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

Objective:To analyze the impact of different intrauterine intervention methods and types of complications on fetal prognosis in cases of giant placental chorioangioma (CA), and determine the indications for various treatment methods by analyzing cases of adverse outcomes.Methods:Relevant articles were retrieved from China National Knowledge Infrastructure, VIP Database, Wanfang Database, and Yiigle using the keywords "placental chorioangioma" and "fetal edema" or "anemia" or "cardiomegaly" or "polyhydramnios," and from PubMed, Embase, and UpToDate databases using the keywords "placental chorionic angioma or chorioangioma" and "fetal edema" or "anemia" or "polyhydramnios" or "hyperdynamic circulation" up to June 30th 2023. The size of the angiomas, fetal complications, intrauterine intervention methods, gestational weeks at intervention, and pregnancy outcomes were analyzed. Fetal and neonatal deaths were defined as adverse outcomes. Statistical analysis was performed using an independent sample t-test, rank-sum test, or Chi-square test (continuity correction Chi-square test or Pearson Chi-square test). Results:(1) A total of 582 articles were retrieved, and 51 articles were finally included, comprising 65 cases. Based on the intrauterine intervention methods, these cases were divided into the symptomatic treatment group (17 cases) and the etiological treatment group (48 cases). There were no statistically significant differences between the two groups in the maximum diameter of the angiomas, the gestational weeks at intervention, or the gestational weeks at delivery. (2) The incidence of adverse outcomes was 3/17 in the symptomatic treatment group and 27.1% (13/48) in the etiological treatment group, with no statistically significant difference. In the etiological treatment group, the incidence of adverse outcomes in cases with fetal edema was 45.4% (10/22), which was significantly higher than the 11.5% (3/26) in cases without fetal edema, and the difference was statistically significant ( χ 2=6.94, P=0.008). (3) An analysis of 13 cases with adverse outcomes revealed that nine cases had highly vascularized chorioangiomas and/or blood supply vessels located close to the umbilical cord insertion point on the placenta, and nine were complicated by fetal edema. The incidence of adverse outcomes for fetoscopic laser coagulation/bipolar coagulation, radiofrequency or microwave ablation, bioglue embolization, anhydrous alcohol ablation, and microcoil embolization were 4/19, 3/4, 1/8, 2/9, and 3/6, respectively. Conclusions:Intrauterine treatment of CA should be individualized. Bioglue embolization may be the first-line treatment; Fetoscopic laser coagulation can be applied to cases where the blood supply vessels are small and superficial;Interstitial laser ablation and radiofrequency ablation can be used for branch-type CA when the main blood supply vessels are located within the hemangioma; Anhydrous alcohol ablation is contraindicated due to its risk of fetal circulation entry; Microcoil embolization has the risk of incomplete occlusion, which should be used with caution.

Objective:To analyze the impact of different intrauterine intervention methods and types of complications on fetal prognosis in cases of giant placental chorioangioma (CA), and determine the indications for various treatment methods by analyzing cases of adverse outcomes.Methods:Relevant articles were retrieved from China National Knowledge Infrastructure, VIP Database, Wanfang Database, and Yiigle using the keywords "placental chorioangioma" and "fetal edema" or "anemia" or "cardiomegaly" or "polyhydramnios," and from PubMed, Embase, and UpToDate databases using the keywords "placental chorionic angioma or chorioangioma" and "fetal edema" or "anemia" or "polyhydramnios" or "hyperdynamic circulation" up to June 30th 2023. The size of the angiomas, fetal complications, intrauterine intervention methods, gestational weeks at intervention, and pregnancy outcomes were analyzed. Fetal and neonatal deaths were defined as adverse outcomes. Statistical analysis was performed using an independent sample t-test, rank-sum test, or Chi-square test (continuity correction Chi-square test or Pearson Chi-square test). Results:(1) A total of 582 articles were retrieved, and 51 articles were finally included, comprising 65 cases. Based on the intrauterine intervention methods, these cases were divided into the symptomatic treatment group (17 cases) and the etiological treatment group (48 cases). There were no statistically significant differences between the two groups in the maximum diameter of the angiomas, the gestational weeks at intervention, or the gestational weeks at delivery. (2) The incidence of adverse outcomes was 3/17 in the symptomatic treatment group and 27.1% (13/48) in the etiological treatment group, with no statistically significant difference. In the etiological treatment group, the incidence of adverse outcomes in cases with fetal edema was 45.4% (10/22), which was significantly higher than the 11.5% (3/26) in cases without fetal edema, and the difference was statistically significant ( χ 2=6.94, P=0.008). (3) An analysis of 13 cases with adverse outcomes revealed that nine cases had highly vascularized chorioangiomas and/or blood supply vessels located close to the umbilical cord insertion point on the placenta, and nine were complicated by fetal edema. The incidence of adverse outcomes for fetoscopic laser coagulation/bipolar coagulation, radiofrequency or microwave ablation, bioglue embolization, anhydrous alcohol ablation, and microcoil embolization were 4/19, 3/4, 1/8, 2/9, and 3/6, respectively. Conclusions:Intrauterine treatment of CA should be individualized. Bioglue embolization may be the first-line treatment; Fetoscopic laser coagulation can be applied to cases where the blood supply vessels are small and superficial;Interstitial laser ablation and radiofrequency ablation can be used for branch-type CA when the main blood supply vessels are located within the hemangioma; Anhydrous alcohol ablation is contraindicated due to its risk of fetal circulation entry; Microcoil embolization has the risk of incomplete occlusion, which should be used with caution.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Based on the data of a national sampling survey, this paper described and analyzed the understanding, attitude, behavior, and their differences and influencing factors of Chinese medical researchers on ethical review of biomedical research involving human subject. The survey found that researchers with master’s degree or below, working in scientific research institutes or universities, no overseas experience, living in the central region and not serving as committee members have relatively poor acquaintance of "ethical review" ; researchers with the characteristics of male, the younger age, living in the western region, knowing less about "ethical review" , agree more with the view that "ethical review consumes too much time and energy" ; researchers who serve as members of the ethics committee are more likely to participate in scientific research projects that have not passed the ethical review process. Therefore, recommendations are put forward: comprehensively popularizing the training of ethical review, focusing on strengthening the vulnerable groups and regions, strictly implementing ethical review laws and regulations, and strengthening evaluation and supervision, so as to improve the service quality and efficiency of ethical review in multiple directions.

BACKGROUND:Mesenchymal stem cells are susceptible to senescence during in vitro expansion,which greatly hinders their application in vivo and in vitro.How to improve the replicative senescence of mesenchymal stem cells is an urgent problem to be solved in tissue engineering. OBJECTIVE:To determine whether vascular endothelial growth factor combined with basic fibroblast growth factor can improve the aging of bone marrow mesenchymal stem cells caused by replicative passage. METHODS:Rat bone marrow mesenchymal stem cells were extracted by whole bone marrow adhesion method.Passage 2 cells were selected as normal control group.Passage 7 and later algebraic cells were selected as aging model group.Vascular endothelial growth factor(50 μg/L),basic fibroblast growth factor(10 μg/L),and their combination were administered.Cell proliferation was detected by CCK-8 assay.Cell senescence was observed by β-galactosidase activity staining.Cytoskeleton size and colony formation ability were observed by phalloidine staining and Giemsa staining,respectively,and the levels of senescence-related genes P16,P21,and P53 were detected by qRT-PCR.Gene expression levels of P16,P21,and P53 were tested by qRT-PCR. RESULTS AND CONCLUSION:(1)Vascular endothelial growth factor combined with basic fibroblast growth factor could promote the proliferation of aged bone marrow mesenchymal stem cells,which began to enter the plateau stage on day 9,and the absorbance value of the combined intervention group was significantly higher than that of the model group on day 9(P<0.05).(2)The phenotypic markers of the cells in the combined intervention group did not change,and the cell morphology changed from broad to slender.(3)Compared with the model group,the positive rate of β-galactosidase was significantly decreased(P<0.01);the number of nuclei increased(P<0.001);the total area of cytoskeleton increased(P<0.01);colony formation ability was enhanced(P<0.05);expression level of P16 was decreased(P<0.01)in the combined intervention group.These results indicate that vascular endothelial growth factor combined with basic fibroblast growth factor can improve the senescence of bone marrow mesenchymal stem cells caused by replicative passage without changing the cell phenotype.

The SWOT model of management was used to analyze the advantages(S),disadvantages(W),opportunities(O)and challenges(T)of the transformation of scientific and technological achievements in a large general hospital in Shandong Province.According to the matrix form,four kinds of strategies are formed,including SO strategy using internal advantages to seize opportunities,ST strategy using internal advantages to resist external threats,WO strategy using external opportunities to o-vercome internal weaknesses and WT strategy overcoming internal weaknesses to avoid external threats,and effective strategies to promote the transformation of scientific and technological achievements in large general hospitals are discussed.

Human skin self-repairs after trauma and surgery. During this process,the ability of the skin to achieve complete functional regeneration and avoid the formation of fibrosis (scarring) or chronic wounds is a key clinical concern. Studies on wound healing have suggested that several factors affect the process of wound healing,including race,age,wound site,and skin tension. However,the lack of systematic analysis of the complete definition and connotation of skin regeneration and fibrosis,as well as the key links in the regulatory network of wound healing,makes clinical application difficult. In this review,we discuss domestic and international literatures to formu-late the concept of skin regeneration and fibrosis,combine the latest research progress on the physiological and pathological processes of wound healing,and propose the key links of the regulatory network that can potentially affect the outcome of skin wound healing. There-fore,this review provides novel theoretical support for the study of wound healing and suggests innovative diagnostic and therapeutic strat-egies for clinical applications.

Objective To investigate the improvement effect and related mechanism of roxadustat on myocardial ischemia-reperfusion(I/R)injury in mice.Methods Twenty four male C57BL/6N mice were randomly divided into the sham operation group,the control group and the roxadustat group,with eight mice in each group.A mouse myocardial I/R model was established.The control group was given 100 μL saline injection containing 5%dimethyl sulfoxide by gavage.The roxadustat group was given 25 mg/kg roxadustat by gavage.The left anterior descending coronary artery of mice in both groups was ligated for 40 minutes,and then reperfusion for 24 hours to establish the myocardial I/R model.In the sham operation group,only the left anterior coronary artery was pierced without ligation.The area of myocardial infarction in mice was detected by triphenyltetrazolium chloride(TTC)staining.The apoptosis of mouse cardiomyocytes was detected by TdT-mediated dUTP nick and labeling(TUNEL)staining.The expression of apoptosis-related proteins bcl-2 associated X protein(Bax),Caspase3 and inflammatory cell markers F4/80 and myeloperoxidase(MPO)were detected by immunohistochemistry staining.The damage of myocardial cells was observed by hematoxylin-eosin(HE)staining.Results The area of myocardial infarction after myocardial I/R was reduced in the roxadustat group compared to the control group and the sham operation group(P＜0.05).The number of apoptotic cells was higher in the control group and the roxadustat group than that in the sham operation group,and the number of apoptotic cells was lower in the roxadustat group than that in the control group(P＜0.05).The expression levels of Bax and Caspase3 proteins in myocardial tissue were higher in the control group and the roxadustat group than those in the sham operation group,while those of the roxadustat group was lower than those of the control group(P＜0.05).The expression levels of F4/80 and MPO proteins in myocardial tissue were lower in the roxadustat group than those in the control group(P＜0.05).In the control group,the myocardial tissue arrangement was disordered,and there was an increase in interstitial vacuoles.Compared with the control group,the myocardial cells were arranged more neatly in the roxadustat group,and the interstitial vacuoles were reduced.Conclusion Roxadustat can reduce the myocardial infarction area after I/R injury,inhibit myocardial cell apoptosis,alleviate myocardial injury,reduce infiltration of myocardial macrophages and neutrophils,and reduce inflammatory injury.

Placental diseases may affect the outcome of pregnancy and long-term health of the mother and fetus. Fetal fraction is a key indicator for the success of non-invasive prenatal testing, and has been associated with gestational age, body mass index and fetal chromosomal aneuploidies. Many studies have found that fetal fraction is also related to placenta-derived diseases and may become a new predictor for such diseases. This article has summarized the association between the two, with an aim to provide new ideas for the prediction of placental diseases.