One-lung ventilation (OLV) is used to isolate one lung during thoracic surgery, but manipulation and positioning can affect heart-lung interaction. Cardiomegaly may exacerbate these changes, especially in the left lateral decubitus (LLD) position.

To investigate the effect of cardiomegaly on heart-lung interaction during OLV, particularly in the LLD position.

A 20-year-old male with recurrent spontaneous pneumothorax was scheduled for right-sided bronchopleural fistula repair via thoracotomy. The patient presented with cardiomegaly (cardiothoracic ratio 75%) and echocardiographic evidence of right ventricular and atrial dilation. In the LLD position, OLV led to desaturation when both lungs were ventilated, but oxygenation improved when only the left lung was ventilated.

Cardiomegaly alters heart-lung interaction during OLV, particularly in the LLD position. The enlarged heart exerts pressure on the left lung, impairing ventilation. When both lungs are ventilated in this position, ventilation is directed toward the right lung, reducing oxygenation and causing desaturation. However, restricting ventilation to the left lung improved oxygenation due to better lung compliance and less interference from the enlarged heart.

Cardiomegaly affects heart-lung interaction during OLV in the LLD position. Oxygenation improves when only the left lung is ventilated, likely due to less compression of the left lung. The supine position may further enhance oxygenation even with bilateral ventilation. This case highlights the importance of considering cardiomegaly in OLV management. This section should be written as per the CARE checklist item 3.

Hemophagocytic syndrome, also known as hemophagocytic lymphohistiocytosis (HLH), is a rare clinical disease that is highly challenging to diagnose, has a low long-term survival rate and a high mortality rate. Currently, due to the particularity of HLH and the lack of effective understanding of the severity and prognosis of the disease in clinical practice, HLH patients are often missed or misdiagnosed in clinical practice, causing them to miss the best opportunity for diagnosis and treatment. This study aimed to retrospectively summarize and analyze the clinical characteristics, diagnosis and treatment, and prognosis of HLH patients from four medical centers, aiming to explore the risk factors affecting the prognosis of HLH patients and further enhance the understanding of HLH.

The clinical data of 162 patients with HLH diagnosed in four medical centers from May 2017 to May 2025 were collected. The general conditions, laboratory results, diagnosis and treatment processes, and prognosis of these patients were analyzed, and univariate and multivariate analyses of prognostic factors were conducted.

A total of 162 HLH patients were included in this study, of whom 90 cases survived (55.56%), 72 cases died (44.44%), and there were 78 male patients (48.15%) and 84 female patients (51.85%), with a median age at onset of 52 years (range: 1-83 years). The most common etiological factor was Epstein-Barr virus (EBV) infection, and the primary presenting symptom was fever. First-line treatment primarily involved anti-infective therapy and symptomatic management, which was administered to 147 cases (90.74%). Prognostic analysis revealed that age, history of malignancy, infection history, presence of dermatological symptoms, APTT, INR, PCT, CRP, TG, TBIL, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, glucocorticoid monotherapy, gamma globulin treatment were significantly associated with patient outcomes in HLH. Tumor history, ferritin level, sCD25, lactate, SOFA score, time to treatment initiation, gamma globulin treatment were independent risk factors for mortality. Univariate Cox regression analysis identified that age, tumor history, history of rheumatic and autoimmune disorders, CRP, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, chemotherapy, glucocorticoid monotherapy, gamma globulin treatment were significant prognostic factors for OS in HLH patients. Multivariate analysis confirmed that tumor history, CRP, ferritin level, sCD25, lactate, SOFA score and time to treatment initiation, chemotherapy, glucocorticoid monotherapy, gamma globulin treatment were independent prognostic factors affecting OS in HLH patients. Age, APTT, INR, ferritin level, SOFA score, time to treatment initiation, glucocorticoid monotherapy, gamma globulin treatment were independent prognostic factors affecting OS in infection-triggered HLH patients. While age, INR, ferritin level, SOFA score, time to treatment initiation, chemotherapy were independent prognostic factors affecting OS in malignancy-associated HLH patients. Combined therapy regimens (especially chemotherapy combined with gamma globulin, glucocorticoid combined with gamma globulin) showed better clinical efficacy and survival benefits in the treatment of HLH.

HLH is a rare clinical disease, EBV was the predominant trigger for HLH. Prognostic factors differed between infection- and malignancy-associated subgroups. Combined regimens, particularly those including gamma globulin, offered superior survival benefits, underscoring the need for etiology-specific treatment strategies.

Histone deacetylase 6 (HDAC6) is a unique, predominantly cytoplasmic enzyme that regulates a broad spectrum of cellular and physiological processes, including cell proliferation, migration, intracellular transport, and differentiation. Its distinct structural configuration, comprising two catalytic deacetylase domains and a zinc finger ubiquitin-binding domain (ZnF-BUZ), enables HDAC6 to deacetylate a variety of non-histone substrates, such as α-tubulin, heat shock protein 90 (Hsp90), cortactin, and peroxiredoxin (Prdx). Furthermore, HDAC6 plays a key role in cellular stress responses and cell survival by facilitating the clearance of misfolded proteins, inducing autophagy, and modulating the unfolded protein response. Despite its cytoprotective roles, HDAC6 has emerged as a therapeutic target due to its involvement in multiple pathological pathways and age-related disorders. Tubastatin A (Tub A), a novel and highly selective HDAC6 inhibitor, demonstrates strong therapeutic potential against neurodegenerative, cardiovascular, autoimmune, metabolic, cancer, and other diseases. Tub A enhances the acetylation of both histone and non-histone proteins, thereby modulating gene expression and diverse cellular processes. It shows pharmacological effects, including anti-inflammatory, neuroprotective, anti-diabetic, anti-obesity, anti-oxidant, and other activities. Moreover, preclinical evidence suggests that Tub A effectively regulates multiple pathological pathways by inhibiting HDAC6, which contributes to ameliorating age-related disorders. Therefore, Tub A represents a promising epigenetic modulator with broad therapeutic relevance. Hence, further comprehensive and large-scale investigations are warranted to elucidate its clinical potential and its roles in disease management, as no clinical data related to Tub A activity are available. This review highlights the therapeutic potential of the selective HDAC6 inhibitor Tub A across various pathological conditions, discusses current preclinical findings, and outlines key challenges and future directions for clinical translation.

Silicosis is an irreversible, progressive occupational lung disease caused by chronic inhalation of crystalline silica (SiO₂), with no approved disease-modifying therapies currently available. Its pathological hallmark is a hostile fibrotic microenvironment driven by excessive reactive oxygen species (ROS), chronic inflammation, and mitochondrial dysfunction in alveolar epithelial type 2 (AEC2) cells; this microenvironment is the primary bottleneck for stem cell-based silicosis therapy, as it severely impairs the engraftment of exogenous AEC2 cells. Metformin (Met) exerts mitochondria-protective effects to preserve AEC2 function, but its clinical translation for silicosis is limited by low oral bioavailability and non-specific systemic distribution. Here, we developed a ROS-responsive biomimetic liposome (TK-PSBs@Met, also termed TPM NPs) for targeted Met delivery to AEC2s in fibrotic lungs, via a design combining pulmonary surfactant (PS)-mediated AEC2 targeting and thioketal (TK)-based ROS-triggered on-demand drug release. In vitro, TPM NPs reversed SiO₂-induced epithelial-mesenchymal transition (EMT), suppressed fibrotic and inflammatory responses, and restored mitochondrial function in A549 cells, a well-established AEC2 cell model. In vivo, TPM NPs significantly boosted the functional engraftment of TdTomato⁺ AEC2 stem cells, promoted alveolar regeneration, and attenuated collagen deposition and inflammation in SiO₂-induced silicosis mice. Mechanistically, TPM NPs mitigated silicotic fibrosis via a dual synergistic mechanism: remodeling the hostile fibrotic microenvironment and activating the AMPK/PGC-1α/NRF1/TFAM signaling axis to restore AEC2 mitochondrial biogenesis. Collectively, this TPM NP-AEC2 combinatorial therapy offers a translatable precision strategy for silicosis treatment and establishes a new paradigm for nanomedicine-augmented stem cell therapy in refractory fibrotic lung diseases.

Neonatal hypoxic-ischemic encephalopathy (NHIE) is a leading cause of morbidity and mortality in term infants. The anesthetic dexmedetomidine (Dex) has been shown to reduce brain damage. In this study, hypoxia-ischemia (HI) in neonatal rats caused significant cerebral infarction, neurological deficits, learning and cognitive impairments, inflammatory responses, and microglia polarization. Dex treatment mitigated HI-induced brain injury in rats. Lipopolysaccharide (LPS) increased inflammation in BV2 cells, elevated M1 polarization markers, and raised the proportion of M1 cells. Dex reduced inflammation and M1 polarization in BV2 cells. Rbm47 was identified as a target of Dex, being downregulated in NHIE rat brain tissues and upregulated by Dex. Rbm47 co-localized with microglia and was decreased as the microglia marker Iba-1 increased. Adenovirus-mediated overexpression of Rbm47 alleviated brain injury in NHIE rats and reduced microglial inflammation and M1 activation, both in vitro and in vivo. Conversely, knockdown of Rbm47 hindered the protective effects of Dex against BV2 cell inflammation and M1 polarization. This study indicates that Rbm47 mediates the protective effects of Dex against NHIE brain injury.

Cardiovascular diseases (CVD) stand as the primary cause of mortality and form the most prevalent disease category. Numerous studies have demonstrated that aging serves as a crucial pathogenic factor in the progression of CVD. Nevertheless, the molecular mechanisms underlying cardiovascular aging have not been fully elucidated. Research in various aging models has consistently shown that aging is attributed to the dysfunction of a complex transcriptional regulatory network that maintains the body's health, tissue homeostasis, and stress resistance. Transcription factors and chromatin regulatory factors are involved in almost all cellular activities, and an increasing amount of evidence indicates that as key regulatory elements, transcription factors and chromatin regulators control cellular senescence by regulating the transcription of related genes. Therefore, the aim of this review is to summarize the specific role of transcriptional regulation in the mechanism of cardiovascular aging, providing new strategies for the treatment of CVD.

Psychological interventions are recommended for people under Crisis Resolution Home Treatment Teams (CRHTTs). Non-registered psychology roles (Assistant Psychologists (APs) and Trainee Associate Psychological Practitioners (TAPPs)) are potentially both cost and clinically effective for delivering brief interventions in CRHTTs. This study aimed to quantitatively examine routine outcome change associated with two brief, skills-based interventions (the Crisis Toolbox (CTB) and the Emotion Coping Skills (ECS)) delivered by APs and TAPPs in one CRHTT. A retrospective service evaluation of 490 service users who accessed either the CTB or ECS between June 2020 and February 2025 was employed. The Clinical Outcomes in Routine Evaluation - 10 (Core-10) and Mental Health Confidence Scale (MHCS) measures were completed pre- and post- intervention. Paired samples t-tests were conducted and demographics (age, gender, and ethnicity) collected. There was a statistically significant effect in improving scores on both measures at the post-intervention timepoint (CORE-10: 8.636, 95% CI [7.810 to 9.461], t(297) = 20.586, p < .001; MHCS: -13.537, 95% CI [-14.827 to -12.237], t{293) = -20.568, p < .001). This significant effect remained when looking at males and females separately. Asian and Black ethnic groups were underrepresented in the sample compared to local demographics, whilst other ethnic groups showed similar representation. Findings suggest that CTB and ECS may be clinically effective in reducing distress and increasing confidence in coping with mental health challenges for service users. Additionally, this evaluation has highlighted the need for better understanding UK ethnic minority representation in CRHTTs and consideration of possible barriers to access.

Neurological disorders represent a leading cause of global mortality and disability, yet treatment options remain limited due to the challenges of targeting pathogenic proteins, particularly those considered "undruggable" by conventional small molecules. Targeted protein degradation (TPD) has expanded the druggable proteome by harnessing proteasomal and lysosomal pathway to eliminate these targets, offering the advantages of lower toxicity and reduced resistance compared to traditional modulation. This review systematically delineates TPD mechanisms according to their degradation pathways, including proteasomal, endosomal-lysosomal, and autophagy-lysosomal systems, and highlights their unique applications in brain diseases. However, the translation of TPD to neurological disease is limited by physicochemical liabilities, cell-type dependence, risks associated with whole-protein ablation, the blood-brain barrier (BBB) and poor brain bioavailability. To address these translational barriers, we emphasize the integration of TPD with drug delivery systems (DDS) as a pivotal strategy. By optimizing pharmacokinetics, stability, and BBB penetration, nano-DDS significantly enhances brain targeting and therapeutic precision. Finally, we evaluate recent progress in nano-TPD systems and offer critical insights into their future trajectory in treating complex brain disorders.

The study aimed to systematically interpret and synthesize data obtained from qualitative research on the life experiences of individuals with fecal incontinence.

A comprehensive literature search covering the years 2010 to 2023 was conducted on December 1, 2023, using the CINAHL, MEDLINE, PubMed, Web of Science, OpenAIRE, and OVID electronic databases. The search process followed PRISMA guidelines. The study was registered in PROSPERO (CRD42024507571).

Qualitative studies focusing on the life experiences of individuals with fecal incontinence were included. A total of 16 studies met the inclusion criteria and were incorporated into the meta-synthesis.

Relevant data from the included studies were systematically extracted, focusing on participants' experiences, perceptions, and coping mechanisms related to fecal incontinence.

Data were analyzed using thematic synthesis. Five analytical themes were identified: (1) the meaning of fecal incontinence for the individual, (2) perceived barriers to the management of fecal incontinence, (3) negative effects of fecal incontinence on life, (4) developing individual coping strategies, and (5) expectations.

Fecal incontinence was found to be more than a physical condition, significantly affecting individuals' mental health as well as their sexual and social lives. Social stigma, taboos, and limited awareness among health care professionals hinder patients from expressing their symptoms and seeking help, often leading to concealment of the condition. These findings highlight the need for educational interventions and awareness campaigns to reduce stigma and address the psychosocial dimensions of fecal incontinence.