Publications by authors named "Yannan Zhao"

Background: Utidelone (UTD1), a genetically engineered epothilone derivative, has been approved in China for use in combination with capecitabine in treating metastatic breast cancer (MBC) patients previously treated with anthracyclines or taxanes.

Objectives: To evaluate the real-world efficacy and safety of UTD1 in Chinese patients with MBC and to explore potential predictors of therapeutic effectiveness.

Design: A multicenter, retrospective, real-world study.

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Neurons in distinct spinal cord segments serve specific functions, raising questions about whether human spinal cord-derived neural stem cells (hscNSCs) retain segment-specific properties crucial for spinal cord injury (SCI) repair. We established a culture system amplifying hscNSCs from cervical, thoracic, and lumbar segments, revealing segment-specific transcriptional profiles and differentiation potentials. Notably, thoracic hscNSCs exhibited elevated hepatocyte growth factor (HGF) expression inherited from the pre-ganglionic column, enhancing their differentiation into motor neurons.

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Background: While CDK4/6 inhibitors combined with endocrine therapy (CDK4/6i+ET) have revolutionized treatment for HR+/HER2- metastatic breast cancer (MBC), inter-lesional estrogen receptor (ER) heterogeneity limits therapeutic efficacy in a subset of patients. Whole-body F-fluoroestradiol (F-FES) PET/CT enables non-invasive ER quantification across all metastatic sites. However, whether F-FES-guided therapy selection improves clinical outcomes in relatively large sample cohorts is not yet well-established.

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Numerous studies have shown that exposure to arsenic (As) or fluoride(F) can damage the reproductive system, but limited evidence exists regarding the combined toxicity and pathogenesis of As and F co-exposure in female reproduction. Moreover, the role of gut microbiota in mediating such toxicity remains unclear. This study investigated the effects of As and F co-exposure on ovarian development and the potential protective role of fecal microbiota transplantation (FMT).

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Spatial transcriptomics and epigenomics have enabled mapping gene regulation in the tissue context. However, it remains poorly understood how spatial gene expression patterns are orchestrated by enhancers. Here we build eSpatial, a computational framework that deciphers spatially resolved enhancer regulation of gene expression by integrating spatial profiles of gene expression and chromatin accessibility.

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Objective: Orthopedic wound infection is a difficult problem in the clinic. Accurate and rapid microbiological test results are essential for case management, antibiotic therapy, and infection control.

Methods: We retrospectively evaluated 1285 specimens (puncture fluid, catheter, secretions, joint fluid, lavage fluid, extraction fluid, blood culture, drainage fluid, cerebrospinal fluid, bone, prosthesis tissue, etc.

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Background: Ferroptosis plays a vital role in cancer development and treatment. The relationship between ferroptosis-related genes and breast cancer prognosis, as well as immunotherapy outcomes, remains unknown.

Objectives: To evaluate the prognostic value of ferroptosis-related genes in breast cancer.

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Stem cell transplantation is a promising strategy to establish neural relays in situ for spinal cord injury (SCI) repair. Recent research has reported short-term survival of exogenous cells, irrespective of immunosuppressive drugs (ISD), results in similar function recovery, though the mechanisms remain unclear. This study aims to validate this short-term repair effect and the potential mechanisms in large animals.

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Various mature tissue-resident cells exhibit progenitor characteristics following injury. However, the existence of endogenous stem cells with multiple lineage potentials in the adult spinal cord remains a compelling area of research. In this study, we present a cross-species investigation that extends from development to injury.

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Objective: With the approval of trastuzumab deruxtecan for the treatment of unresectable/metastatic HER2-low breast cancer, human epidermal growth factor receptor 2 (HER2)-low has emerged as a clinically actionable biomarker. There is an urgent need for a deeper understanding of HER2-low breast cancer patients. Therefore, this study was conducted to explore the clinicopathological characteristics, the evolution of HER2-low status, and its impact on the prognosis of hormone receptor (HoR)-negative/HER2-low metastatic breast cancer (MBC) patients.

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Spinal cord injury (SCI) leads to fibrotic scar formation at the lesion site, yet the heterogeneity of fibrotic scar remains elusive. Here we show the heterogeneity in distribution, origin, and function of fibroblasts within fibrotic scars after SCI in mice and female monkeys. Utilizing lineage tracing and single-cell RNA sequencing (scRNA-seq), we found that perivascular fibroblasts (PFs), and meningeal fibroblasts (MFs), rather than pericytes/vascular smooth cells (vSMCs), primarily contribute to fibrotic scar in both transection and crush SCI.

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Article Synopsis
  • Spinal cord injury (SCI) is a serious neurological condition that leads to significant loss of movement and sensory function, posing a major global health challenge.
  • Electroactive bioscaffolds have been developed to aid in spinal cord regeneration by creating conductive pathways and fostering a supportive environment for nerve repair, mimicking the natural spinal cord.
  • The review discusses the underlying issues caused by SCI, highlights the importance of electrical signals in the repair process, and summarizes advancements in conductive and piezoelectric bioscaffolds, while also addressing future challenges and opportunities in this field.
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Bioelectricity plays a crucial role in organisms, being closely connected to neural activity and physiological processes. Disruptions in the nervous system can lead to chaotic ionic currents at the injured site, causing disturbances in the local cellular microenvironment, impairing biological pathways, and resulting in a loss of neural functions. Electromagnetic stimulation has the ability to generate internal currents, which can be utilized to counter tissue damage and aid in the restoration of movement in paralyzed limbs.

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Neonatal spinal cord tissues exhibit remarkable regenerative capabilities as compared to adult spinal cord tissues after injury, but the role of extracellular matrix (ECM) in this process has remained elusive. Here, we found that early developmental spinal cord had higher levels of ECM proteins associated with neural development and axon growth, but fewer inhibitory proteoglycans, compared to those of adult spinal cord. Decellularized spinal cord ECM from neonatal (DNSCM) and adult (DASCM) rabbits preserved these differences.

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Repairing spinal cord injury (SCI) is a global medical challenge lacking effective clinical treatment. Developing human-engineered spinal cord tissues that can replenish lost cells and restore a regenerative microenvironment offers promising potential for SCI therapy. However, creating vascularized human spinal cord-like tissues (VSCT) that mimic the diverse cell types and longitudinal parallel structural features of spinal cord tissues remains a significant hurdle.

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Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.

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Background: Experimental studies have suggested exposure to bisphenol A (BPA) and its alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), may exert adverse effects on ovarian reserve, but human evidence is limited. Moreover, the potential predictors of exposure to bisphenols among women seeking infertility treatment have not been reported.

Objective: To explore whether individual or mixture of BPA, BPF, and BPS were related to antral follicle count (AFC), and further identify the predictors of exposure to bisphenols among women seeking assisted reproductive treatment.

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In women, a healthy and functional vagina is important for the maintenance of a good quality of life. Various factors, including congenital anomalies, cancer, trauma, infections, inflammation, or iatrogenic injuries, can lead to damage or loss of the vaginal structure, necessitating repair or replacement. Often, such reconstruction procedures involve the use of nonvaginal tissue substitutes, like segments of the large intestine or skin, which are less than ideal both anatomically and functionally.

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Background: The 18F-fluoroestradiol positron emission tomography/computed tomography (18F-FES PET/CT) technique provides a convenient method to evaluate the overall estrogen receptor (ER) expression in metastatic breast cancer (MBC) patients. There are long debates on the characteristics and treatment strategy of patients with positive primary ER lesions but negative ER expression in metastatic disease. 18F-FES PET offers an opportunity to answer this question.

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Spinal cord injury (SCI) causes tissue structure damage and composition changes of the neural parenchyma, resulting in severe consequences for spinal cord function. Mimicking the components and microstructure of spinal cord tissues holds promise for restoring the regenerative microenvironment after SCI. Here, we have utilized electrospinning technology to develop aligned decellularized spinal cord fibers (A-DSCF) without requiring synthetic polymers or organic solvents.

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Environmental arsenic (As) or high-fat diet (HFD) exposure alone are risk factors for the development of cardiovascular disease (CVDs). However, the effects and mechanisms of co-exposure to As and HFD on the cardiovascular system remain unclear. The current study aimed to investigate the combined effects of As and HFD on vascular injury and shed some light on the underlying mechanisms.

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Objective: Despite the promising efficacy of the novel antibody-drug conjugate trastuzumab deruxtecan in treating Hormone Receptor (HoR)-positive/Human Epidermal Growth Factor Receptor 2 (HER2)-low metastatic breast cancer (MBC), its categorization as a distinct entity remains disputed, as does the divergence in its endocrine and chemotherapy outcomes. This study aimed to elucidate the clinical characteristics, primary/metastatic lesion HER2 expression, and treatment outcomes of HoR-positive/HER2-low patients.

Methods: We included HoR-positive/HER2-negative MBC patients who underwent 1 and 2 line endocrine treatment from July 2010 to October 2022 at the Fudan University Shanghai Cancer Center, comparing the clinical pathological characteristics, HER2 expression in primary/metastatic lesions, treatment, and therapeutic effects of the HER2-low and HER2-zero groups.

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Spinal cord injury (SCI) leads to severe sensory and motor dysfunction below the lesion. However, the cellular dynamic responses and heterogeneity across different regions below the lesion remain to be elusive. Here, we used single-cell transcriptomics to investigate the region-related cellular responses in female rhesus monkeys with complete thoracic SCI from acute to chronic phases.

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Therapeutic options are limited for severe lung injury and disease as the spontaneous regeneration of functional alveolar is terminated owing to the weakness of the inherent stem cells and the dyscrasia of the niche. Umbilical cord mesenchymal-derived stem cells (UC-MSCs) have been applied to clinical trials to promote lung repair through stem cell niche restruction. However, the application of UC-MSCs is hampered by the effectiveness of cell transplantation with few cells homing to the injury sites and poor retention, survival, and proliferation in vivo.

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Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold . Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation.

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