Adipose tissue is inextricably linked to nutritional balance and metabolic diseases, and the way of adipocytes differentiation will directly affect the health of adipose tissue. Preadipocytes are cells that are present at adipose depot and restricted to becoming mature adipocytes specificity. Their favorable differentiation ability to differentiate into healthy mature adipocytes as well as undergo hyperplasia (the expansion of adipose tissue by de novo adipocytes) rather than hypertrophy (the expansion of adipose tissue by increasing the size of already being adipocytes) is crucial for regenerative medicine and obesity-related diseases.Despite much effort has focused on the factors and mechanism about preadipocyte's adipogenic differentiation, the precise regulatory mechanism is still not completely clear. Based on the related research in recent years, this review discusses the ambiguous definition, the origin and terminal differentiation of preadipocytes in brief, summarizes the surface markers of preadipocytes in detail which include stem cell surface markers (such as CD29, CD34, CD38 and SCA1), perivascular markers (such as PDGFRα and PDGFRβ), ZFP423 (zinc-finger protein 423), Pref-1/DLK1 (preadipocyte factor 1). The deep look at preadipocytes provides new ideas for clinical diagnosis and treatment. The clinical application potential of preadipocytes in the treatment of soft tissue defects, obesity-related metabolic diseases, tumors (breast cancer and prostate cancer), and wound healing is further discussed in this review.

Myocardial infarction (MI) is cardiomyocyte necrosis caused by myocardial ischemia and hypoxia, and is the leading cause of death and disability in the world. Although direct percutaneous coronary intervention (PCI) can restore epicardial coronary blood flow and reduce the mortality of MI, some patients with MI will still develop into chronic heart failure. As an important complication caused by reperfusion therapy, intramyocardial hemorrhage (IMH) is defined as red blood cell extravasation caused by severe microvascular injury, and can be used as an independent predictor of the adverse ventricular remodeling after myocardial infarction, which is the pathological basis of heart failure after myocardial infarction. At present, the main evaluation method for IMH is cardiac magnetic resonance imaging (MRI), especially the qualitative and quantitative evaluation of intracardial bleeding can be achieved by T₂* sequence. It has been shown that iron deposition after degradation of IMH exacerbates the inflammatory response, leading to the aggregation of macrophages and secretion of matrix metalloproteinases, which are involved in subsequent adverse ventricular remodeling. The recent progress of clinical and basic research on the relationship between IMH and the adverse ventricular remodeling after MI are reviewed in present paper, hoping to be helpful for the prevention and treatment of IMH in the future.

Pulmonary arterial hypertension (PAH) is a progressive disease with poor prognosis, which may lead to right heart dysfunction, resulting in a series of clinical symptoms and even death, and there is still a lack of effective treatment. The etiology of PAH is complex, in which epigenetic changes play an important role in its pathogenesis. Histone acetylation modification is one of the most widely and deeply studied epigenetic modifications. The histone acetylation is mainly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), which play a key role in chromatin and gene regulation, and is closely related to the occurrence of PAH. Targeted histone acetylation pathway has a certain therapeutic potential for PAH. This article reviews the research progress on the effect of HDACs on PAH, in order to further understand the pathogenesis of PAH and provide a new direction of treatment.

The purpose of Bacillus Calmette-Guérin (BCG) vaccination is to prevent Mycobacterium tuberculosis infection, but studies have shown that BCG activates innate immunity, causes epigenetic reprogramming and metabolic changes of myeloid cells, and forms innate immune memory or trained immunity. When bone marrow-like cells are stimulated by pathogens again, they show enhanced immune response and promote the host's nonspecific defense ability. Innate immune memory is also called training immunity. In recent years, BCG-induced innate immune memory has attracted much attention, and it will guide the design of novel vaccine. This article reviews the application of BCG in prevention and treatment of corone virus disease 2019, the non-specific protection and mechanism of BCG-mediated trained immunity.

At present, there is a relatively complete guideline for heart failure with ejection fraction reduction (HFrEF), but there is still a lack of evidence-based medical evidence for heart failure with preserved ejection fraction (HFpEF) treatment criteria.In recent years, a large amount of evidence has emerged that a new oral hypoglycemic drug sodium-glucose cotransporter 2 inhibitor(SGLT2i) can significantly reduce the risk of cardiovascular death and the hospitalization rate of heart failure in patients with type 2 diabetes mellitus, and improve the prognosis of HFrEF. However, there is still a lack of overall understanding of the mechanism and research progress of SGLT2i in the treatment of HFpEF. This article reviews the pathological mechanism of HFpEF, the mechanism of action of SGLT2i and the related research on the treatment of HFpEF, in order to provide reference for the clinical drug treatment of HFpEF.

Objective To search for genes related to the occurrence and development of retinoblastoma (RB). Methods In this study, firstly, we obtained 3 gene expression datasets from the Gene Expression Omnibus (GEO) database. After they were merged, the sva package in R software was applied to remove the batch effects of these three datasets. The differentially expressed genes (DEGs) were identified by limma package. ClusterProfiler package was used to analyze GO enrichment and KEGG pathway of DEGs. STRING database and Cytoscape software were used to construct the protein-protein interaction network (PPI). CytoHubba was applied to find the hub gene of PPI network. Weighted gene co-expression network analysis (WGCNA) was utilized to identify key modules associated with clinical information. The key genes of the key modules were further searched. Then, Y79, WERI-RB-1 and ARPE-19 cells were cultured in vitro, and the mRNA expression levels of five key genes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 20 RB tissue samples were collected. Immunohistochemistry was used to detect the expression of key proteins. Results A total of 1254 DEGs were identified, among which 422 were up-regulated and 832 were down-regulated. In GO analysis, DEGs were mainly related to protein heterodimerization activity, cation transmembrane transporter activity, and chromatin binding. In KEGG analysis, DEGs were mainly enriched in cell cycle, phototransduction, and DNA replication. A total of 79 hub genes in the PPI network were obtained. In the co-expression network, DEGS were divided into 11 co-expressed gene modules. According to Pearson correlation coefficient between each module and clinical traits, 5 important modules including blue, pink, turquoise, red and brown were identified, among which blue module had the highest correlation coefficient with age at diagnosis (r=0.65). After comprehensive analysis, we obtained 5 hub genes including structural maintenance of chromosome 4(smc4), minichromosome maintenance complex component 6 (mcm6), centromere protein K (cenpk), kinesin family member 15(kif15), protein regulator of cytokinesis 1 (prc1). The qRT-PCR results showed that the mRNA relative expression levels of prc1 and cenpk in Y79/WERI-RB-1 cells were higher than those in ARPE-19 (P<0.05). Immunohistochemistry results indicated that PRC1 protein was higher expressed in RB tissue samples (P<0.05). Conclusion smc4, mcm6, cenpk, kif15, and prc1 were identified as hub genes by bioinformatics analysis, and the increased expression of PRC1 protein in RB may play an important role in the occurrence and development of RB.

Objective To investigate the effect of AKT/mTOR and JAK/STAT pathways co-activation on axon regeneration and function recovery in C₅ spinal cord injury mice. Methods Forty adult C57/BL mice were randomly divided into PTEN/SOCS3 group (injected PTEN virus and SOCS3 virus), PTEN group (injected PTEN virus), SOCS3 group (injected SOCS3 virus) and control group (injected empty control virus), 10 mice in each group. Adeno-associated-virus (AAV) were injected into the sensorimotor cortex. The activation of AKT/mTOR and JAK/STAT pathways in pyramidal neurons was detected by measuring the expression of p-S6 and p-STAT3 using immunofluorescence staining. Two weeks after injection, all the mice received C₅ crush injury. Biotinylated dextran amine (BDA) tracer was used to label corticospinal tract. The horizontal ladder and cylinder rearing tests were used to assess motor function recovery at pre-injury, and one week, two weeks, four weeks and six weeks after injury. Results Immunofluorescence staining results showed that AAV successfully infected the sensorimotor cortex pyramidal neurons.The expression of p-S6 in PTEN/SOCS3 group and PTEN group were significantly increased, the fluorescence intensity of p-S6[(25.429±2.991) AU and (26.171±2.140) AU] were significantly higher than SOCS3 group and control group [(9.544±2.474) AU and (9.558±1.650) AU] (P<0.001). The expression of p-STAT3 in PTEN/SOCS3 group and SOCS3 group were obviously increased, compared with PTEN group and control group [(12.952±1.282) AU and (14.394±1.983) AU], the fluorescence intensity of p-STAT3 in PTEN/SOCS3 group and SOCS3 group [(48.900±6.310) AU and (46.721±5.169) AU] were significantly higher (P<0.001). Compared with control group, the other three groups showed obvious axon regeneration after corticospinal tract injury. The regeneration distance and number were longer and more in PTEN/SOCS3 group (P<0.05). There was no significant difference between four groups in horizontal ladder and cylinder rearing tests at various time points (P>0.05). Conclusion Co-activation of AKT/mTOR and JAK/STAT pathways could improve neurons intrinsic regenerative growth capacity and successfully promote axon regeneration in adult spinal cord injury mice, but could not have better early motor function recovery.

Objective To investigate the therapeutic effects of low-frequency ultrasound combined with 5-fluorouracil(5-FU) nanobubbles on post radiofrequency ablation (RFA) hepatocellular carcinoma (HCC) nude mice. Methods A xenograft HCC mouse model was established in 60 BALB/c nude mice (6-8 weeks) using human hepatocellular carcinoma cell lines (HepG2).The mice were randomized into four groups after RFA ablation of 80%: saline group, 5-fluorouracil loaded nanobubbles (5-FU)group, non-low frequency ultrasound irradiated 5-FU-loaded nanobubbles (non-low frequency ultrasound + 5-FU) group, and low-frequency ultrasound irradiated 5-FU-loaded nanobubbles (low-frequency ultrasound + 5-FU) group. The nude mice of the last three groups received a tail vein injection of 5-FU loaded nanobubbles (0.1 μg/μl), 200 μl each time, once every three days, and three consecutive injections. The low-frequency ultrasound + 5-FU group received additional irradiation of low-frequency ultrasound (1 MHz, 2 W/cm²) for 5 min after being injected into the nanobubble. The growing status, tumor size and survival time of nude mice bearing tumor in each group were observed and compared. At the end of the treatment, the tumor tissue was taken, apoptosis index was detected through the TUNEL method, and the tumor neovascular density (MVD) was detected by the CD34-MVD method. The apoptosis index and MVD values were compared in each group. Results After treatment, the nude mice in the different groups exhibited weight loss, a reduction in activity, appetite loss, and other symptoms to varying degrees. However, the growing status of tumor-bearing nude mice in low-frequency ultrasound + 5-FU group was significantly better than the other three groups. The tumor volume of nude mice in each group gradually increased. The tumor growth rate of low-frequency ultrasound+ 5-FU group was significantly lower than that of the other three groups, and the difference was statistically significant (P<0.05).The survival time of tumor-bearing nude mice in low-frequency ultrasound+5-FU group was significantly longer than that of the other three groups, and the difference was statistically significant (P<0.05). The apoptotic index of tumor cells in each group: low frequency ultrasound + 5-FU group (43.2%±4.4%) > non-low frequency ultrasound + 5-FU group (31.3%±4.3%) > 5-FU group(20.7%±2.9%) > saline group (10.8%±2.4%), and there were statistically significant in each group (P<0.05). Meanwhile, except for the low-frequency ultrasound + 5-FU group, multiple positive staining areas were seen in the tumors of the other three groups, and there were more positively stained tumor tissues. The MVD values (piece/HP) of each group: low frequency ultrasound + 5-FU group (8.9±1.3) < non-low frequency ultrasound + 5-FU group (20.1±3.2) <5-FU group (25.0±4.2) <saline group (29.9±2.0), and there were statistically significant in each group (P<0.05). Conclusions 5-fluorouracil loaded nanobubbles combined with low-frequency ultrasound could further improve drug targeting, effectively inhibit the growth of HCC, which can significantly inhibit residual cancer cells after RFA.

Objective To investigate the role of CYFIP2 gene in proliferation and migration of renal clear cell carcinoma(KIRC). Methods The TCGA database was used to analyze the expression of CYFIP2 gene in KIRC and the correlation between the expression and clinicopathological factors. The KIRC cell line 786-O was transfected with siRNA-CYFIP2 to knockdown the CYFIP2 gene, and the CYFIP2 gene stable overexpression system was constructed by infecting 786-O cells with viral particles carrying the CYFIP2 gene. The 786-O cells were used as the knockdown group (siRNA-CYFIP2, si-CYFIP2) after the CYFIP2 gene was knockdown, and set the corresponding control group si-NC; the 786-O cells were used as the overexpression group (Over Expression-CYFIP2, OE-CYFIP2) after performing CYFIP2 gene overexpression, and set the corresponding control group OE-NC.Subsequently, cell proliferation assays and Transwell assays were performed to analyze the differences in proliferative activity and migration ability of 786-O cells after knockdown or overexpression of CYFIP2 gene. Results The expression of CYFIP2 in KIRC was significantly lower (P<0.0001) in the TCGA database and decreased with the progression of tumor staging (P<0.05); CYFIP2 gene was also expressed at a low level after the occurrence of lymph node metastasis and distal metastasis (P_N<0.05, P_M<0.01); the 5-year survival rate of patients was significantly higher in the group with high CYFIP2 expression than that in the group with low expression (P<0.05). The cell proliferation activity assay showed that the proliferation activity was significantly enhanced in si-CYFIP2 group than that in si-NC group (P<0.0001) and the number of cell migration was significantly increased (P<0.0001), while the proliferation activity and migration ability of OE-CYFIP2 group were significantly inhibited (P<0.001) compared with that of OE-NC group. Conclusion The CYFIP2 gene had a significant inhibitory effect on the proliferation and migratory ability of KIRC cells and may have a potential antitumor effect, which can be one of the candidate genes for the subsequent clinical diagnosis and treatment of KIRC.

Objective To investigate the effect of fatty acid binding protein 4 (FABP4) in cardiomyocyte pyroptosis induced by homocysteine (Hcy). Methods The cultured rat cardiomyocytes were divided into two groups: control group(0 mmol/L Hcy) and Hcy group (3 mmol/L Hcy). The expression of FABP4 and pyroptosis related proteins [NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β)] were detected by Western blotting. The expression level of FABP4 mRNA was detected by qRT-PCR. The changes of expression of pyroptosis associated proteins were detected by immunofluorescence staining. The cultured cardiomyocytes were treated with FABP4 inhibitor (BMS-309403), and then divided into control group (0 mmol/L Hcy), Hcy group (3 mmol/L Hcy) and Hcy+BMS-309403 group (3 mmol/L Hcy and 50 μmol/L BMS-309403), and the expression levels of pyroptosis related proteins were then re-detected. Results Compared with control group, Western blotting showed that the expression levels of FABP4, NLRP3, caspase-1 and IL-1β in Hcy group increased significantly (P<0.05); Compared with control group, qRT-PCR results showed that the expression of FABP4 in Hcy group increased significantly (P<0.05); Compared with control group, immunofluorescence staining results showed that the fluorescence intensity of NLRP3, caspase-1 and IL-1β in Hcy group increased significantly. After adding FABP4 inhibitor (BMS-309403) and Hcy treatment, the expression levels of FABP4, NLRP3, caspase-1 and IL-1β in Hcy+BMS-309403 group decreased significantly compared with Hcy group (P<0.05 or P<0.01). Conclusion FABP4 may promote cardiomyocytes pyroptosis induced by homocysteine.