OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

This article reviews the application and future prospects of complement component 5 (C5) inhibitors in kidney transplantation for sensitized recipients. Kidney transplantation significantly improves the survival and quality of life for patients with end-stage kidney disease. However, donor kidney shortages and human leukocyte antigen (HLA) sensitization are major obstacles. HLA-sensitized candidates, particularly highly sensitized ones, face a significantly elevated risk of post-transplant rejection due to pre-existing HLA antibodies. Eculizumab, a terminal complement inhibitor, inhibits rejection by preventing the cleavage of C5 into C5a and C5b, thus blocking the formation of the membrane attack complex and suppressing complement-dependent cytotoxicity.

Fibrosis is a pathological process characterized by an increase in connective tissue and a decrease in parenchymal cells within organ tissues.During its progression,fibrosis can lead to structural damage and functional decline of the affected organ.In recent years,it has found that non-selective cation channel transient receptor potential vanilloid subfamily 1(TRPV1)channel is closely related to fibrosis.When this channel is activated,it can increase the intracellular cation concentration and cause corresponding physiological and pathological changes,playing a particularly crucial role in regulating tissue fibrosis.Animal models have become important tools in studies into the mechanism by which the TRPV1 channel induces organ fibrosis.This article reviews the role of TRPV1 channels in the fibrosis of organs such as the heart,kidney,and pancreas in mice.The relevant signaling pathways in which TRPV1 channels participate to regulate fibrosis are summarized to provide new ideas for studying the pathogenesis of fibrosis and the development of targeted drugs.

Objective:To explore the efficacy of interventional therapy for transplant renal artery stenosis (TRAS) and the 1-, 2-, and 3-year survival rates of recipients after treatment.Methods:This is a retrospective case series study. Forty TRAS recipients who underwent interventional treatment at Zhengzhou University People's Hospital between April 2016 and April 2021 were included as the study group. The Kaplan-Meier method was used to calculate the survival rates of the transplanted kidneys and recipients, and survival curves were plotted. The improvement in graft function and blood pressure after interventional therapy in the study group was further analyzed.Results:The 1- and 3-year graft survival rates in the study group after interventional therapy were 87.5% and 82.5%, respectively; the 1-, 2-, and 3-year recipient survival rates were all 100%. One month after interventional therapy, the peak systolic velocity (PSV) and resistance index (RI) of the transplanted kidneys were (235.4±135.1) cm/s and 0.60±0.07, respectively, which were significantly different from the pre-treatment values [(482.8±180.6) cm/s and 0.52±0.12, respectively; both P<0.001]. Serum creatinine levels at 1, 2, and 3 years after interventional therapy were (166.6±93.7) μmol/L, (137.4±57.2) μmol/L, and (137.4±57.9) μmol/L, respectively, all significantly lower than the pre-treatment level [(242.9±156.8) μmol/L; P=0.001, P<0.001, and P<0.001, respectively]. Systolic blood pressure at 1, 2, and 3 years after treatment was (138.5±11.1) mmHg (1 mmHg=0.133 kPa), (134.0±12.0) mmHg, and (130.8±10.8) mmHg, respectively, all significantly lower than the pre-treatment value [(153.8±9.8) mmHg; all P<0.001]. Diastolic blood pressure at 1, 2, and 3 years after treatment was (84.4±9.9) mmHg, (83.7±10.1) mmHg, and (81.9±6.9) mmHg, respectively, all significantly lower than the pre-treatment value [(93.5±12.8) mmHg; P=0.002, P=0.001, and P<0.001, respectively]. Conclusions:Interventional therapy can enable the majority of kidney transplant recipients diagnosed with TRAS to avoid the need for further dialysis, and it has positive effects on both transplant renal function and blood pressure control.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Objective:To evaluate the efficacy of 3D printing technology combined with computer navigation-assisted screw implantation in the treatment of atlantoaxial instability (AAI) complicated by vertebral artery anomalies.Methods:A retrospective case series study was conducted to analyze the clinical data of 23 patients with AAI complicated by vertebral artery anomalies who were admitted to Honghui Hospital of Xi′an Jiaotong University between January 2019 and January 2023, including 10 males and 13 females, aged 19-70 years [(51.0±13.3)years]. Vertebral artery anomalies were categorized into unilateral high-riding vertebral artery with unilateral dominance ( n=14), bilateral high-riding vertebral arteries with unilateral dominance ( n=6), and ponticulus posticus ( n=3). All the patients underwent preoperative planning using a 3D-printed model of the atlantoaxial complex with the vertebral artery, followed by posterior atlantoaxial pedicle screw fixation with computer-assisted navigation. Operative duration and intraoperative blood loss were recorded. The accuracy of pedicle screw placement was assessed at 3 days postoperatively using the Gertzbein-Robbins classification. Visual analogue scale (VAS) scores and Japanese Orthopedic Association (JOA) scores were evaluated preoperatively, at 3 days, 3 months postoperatively, and at the last follow-up. Bony fusion was assessed using cervical CT with 3D reconstruction at the last follow-up. Complications were also observed. Results:All the patients were followed up for 12-19 months [(15.1±1.9)months]. The operative duration was 125-167 minutes [(140.6±10.9)minutes] and intraoperative blood loss was 200-600 ml [(295.7±77.8)ml]. At 3 days postoperatively, all the 66 pedicle screws were safely placed, with 60 screws (91%) rated as Gertzbein-Robbins Grade 0 and 6 screws (9%) as Grade 1. At 3 days and 3 months postoperatively, and at the last follow-up, the VAS scores were (4.0±1.0)points, (2.0±0.6)points, and (1.3±0.5)points, and the JOA scores were (14.2±1.2)points, (16.0±0.8)points, and (16.6±0.5)points, both of which were not only significantly improved compared with preoperative (5.6±1.3)points and (12.8±1.5)points, but also further improved over time ( P<0.05). At the last follow-up, 22 patients (96%) achieved satisfactory atlantoaxial bony fusion. No vertebral artery injury, spinal cord or nerve injury, cerebrospinal fluid leakage, or screw loosening were observed in any patients. Conclusion:For patients with AAI complicated by vertebral artery anomalies, 3D printing combined with computer navigation-assisted navigation for atlantoaxial pedicle screw implantation offers multiple advantages, including minimal surgical trauma, high screw placement accuracy, pain relief, neurological function improvement, high fusion rate, and lowered incidence of complications.

Objective:To analyse the effect of ultrasound-guided percutaneous liver biopsy and the coaxial biopsy needle tract radiofrequency ablation on patients diagnosed with hepatocellular carcinoma who are considered to be at risk of bleeding.Methods:The data of 117 patients with hepatocellular carcinoma who underwent coaxial biopsy needle tract radiofrequency ablation after ultrasound-guided percutaneous liver biopsy in Peking University First Hospital from March 2019 to April 2023 were retrospectively analysed. There were 95 males and 22 females, with the age of (62.0±11.8) years. A comprehensive analysis was conducted on the following variables: the pre-puncture platelet count, the international standardised ratio, anticoagulation therapy, the haemoglobin (Hb) level, the success rate of the liver puncture, the qualified rate of liver puncture specimens, the number of puncture samples, the length of hospital stay, the Hb level after puncture, bleeding within 10 days post-operation, and complications after ablation, including biliary fistula, hemothorax and organ perforation.Results:Among the 117 patients, 60 cases (51.3%) had an international normalized ratio >1.1, 40 cases (34.2%) had thrombocytopenia, that is, <150×10 9/L, and 17 cases (14.5%) received continuous anticoagulation therapy before the operation. It is evident that all 117 patients successfully completed the ultrasound-guided percutaneous liver biopsy, and that all liver biopsy specimens were qualified. The absence of biliary fistula, hemothorax, organ perforation or death in the patients post-ablation was noted. According to the adverse event evaluation criteria, version 5.0, 113 cases (96.6%) were classified as grade 1 and 4 cases (3.4%) were classified as grade 3. The Hb concentration of patients with minor bleeding (grade 1) prior to puncture was (119.7±22.2) g/L, which was significantly higher than the Hb concentration of patients with severe bleeding (grade 3), (76.0±10.4) g/L ( t=3.92, P=0.010). A meticulous examination of the data revealed that there were no statistically significant differences between the two groups with regard to pre-puncture platelet count, pre-puncture international standardised ratio, pre-puncture proportion of receiving anticoagulant drugs, length of hospital stay and number of puncture samples (all P>0.05). Conclusion:For patients with hepatocellular carcinoma who are at risk of bleeding, ultrasound-guided percutaneous liver biopsy followed by coaxial biopsy needle tract radiofrequency ablation can obtain satisfactory liver tissue samples and is relatively safe. There were differences in hemoglobin levels before puncture among patients with different bleeding after puncture.

Objective To explore the application value of simple drawing line puncture combined with visual articular process arthroplasty in lateral foraminoscopy.Methods A retrospective analysis was performed on 89 patients with single-segment lumbar disc herniation treated with lateral foraminoscopy from May 2019 to December 2022,including traditional transforaminal endoscopic spine system(TESSYS)technology(conventional group,35 cases)and simple drawing line puncture combined with visual articular process arthroplasty(modified group,54 cases).The fluoroscopy times,puncture time,and operation time of the two groups were compared.The Visual Analogue Score(VAS),Oswestry Disability Index(ODI),and MacNab criteria were used to evaluate the surgical effect at 3 d after surgery and at the last follow-up.Results All the operations were successfully completed without conversion to open surgery.In the conventional group,there was 1 case of L4 nerve root injury,who was considered intraoperative nerve root compression injury.There was no abnormality in lower limb muscle strength after surgery,but hyperalgesia and numbness in the innervated cutaneous area accompanied by nocturnal cramps.The patient was given treatment with pregabalin,mecobalamin,vitamin B1 and B6 for 2 months,and returned to normal at 1 year of follow-up.The other cases had no complications such as dural injury,abdominal organ injury,or incision infection.Recurrence occurred in 1 case in the conventional group and 2 cases in the modified group,and all the 3 cases occurred within 3 months after operation.Among them,2 patients had severe symptoms and underwent endoscopic revision again,and the other patient improved after conservative treatment.Compared with the conventional group,the puncture times[(1.8±0.7)times vs.(7.5±1.1)times,t=27.543,P=0.000].fluoroscopy times[(5.7±1.8)times vs.(23.2±2.2)times,t=41.235,P=0.000]and operation time[(72.7±7.2)min vs.(92.7±7.7)min,t=12.317,P=0.000]in the modified group were significantly reduced or shortened,and there was no significant difference in postoperative hospital stay[(3.2±0.6)d vs.(3.3±0.6)d,t=0.062,P=0.951]between the two groups.The conventional group was followed up for(14.0±1.3)months and the modified group was followed up for(13.6±1.2)months.There were no significant differences in VAS scores[(1.5±0.6)points vs.(1.6±0.7)points,t=0.751,P=0.455].ODI[(10.8±3.4)％vs.(11.8±3.9)％,t=1.284,P=0.202].and excellent and good rate of MacNab criteria[100％(54/54)vs.100％(35/35),Z=-0.981,P=0.327]between the two groups at the last follow-up.Conclusions Simple drawing line puncture combined with visual articular process arthroplasty can significantly improve the accuracy of intervertebral foramen aspiration,with simple operation,reduced X-ray exposure for doctors and patients,shortened operation time,and improved surgical safety.It is worthy of promotion and application in percutaneous foraminoscopy.

Objective:To investigate the technical application pathways of artificial intelligence(AI)in laboratory information management systems(LIMS)and its role in promoting laboratory management efficiency and intelli-gence.Methods:Through the integration of traditional AI technologies(e.g.,machine learning,computer vision)with large language models,this study demonstrated the application of various AI technologies in scenarios such as intelligent Q&A for local knowledge bases,comprehensive review of inspection processes,intelligent data visualization,and image recognition.Results:Through the implementation of AI applications in laboratory settings,AI significantly enhanced management efficiency:the intelligent Q&A system achieved over 90％accuracy,auto-mated inspection processes reduced manual workload by 40％,and image recognition precision reached 89％-100％.Conclusion:AI provides efficient and precise solutions for laboratory management via multimodal integration and process optimization.Future efforts should focus on strengthening data security and model interpret-ability to promote comprehensive intelligent development.

BACKGROUND:In recent years,improving the health of skeletal muscles through exercise has become an important research concern for scholars.Appropriate exercise has a positive effect on skeletal muscles.Among them,how to activate the sphingosine kinase1(SphK1)/sphingosine-1-phase(S1P)/sphingosine-1-phase receptor2(S1PR2)signaling pathway during exercise so as to improve the health of skeletal muscles is receiving attention from researchers. OBJECTIVE:To investigate how exercise improves the health of skeletal muscles through the SphK1/S1P/S1PR2 signaling pathway,and to explore new methods for treating related muscle diseases in order to improve human skeletal muscle health. METHODS:The first author searched for relevant literature from the establishment of the database to the present in the Web of Science,PubMed,CNKI,WanFang,and VIP databases.The search terms were"signaling pathway,SphK1,S1P,S1PR2,skeletal muscle,satellite cell,myogenesis,exercise"in Chinese and English.Finally,69 articles were included for review and analysis. RESULTS AND CONCLUSION:The SphK1/S1P/S1PR2 signaling pathway is a complex regulatory network that triggers downstream signal transduction processes by SphK1 to catalyze the interaction between S1P and receptors such as S1PR2,thereby regulating multiple biological functions of cells,tissues,organs,and systems.The SphK1/S1P/S1PR2 signaling pathway can regulate satellite cell proliferation and myoblast differentiation,improving myogenesis.The physiological basis of the SphK1/S1P/S1PR2 signaling pathway and the potential impact of exercise on it were analyzed through literature research.Acute aerobic exercise can increase the expression of SphK1 in skeletal muscle.Both human and animal studies have confirmed that acute and long-term exercise can increase the expression of S1P in skeletal muscle.In addition,studies have shown that long-term resistance exercise can increase the expression of S1PR2 in skeletal muscle.Some experimental results indicate that acute and long-term exercise have no significant effect on muscle or blood S1P levels,and the reason for different results may be due to different research subjects,methods,intensities,and frequencies selected,while the specific mechanism is not yet clear.Research suggests that exercise can promote the expression of the SphK1/S1P/S1PR2 signaling pathway in skeletal muscle and regulate downstream related signaling pathways.Research on this signaling pathway may provide new strategies and methods for the treatment of skeletal muscle diseases,thereby improving skeletal muscle health.In the future,we should deepen the research on the association between SphK1/S1P/S1PR2 signaling pathway and skeletal muscle health,further reveal its regulatory relationship with satellite cells and myoblasts as well as its interactions with the upstream and downstream pathways,explore its clinical application value,take into account the changes of this pathway when formulating the rehabilitation program,explore the specific mechanisms by which different types of exercise affect the SphK1/S1P/S1PR2 signaling pathway in skeletal muscles,and use the SphK1/S1P/S1PR2 signaling pathway as a potential therapeutic target for diseases.Further development and application of human muscle models should be developed to improve research depth and accuracy.