Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

ObjectiveTo evaluate the quality of clinical practice guidelines and expert consensus statements on knee osteoarthritis （KOA） based on the Appraisal of Guidelines for Research & Evaluation Ⅱ （AGREE Ⅱ）， thus providing a new perspective for clinical selection as well as guideline development and updating. MethodsA systematic search was conducted for KOA-related guidelines and consensus statements published from November 1， 2019 to December 31， 2025. The databases and platforms searched included CNKI， VIP， Wanfang Data， PubMed， Web of Science， the National Institute for Health and Care Excellence （NICE）， SinoMed， Yimaitong， and relevant official websites. Two researchers independently screened the literature， and four researchers used AGREE Ⅱ to score the included documents and completed the quality appraisal after reaching a unified understanding. Subgroup analyses were further performed according to developing organization， document type， medical approach， funding status， and region of development， and longitudinal comparisons were conducted by year of publication. ResultsA total of 23 guidelines and consensus statements were included. The standardized scores of the six AGREE Ⅱ domains， from the highest to the lowest， were clarity of presentation ［（70.36±8.13）%］， scope and purpose ［（67.46 ± 11.44）%］， editorial independence ［（64.50±20.01）%］， rigor of development ［（62.24±15.26）%］， stakeholder involvement ［（55.73±10.29）%］， and applicability ［（53.89±13.17）%］. In terms of overall recommendation， 6 documents were rated as grade A and 17 as grade B. Stratified analyses showed that professional organizations scored higher than comprehensive organizations. The overall scores of traditional Chinese medicine/integrative medicine and Western medicine guidelines （or consensus statements） were similar. Guidelines scored higher than consensus statements. The overall scores were similar between documents with reported funding and those without reported funding. International guidelines scored higher than domestic guidelines. Longitudinal comparisons showed that the largest number of documents was published in 2021. The overall scores were higher in 2021—2022， and some domain scores declined in 2023—2024. Overall， the quality of recent guidelines and consensus statements for KOA showed slight fluctuations， without a clear linear trend. ConclusionThe included guidelines and consensus statements for KOA can generally serve as references for clinical practice. However， the quality across domains remains uneven， and stakeholder involvement and applicability are still weak domains. Future guideline development and updating should further improve methodological standardization and transparency in reporting.

Objective:To establish ferroptosis-related risk characteristics, to evaluate the prognostic correlation of ferroptosis-related genes in hepatocellular carcinoma, and to explore the complex relationship between hepatocellular carcinoma, ferroptosis and immune microenvironment.Methods:The bioinformatics analysis involved obtaining ferroptosis-related differentially expressed genes (DEGs) from the GeneCards database and the cancer genome atlas database. The biological functions of ferroptosis-related DEGs were analyzed using gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment. Ferroptosis-related DEGs clusters were identified using univariate Cox regression analysis and cluster analysis, etc. The correlation between ferroptosis-related DEGs clusters and tumor immune microenvironment and tumor occurrence score was evaluated using immunopanoramic analysis and tumor-related score analysis. Based on ferroptosis-related characteristics, a ferroptosis-related characteristic spectrum and nomogram were constructed using multivariate Cox regression and correlation analysis, etc. The correlation between the risk characteristics and tumor immune microenvironment, tumor occurrence score and gene mutation were evaluated using immune panoramic analysis, tumor-related score analysis and gene mutation analysis. In the experimental verification stage, the mRNA expression levels of aurora kinase A ( Aurka), acetyl-CoA carboxylase alpha ( Acaca) and arrestin domain containing 3 ( Arrdc3) in mouse primary hepatocytes and mouse hepatoma Hepa1-6 cells were verified by real-time reverse transcription-PCR (RT-qPCR). The mRNA expression levels of AURKA, ACACA and ARRDC3 in adjacent normal tissues and tumor tissues of patients with hepatocellular carcinoma were verified by RT-qPCR. A heat map was used to show the correlation between clustering and clinical parameters, and this was analyzed using a chi-square test. Significance analysis was performed using a two-sided unpaired t test. Results:A total of 35 up-regulated genes and 19 down-regulated genes were identified. These genes were mainly involved in biological processes and signaling pathways related to ferroptosis, oxidative stress and fatty acid metabolism. A total of 14 ferroptosis-related DEGs were identified to be associated with prognosis. The clusterring effect was best when hepatocellular carcinoma patients were divided into two subgroups. The survival rate of cluster 2 was lower than that of cluster 1 ( P<0.05). There was no significant difference in the tumor immune dysfunction and exclusion (TIDE) score between cluster 2 and cluster 1 ( P=0.43). Cluster 1 exhibited higher levels of immune cell infiltration, particularly CD4 + T cells ( P<0.01). The expression levels of 10 major histocompatibility complex (MHC) molecule-related genes were higher in cluster 1. The angiogenesis activity score ( P=0.048) and stemness score ( P=0.038) of cluster 2 were increased, and the expression levels of programmed death-1 ( PDCD1) and cytotoxic T lymphocyte-associated antigen-4 ( CTLA-4) in cluster 2 (5.924±0.013 and 5.475±0.042) were higher than those in cluster 1 (4.539±0.143 and 4.372±0.176) (both P<0.05). The expression levels of AURKA, glucose-6-phosphate dehydrogenease ( G6PD), ACACA, GABA type A receptor associated protein like 1 ( GABARAPL1) and ARRDC3 were correlated with the T stage, clinical stage and survival status of hepatocellular carcinoma. The survival rate of the high-risk group was lower than that of the low-risk group with time ( P<0.01). The area under the curve of the risk characteristics at 1, 3 and 5 years was 0.797, 0.717 and 0.639, respectively. The actual survival time 1, 3, and 5 years was highly consistent with the corresponding predicted survival time. The levels of memory B cell infiltration, angiogenesis activity score and cell stemness score, programmed death-ligand 1, CTLA-4, hepatitis A virus cell receptor 2, lymphocyte activation gene 3 and PDCD1 gene expression (0.013 8±0.036 0, 0.884±0.212, 0.387±0.135, 6.273±0.228, 5.847±0.331, 8.179±0.259, 6.859±0.263 and 5.142±0.326) in the high-risk group were higher than those in the low-risk group (0.001 5±0.021 0, 0.874±0.132, 0.298±0.125, 5.866±0.132, 3.742±0.237, 7.236±0.321, 6.324±0.242 and 4.513±0.211) ( P<0.05, 0.01). The expression levels of MHC molecule-related genes in the high-risk group were also higher than those in the low-risk group ( P<0.05, 0.01), while the infiltration levels of resting mast cells, activated natural killer cells, and resting natural killer cells (0.043 2±0.135 0, 0.032 1±0.143 0 and 0.016 3±0.001 9) and the TIDE score (0.072 0±0.018 0) in the high-risk group were lower than those in the low-risk group (0.054 9±0.023 0, 0.042 7±0.017 0, 0.024 6±0.021 2 and 0.094 0±0.013 5) ( P<0.05, 0.01). The top five genes with the highest mutation frequency in the high-risk group were tumor protein P53 ( TP53, 43%), titin ( TTN, 21%), catenin beta 1 ( CTNNB1, 20%), mucin 16 ( MUC16, 18%) and piccolo presynaptic cytomatrix protein ( PCLO, 11%). The top five genes with the highest mutation frequency in the low-risk group were CTNNB1 (30%), TTN (24%), albumin ( ALB, 16%), MUC16 (15%) and PCLO (11%). The cube protein and PCLO showed the co-occurrence of gene mutations in the high-risk group, while MUC16 and axis 1 protein showed the co-occurrence of gene mutations in the low-risk group. There was no significant difference in tumor mutation burden (TMB) between the high-risk group (1.374±0.026) and the low-risk group (1.303±0.081) ( P=0.073). There was no significant difference in survival time between the high-TMB group (2.3 years) and the low-TMB group (3.8 years) ( P=0.293). The mutation rates of AURKA, G6PD, ACACA, GABARAPL1 and ARRDC3 genes (2.0%, 2.0%, 4.0%, 0.3% and 0.6%) were relatively low. The relative expression levels of Aurka, Acaca and Arrdc3 mRNA in Hepa1-6 cells (13.331±0.000, 6.619±0.000 and 1.209±0.002) were higher than those in mouse primary hepatocytes (1.000±0.000, 1.000±0.000 and 1.000±0.000) (all P<0.01). The relative expression levels of AURKA, ACACA and ARRDC3 mRNA in tumor tissues of patients with hepatocellular carcinoma (2.102±0.365, 2.476±0.351 and 11.460±9.189) were higher than those in adjacent normal tissues of patients with hepatocellular carcinoma (1.122±0.648, 0.831±0.935 and 0.852±0.171) ( P<0.05, 0.01). Conclusions:This study constructed a prognostic signature comprising five ferroptosis-related genes ( AURKA, G6PD, ACACA, GABARAPL1, and ARRDC3) that is highly correlated with clinical hepatocellular carcinoma data. This study highlights the significance of ferroptosis-related genes as prognostic markers for hepatocellular carcinoma and provides insights into the complex relationship between hepatocellular carcinoma, ferroptosis, and the immune microenvironment.

OBJECTIVE: To investigate the effects of using different filters in continuous renal replacement therapy (CRRT) on the mortality, inflammatory mediator level and hemodynamics in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A prospective study was conducted. The patients with SA-AKI undergoing first CRRT admitted to the critical care medicine department of General Hospital of Ningxia Medical University from August 2022 to October 2023 were enrolled as the study objects, and they were divided into observation group and control group by random number table method. All patients received routine treatment including anti-infection, optimized volume management and organ function support. On this basis, the observation group was treated with oXiris filter for CRRT, while the control group was treated with ordinary filter for CRRT, and the first treatment time was ≥ 36 hours. General data of the two groups were collected and compared. At the same time, the inflammatory indicators [high-sensitivity C-reactive protein (hs-CRP), procalcitonin (PCT), interleukin-6 (IL-6)], sequential organ failure assessment (SOFA) score, mean arterial pressure (MAP), blood lactic acid (Lac), noradrenaline dosage and other related indicators were collected before CRRT treatment and 24 hours and 48 hours after treatment, and the 7-day and 28-day mortality of patients were recorded. RESULTS: Finally, 65 patients were enrolled, including 30 in the observation group and 35 in the control group. There were no significant differences in baseline data including age, gender, acute kidney injury (AKI) stage and infection source between the two groups. The 7-day mortality of observation group was significantly lower than that of control group [16.7% (5/30) vs. 42.9% (15/35), P < 0.05]. There was no significant difference in 28-day mortality between the observation group and the control group [36.7% (11/30) vs. 54.3% (19/35), P > 0.05]. There were no significant differences in inflammation indicators, SOFA score, MAP, Lac and norepinephrine dosage before treatment between the two groups. After 24-hour and 48-hour treatment, the hemodynamics of the two groups were stable compared with before treatment, the inflammatory indicators, SOFA score, Lac and norepinephrine dosage were reduced to varying degrees, and MAP was significantly increased. In the observation group, hs-CRP, PCT, IL-6, SOFA score, MAP, and norepinephrine dosage showed statistical significance at 24 hours after treatment as compared with before treatment [hs-CRP (mg/L): 125.0 (105.0, 171.2) vs. 280.5 (213.2, 313.8), PCT (μg/L): 51.0 (20.0, 62.8) vs. 71.0 (10.8, 100.0), IL-6 (ng/L): 1 762.2 (300.8, 4 327.5) vs. 4 447.5 (630.4, 5 000.0), SOFA score: 13.0 (12.0, 14.0) vs. 16.0 (15.0, 17.0), MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 79.00±12.87 vs. 65.20±11.70, norepinephrine dosage (μg×kg^-1×min^-1): 0.82±0.33 vs. 1.63±0.51, all P < 0.05]. In the control group, PCT and MAP showed statistical significance after 48 hours of treatment as compared with before treatment. Compared with the control group, hs-CRP, SOFA score and norepinephrine dosage after 48 hours of treatment in the observation group were significantly decreased [hs-CRP (mg/L): 87.2 (74.2, 126.0) vs. 157.0 (88.0, 200.0), SOFA score: 11.0 (10.0, 12.0) vs. 12.0 (10.0, 14.0), norepinephrine dosage (μg×kg^-1×min^-1): 0.51±0.37 vs. 0.81±0.58, all P < 0.05], MAP was significantly increased (mmHg: 82.00±8.71 vs. 77.77±7.80, P < 0.05). CONCLUSION In the treatment of CRRT, oXiris filter can reduce the short-term mortality of SA-AKI patients, lower inflammatory mediators levels and improve hemodynamics, showing therapeutic advantages over conventional filters.
Humans ; Acute Kidney Injury/etiology* ; Sepsis/therapy* ; Prospective Studies ; Interleukin-6 ; Continuous Renal Replacement Therapy/methods* ; C-Reactive Protein ; Male ; Female ; Middle Aged ; Hemodynamics ; Procalcitonin ; Aged

OBJECTIVE: To investigate the predictive value of inflammatory indicator and serum cystatin C (Cys C) for the prognosis of patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A prospective observational study was conducted. Patients with SA-AKI admitted to the intensive care unit (ICU) of the General Hospital of Ningxia Medical University from January 2022 to December 2023 were selected as the study subjects. General patient data, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), inflammatory indicator, and serum Cys C levels were collected. The 28-day survival status of the patients was observed. A multivariate Logistic regression model was used to analyze the risk factors affecting the poor prognosis of SA-AKI patients. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive efficacy of each risk factor for the prognosis of SA-AKI patients. RESULTS: A total of 111 SA-AKI patients were included, with 65 patients (58.6%) in the survival group and 46 patients (41.4%) in the death group. The SOFA score, APACHE II score, interleukin-6 (IL-6), procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), and serum Cys C levels in the death group were significantly higher than those in the survival group [SOFA score: 15.00 (14.00, 17.25) vs. 14.00 (11.00, 16.00), APACHE II score: 26.00 (23.75, 28.00) vs. 23.00 (18.50, 28.00), IL-6 (ng/L): 3 731.00±1 573.61 vs. 2 087.93±1 702.88, PCT (μg/L): 78.19±30.35 vs. 43.56±35.37, hs-CRP (mg/L): 266.50 (183.75, 326.75) vs. 210.00 (188.00, 273.00), serum Cys C (mg/L): 2.01±0.61 vs. 1.62±0.50, all P < 0.05]. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.273, 95% confidence interval (95%CI) was 1.012-1.600, P = 0.039], IL-6 (OR = 1.000, 95%CI was 1.000-1.001, P = 0.043), PCT (OR = 1.018, 95%CI was 1.002-1.035, P = 0.030), and Cys C (OR = 4.139, 95%CI was 1.727-9.919, P = 0.001) were independent risk factors affecting the 28-day prognosis of SA-AKI patients. ROC curve analysis showed that the area under the curve (AUC) of SOFA score, IL-6, PCT, and Cys C in predicting the 28-day prognosis of SA-AKI patients were 0.682 (95%CI was 0.582-0.782, P = 0.001), 0.753 (95%CI was 0.662-0.843, P < 0.001), 0.765 (95%CI was 0.677-0.854, P < 0.001), and 0.690 (95%CI was 0.583-0.798, P = 0.001), respectively. The combined predictive value of these four indicators for the prognosis of SA-AKI patients were superior to that of any single indicator, with an AUC of 0.847 (95%CI was 0.778-0.916, P < 0.001), a sensitivity of 95.7%, and a specificity of 56.9%. CONCLUSION The combination of SOFA score, IL-6, PCT, and Cys C provides a reliable predictive value for the prognosis of SA-AKI patients.
Humans ; Acute Kidney Injury/mortality* ; APACHE ; C-Reactive Protein ; Cystatin C/blood* ; Interleukin-6/blood* ; Logistic Models ; Predictive Value of Tests ; Procalcitonin/blood* ; Prognosis ; Prospective Studies ; Risk Factors ; ROC Curve ; Sepsis/mortality*

Objective: To explore the association between mammalian sterile 20-like kinase 2(MST2) gene polymorphism and haplotype and the risk of colorectal cancer, rectal cancer, and colon cancer in the Han population in Baotou area by case-control association study. Methods: A total of 390 patients with colorectal cancer diagnosed by pathology and 413 normal physical examination pop-ulation were collected, and 2 mL of peripheral blood was taken for subsequent gene genotyping. Single nucleotide polymorphisms(SNPs) of MST2 gene were screened according to the genetic polymorphism data of Chinese Han population provided by the NCBI-Hapmap database. Gene genotyping was performed by Taqman method. Logistic regression was used to calculate the association between each SNP and the risk of colorectal cancer, colon cancer, and rectal cancer under codominant, dominant, overdominant, and recessive genetic models. Results: Five SNPs of MST2 gene were screened, namely rs11783149, rs10955176, rs7827435, rs4075986, rs3019295. Among them, SNP rs4075986 was associated with the risk of colorectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=2.473(1.844-3.316) could increase the risk of colorectal cancer. Compared with the rs4075986 GG genotype, carrying the AG+AA genotype [OR(95%CI)=2.475(1.844-3.323) could increase the risk of colorectal cancer. SNP rs4075986 and rs3019295 were associated with the risk of rectal cancer. Compared with the rs4075986 GG+AA genotype, carrying the AG genotype [OR(95%CI)=3.411(2.387-4.874)] could increase the risk of rectal cancer. Compared with the rs3019295 GG+AA genotype, carrying the AG genotype [OR(95%CI)=0.706(0.501-0.996)] could reduce the risk of rectal cancer. SNP rs11783149 and rs4075986 were associated with the risk of colon cancer. Compared with the rs11783149 CC genotype, carrying the TT [OR(95%CI)=10.883(1.186-99.862)] and CT [OR(95%CI)=1.665(1.036-2.675)] genotype could increase the risk of colon cancer, respectively. Compared with the rs4075986 GG genotype, the AG+AA genotype [OR(95%CI)=1.824(1.262-2.638)] could increase the risk of colon cancer. Conclusion MST2 gene SNP rs3019295 AG genotype may be protective factor for rectal cancer. SNP rs11783149 CT and TT genotypes maybe risk factors for colon cancer. SNP rs4075986 AG and AG+AA genotypes may be a common risk factors for colorectal cancer, rectal cancer and colon cancer.

OBJECTIVE: To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. METHODS: A female IP patient with a heterozygous IKBKG c.1167dup variant but without family genetic data who sought genetic counseling at Women and Children' Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT tests, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: A total of seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38+6 weeks of gestation. CONCLUSION For IP patients with de novo mutation or without family genetic samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.
Female ; Humans ; Male ; Pregnancy ; Genetic Testing/methods* ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; I-kappa B Kinase/genetics* ; Incontinentia Pigmenti/diagnosis* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Infant, Newborn

Objective:To investigate the changes of pathogenic bacteria distribution and immune response of urinary tract infection(UTI)after pyeloureteroplasty in children.Methods:A total of 150 children with obstructive hydronephroplasty who received pyeloureteroplasty in Qinghai Women and Children's Hospital from February 2020 to June 2023 were selected as the study objects.The postoperative urine of the children was collected,the pathogens were identified by automatic bacterial analyzer,and the patients were divided into infected group and uninfected group according to the infection status.The detection of pathogenic bacteria in children with UTI was analyzed.The clinical data of the two groups were compared,and the influencing factors of postoperative UTI were screened by Logistic regression analysis,and the prediction model was established and verified.The changes of immune response were compared between the two groups.Results:UTI occurred in 56 cases(37.33%)of 150 children who underwent pyeloureteroplasty.There were 58 strains of gram-negative bacteria,29 strains of gram-positive bacteria and 2 strains of fungi isolated.The main pathogenic bacteria was Escherichia coli.Multivariate Logistic regression analysis showed that serum creatinine(SCr)and hydronephrosis volume/renal volume(HV/RV)levels increased,urinary catheter retention time,urinary bag replacement time and hospital stay were risk factors for UTI after pyeloureteroplasty in children,increased age and elevated albumin(Alb)were protective factors(P<0.05).Through Bootstrap self-sampling,the prediction model had good differentiation and accuracy.There was no significant difference in the levels of CD4+,CD8+and IgM between the two groups before surgery(P>0.05),and the levels of CD4+,CD8+and IgM were signi-ficantly improved between the two groups after surgery,and the improvement degree of the uninfected group was significantly better than that of the infected group(P<0.05).Conclusion:The pathogens of UTI in children after pyeloureteroplasty are mainly gram-nega-tive bacteria,and the immune function is increased 7 days after the operation.

Background and purpose:The microphthalmia-associated transcription factor(MITF)plays a complex role in melanoma pathogenesis and progression.It is known to regulate multiple processes both in melanocytes and melanoma cells.While numerous studies have explored MITF in cutaneous melanoma(CM),research in acral melanoma(AM)is still limited.This study retrospectively analyzed the correlation between MITF expression and clinical,pathological characteristics and prognosis in AM patients,providing a basis for prognosis evaluation and personalized treatment plan formulation for patients.Methods:Patients who underwent primary resection of AM at Fudan University Shanghai Cancer Center from March 2008 to February 2022 were included.All surgical samples were diagnosed by clinical histopathology and used to construct the tissue microarray(TMA).This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center(approval number:2203-ZZK-69-3).Cutting complete tissue microarray and evaluating MITF expression levels by immunohistochemistry(IHC)staining were carried out.The results were independently assessed and scored by three pathologists.Clinical and pathological data were collected from the hospital's electronic medical record system,and each patient's data was matched to their corresponding tissue sample on the chip.Patients were stratified into two groups based on MITF expression levels.Statistical analyses were performed to assess differences in clinical,pathological characteristics and survival outcomes between these two groups.Results:A total of 137 AM patients were included.MITF expression was significantly associated with T stage,N stage,American Joint Committee on Cancer(AJCC)stage,clark level,sentinel lymph node status,and presence of ulceration.Among these,N stage and ulceration were independent risk factors for high expression of MITF after adjusting for confounding factors.Survival analysis showed that AM patients with high MITF expression or higher T stage were associated with shorter disease-free survival(DFS).Patients with high MITF expression showed no significant difference in overall survival(OS)between observation or cytokine therapy and adjuvant immune checkpoint inhibitor(ICI)therapy,whereas those with low MITF expression derived significant survival benefits from ICI treatment.Conclusion:A higher N stage or the presence of ulceration indicates high MITF expression in tumor cells,with high MITF levels serving as a warning signal for early recurrence,metastasis,and even death.Patients with low MITF expression could receive improved OS with early adjuvant ICI therapy.MITF could not only serve as an auxiliary diagnostic marker for melanoma but also provide a basis for clinical prognosis assessment and the formulation of personalized treatment plans.

Objective To discuss the clinical efficacy of microwave ablation(MWA)combined with percutaneous vertebroplasty(PVP),radiofrequency ablation(RFA)combined with PVP,and simple PVP in the treatment of vertebral metastatic tumors.Methods A total of 65 patients with vertebral metastatic tumors,who were admitted to the Northern Jiangsu People's Hospital of China to receive treatment from January 2019 to June 2023,were enrolled in this study.The patients were divided into MWA plus PVP group(M+P group,n=25,27 diseased vertebral bodies in total),RFA plus PVP group(R+P group,n=20,23 diseased vertebral bodies in total),and simple PVP group(P group,n=20,24 diseased vertebral bodies in total).Visual analog scale(VAS)score was used to assess the preoperative pain degree and the postoperative relief degree.Bone cement distribution and leakage at one week after surgery were evaluated.Results Successful operation was accomplished in all of the patients.No serious procedure-related complications occurred in all the patients of three groups.In R+P group,P group and M+P group,the preoperative mean VAS scores were(8.48±0.80)points,(8.57±0.98)points and(8.20±1.00)points respectively;the differences among the three groups were not statistically significant(P＞0.05).One week after operation,the pain was significantly relieved in all the patients of three groups;the mean VAS scores in R+P group,P group and M+P group were(4.10±0.85)points,(3.17±0.93)points and(2.44±1.23)points respectively,and the reduction in VAS score was most pronounced in M+P group(P＜0.05).Six months after operation;the mean VAS scores in R+P group,P group and M+P group were(1.87±0.84)points,(4.60±1.09)points and(1.48±0.71)points respectively;and the reduction in VAS score was most pronounced in the M+P group(P＜0.05).The used amount of bone cement in M+P group,R+P group and P group was(7.54±1.44)mL,(5.48±1.12)mL and(4.59±1.56)mL respectively,the difference among the three groups was statistically significant(P＜0.05).The vascular leakage rate(34.8％)and non-vascular leakage rate(52.2％)in P group were remarkably higher than those in R+P group and in M+P group(P＜0.05).No statistically significant difference in the rate of cement leakage existed between R+P group and M+P group(P＞0.05).Conclusion For the treatment of vertebral metastases,MW A plus PVP is superior to RFA plus PVP in pain relief rate.