Protocatechuic aldehyde sensitizes BRAF-mutant melanoma cells to temozolomide through inducing FANCD2 degradation.

Temozolomide (TMZ)-based chemotherapy is a primary regimen for melanoma patients who have failed targeted therapy or immunotherapy. However, the low response rate of TMZ-based chemotherapy challenges the patients' prognosis. BRAF mutation is the most frequently mutated site in melanoma.

N-glycosylation in the SERPIN domain of the C1-esterase inhibitor in hereditary angioedema.

Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting in poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH is a heavily glycosylated protein in the serine protease inhibitor (SERPIN) family, yet the role of these glycosylation sites remains unclear. To elucidate the functional impact of N-glycosylation in the SERPIN domain of C1-INH, we engineered 4 sets consisting of 26 variants at or near the N-linked sequon (NXS/T).

H3K14la drives endothelial dysfunction in sepsis-induced ARDS by promoting SLC40A1/transferrin-mediated ferroptosis.

Pulmonary endothelial cell (EC) activation is a key factor in acute respiratory distress syndrome (ARDS). In sepsis, increased glycolysis leads to lactate buildup, which induces lysine lactylation (Kla) on histones and other proteins. However, the role of protein lactylation in EC dysfunction during sepsis-induced ARDS remains unclear.

Disseminated intravascular coagulation: cause, molecular mechanism, diagnosis, and therapy.

Disseminated intravascular coagulation (DIC) is a complex and serious condition characterized by widespread activation of the coagulation cascade, resulting in both thrombosis and bleeding. This review aims to provide a comprehensive overview of DIC, emphasizing its clinical significance and the need for improved management strategies. We explore the primary causes of DIC, including sepsis, trauma, malignancies, and obstetric complications, which trigger an overactive coagulation response.

Comparison of Influence of Office and 24-h Central Aortic Blood Pressure on Target Organ Damage in Hypertension.

The aim of this study was to explore whether 24-h ambulatory central (aortic) blood pressure (BP) has an advantage over office central aortic BP in screening for hypertension-mediated target organ damage (HMOD). A total of 714 inpatients with primary hypertension and the presence of several cardiovascular risk factors or complications involving clinical HMOD were enrolled. Twenty-four hour central aortic BP was measured by means of a noninvasive automated oscillometric device (Mobil-O-Graph).

Association of Total Mortality and Cardiovascular Endpoints With the Timing of the First and Second Systolic Peak of the Aortic Pulse Wave.

Prognostic significance of the timing in the cardiac cycle of the first (TP1) and second (TP2) systolic peak of the central aortic pulse wave is ill-defined. Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of adverse health outcomes associated with TP1 and TP2, estimated by the SphygmoCor software, were assessed in the International Database of Central Arterial Properties for Risk Stratification (IDCARS) (n = 5529). Model refinement was assessed by the integrated discrimination (ID) and net reclassification (NR) improvement.

IFNγ regulates ferroptosis in KFs by inhibiting the expression of SPOCD1 through DNMT3A.

Keloid is benign skin tumor, and their curing is relatively difficult due to the unclear mechanism of formation. Inducing ferroptosis of keloid fibroblasts (KFs) may become a new method for treating keloid. Here, we discover interferon (IFN)γ could induce KFs ferroptosis through inhibiting SPOC domain-containing protein 1 (SPOCD1), serving as a mode of action for CD8T cell (CTL)-mediated keloid killing.

A Mortise and Tenon Framework Composed of Costal Cartilage and Expanded Polytetrafluoroethylene in Rhinoplasty for Asians: Application Ⅱ of Dai Exogenous Extension Stent Concept.

Background: The septum is often underdeveloped in East Asian populations, and traditional endogenous extension stents may not adequately fulfill the requirements for rhinoplasty. Herein, we present an innovative exogenous extension framework featuring a mortise and tenon structure specifically designed for East Asians.

Methods: This framework comprises a mushroom-shaped rib cartilage component and a lancet-shaped expanded polytetrafluoroethylene (ePTFE) element, which are interconnected through a mortise and tenon design.

Automatic machine learning accurately predicts the efficacy of immunotherapy for patients with inoperable advanced non-small cell lung cancer using a computed tomography-based radiomics model.

Purpose: Patients with advanced non-small cell lung cancer (NSCLC) have varying responses to immunotherapy, but there are no reliable, accepted biomarkers to accurately predict its therapeutic efficacy. The present study aimed to construct individualized models through automatic machine learning (autoML) to predict the efficacy of immunotherapy in patients with inoperable advanced NSCLC.

Methods: A total of 63 eligible participants were included and randomized into training and validation groups.

Immunotherapy Using HBV Vaccine Pulsed DCs and Induced T-Cells Combined Antiviral Drugs in Treatment Naive CHB Patients-A Multi-Centre Phase II Study.

Dendritic cells are the most potent antigen-presenting cells in immune therapeutic approaches for chronic hepatitis B (CHB) infection. Here, we developed a clinical trial to evaluate the efficacy and safety of autologous HBV vaccine-pulsed DCs and their induced T cells (HPDCT) in CHB patients. This was a randomised, prospective, open-label, multicentre, superiority study and 309 treatment-naive CHB patients were divided into HPDCT plus nucleos(t)ide analogues (NAs) group (n = 84), NAs mono-therapy group (n = 82), HPDCT plus Peg-interferon (Peg-IFN) group (n = 69), Peg-IFN mono-therapy group (n = 74).

Digital devices usage and neck and shoulder pain among college students: a cross-sectional study in China.

Neck and shoulder pain (NSP) is a common issue among college students, yet no studies have linked digital device usage to NSP prevalence in China. This cross-sectional survey aimed to explore this relationship among students in Shanghai. A total of 6,000 students were randomly selected, with 4,848 (80.

Tangeretin alleviates sepsis-induced acute lung injury by inhibiting ferroptosis of macrophage via Nrf2 signaling pathway.

Background: Sepsis-induced acute lung injury (ALI) is a severe clinical condition accompanied with high mortality. Tangeretin, which is widely found in citrus fruits, has been reported to exert antioxidant and anti-inflammatory properties. However, whether tangeretin protects against sepsis-induced ALI and the potential mechanisms remain unclear.

The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.

Objective: To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.

Design: Multicentre, double blinded, placebo controlled phase 3 trial.

Setting: 22 centres in China, September 2016 to December 2020.

Single-cell RNA-sequencing and spatial transcriptomic analysis reveal a distinct population of APOE cells yielding pathological lymph node metastasis in papillary thyroid cancer.

Background: Thyroid cancer is one of the most common endocrine tumors worldwide, especially among women and the metastatic mechanism of papillary thyroid carcinoma remains poorly understood.

Methods: Thyroid cancer tissue samples were obtained for single-cell RNA-sequencing and spatial transcriptomics, aiming to intratumoral and antimetastatic heterogeneity of advanced PTC. The functions of APOE in PTC cell proliferation and invasion were confirmed through in vivo and in vitro assays.

Standard: Human gastric organoids.

Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications.

The Role and Implications of Epidermal Dysfunction in the Pathogenesis of Inflammaging.

Inflammaging has long been linked to the pathogenesis of various aging-associated disorders, including cardiovascular disease, obesity, type 2 diabetes, and dementia. Yet, the origins of inflammaging remain unclear. Although inflammatory dermatoses such as psoriasis and atopic dermatitis predispose to the development of certain aging-associated disorders, suggesting a pathogenic role of cutaneous inflammation in these disorders, the great majority of aged humans do not have inflammatory dermatoses.

Hearing loss rather than vestibular loss identifies patient subgroups with different outcomes in Meniere's disease.

Objective: This study investigates the relationship between Meniere's disease (MD) duration and both hearing thresholds and vestibular dysfunction.

Design: Retrospective cohort study. First, the relationships between MD duration and pure-tone audiometry thresholds for each frequency, the canal paresis (CP) ratio, and the vestibulo-ocular reflex (VOR) gain were analysed.

Construction and evaluation of a multifactorial clinical model for discriminating benign and malignant breast tumors using LASSO algorithm based on retrospective cohort study.

Breast cancer is one of the malignant tumors that seriously threaten women's health, and early diagnosis and detection of breast cancer are crucial for effective treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is an important diagnostic tool that allows for the dynamic observation of blood flow characteristics of breast tumors, including small lesions within the affected tissue. Currently, it is widely used in clinical practice and has been shown promising prospects.

circ-ZEB1 Enhances NSCLC Metastasis and Proliferation by Modulating the miR-491-5p/EIF5A Axis.

Circular RNAs (circRNAs), covalently closed single-stranded RNAs, have been implicated in cancer progression. A previous investigation revealed that circ-ZEB1 is expressed abnormally in liver cancer. However, the roles of circ-ZEB1 in non-small cell lung cancer (NSCLC) are unknown.

A multicenter retrospective study of early cardiac toxicity in operable breast cancer patients receiving concurrent dual or mono anti-HER2 therapy with postoperative radiation therapy.

Purpose: This study aims to assess whether dual anti-HER2 therapy with trastuzumab and pertuzumab increases early cardiac toxicity compared to trastuzumab alone in breast cancer (BC) patients receiving postoperative radiation therapy (RT).

Methods: Consecutive operable BC patients receiving postoperative RT and trastuzumab with or without pertuzumab between January 2017 and September 2020 at seven tertiary hospitals in China were retrospectively reviewed. Cardiac examinations included echocardiography, electrocardiogram (ECG), NT-proBNP, and cTnI at baseline before RT and during the follow-up.

Adjuvant effect of green tea intake on treatment of patients with acute venous thromboembolism.

Background: Although there have been reports that green tea intake has thromboprophylactic effect, it was still unknown whether it had adjuvant effect on the basis of conventional anticoagulation for patients diagnosed with venous thromboembolism (VTE).

Methods: VTE patients were retrospectively classified into green tea group and no green tea group in a 1:1 ratio using propensity score matching, based on whether they drank green tea during the 3 months' period after VTE diagnosis. Primary outcomes were VTE recurrence at 3 months after VTE diagnosis and VTE-related death during 3 months after VTE diagnosis.

TREM1 interferes with macrophage mitophagy via the E2F1-mediated TOMM40 transcription axis in rheumatoid arthritis.

Elevated synovial expression of the triggering receptor expressed on myeloid cells 1 (TREM1) has been identified as a significant biomarker for assessing disease activity in rheumatoid arthritis (RA). The upregulated expression of TREM1, induced by inflammatory mediators in infiltrating macrophages, plays a critical role in synovitis and joint destruction in RA. Our previous sequencing data linked TREM1 activation to aberrant mitophagy.

Percutaneous irreversible electroporation of renal cell carcinomas in an acquired solitary kidney: A primary study.

Objective: To evaluate the postoperative complications and prognosis of renal cell carcinoma (RCC) in a solitary kidney after irreversible electroporation (IRE).

Materials And Methods: A total of 8 patients with 9 RCCs in a solitary kidney treated with computed tomography (CT)-guided IRE from February 2017 to September 2020 were retrospectively analyzed. Follow-up included contrast-enhanced CT or magnetic resonance imaging examinations at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and each year after IRE and the evaluation of the incidence of postoperative complications, renal function changes, local tumor recurrence, and metastasis.