NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective To screen differentially-expressed circRNA in plasma exosomes of patients with non-small cell lung cancer(NSCLC)and verify its diagnostic value for NSCLC.Methods The plasma exosomes of six patients with NSCLC and six healthy people were analyzed by circRNA sequencing.The expression of hsa_circ_0052513 in plasma exosomes of 60 NSCLC patients and 60 healthy controls was detected by qRT-PCR.The expression level of hsa_circ_0052513 in plasma exosomes of NSCLC patients before and after surgery was detected by qRT-PCR.The correlation between the expression of plasma exosomal hsa_circ_0052513 and clinical data of patients with NSCLC was statistically analyzed.Results Sequencing results showed that the expression of hsa_circ_0052513 in the plasma exosomes of NSCLC patients was higher than that of healthy controls,and the results were confirmed by qRT-PCR.Hsa_circ_0052513 was decreased in patients with NSCLC after tumor resection(P<0.05).The high expression of plasma exosomal hsa_circ_0052513 in patients with NSCLC was correlated with tumor size,distant metastasis,and TNM stage of NSCLC(all P<0.05).The area under the curve of plasma exosomal hsa_circ_0052513 in the diagnosis of patients with NSCLC was 0.7904(P<0.0001).Conclusion Hsa_circ_0052513 is highly expressed in the plasma exosomes of patients with NSCLC and is related to tumor size,metastasis,and TNM stage.Hence,Hsa_circ_0052513 could be a new diagnostic marker for NSCLC.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

The reprogramming of lipid metabolism is a significant factor influencing various aspects of head and neck squamous cell carcinoma,including its occurrence,development,metastasis,and resistance to radio-chemotherapy.There is a considerable elevation in the expression levels of enzymes and genes related to lipid metabolism in tumor tissues compared to normal tissues.This up-regulation is associated with both treatment resistance and a poor prognosis.This review focuses mainly on alterations in lipid metabolism in head and neck squamous cell carcinoma.It systematically explores the atypical expression and clinical significance of lipid metabolism-related enzymes,evaluates their influence on treatment resistance,elucidates the underlying mechanisms of this resistance,and discus-ses current and potential targeted therapeutic approaches.The comprehensive analysis comprises four pivotal aspects:de novo lipogene-sis,fatty acid oxidation,glycerophospholipids metabolism,and mevalonate and cholesterol synthesis pathways.Feasible strategies,such as the adjustment of dietary structure,the administration of multi-target drugs,and the utilization of combination treatment thera-pies,are deliberated as potential interventions to modulate lipid metabolism,reverse treatment resistance,and enhance the efficacy of anti-cancer treatments.

Head and neck cancer is the seventh most common cancer in the world,accounting for about 10%of all malignant tumors.Radiotherapy is an important treatment for head and neck cancer.Osteonecrosis of the jaws(ORNJ)is a refractory complication after ra-diotherapy for head and neck cancer,which often manifests as osteonecrosis of the jaw and soft tissue exposure.The current pathogene-sis of ORNJ has not been fully clarified and its treatment remains challenging.The traditional treatment for this disease is partial resec-tion of necrotic jaw bone and reconstruction with osteocutaneous flap.However,in recent years,some new techniques and ideas have been used to treat the disease.For mild osteoradionecrosis of the jaw,the treatment concept tends to be conservative.This article mainly summarizes the latest research progress at home and abroad,and reviews the pathogenesis,clinical manifestations and treatment strate-gies for osteoradionecrosis of the jaws.

Bone defects caused by different causes such as trauma, severe bone infection and other factors are common in clinic and difficult to treat. Usually, bone substitutes are required for repair. Current bone grafting materials used clinically include autologous bones, allogeneic bones, xenografts, and synthetic materials, etc. Other than autologous bones, the major hurdles of rest bone grafts have various degrees of poor biological activity and lack of active ingredients to provide osteogenic impetus. Bone marrow contains various components such as stem cells and bioactive factors, which are contributive to osteogenesis. In response, the technique of bone marrow enrichment, based on the efficient utilization of components within bone marrow, has been risen, aiming to extract osteogenic cells and factors from bone marrow of patients and incorporate them into 3D scaffolds for fabricating bone grafts with high osteoinductivity. However, the scientific guidance and application specification are lacked with regard to the clinical scope, approach, safety and effectiveness. In this context, under the organization of Chinese Orthopedic Association, the Expert consensus for the clinical application of autologous bone marrow enrichment technique for bone repair ( version 2023) is formulated based on the evidence-based medicine. The consensus covers the topics of the characteristics, range of application, safety and application notes of the technique of autologous bone marrow enrichment and proposes corresponding recommendations, hoping to provide better guidance for clinical practice of the technique.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Oral squamous cell carcinoma(OSCC),a common malignancy of the head and neck,ranks sixth worldwide in terms of cancers with the most negative impact,owing to tumor relapse rates,cervical lymphnode metastasis,and the lack of an efficacious systemic therapy.Its prognosis is poor,and its mortality rate is high.Octamer-binding transcription factor 4(OCT4)is a member of the Pit-Oct-Unc(POU)family and is a key reprogramming factor that produces a marked effect in preserving the pluripotency and self-renewal state of embryonic stem cells(ESCs).According to recent studies,OCT4 participates in retaining the survival of OSCC cancer stem cells(CSCs),which has far-reaching implications for the occurrence,recurrence,metastasis,and prognosis of oral carcinogenesis.Therefore,we summarize the structure,subtypes,and function of OCT4 as well as its role in the occurrence,progression,and prognosis of OSCC.

Polyetheretherketone (PEEK) has been widely applied in orthopedics because of its excellent mechanical properties, radiolucency, and biocompatibility. However, the bioinertness and poor osteointegration of PEEK have greatly limited its further application. Growing evidence proves that physical factors of implants, including their architecture, surface morphology, stiffness, and mechanical stimulation, matter as much as the composition of their surface chemistry. This review focuses on the multiple strategies for the physical modification of PEEK implants through adjusting their architecture, surface morphology, and stiffness. Many research findings show that transforming the architecture and incorporating reinforcing fillers into PEEK can affect both its mechanical strength and cellular responses. Modified PEEK surfaces at the macro scale and micro/nano scale have positive effects on cell-substrate interactions. More investigations are necessary to reach consensus on the optimal design of PEEK implants and to explore the efficiency of various functional implant surfaces. Soft-tissue integration has been ignored, though evidence shows that physical modifications also improve the adhesion of soft tissue. In the future, ideal PEEK implants should have a desirable topological structure with better surface hydrophilicity and optimum surface chemistry.
Benzophenones ; Ketones/chemistry* ; Polyethylene Glycols/chemistry* ; Polymers/chemistry* ; Surface Properties