treating to new targets

The indication for surgery for tricuspid regurgitation (TR) has reached a major turning point. It has become clear that the presence of moderate or severe TR alone worsens the prognosis of life, and the previous guidelines of Japanese Circulation Society, in which the indication for surgery was recommended at the timing of "right heart failure difficult to treat medically," now recommends surgery with a trigger of "repeated right heart failure" in the 2020 edition. In addition, a new repair technique targeting at subvalvular structure has been developed for end-stage TR to overcome a high TR recurrence rate that is associated with severe right ventricular enlargement and leaflet tethering...

BACKGROUND: Lactational mastitis is a common painful and debilitating inflammation of breast tissue, generally treated conservatively or with pus puncture in case of breast abscess. However, treating mastitis in patients with implantable surgical material located in the affected breast region can be extremely challenging. We present an unusual case of lactational mastitis complicated by pacemaker pocket infection in a breastfeeding mother. CASE PRESENTATION: A 35-year-old pacemaker-dependent female developed lactational mastitis seven weeks postpartum...

Hypertension is a prominent contributor to vascular injury. Deubiquinatase has been implicated in the regulation of hypertension-induced vascular injury. In the present study we investigated the specific role of deubiquinatase YOD1 in hypertension-induced vascular injury. Vascular endothelial endothelial-mesenchymal transition (EndMT) was induced in male WT and YOD1-/- mice by administration of Ang II (1 μg/kg per minute) via osmotic pump for four weeks. We showed a significantly increased expression of YOD1 in mouse vascular endothelial cells upon Ang II stimulation...

Double-stranded RNA-activated protein kinase R (PKR) is highly expressed in colorectal cancer (CRC). However, the role of PKR in CRC remains unclear. The aim of this study was to clarify whether C16 (a PKR inhibitor) exhibits antitumor effects and to identify its target pathway in CRC. We evaluated the effects of C16 on CRC cell lines using the MTS assay. Enrichment analysis was performed to identify the target pathway of C16. The cell cycle was analyzed using flow cytometry. Finally, we used immunohistochemistry to examine human CRC specimens...

Acute pancreatitis (AP) is a common systemic inflammatory disease resulting from the activation of trypsinogen by various incentives in ICU. The annual incidence rate is approximately 30 out of 100,000. Some patients may progress to severe acute pancreatitis, with a mortality rate of up to 40%. Therefore, the goal of this article is to explore the key genes for effective diagnosis and treatment of AP. The analysis data for this study were merged from two GEO datasets. 1357 DEGs were used for functional enrichment and cMAP analysis, aiming to reveal the pathogenic genes and potential mechanisms of AP, as well as potential drugs for treating AP...

Uveal Melanoma (UM) is a rare disease, yet it is the most common primary intraocular malignancy in adult patients. Despite continuous advancements and research, the risk of metastasis remains high. It is possible to stratify patients according to their risk of metastases using a variety of known risk factors. Even though there is no gold standard for the prognostication of patients with uveal melanoma, it is becoming increasingly clear that combining histo-pathological, patient-related and molecular prognostic markers allows a more accurate prediction of the metastatic risk than by using one parameter...

BACKGROUND: The U.S. antibiotic market failure has threatened future innovation and supply. Understanding when and why clinicians underutilize recently approved gram-negative antibiotics might help prioritize the patient in future antibiotic development and potential market entry rewards. OBJECTIVE: To determine use patterns of recently U.S. Food and Drug Administration (FDA)-approved gram-negative antibiotics (ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, plazomicin, eravacycline, imipenem-relebactam-cilastatin, and cefiderocol) and identify factors associated with their preferential use (over traditional generic agents) in patients with gram-negative infections due to pathogens displaying difficult-to-treat resistance (DTR; that is, resistance to all first-line antibiotics)...

UNLABELLED: Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority...

BACKGROUND: Anlotinib is a new type of tyrosine kinase inhibitor that targets vascular endothelial growth factor receptors 1/2/3, platelet-derived growth factor receptors α/β, and fibroblast growth factor receptors 1-4 and c-Kit, with a broad spectrum of inhibitory effects on tumor angiogenesis and growth. It has been proven effective in HER2-negative metastatic breast cancer, but its efficacy in early-stage triple-negative breast cancer (TNBC) is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy in patients with TNBC...

BACKGROUND AND AIMS: The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing. METHODS: Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2)...

ObjectiveThe study aimed to explore the perspective of healthcare workers on the resources they need to provide quality rehabilitation for people recovering from coronavirus disease 2019 (COVID-19) infection.MethodsA descriptive qualitative approach using reflexive thematic analysis was employed. Focus groups and interviews were performed with nine healthcare workers (one intensive care unit physiotherapist, one respiratory therapist and seven occupational therapists) with experience treating patients recovering from COVID-19 infection within hospital and in the community...

Solute carriers (SLCs) control the flow of small molecules and ions across biological membranes. Over the last 20 years, the pace of research in SLC biology has accelerated markedly, opening new opportunities to treat metabolic diseases, cancer and neurological disorders. Recently, new families of atypical SLCs, with roles in organelle biology, metabolite signaling and trafficking, have expanded their roles in the cell. This Perspective discusses work leading to current advances and the emerging opportunities to target and modulate SLCs to uncover new biology and treat human disease...

Cancer, a complex and multifactorial disease, presents a significant challenge to global health. Despite significant advances in surgical, radiotherapeutic and immunological approaches, which have improved cancer treatment outcomes, drug therapy continues to serve as a key therapeutic strategy. However, the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects, and thus there remains a critical need to develop novel cancer therapeutics. One promising strategy that has received widespread attention in recent years is drug repurposing: the identification of new applications for existing, clinically approved drugs...

Therapeutic strategies are the hot-spot issues in treating patients with advanced oral squamous cell carcinoma (OSCC). Mounting studies have proved that triggering ferroptosis is one of the promising targets for OSCC management. In this study, we performed a first attempt to collect the current evidence on the proposed roles of ferroptosis in OSCC through a comprehensive review. Based on clinical data from the relevant studies within this topic, we found that ferroptosis-associated tumor microenvironment, ferroptosis-related genes (FRGs), and ferroptosis-related lncRNAs exhibited a potent prognostic value for OSCC patients...

HCN channels are important for regulating heart rhythm and nerve activity and have been studied as potential drug targets for treating depression, arrhythmia, nerve pain and epilepsy.Despite possessing unique pharmacological properties, HCN channels share common characteristics in that they are activated by hyperpolarization and modulated by cAMP and other membrane lipids. However, the mechanisms of how these ligands bind and modulate HCN channels are unclear. In this study, we solved structures of full-length human HCN3 using cryo-EM and captured two different states, including a state without any ligand bound and a state with cAMP bound...

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic nephropathy (DN) is a typical chronic microvascular complication of diabetes, characterized by proteinuria and a gradual decline in renal function. At present, there are limited clinical interventions aimed at preventing the progression of DN to end-stage renal disease (ESRD). However, Chinese herbal medicine presents a distinct therapeutic approach that can be effectively combined with conventional Western medicine treatments to safeguard renal function...

BACKGROUND: As global populations age and become susceptible to neurodegenerative illnesses, new therapies for Alzheimer disease (AD) are urgently needed. Existing data resources for drug discovery and repurposing fail to capture relationships central to the disease's etiology and response to drugs. OBJECTIVE: We designed the Alzheimer's Knowledge Base (AlzKB) to alleviate this need by providing a comprehensive knowledge representation of AD etiology and candidate therapeutics...

AIMS: This study investigated whether an activated R-mode in patients carrying a cardiac implantable electronic device (CIED) is associated with worse prognosis during and after an episode of acutely decompensated heart failure (AHF). METHODS: Six hundred and twenty-three patients participating in an ongoing prospective cohort study that phenotypes and follows patients admitted for AHF were studied. We compared CIED carriers with activated R-mode stimulation (CIED-R) to CIED carriers not in R-mode (CIED-0) and patients without CIEDs (no-CIED)...

BACKGROUND: The aim of this study was to evaluate the early results of the CE-marked standardized device combination consisting of Endurant and the Radiant chimney graft (En-ChEVAR) for the treatment of juxtarenal aortic aneurysms. METHODS: We analyzed multicentric non-industry sponsored case series evaluating the EnChEVAR technique for patients treated between December 2022 and February 2024. Clinical, perioperative procedure-related and radiological data were collected...

KEY CLINICAL MESSAGE: High-dose intravenous immunoglobulin exhibits great potential in the treatment of Netherton syndrome. ABSTRACT: Netherton syndrome (NS) is a rare autosomal recessive genodermatosis (OMIM #256500) characterized by superficial scaling, atopic manifestations, and multisystemic complications. It is caused by loss-of-function mutations in the SPINK5 gene, which encode a key kallikrein protease inhibitor. There are two subtypes of the syndrome that differ in clinical presentation and immune profile: ichthyosiform erythroderma and ichthyosis linearis circumflexa...