Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial.

Background: The unmet needs of managing patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer who progress after cyclin-dependent kinase (CDK)4/6 inhibitor (CDK4/6i) treatment remain unclarified.

Methods: This was a phase 1b/2, single-arm, open-label study that enrolled 29 patients with HR+/HER2- breast cancer who experienced first-line palbociclib treatment failure. The primary endpoint was the incidence of dose-limiting toxicity (DLT).

Preclinical study and phase 2 trial of neoadjuvant pyrotinib combined with chemotherapy in luminal/HER2-low breast cancer: PILHLE-001 study.

The prognosis of patients with luminal/human epidermal growth factor receptor 2 (HER2)-low early breast cancer (EBC) needs to be improved. This preclinical study and phase 2 trial (ChiCTR2100047233) aims to explore the efficacy and safety of pyrotinib (a pan-HER tyrosine kinase inhibitor) plus chemotherapy in this population. Our preclinical experiments indicate a synergistic anti-tumor effect of pyrotinib plus chemotherapy in luminal/HER2-low (immunochemistry [IHC] 2+/fluorescent in situ hybridization [FISH]-negative) breast cancer models.

RVD2 emerges as a serological marker in relation to severity and six-month clinical outcome following acute intracerebral hemorrhage: A prospective cohort study from a single academic institution.

Background: Resolvin D2 (RvD2), with an anti-inflammatory activity, harbors a neuroprotective property. Here, serum RvD2 levels were detected with an attempt to explore its prognostic implication in human acute intracerebral hemorrhage (ICH).

Methods: In this prospective cohort study, serum RvD2 levels of 301 ICH patients, coupled with 100 heathy individuals, were gauged.

Patient-reported outcome and survival in premenopausal hormone receptor-positive breast cancer patients at moderate to high risk: comparing toremifene with aromatase inhibitor in a real-world study.

Toremifene, a selective estrogen receptor modulator, is commonly used in China for premenopausal breast cancer patients. This real-world study aimed to compare patient-reported outcome (PRO) and survival between toremifene and aromatase inhibitor (AI) plus ovarian function suppression (OFS) in patients with moderate-/high-risk premenopausal hormone receptor (HR)-positive breast cancer. The primary endpoint was PROs, assessed using SF-36 and EQ-5D-5L questionnaires between January and March 2023.

Efficacy and safety of eculizumab in Guillain-Barré syndrome: A phase 3, multicenter, double-blind, randomized, placebo-controlled clinical trial.

Background And Aims: Guillain-Barré syndrome (GBS) is an acute, self-limited, immune-mediated peripheral neuropathy. Current treatments for GBS include intravenous immunoglobulin (IVIg) and plasma exchange, which may not sufficiently benefit severely affected patients. This study evaluated the efficacy and safety of eculizumab add-on therapy to IVIg (standard-of-care treatment) in patients with severe GBS.

Two-lung ventilation with artificial pneumothorax on cerebral desaturation and early postoperative cognitive outcome: a randomized controlled trial.

Background: The effect of two lung ventilation (TLV) with carbon dioxide artificial pneumothorax on cerebral desaturation and postoperative neurocognitive changes in elderly patients undergoing elective minimally invasive esophagectomy (MIE) is unclear.

Objectives: The first aim of this study was to compare the effect of TLV and one lung ventilation (OLV) on cerebral desaturation. The second aim was to assess changes in early postoperative cognitive outcomes of two ventilation methods.

Association between Homologous Recombination Repair Defect Status and Long-Term Prognosis of Early HER2-Low Breast Cancer: A Retrospective Cohort Study.

Background: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC.

Urolithin B Attenuates Cerebral Ischemia-reperfusion Injury by Modulating Nrf2-regulated Anti-oxidation in Rats.

Ischemia-reperfusion (IR) induces a wide range of irreversible injuries. Cerebral IR injury (IRI) refers to additional brain tissue damage that occurs after blood flow is restored following cerebral ischemia. Currently, no established methods exist for treating IRI.

Dural Puncture Epidural with 25-G Spinal Needles versus Conventional Epidural Technique in Conjunction with PIEB for Labor Analgesia: A Randomized Trial.

Purpose: To compare the effect of Dural puncture epidural (DPE) and conventional epidural (EP), in conjunction with programmed intermittent epidural bolus (PIEB) and low-concentration ropivacaine strategy.

Methods: After written informed consent was obtained, healthy nulliparous women with singleton pregnancies, vertex presentation at 38-42 weeks' gestation, cervical dilation of 3-5 cm, and a desire for pain relief were randomly assigned to DPE or EP group. Dural matter was puncture with 25G Whitacre needle in DPE group.

2A peptide from ERBV-1 efficiently separates endogenous protein domains in the fission yeast .

2A peptides are widely used for polycistronic gene expression from vectors. In contrast, the separation of endogenous genes via 2A peptides has been largely unexplored. We show that in fission yeast , the "cleaving" efficiency of the 2A peptide from ERBV-1 (Equine rhinitis B virus 1) range from ~70% to ~99% for End4 at different insertion sites.

Efficacy and Safety of Ravulizumab, a Complement C5 Inhibitor, in Adults With Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial.

Importance: Additional therapies for amyotrophic lateral sclerosis (ALS) are urgently needed. Immune-mediated complement activation may be involved in ALS pathogenesis as evidenced by the upregulation of terminal components; thus, complement inhibition could potentially slow progression.

Objective: To evaluate the safety and efficacy of the terminal complement C5 inhibitor ravulizumab in adults with ALS.

A prospective cohort study on decreased serum apelin-13 levels after human aneurysmal subarachnoid hemorrhage: associations with severity and prognosis.

Apelin-13 may have neuroprotective effects. We aimed to determine whether serum apelin-13 could serve as a potential biomarker for severity, delayed cerebral ischemia (DCI), and prognosis after human aneurysmal subarachnoid hemorrhage (aSAH). In this prospective, observational, cohort, single-center study of 139 patients with aSAH and 139 healthy individuals, serum apelin-13 levels were determined.

Construction of stemness gene score by bulk and single-cell transcriptome to characterize the prognosis of breast cancer.

Breast cancer (BC) is a heterogeneous disease characterized by significant differences in prognosis and therapy response. Numerous prognostic tools have been developed for breast cancer. Usually these tools are based on bulk RNA-sequencing (RNA-Seq) and ignore tumor heterogeneity.

Dural puncture epidural with 25-G spinal needles versus conventional epidural technique for labor analgesia: A systematic review of randomized controlled trials.

Background: Dural mater is punctured by using a spinal needle without drugs administrated into intrathecal space directly in dural puncture epidural (DPE) analgesia.

Objective: This study aimed to summarize the evidence of benefits and risks of DPE analgesia with 25-G spinal needles for labor pain relief.

Methods: DPE analgesia with EP analgesia for labor pain relief were systematically searched.

Association of FTH1-Expressing Circulating Tumor Cells With Efficacy of Neoadjuvant Chemotherapy for Patients With Breast Cancer: A Prospective Cohort Study.

Background: The association between different phenotypes and genotypes of circulating tumor cells (CTCs) and efficacy of neoadjuvant chemotherapy (NAC) remains uncertain. This study was conducted to evaluate the relationship of FTH1 gene-associated CTCs (F-CTC) with/without epithelial-mesenchymal transition (EMT) markers, or their dynamic changes with the efficacy of NAC in patients with non-metastatic breast cancer.

Patients And Methods: This study enrolled 120 patients with non-metastatic breast cancer who planned to undergo NAC.

ROS-dependent cell death of Heterosigma akashiwo induced by algicidal bacterium Hahella sp. KA22.

Marine algicidal bacteria and their metabolites are considered to be one of the most effective strategies to mitigate the harmful algal blooms (HABs). The bacterium Hahella sp. KA22 has previously been confirmed to have strong algicidal activity against the HABs causing microalgae, Heterosigma akashiwo.

Novel roles of RNA-binding proteins in drug resistance of breast cancer: from molecular biology to targeting therapeutics.

Therapy resistance remains a huge challenge for current breast cancer treatments. Exploring molecular mechanisms of therapy resistance might provide therapeutic targets for patients with advanced breast cancer and improve their prognosis. RNA-binding proteins (RBPs) play an important role in regulating therapy resistance.

Single and composite damage mechanisms of soil polyethylene/polyvinyl chloride microplastics to the photosynthetic performance of soybean (x [L.] merr.).

Introduction: Adverse impacts of soil microplastics (MPs, diameter<5 mm) on vegetative growth and crop production have been widely reported, however, the single and composite damage mechanisms of polyethylene (PE) /polyvinyl chloride (PVC) microplastics (MPs) induced photosynthesis inhibition are still rarely known.

Methods: In this study, two widely distributed MPs, PE and PVC, were added to soils at a dose of 7% (dry soil) to examine the single and composite effects of PE-MPs and PVC-MPs on the photosynthetic performance of soybean.

Results: Results showed PE-MPs, PVC-MPs and the combination of these two contaminants increased malondialdehyde (MDA) content by 21.

Mitochondrial dysfunction induces ALK5-SMAD2-mediated hypovascularization and arteriovenous malformations in mouse retinas.

Although mitochondrial activity is critical for angiogenesis, its mechanism is not entirely clear. Here we show that mice with endothelial deficiency of any one of the three nuclear genes encoding for mitochondrial proteins, transcriptional factor (TFAM), respiratory complex IV component (COX10), or redox protein thioredoxin 2 (TRX2), exhibit retarded retinal vessel growth and arteriovenous malformations (AVM). Single-cell RNA-seq analyses indicate that retinal ECs from the three mutant mice have increased TGFβ signaling and altered gene expressions associated with vascular maturation and extracellular matrix, correlating with vascular malformation and increased basement membrane thickening in microvesels of mutant retinas.

Galangin ameliorates osteoarthritis progression by attenuating extracellular matrix degradation in chondrocytes via the activation of PRELP expression.

Osteoarthritis (OA) is primarily characterized by progressive degeneration and destruction of articular cartilage. Currently, there is no effective method to treat OA. The metabolic disturbance of cartilage extracellular matrix (ECM) and oxidative stress are critical to promote OA progression.

Small Molecular Inhibitors Reverse Cancer Metastasis by Blockading Oncogenic PITPNM3.

Most cancer-related deaths are a result of metastasis. The development of small molecular inhibitors reversing cancer metastasis represents a promising therapeutic opportunity for cancer patients. This pan-cancer analysis identifies oncogenic roles of membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3), which is crucial for cancer metastasis.

Expert consensus statement on therapeutic drug monitoring and individualization of linezolid.

Linezolid is an oxazolidinone antibacterial drug, and its therapeutic drug monitoring and individualized treatment have been challenged since its approval. With the in-depth clinical research of linezolid, we have changed our attitude toward its therapeutic drug monitoring and our view of individualized treatment. On the basis of summarizing the existing clinical studies, and based on the practical experience of each expert in their respective professional fields, we have formed this expert consensus.

Chlorogenic acid promotes angiogenesis and attenuates apoptosis following cerebral ischaemia-reperfusion injury by regulating the PI3K-Akt signalling.

Context: Chlorogenic acid (CGA) has good antioxidant effects, but its explicit mechanism in cerebral ischaemia-reperfusion injury is still uncertain.

Objective: We studied the effect of CGA in human brain microvascular endothelial cells (HBMECs) under OGD/R damage.

Materials And Methods: HBMECs in 4 groups were treated with oxygen-glucose deprivation/re-oxygenation (OGD/R) (4+ 24 h), normal no CGA treatment and different concentrations (20, 40 or 80 μM) of CGA.

Autophagy-Associated Immunogenic Modulation and Its Applications in Cancer Therapy.

Autophagy, a lysosome-mediated cellular degradation pathway, recycles intracellular components to maintain metabolic balance and survival. Autophagy plays an important role in tumor immunotherapy as a "double-edged sword" that can both promote and inhibit tumor progression. Autophagy acts on innate and adaptive immunity and interacts with immune cells to modulate tumor immunotherapy.

DL-3-N-Butylphthalide Promotes Cartilage Extracellular Matrix Synthesis and Inhibits Osteoarthritis Development by Regulating FoxO3a.

Osteoarthritis (OA) has been reported as a progressive disease in the elderly, primarily characterized by degenerated articular cartilage. There has been no satisfactory drug for the treatment of OA. DL-3-n-butylphthalide (NBP), a small molecule compound extracted from celery seeds, may have antiapoptotic, antioxidant, and anti-inflammatory activities in numerous studies.