EMB expression caused a 1.6-fold increase in active tension and a 38% slower activation rate compared to controls, but did not change relaxation parameters. These characterizations and comparisons highlight the scientific value of expressing customizable sarcomeric proteins in transgenic Drosophila jump muscle myofibrils to elucidate their contributions to muscle activation and relaxation.
In patients with anticipated difficult airways, suboptimal airway management may increase perioperative morbidity and mortality. Combining video laryngoscopy (VL) with a flexible intubation scope (FIS) has been shown to enhance visualization and facilitate endotracheal tube passage in patients with known or anticipated difficult airways. To date, randomized evidence supporting this approach remains limited. In this prospective, randomized trial, 135 adults with anticipated difficult airways undergoing elective surgery were randomized 1:1 to intubation with FIS alone or a combined technique using FIS with VL (FIS/VL). The primary end point was the composite rate of difficult endotracheal tube (ETT) placement, defined by one or more of the following: (1) first-attempt intubation time >60 seconds; (2) failure to intubate on the first attempt; or (3) provider assessment of the intubation process as difficult. Provider-rated ease of intubation was recorded immediately following the procedure by the anesthesiologist performing the intubation using a 5-point Likert scale. Scores of 1 (extremely easy), 2 (somewhat easy), and 3 (resistance to tube advancement) were classified as Not Difficult, whereas scores of 4 (difficult) and 5 (unsuccessful) were classified as Difficult/Unsuccessful. For analysis and reporting, the Likert-scale ratings were dichotomized into a binary outcome (Not Difficult vs Difficult/Unsuccessful). The secondary outcome was total intubation time. A total of 144 patients were screened and enrolled, and 135 patients were randomized. Of these, 66 patients were assigned to the FIS/VL arm and 69 patients to the FIS arm. Among the 135 randomized patients, 128 provided analyzable data for the composite primary end point. Overall, the first-pass success rate was 54/58 (93.1%) in the FIS/VL group versus 50/64 (78.1%) in the FIS group; P = .020. Intubation time greater than 60 seconds was similar between groups (33/66 [52.4%] in the FIS arm vs 24/61 [39.3%] in the FIS/VL arm; P = .145). Provider-rated ease of intubation considered difficult or unsuccessful occurred in 4/64 (6.1%) of FIS/VL compared to 13/67 (19.4%) of FIS cases (P = .025). Among the 128 evaluable patients (61 FIS/VL, 67 FIS), the composite primary end point- difficult ETT placement defined as (1) first-attempt intubation time >60 seconds, (2) failure on first attempt at intubation, or (3) provider-rated difficult intubation occurred in 28/61 (45.9%) of FIS/VL versus 40/67 (59.7%) of FIS cases [Risk difference (95% CI) = -0.14 (-0.31 to 0.03); P = .118]. In adults with anticipated difficult airways, adding VL to FIS did not significantly reduce the composite rate of difficult ETT placement, although it was associated with fewer repeat attempts and fewer provider-rated difficult/unsuccessful intubations. These findings support the clinical value of dual-visualization strategies to improve first-pass performance metrics, whereas larger trials are needed to determine their effect on composite difficulty end points.
The prevalence of overweight and obesity is increasing, which may lead to adverse health-related outcomes and severe economic burdens. Therefore, early attempts to find the intervention targets to reduce its prevalence are important. This study aimed to identify the association of lifestyle behaviors with overweight and obesity in Shenzhen, China. This population-based cross-sectional survey was conducted in Longhua District, Shenzhen. Data on socio-demographic information, lifestyle behaviors, and disease-related characteristics were collected. The body mass index (BMI) value was calculated by using weight in kilograms (kg) divided by the square of height in meters (m2). A BMI value of 24.0-28.0 and ≥28.0 kg/m2 was considered as overweight and obesity, respectively. Multivariable logistic regression analyses were used to identify the independent associations of lifestyle factors with overweight/obesity. Subgroup and moderation analyses were performed to examine the potential modifying effects of age, sex, marital status, and income level. A total of 1,429 participants were included in this study. The prevalence of overweight/obesity was 46.5% [95% confidence interval (CI): 43.9-49.1%]. Multivariable analyses showed those who did not consume spicy food daily [adjusted odds ratio (aOR) = 0.76, 95% CI: 0.59-0.96] and those who napped for 1-30 min per day (aOR = 0.64, 95% CI: 0.46-0.88) were at a lower risk of overweight/obesity. Subgroup analyses showed that the association between daily nap duration and overweight/obesity was moderated by sex and marital status. Almost half of the general adults in Shenzhen were obese or overweight. Daily nap duration and the frequency of spicy food consumption may be served as intervention targets.
The Editor in Chief and the Publisher are issuing an expression of concern regarding the following article: Minozzi M, Nordio M, Pajalich R. The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):537-40. PMID: 23467955. Post-publication concerns have been raised regarding the reliability of certain data and statistical analyses, including possible inaccuracies in the reported p-values, missing ethics approval information, and a potentially undeclared conflict of interest. The journal contacted the authors requesting clarification and supporting documentation regarding the issues outlined above, but no response has been received despite several follow-up attempts. The journal has therefore decided to issue this Expression of Concern to alert readers that these matters remain unresolved. Readers are advised to interpret the findings of the article with caution. Further updates will be provided if additional findings emerge from the ongoing investigation. The Publisher apologizes for any inconvenience this may cause.
Desmoplastic Small Round Cell Tumor (DSRCT) is an ultra-rare, highly aggressive sarcoma that predominantly affects young individuals. DSRCT is defined by the characteristic chromosomal translocation t(11;22) (p13;q12), which results in the oncogenic EWSR1::WT1 fusion gene. DSRCT typically presents as multiple, disseminated nodules within the abdominopelvic cavity. Patients with DSRCT typically receive an intensive multimodal treatment regimen comprising multi-agent chemotherapy, extensive cytoreductive surgery, that could be followed by whole abdominopelvic radiotherapy. Attempts to improve patient outcomes over the past two decades have yielded limited results, leading to a persistent lack of improvement in prognosis. There is an urgent, unmet clinical need for innovative and effective treatments guided by a deeper understanding of DSRCT biology. Recent efforts have successfully generated extensive multi-omic data and a growing number of patient-derived models. This information has deepened our understanding of the EWSR1::WT1 translocation's oncogenic mechanisms and revealed critical DSRCT dependencies, leading to the identification of several putative therapeutic targets. Clinical translation of these findings as well as conduction of further preclinical research requires an international, multidisciplinary collaborative effort to propel preclinical and clinical studies. This review was conducted by the DSRCT Working Group of OCTOPUS ("Optimising Combination Therapy fOr Paediatric, adolescent and yoUng adult patients with non-rhabdomyosarcoma soft tissue Sarcomas") to consolidate existing knowledge on preclinical translational aspects of DSRCT and guide future cooperative research.
Mussel foot proteins (Mfps) hold immense potential for medicine and bioengineering, owing to their exceptional adhesion and biocompatibility. However, traditional extraction from mussels is low-yield and ecologically unsustainable. While microbial synthesis offers a green alternative, the intrinsic hydrophobicity and adhesiveness of Mfps often induce severe host cytotoxicity, resulting in low yields. Initially, attempts to express Mcofp-3 in Escherichia coli were limited to 60 mg L-1 due to such cytotoxic effects. To overcome this bottleneck, we developed a hyaluronic acid (HA)-driven "condensate-based sequestration" strategy. This approach leverages electrostatic interactions to sequester Mcofp-3 into condensates, thereby shielding the host cells and alleviating metabolic stress. This strategy significantly restored cell viability, increasing the titer to 460 mg L-1 in shake flasks. Moreover, the process was successfully scaled up to a 50 L fed-batch fermentation, achieving a final titer of 1.6 g L-1. Following production, in vitro 3,4-dihydroxyphenylalanine (DOPA) modification was performed using immobilized TyrVs-CipA, yielding functional Mcofp-3 that exhibited anti-inflammatory activity and enhanced cell migration capabilities. This work establishes a versatile, green paradigm for the high-yield production of proteins with low yields and increased toxicity in bacterial expression systems. Mussel foot proteins (Mfps) are prized bio-adhesives for medical applications, yet their supply remains limited. Harvesting mussels is environmentally unsustainable, while microbial synthesis is challenging due to the severe toxicity of these proteins to host cells. In this study, we developed a "condensate-based sequestration" strategy to overcome this bottleneck. By employing hyaluronic acid to isolate the toxic proteins within the bacteria, we shielded the host cells and achieved high-yield production. This approach enabled the gram-scale synthesis of modified Mfps with desirable bioactivity. Beyond synthesizing Mfps, this strategy establishes a versatile, green platform for manufacturing a wide range of other "difficult-to-express" toxic proteins that are currently commercially unviable.
The definition of activity cliffs (ACs) depends on compound similarity and activity difference criteria and on activity data types. ACs are usually defined as pairs or groups of structurally similar compounds or structural analogues that are active against the same target, but have large differences in potency (requiring numerical potency values, preferably equilibrium constants). In addition, ACs have also been defined as pairs of structural analogues that are active or inactive in screening assays. In medicinal chemistry, ACs are of particular interest because they often reveal structure-activity relationship (SAR) determinants during compound optimization. In cheminformatics, ACs present challenging test cases for machine learning (ML) and activity predictions because they represent an extreme form of SAR discontinuity in compound data sets. Given their composition, ACs are notoriously difficult to predict based on chemical structure representations. Various attempts have been made to predict compound pairs forming ACs or the activity of AC compounds via ML, often reporting high accuracy. However, in the absence of data leakage from training to test sets, AC prediction accuracy based on chemical structure is low or moderate at best. As an alternative to structural representations, biological/functional compound descriptors might be considered such as biological assay profiles, which have been investigated for other compound activity prediction. In this work, we report the prediction of AC compounds based on bioactivity profiles derived from a compound profiling matrix using data partitioning schemes designed to control information or data leakage during ML. Under these stringent conditions, AC compound predictions based on bioactivity profiles often failed. However, we also observed subsets of highly accurate predictions and explored in detail why these predictions succeeded, but others failed. The analysis revealed a critically important role of assay similarity for successful AC compound predictions. Most profile assays did not measurably influence the predictions. By contrast, accurate predictions mostly depended on the presence of one or at most a few profile assays that were similar to test assays. In most cases, these profile assays could be identified and exploited for predictions by nearest neighbor searching, thus putting ML performance into perspective.Scientific contribution As an alternative to the generally difficult prediction of ACs based on chemical structure, we introduce prediction of AC compounds based on bioactivity profiles. We show that accurate activity predictions of AC compounds do not depend on the global information content of assay profiles, but are largely determined by nearest neighbor relationships between profile and test assays.
Suicidal ideation affects 10% of primary care patients. Although guidelines recommend screening, few tools are suitable for use in this setting, and protective factors are often overlooked. This study aimed to develop a brief questionnaire to assess suicidality in primary care. The Suicide Prevention for Primary Care Questionnaire (SuPr-10) was validated in 521 participants with a PHQ-9 score ≥ 6 across six subsamples. Its structure was analyzed using exploratory and confirmatory factor analysis, item analysis, and psychometric evaluation. Diagnostic accuracy was assessed via logistic regression and ROC analysis, and patient acceptance was measured in a follow-up survey. A two-factor structure with ten items was identified: I. protective scale (ω = .817) and II. risk scale (ω = .928), showing strong correlations with suicidality (r = -.529, .854) and depression (r = -.736, .626) scales. SuPr-10 showed acceptable discriminatory ability for identifying individuals with a history of suicide attempts (AUC = .765; 83% sensitivity, 56% specificity). It provides a structured assessment of suicidal tendencies and protective factors in primary care patients with depressive symptoms, supporting clinical decision-making and resource-focused communication. These findings are based on a clinically enriched, German-speaking sample, do not imply prospective prediction of suicidal behavior, and require validation in broader primary care populations.
Hepatocellular carcinoma (HCC) is a highly aggressive disease associated with a poor prognosis. The present study attempts to discover the potential of esculentoside A (EsA) in inhibiting HCC progression. Cell viability was assessed using the Cell Counting Kit-8 assays. At the same time, stemness and malignant behaviors were evaluated through sphere formation, Western blot (WB), flow cytometry, colony formation assays, and TUNEL. EsA treatment suppressed HCC cell proliferation, migration, invasion, and stemness in vitro and tumor growth in vivo. Bioinformatics identified retinoic acid receptor-related orphan receptor beta (RORB) as a potential target of EsA, and EsA induced RORB expression in HCC cells. EsA also inhibited Wnt signaling activity, as shown by TOP/FOP Flash assays and WB. Knockdown of RORB through lentivirus infection reversed the effects of EsA. At the same time, Wnt pathway inhibitor rescued the promotive role of RORB knockdown in HCC malignant behaviors, suggesting that EsA inhibited HCC progression via the RORB/Wnt axis. RORB expression was reduced and associated with higher Wnt signaling in tumor tissues from patients with HCC, and low RORB expression showed significant correlation with higher TNM staging in HCC patients. This study offers novel insights into the molecular mechanism of EsA in HCC.
Ventilator dependence is a major cause of morbidity and mortality in patients with high cervical spinal cord injury (CSCI), largely due to diaphragmatic dysfunction. Conventional assessment of inspiratory muscle strength, such as maximal inspiratory pressure (MIP), is often unreliable in this population because it requires adequate patient cooperation. Objective bedside tools to evaluate diaphragmatic function are therefore essential to guide ventilator weaning and clinical decision-making. We report the case of a 29-year-old man with high CSCI who developed acute respiratory failure and repeated weaning failure after cervical spine surgery. Serial MIP measurements could not be obtained despite initial spontaneous breathing, limiting volitional assessment of diaphragmatic function. Bedside diaphragmatic ultrasound was performed serially to assess diaphragmatic thickness, thickening fraction (TF), and excursion. Ultrasound demonstrated absent diaphragmatic excursion during unsupported breathing and progressively reduced TF despite ventilatory support, consistent with severe diaphragmatic dysfunction. These findings supported the decision to proceed with early percutaneous tracheostomy after failed extubation attempts. Diaphragmatic ultrasound provided an objective, noninvasive assessment of diaphragmatic function when volitional measures were unreliable, directly informing ventilatory management in a patient with high CSCI (C5 AIS B). This case highlights the clinical value of serial diaphragmatic ultrasound in complex weaning scenarios, suggesting its potential role in respiratory and rehabilitation care to guide timely decisions such as early tracheostomy.
Adolescent depressive disorder is a clinically heterogeneous condition with poorly understood molecular mechanisms. Protein N-glycosylation, a key post-translational modification involved in immune regulation and neuronal communication, has not been systematically investigated across depressive subtypes in youth. Understanding glycosylation alterations may reveal novel biochemical pathways underlying disease heterogeneity and pathophysiology. We applied a site-specific glycoproteomic approach integrating liquid chromatography-tandem mass spectrometry (LC-MS/MS) and StrucGP to profile serum N-glycosylation in adolescents with major depressive disorder (MDD), MDD with non-suicidal self-injury (NSSI), and MDD with suicide attempts (SA), compared with healthy controls. Serum samples were pooled by group (10 individuals per pool), and glycan alterations were identified using predefined fold-change thresholds. This approach is classified as an exploratory research strategy, which does not support statistical inference. All depressive subtypes displayed shared alterations, characterized by reduced bi-antennary glycans and LacNAc/Lewis structures, alongside elevated tetra-antennary sialylation, particularly N6H7S4. Candidate subtype-associated patterns were also observed: increased tri-antennary sialylation in NSSI, and selective upregulation of N6H7S4 on ORM2 in SA. Differentially glycosylated proteins, including SERPING1 and A2M, were enriched in immune, complement, and coagulation pathways. Notably, protein-level changes were minimal in label-free quantification, suggesting glycan-specific dysregulation. This exploratory study identifies candidate subtype-dependent alterations in N-glycosylation in adolescent depression, which may implicate glycan-mediated immune and neuroinflammatory mechanisms in its molecular heterogeneity. This study provides a preliminary, pooled-sample based catalog of candidate site-specific N-glycosylation alterations for adolescent depression, warranting validation in larger, individual-level cohorts.
Intracardiac thrombi are a rare manifestation of antiphospholipid syndrome (APS), with biventricular involvement being exceedingly uncommon. A 70-year-old woman with recent Takotsubo cardiomyopathy was admitted with cardiogenic shock. Imaging demonstrated large biventricular thrombi. Initial laboratory testing was consistent with probable APS. Inotropic support and anticoagulation were initiated. After failed attempts to wean inotropes, the patient elected hospice care. This case highlights the diagnostic uncertainty and limited evidence guiding management of extensive intracardiac thrombosis in patients with suspected APS presenting with cardiogenic shock. Beyond anticoagulation, the evidence base for managing intracardiac thrombi in probable APS is limited to case reports, and there are large risks associated with invasive strategies for removing intracardiac thrombi. Rapid development of extensive multichamber intracardiac and systemic thrombosis should prompt evaluation for APS. Anticoagulation remains the cornerstone of therapy; evidence guiding invasive strategies is limited.