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:H-type vessels(CD31hiEmcnhi)possess unique functionalities that offer new perspectives and entry points for comprehensively understanding the mechanisms of vascular-mediated bone metabolism regulation.This has triggered a significant paradigm shift in bone science research from a"bone-centric"approach to an"integrative bone-vascular"framework.OBJECTIVE:To perform a visual analysis based on literature data in the field of H-type vessels,aiming to identify research hotspots and emerging trends.METHODS:A systematic search was conducted in the CNKI and Web of Science databases for English and Chinese publications related to H-type vessels,covering the period from 2014 to 2024.The CiteSpace 6.2.R4 information visualization software was utilized to analyze and visualize data on publication countries,authors,institutions,keywords,and timeline views.RESULTS AND CONCLUSION:(1)A total of 59 Chinese and 185 English publications were included in the analysis.Since the introduction of the H-type vessel concept in 2014,the number of related research publications has been steadily increasing,accompanied by a significant growth in academic output.China leads the research in this domain,with major institutions including Southern Medical University,Sichuan University,and Shanghai Jiao Tong University.Keyword analysis indicated that current research hotspots primarily focus on the generation and regulatory mechanisms of H-type vessels,their roles in bone formation and remodeling,and their associations with bone metabolic diseases.Additionally,emerging keywords such as"induced membrane,""cartilage repair,"and"traditional Chinese medicine"suggest that research is progressively moving towards diversification and multidisciplinary integration.(2)H-type vessels play a crucial role in the development and progression of bone diseases,and relevant studies are pivotal for a deeper understanding of the physiological and pathological processes of bone tissue.Future research should further elucidate the specific mechanisms of H-type vessels in various disease contexts and promote the clinical translation of basic research findings.These efforts will provide innovative ideas and strategies for the prevention and treatment of bone-related diseases.

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:H-type vessels(CD31hiEmcnhi)possess unique functionalities that offer new perspectives and entry points for comprehensively understanding the mechanisms of vascular-mediated bone metabolism regulation.This has triggered a significant paradigm shift in bone science research from a"bone-centric"approach to an"integrative bone-vascular"framework.OBJECTIVE:To perform a visual analysis based on literature data in the field of H-type vessels,aiming to identify research hotspots and emerging trends.METHODS:A systematic search was conducted in the CNKI and Web of Science databases for English and Chinese publications related to H-type vessels,covering the period from 2014 to 2024.The CiteSpace 6.2.R4 information visualization software was utilized to analyze and visualize data on publication countries,authors,institutions,keywords,and timeline views.RESULTS AND CONCLUSION:(1)A total of 59 Chinese and 185 English publications were included in the analysis.Since the introduction of the H-type vessel concept in 2014,the number of related research publications has been steadily increasing,accompanied by a significant growth in academic output.China leads the research in this domain,with major institutions including Southern Medical University,Sichuan University,and Shanghai Jiao Tong University.Keyword analysis indicated that current research hotspots primarily focus on the generation and regulatory mechanisms of H-type vessels,their roles in bone formation and remodeling,and their associations with bone metabolic diseases.Additionally,emerging keywords such as"induced membrane,""cartilage repair,"and"traditional Chinese medicine"suggest that research is progressively moving towards diversification and multidisciplinary integration.(2)H-type vessels play a crucial role in the development and progression of bone diseases,and relevant studies are pivotal for a deeper understanding of the physiological and pathological processes of bone tissue.Future research should further elucidate the specific mechanisms of H-type vessels in various disease contexts and promote the clinical translation of basic research findings.These efforts will provide innovative ideas and strategies for the prevention and treatment of bone-related diseases.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Intra-abdominal Hernia with Bowel Obstruction Triggering Multi-organ Failure: The Role of Preoperative Enteritis This report details the clinical course of a 41-year-old male who developed fulminant multiple organ dysfunction syndrome following emergency surgery for a strangulated intra-abdominal hernia. Preoperative manifestations, including diarrhea and marked leukocytosis, pointed towards an underlying infectious enteritis. We posited that surgical release of the obstructed, ischemic bowel segment precipitated a massive systemic influx of endotoxins and inflammatory mediators, triggering septic shock and rapid sequential organ failure. This case underscored the critical need to suspect concomitant gastrointestinal infection in patients presenting with mechanical bowel obstruction accompanied by infectious signs. Aggressive perioperative sepsis management encompassing early empiric antimicrobial therapy, vigilant hemodynamic monitoring, and preparedness for advanced organ support is essential to mitigate this severe complication.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

The"capitation payment with retained surplus and shared accountability for reasonable overruns"mechanism constitutes a pivotal institutional framework for advancing the high-quality development of County Medical Communities(CMCs).This study addresses two critical operational challenges:identifying the sources of medical insurance fund surplus and optimizing the governance of fund retention processes.Grounded in transaction cost theory,we develop an analytical framework examining the formation of medical insurance fund surplus through the dual lenses of intra-organizational dynamics within CMCs and external medical insurance payment mechanism design.Utilizing Deqing County,Zhejiang Province as an empirical case,this research proposes a five-pronged strategy:Clarifying generation channels of insurance fund surplus,scientifically determining regional medical insurance budgets,implementing bundled payment mechanisms for CMCs,adopting hybrid payment models integrating unified and differentiated approaches,and establishing performance-based incentive systems.These findings elucidate the formative pathways of medical insurance fund surplus while offering theoretical and practical insights for enhancing payment system reforms to support CMC development.

Objective:To investigate the clinical efficacy of extended abdominal wall resec-tion combined with reconstruction for abdominal wall aggressive fibromatosis (AF).Methods:The retrospective and descriptive study was conducted. The clinical data of 70 patients with abdominal wall AF who were admitted to 3 medical centers, including The First Affiliated Hospital of the University of Science and Technology of China, between January 2009 and July 2024 were collected. There were 6 males and 64 females, aged (36±13)years. All patients underwent extended abdominal wall resection combined with abdominal wall reconstruction. Observation indicators: (1) surgical situations; (2) tumor recurrence and postoperative complications. Comparisons of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1)Surgical situations. All 70 patients underwent extended abdominal wall resection combined with abdominal wall recons-truction. The operation time was 90(91)minutes and duration of postoperative hospital stay was 10(6)days. Of the 70 patients, 41 patients underwent abdominal wall AF resection plus polypropylene mesh abdominal wall reconstruction, with a defect area of 60(54)cm2. The mesh placement method was uniformly Sublay repair. The remaining 29 patients underwent abdominal wall AF resection plus direct suture repair, with a defect area of 34(31)cm2. There was a significant difference in the abdominal wall defect area between the two groups ( U=291.00, P<0.05). All 70 patients achieved R 0 resection. The distance from surgical margin to tumor edge was 2-3 cm in 39 cases and >3 cm in 31 cases. (2) Tumor recurrence and postoperative complications. All 70 patients were followed up for 78(90)months. During follow-up, 10 patients developed tumor recurrence (5 cases with mesh reinforced abdominal wall reconstruction and 5 cases with direct suture repair). Among them, one case was monitored, one case underwent radiotherapy, and neither received further surgical treatment. The remaining 8 patients underwent repeat R 0 resection, and no further recurrence occurred. There was no significant difference in recurrence rate between the patients with mesh reconstruction and patients with direct suture repair ( χ2=0.06, P>0.05). The postoperative recurrence rate was 9.7%(3/31) in patients with the distance from surgical margin to tumor edge >3 cm, versus 17.9%(7/39) in patients with the distance from surgical margin to tumor edge of 2-3 cm, showing no significant difference between them ( χ2=0.97, P>0.05). Sixty patients had no tumor recurrence. During follow-up, none of the 70 patients developed incisional hernia. Two patients experienced postoperative wound infection, and 6 cases developed postoperative chronic pain. Conclusion:Extended abdominal wall resection combined with reconstruction is safe and feasible for abdominal wall AF.

Enhancer of zeste homolog 2(EZH2)is a histone methyltransferase It mediates trimethylation of lysine 27 on histone H3,thereby facilitating the epigenetic silencing of downstream genes.In conjunc-tion with SUZ12,EED,and other components,it constitutes the polycomb repressive complex 2(PRC2)complex.While EZH2 is intricately involved in cellular proliferation and cardiac development,the chan-ges in its expression during cardiac terminal differentiation remain elusive.In this study,we employed differential gene expression analysis of embryonic and adult myocardial cells using the GEO database,and found that EZH2 is highly expressed in embryonic myocardium,but is present at very low levels in adult myocardium(P＜0.0001).Conversely,the expression changes of PRC2 members SUZ12 and EED are not as pronounced.Online analysis through the Tabula Muris database indicates that under physiological conditions,various cell subpopulations in the adult mouse heart exhibit negligible expression of EZH2.Immunohistochemical staining of mouse cardiac tissues shows that EZH2 is highly expressed in embryonic and neonatal myocardium but declines progressively from the first day after birth(P＜0.0001),becoming almost undetectable by the third day.Western blotting further confirms the rapid disappearance of EZH2 expression post-birth(P＜0.05),with EZH1 compensating for the downregulation of EZH2 to maintain H3K27me3 modification levels.Additionally,using the P19 teratocarcinoma stem cell model for cardio-myocyte differentiation,it is observed that EZH2 is significantly upregulated during the transition from cardiac progenitor cells to spontaneously beating cardiomyocytes,correlating with the expression of the cardiomyocyte transcription factor Gata4(P＜0.01).Targeted degradation of EZH2 using the small mole-cule drug MS1943 significantly inhibits the proliferation of induced cardiomyocytes,as evidenced by 5-e-thynyl-2'-deoxyuridine(EdU)incorporation assays(P＜0.01),and RT-qPCR reveals a marked in-crease in the expression of the proliferation inhibitor CDKN1A(P＜0.01).In summary,the high expres-sion of EZH2 in embryonic myocardial cells is associated with enhanced cell proliferation.The rapid loss of EZH2 expression postnatally correlates with the loss of proliferative capacity in cardiomyocytes,mark-ing it as a key indicator of cardiac terminal differentiation.