Pyruvate Kinase M2-Responsive Release of Paclitaxel and Indoleamine 2,3-Dioxygenase Inhibitor for Immuno-Chemotherapy of Nonsmall Cell Lung Cancer.

Paclitaxel (PTX) is a first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC) but it can induce indoleamine 2,3-dioxygenase (IDO) activation, which severely lowers down its immuno-chemotherapeutic effect. To address this issue, a smart peptide hydrogelator Nap-Phe-Phe-Phe-Lys-Ser-Thr-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-T), which co-assembles with PTX and an IDO inhibitor GDC0919 to form a hydrogel GP@Gel Nap-T, is rationally designed. Upon specific phosphorylation by pyruvate kinase M2 (PKM2), an overexpressed biomarker of NSCLC, Nap-T is gradually converted to Nap-Phe-Phe-Phe-Lys-Ser-Thr(HPO)-Gly-Gly-Lys-Ala-Pro-Arg-OH (Nap-Tp), leading to dehydrogelation and sustained release of PTX and GDC0919 within NSCLC tissues.

Vericiguat enhances the therapeutic efficacy of mesenchymal stem cells-derived exosomes in acute myocardial infarction through microRNA-1180-3p/ETS1 pathway.

Reversing cardiac fibrosis contributes to the restoration of cardiac function in acute myocardial infarction (MI). Exosomes-derived mesenchymal stem cells (MSCs) have been established as potential biomarkers of cardiovascular diseases. While vericiguat has demonstrated promising outcomes in MI via reverse hypertrophy and fibrosis, previous studies about vericiguat pretreatment with MSCs is limited.

Elastase-targeting biomimic nanoplatform for neurovascular remodeling by inhibiting NETosis mediated AlM2 inflammasome activation in ischemic stroke.

Neutrophil elastase (NE) is a protease released by activated neutrophils in the brain parenchyma after cerebral ischemia, which plays a pivotal role in the regulation of neutrophil extracellular traps (NETs) formation. The excess NETs could lead to blood-brain barrier (BBB) breakdown, overwhelming neuroinflammation, and neuronal injury. While the potential of targeting neutrophils and inhibiting NE activity to mitigate ischemic stroke (IS) pathology has been recognized, effective strategies that inhibit NETs formation remain under-explored.

Real-world data analysis of next-generation sequencing and corresponding clinical characteristics in thyroid tumor.

Next-generation sequencing (NGS) is of great benefit to clinical practice in terms of identifying genetic alterations. This study aims to clarify the gene background and its influence on thyroid tumors in the Chinese population. NGS data and corresponding clinicopathological features (sex, age, tumor size, extrathyroidal invasion, metastasis, multifocality, and TNM stage) were collected and analyzed retrospectively from 2844 individual thyroid tumor samples from July 2021 to August 2022.

Evaluation of staged autologous blood transfusion during extracorporeal membrane oxygenation decannulation: A retrospective study.

Background: Clinical blood resources are scarce and autologous blood transfusion for extracorporeal membrane oxygenation (ECMO) withdrawal is less studied.

Objectives: To assess the use of staged autotransfusion during ECMO decannulation.

Methods: The study included ECMO withdrawal patients.

The impact of ankle movements on venous return flow: A comparative study.

Objective: To compare the haemodynamic effects of different ankle movements combined ankle and toe movements on the femoral vein of the lower extremity.

Methods: 28 healthy volunteers participated in the study. Doppler ultrasound was used to measure peak systolic velocity and time-averaged mean velocity of the common femoral vein during ankle dorsiflexion, ankle dorsiflexion with simultaneous toe extension, ankle plantarflexion, and ankle plantarflexion with simultaneous toe flexion.

The role of pre-onset hair hormone in predicting the prognosis of patients with severe pneumonia and acute COVID-19 outbreak.

Numerous research works have investigated the potential impact of endocrine hormones on the severity of COVID-19-related pneumonia in individuals. However, there are few studies on the effect of pre-onset neuroendocrine hormones on the prognosis of COVID-19 patients. This study looked into the prognostic value of pre-onset hair hormone levels in COVID-19 infected individuals.

DNA methylation markers for risk of metastasis in a cohort of men with localized prostate cancer.

Accurately identifying life-threatening prostate cancer (PCa) at time of diagnosis remains an unsolved problem. We evaluated whether DNA methylation status of selected candidate genes can predict the risk of metastasis beyond clinical risk factors in men with untreated PCa. A nested case-control study was conducted among men diagnosed with localized PCa at Kaiser Permanente California between 01/01/1997-12/31/2006 who did not receive curative treatments.

A distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy sensitive than papillary thyroid cancer.

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer.

Neural Circuitry Polarization in the Spinal Dorsal Horn (SDH): A Novel Form of Dysregulated Circuitry Plasticity during Pain Pathogenesis.

Pathological pain emerges from nociceptive system dysfunction, resulting in heightened pain circuit activity. Various forms of circuitry plasticity, such as central sensitization, synaptic plasticity, homeostatic plasticity, and excitation/inhibition balance, contribute to the malfunction of neural circuits during pain pathogenesis. Recently, a new form of plasticity in the spinal dorsal horn (SDH), named neural circuit polarization (NCP), was discovered in pain models induced by HIV-1 gp120 and chronic morphine administration.

Targeting MHC-I inhibitory pathways for cancer immunotherapy.

The MHC-I antigen presentation (AP) pathway is key to shaping mammalian CD8 T cell immunity, with its aberrant expression closely linked to low tumor immunogenicity and immunotherapy resistance. While significant attention has been given to genetic mutations and downregulation of positive regulators that are essential for MHC-I AP, there is a growing interest in understanding how tumors actively evade MHC-I expression and/or AP through the induction of MHC-I inhibitory pathways. This emerging field of study may offer more viable therapeutic targets for future cancer immunotherapy.

Key roles of autophagosome/endosome maturation mediated by Syntaxin17 in methamphetamine-induced neuronal damage in mice.

Background: Autophagic defects are involved in Methamphetamine (Meth)-induced neurotoxicity. Syntaxin 17 (Stx17), a member of the SNARE protein family, participating in several stages of autophagy, including autophagosome-late endosome/lysosome fusion. However, the role of Stx17 and potential mechanisms in autophagic defects induced by Meth remain poorly understood.

Hospital‑acquired pneumonia caused by during extracorporeal membrane oxygenation treatment: A case report and literature review.

() is an ascosporogenic species of yeast that belongs to the genus and the family of Saccharomycetaceae. It has recently been found to cause various types of infections, particularly in critically ill immunocompromised patients. The present study describes a case of hospital-acquired pneumonia caused by during veno-arterial extracorporeal membrane oxygenation.

Ventricular fibrillation/ventricular tachycardia within 72 h of VA-ECMO: incidence, outcomes, risk factors, and management.

Aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an important technique for the treatment of refractory cardiogenic shock and cardiac arrest; however, the early management of ventricular fibrillation/ventricular tachycardia (VF/VT), within 72 h of VA-ECMO, and its effects on patient prognosis remain unclear.

Methods And Results: We retrospectively analysed patients at the First Affiliated Hospital of Nanjing Medical University who underwent VA-ECMO between January 2017 and March 2022. The patients were divided into two groups, VF/VT and nVF/VT, based on whether or not VF/VT occurred within 72 h after the initiation of VA-ECMO.

The neuro-prognostic value of the ion shift index in cardiac arrest patients following extracorporeal cardiopulmonary resuscitation.

Background: The ion shift index (ISI) as a prognostic indicator that can show the severity of hypoxic-ischemic injury. We aimed to evaluate the performance of the ISI in predicting unfavorable neurological outcomes at hospital discharge in cardiac arrest (CA) patients following extracorporeal cardiopulmonary resuscitation (ECPR) and to compare its performance to other prognostic predictors.

Methods: This was a retrospective observational study including adult CA patients treated with ECPR between January 2018 and December 2022 in a tertiary hospital.