BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

The self-remodeling of scleral extracellular matrix(ECM)is a significant characteristic alterationin the development of myopia, and it also influences the progression of myopia. The mechanisms of scleral remodeling are intricate, with transforming growth factor-β(TGF-β)and its associated signaling pathways playing a pivotal role. This review systematically summarizes the major metabolic changes in scleral ECM, the molecular mechanisms of the TGF-β signaling pathway, and its regulatory effects on scleral remodeling during myopic development, aiming to provide new insights and potential strategies for the treatment and prevention of myopia.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

[Objective] To retrospectively analyze the detection results of alanine aminotransferase (ALT) unqualified repeat blood donors in Guangzhou, so as to provide evidence for further expanding the repeat blood donor pool, reducing the rate of blood discarding and improving the qualified rate of blood test. [Methods] Blood donors with unqualified ALT in Guangzhou Blood Center from January 2018 to April 2024 were selected as the research objects. The past blood donation and population characteristics were analyzed according to the number of blood donations and ALT unqualified times. [Results] Among repeat blood donors with previous ALT disqualification, 99.5% to 99.7% did not have reactive markers for transfusion-transmitted diseases (TTD), which was higher than the rate among first-time blood donors with unqualified ALT (95.8%) (P<0.05). The rate of single-item ALT disqualification in repeat blood donors was higher in males than in females (P<0.05); it also varied by age (18-25 years > 26-35 years > 36-45 years > over 45 years) (P<0.05); and by quarter (third and fourth quarters > first and second quarters) (P<0.05). The ALT unqualified rate was significantly higher whole blood donors than that of platelet donors and returning blood donors (P<0.05). The overall ALT level (51.0 U/L), individual ALT level (56.0 U/L) and individual ALT unqualified rate (66.7%) of repeat blood donors with multiple ALT disqualifications were higher than those of repeat blood donors with single-item ALT disqualifications (26.0 U/L, 38.5 U/L, and 33.3%, respectively) (P<0.05). Moreover, as the number of ALT disqualifications increased, the overall level of ALT in repeat blood donors also increased (P<0.05), and the average level of individual ALT and individual ALT unqualified ratio tended to increase. Repeat blood donors with frequent ALT disqualifications had higher ALT levels (69.0 U/L). [Conclusion] The ALT unqualified rates of repeat blood donors were mostly non-specific elevation without TTD. Repeat blood donors with multiple ALT disqualifications tend to have continuous high ALT. Moreover, and with the increase of ALT disqualifications times, the overall ALT levels the average individual ALT levels and individual ALT unqualified rates showed an increasing trend.

[Objective]To analyze the clinical characteristics,efficacy of growth hormone(GH)therapy,and follow-up of a child with Rauch-Steindl syndrome(RAUST)caused by NSD2 gene mutation,aiming to enhance pediatricians'understanding of this disorder.[Methods]We summarized the clinical features,gene test results,outcomes of GH therapy,and follow-up data of a child with RAUST syndrome caused by NSD2 mutation admitted to the Pediatric Endocrinology Department of Sun Yat-sen Memorial Hospital in April 2017,and then conducted a comparative analysis with relevant literature.[Results]The 2.9-year-old boy at initial visit was born prematurely at 36 weeks of gestation,with a birth weight of 1.7 kg and a body length of 42.0 cm.Clinical manifestations included intrauterine growth retardation,delayed language and motor development,extreme short stature(82.0 cm,-3.7 SD),emaciation,and distinctive facial features(triangular face,narrow jaw,prominent forehead,arched eyebrows,sparse eyebrows,high anterior hairline,crowded dentition),accompanied by bilateral cryptorchidism.Bone age was delayed by 1.4 years.Karyotyping and chromosomal microarray analysis were normal.GH therapy initiated at 3.8 years old yielded annual growth rates of 4.9-6.6 cm/year.When the treatment was discontinued at the age of 8.0,the boy's height was 113.7 cm(-3.0 SD),with subsequent decline in growth velocity.Whole exome sequencing in July 2024 identified a frameshift variant c.4028del(p.Pro1343Glnfs*49)in NSD2,which was confirmed as de novo pathogenic variation by parental Sanger sequencing.[Conclusions]This study reports the clinical features of RAUST syndrome caused by NSD2 mutation and explores the long-term efficacy of GH therapy.The findings contribute to a better understanding of this rare syndrome and further optimize its diagnosis and management.

Objective To explore the constituent elements of patients'sense of gain experience and provide theoretical insights for improving patient satisfaction with healthcare services.Methods Purposive sampling and convenience sampling were employed to select 46 experts in health management from universities,hospitals,government agencies,and academic societies across China for semi-structured interviews.Qualitative analysis of the interview data was conducted using grounded theory.Results Through three-level coding,159 initial concepts,19 categories,7 main categories,and 2 core categories were identified.A conceptual framework for the constituent elements of patients'sense of gain experience was constructed,centered on two core dimensions:micro-level experience and macro-level acquisition.Conclusion The concept of"patients'sense of gain experience"enriches the theoretical framework of"sense of gain"and breaks through the unidimensional approach to evaluating medical service quality.Its enhancement requires collaborative efforts from multiple stakeholders,including medical institutions,governments,policymakers,and other actors.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.