Purpose: This study aims to survey the demographic status of aesthetic plastic surgeons in an economically developed region and to investigate their continuing training needs in contents, training methods, and barriers in private and government hospitals. Methods: A cross-sectional survey with a self-administered questionnaire was conducted from January to December, 2022 in Guangdong, China. In-depth interviews were conducted with key informants to gain insights on the current demographic status. Demographic data and training needs assessment were collected and compared with the chi-square test, Fisher’s test, Mann-Whitney U-test using R software. Results: The disparity of surgeons’ demographic data between private and government hospitals was small. Over 60% of practicing aesthetic plastic surgeons transferred from other specialties, and one third of them had less than three years of working experience. Half of surgeons attended training less than three times with an affordable expense of 1000-5000RMB. Almost 80% of them had strong willingness to attend a continuing training program. They prefer to attend further study in a tertiary hospital, with a short topic-focused training course and operation demonstrations. Their favorable training contents were rhinoplasty, eye surgery, and new technologies. Our questionnaire survey revealed the likelihood that the surgeons had a graduate degree in government hospitals outweighed those in private hospitals (P<0.05). Results also showed that the government hospitals focused more on repair and reconstructive surgery and academic research, whereas, private hospitals focused on market needs and were more profit-driven, where the organizational needs had influence on their different training needs for aesthetic plastic surgeons. Conclusion: It would be favorable to take the demographic status of aesthetic plastic surgeons and organizational needs into consideration in designing a continuing training program in plastic surgery.

Osteoarthritis (OA) is considered to be the most common joint disorder. Exogenous drug intervention is one of the effective means for OA treatment. Clinical applications of numerous drugs are restricted owing to the short retention as well as rapid clearance in the joint cavity. A wide variety of carrier-based nanodrugs have been developed, but additional carriers may bring unexpected side effects or even toxicity. Herein, by exploiting the spontaneous fluorescence of Curcumin, we designed a new carrier-free self-assembly nanomedicine Curcumin (Cur)/icariin (ICA) nanoparticles with adjustable particle size, which is composed of two small-molecule natural drugs assembled via π–π stacking interaction. Experimental results revealed that Cur/ICA NPs endowed with little cytotoxicity, high cellular uptake and sustained drug release, could inhibit secretion of inflammatory cytokines and reduce cartilage degeneration. Moreover, both the in vitro and in vivo experiments showed the NPs exerted superior synergism effects in anti-inflammatory and cartilage protection than either Cur or ICA alone, and self-monitored its retention by autofluorescence. Thus, the new self-assembly nano-drug combining Cur and ICA represents a new strategy for the treatment of osteoarthritis.

Chronic refractory wounds (CRW) are one of the most serious clinical challenges for surgeons to address. Stromal vascular fraction gels (SVFG), including human adipose stem cells (hASCs), have excellent vascular regenerative and tissue repair properties. Here, we combined single-cell RNA sequencing (scRNA-seq) of leg subcutaneous adipose tissue samples with scRNA-seq data from abdominal subcutaneous adipose tissue, leg subcutaneous adipose tissue, and visceral adipose tissue samples from public databases. The results showed specific differences in cellular levels in adipose tissue from different anatomical site sources. We identified cells including CD4+ T cells, hASCs, adipocyte (APC), epithelial (Ep) cells, and preadipocyte. In particular, the dynamics between groups of hASCs, epithelial cells, APCs, and precursor cells in adipose tissue of different anatomical site origins were more significant. Furthermore, our analysis reveals alterations at the cellular level and molecular level, as well as the biological signaling pathways involved in these subpopulations of cells with specific alterations. In particular, certain subpopulations of hASCs have higher cell stemness, which may be related to lipogenic differentiation capacity and may be beneficial in promoting CRW treatment and healing. In general, our study captures a human single-cell transcriptome profile across adipose depots, the cell type identification and analysis of which may help dissect the function and role of cells with specific alterations present in adipose tissue and may provide new ideas and approaches for the treatment of CRW in the clinical setting.

Background Acquired immunodeficiency syndrome (AIDS) is associated with a high rate of pulmonary infections (bacteria, fungi, and viruses). To overcome the low sensitivity and long turnaround time of traditional laboratory-based diagnostic strategies, we adopted metagenomic next-generation sequencing (mNGS) technology to identify and classify pathogens. Results This study enrolled 75 patients with AIDS and suspected pulmonary infections who were admitted to Nanning Fourth People’s Hospital. Specimens were collected for traditional microbiological testing and mNGS-based diagnosis. The diagnostic yields of the two methods were compared to evaluate the diagnostic value (detection rate and turn around time) of mNGS for infections with unknown causative agent. Accordingly, 22 cases (29.3%) had a positive culture and 70 (93.3%) had positive valve mNGS results ( P value < 0.0001, Chi-square test). Meanwhile, 15 patients with AIDS showed concordant results between the culture and mNGS, whereas only one 1 patient showed concordant results between Giemsa-stained smear screening and mNGS. In addition, mNGS identified multiple microbial infections (at least three pathogens) in almost 60.0% of patients with AIDS. More importantly, mNGS was able to detect a large variety of pathogens from patient tissue displaying potential infection and colonization, while culture results remained negative. There were 18 members of pathogens which were consistently detected in patients with and without AIDS. Conclusions In conclusion, mNGS analysis provides fast and precise pathogen detection and identification, contributing substantially to the accurate diagnosis, real-time monitoring, and treatment appropriateness of pulmonary infection in patients with AIDS.

目的 观察局部皮下注射自体脂肪基质细胞胶对剖宫产术后腹部切口的愈合效果.方法 随机选取行剖宫产术的产妇120例为研究对象,按照1∶1比例随机分为治疗组和对照组,各60例.两组均采用剖宫产进行分娩,治疗组术后于切口周围局部皮下注射自体脂肪基质细胞胶治疗,对照组术后常规护理.对比两组患者术后住院天数、术后42 d瘢痕宽度、术后3个月及6个月的瘢痕指数、术后切口愈合级别以及患者满意度.结果 治疗组术后住院天数短于对照组,术后3个月、6个月瘢痕指数评分均低于对照组,差异均有统计学意义(均P＜0.05).两组术后42 d的瘢痕宽度及术后切口愈合级别比较,差异均无统计学意义(均P＞0.05).治疗组患者的满意度得分高于对照组,差异有统计学意义(P＜0.05).结论 局部皮下注射自体脂肪基质细胞胶可减少剖宫产术后腹部切口瘢痕形成,有助于促进伤口愈合,缩短患者的住院天数,提高患者满意度.

本文就当前脂肪干细胞(Ddipose-derived stem cells,ADSCs)与富血小板纤维蛋白(Platelet-rich fibrin,PRF)治疗皮肤软组织放射性损伤的研究概况进行探讨.相对于传统的治疗方式,ADSCs与PRF对于改善皮肤放射性损伤具有独特的优势.放射会使皮肤受到氧化损伤并产生细胞凋亡,从而引起红斑水肿、湿性脱屑等组织病理学改变;而ADSCs的抗凋亡、旁分泌生长因子、抗瘢痕的功能可以针对皮肤放射性损伤机制,减轻放射性损伤创面炎症,提高微血管密度,同时促进创面再上皮化,从而有效地改善皮肤放射性损伤;PRF释放的高浓度生长因子可明显提高创面的愈合率,并且PRF的生物特性能进一步优化ADSCs修复损伤的作用.结合ADSCs联合PRF治疗皮肤放射性损伤的研究现状,对今后的实验研究和临床治疗方向进行展望.

背景与目的:基质细胞衍生因子1α(SDF-1α)是一种定向诱导细胞迁移的趋化因子,研究显示,间充质干细胞(MSCs)在受损组织中可以沿着SDF-1梯度迁移到损伤部位并参与组织修复,然而目前尚缺乏SDF-1α诱导脂肪来源干细胞(ASCs)对糖尿病缺血下肢进行组织修复的体内研究.因此,本研究探讨SDF-1α促进大鼠脂肪来源干细胞(rASCs)向糖尿病大鼠缺血下肢肌肉组织迁移及对组织修复的影响.方法:取SD大鼠脂肪组织分离培养rASCs,行细胞形态观察,鉴定成脂、成软骨及成神经分化能力,并使用带绿色荧光蛋白(GFP)的腺病毒转染和标记rASCs.将大鼠用STZ法构建糖尿病模型,并结扎大鼠的右下肢股动脉造成下肢缺血后,随机分为两组,通过尾静脉向两组大鼠体内注射rASCs,其中一组在患肢中段部位肌肉处注射SDF-1α蛋白(SDF-1α+rASCs组),另一组则用同样方式注射等量磷酸盐缓冲溶液(rASCs组).治疗后的第1、2周行大鼠双下肢血流量检测,计算及比较各组大鼠的缺血下肢-健侧下肢血流比值.在第4周时处死大鼠,取缺血部位的肌肉组织行HE染色,观察不同治疗方法组中肌肉组织的排列情况.以因子Ⅷ(FⅧ)作为微血管的标记,行免疫荧光染色,荧光显微镜下观察组织中FVIII及GFP的分布情况.结果:所培养的细胞呈长梭形或多角形样生长,并可向脂肪、软骨、神经细胞多向分化,鉴定为rASCs.糖尿病下肢缺血大鼠下肢血流量检测结果显示,在治疗后第1周SDF-1α+rASCs组的缺血下肢-健侧下肢血流比值明显高于rASCs组(0.33±0.03vs.0.26±0.02,P--0.016),治疗后第2周可发现上述差异进一步扩大(0.60±0.02vs.0.47±0.01,P=0.050).HE染色结果显示,在治疗后第4周SDF-1α+rASCs组大鼠的肌肉组织排列更为整齐.免疫荧光结果显示,SDF-1α+rASCs组的骨骼肌组织中rASCs的数量在治疗后第4周明显高于rASCs组(P＜0.05),还能观察到红色荧光(FⅧ)与绿色荧光(rASCs)的重叠.结论:通过提高缺血部位的SDF-1α的浓度能够有效增加迁移至患处的rASCs数量,从而获得优化rASCs改善患肢血流灌注,促进肌肉组织修复的明显效果.此外,rASCs分化为血管内皮细胞可能是rASCs促进缺血肌肉修复的关键机制之一.

Background Studies have found that the abnormality of the Hedgehog signaling pathway is related to the occurrence and development of a variety of tumors, but the effect of this signaling pathway on melanoma cells is still unclear. Methods This study aimed to discuss the effect of Hedgehog signaling pathway on the proliferation and apoptosis of human malignant melanoma A375 cells and explore its possible mechanism in the proliferation and apoptosis of melanoma cells. Different concentrations of Hedgehog signaling pathway inhibitor cyclopamine (5, 10, 20 and 40 μM) were used to treat human melanoma A375 cells for 24, 48, and 72 h, and set a blank control group (0 μM). Trypan blue cell counting method was used to detect cell viability. MTT method was used to detect the inhibition rate of cell proliferation. Transwell was used to detect cell invasion, and flow cytometry was used to detect cell apoptosis. Results Through the trypan blue cell counting method and MTT experiment, it was found that the Hedgehog signaling pathway inhibitor cyclopamine has an inhibitory effect on the proliferation and viability of melanoma A375 cells (P < 0.05), and the proliferation inhibitory effect is enhanced with prolonged action time in a dose- and time-dependent manner. Transwell experiment showed that compared with the blank control group, the invasion and migration ability of the treated melanoma A375 cells are significantly reduced, and the difference is statistically significant (P < 0.05). Cell apoptosis experiment showed that compared with the blank control group, the apoptosis rate of A375 cells is significantly higher after treated by 40 μM cyclopamine for 24 h, and the difference is statistically significant (P < 0.05). Gli1 and Bcl-2 protein are highly expressed in melanoma A375 cells, and their expressions show a downward trend (P < 0.05) after being treated by cyclopamine. Conclusion Cyclopamine inhibits cell proliferation and induces cell apoptosis by downregulating Gli1. Hedgehog signaling pathway can be used as a new target for the treatment of malignant melanoma, and multiple measures can be used to inhibit the signaling pathway to achieve a therapeutic effect.

Spine surgery is typically having a relationship to high degrees of pain and immobility. It is a known fact that the implementation of an enhanced recovery after surgery (ERAS) approach has led to a paradigm shift in various surgical specialties. These protocols require doctors, nurses, anesthesiologists, patients, and their families to agree to strengthen communication with each other, and involve a long timeline and teamwork from start to finish. To our knowledge, the role of nursing in the ERAS of spine surgery has not been reported before. The purpose of this study is to summarize the role of nursing in ERAS programs in accordance with surgical periods. The methods applied for this review include literature review of the world's acknowledged databases such as Springer Link, PubMed, Embase, and Wanfang, especially in the period of 2000–2015. A total of 9 studies fulfilled the eligibility criteria and were included in the review. The findings confirm that the nursing work continued throughout the perioperative procedure, which plays a key role in the successful ERAS pathway. According to different nursing measures, ERAS nursing can effectively promote the postoperative recovery of spine surgical patients, with fewer postoperative complications and increased patient satisfaction.

Background Therapeutic studies against human immunodeficiency virus type 1 (HIV-1) infection have become one of the important works in global public health.Methods Differential expression analysis was performed between HIV-positive (HIV+) and HIV-negative (HIV-) patients for GPL6947 and GPL10558 of GSE29429. Coexpression analysis of common genes with the same direction of differential expression identified modules. Module genes were subjected to enrichment analysis, Short Time-series Expression Miner (STEM) analysis, and PPI network analysis. The top 100 most connected genes in the PPI network were screened to construct the LASSO model, and AUC values were calculated to identify the key genes. Methylation modification of key genes were identified by the chAMP package. Differences in immune cell infiltration between HIV + and HIV- patients, as well as between antiretroviral therapy (ART) and HIV + patients, were calculated using ssGSEA.Results We obtained 3610 common genes, clustered into nine coexpression modules. Module genes were significantly enriched in interferon signalling, helper T-cell immunity, and HIF-1-signalling pathways. We screened out module genes with gradual changes in expression with increasing time from HIV enrolment using STEM software. We identified 12 significant genes through LASSO regression analysis, especially proteasome 20S subunit beta 8 (PSMB8) and interferon alpha inducible protein 27 (IFI27). The expression of PSMB8 and IFI27 were then detected by quantitative real-time PCR. Interestingly, IFI27 was also a persistently dysregulated gene identified by STEM. In addition, 10 of the key genes were identified to be modified by methylation. The significantly infiltrated immune cells in HIV + patients were restored after ART, and IFI27 was significantly associated with immune cells.Conclusion The above results provided potential target genes for early diagnosis and treatment of HIV + patients. IFI27 may be associated with the progression of HIV infection and may be a powerful target for immunotherapy.

Background: To evaluate the effect of highly purified stromal vascular fraction gel (SVFG) combined with advanced platelet-rich fibrin extract (APRFE) in treatment of irradiated skin and soft tissue injury. Methods: The subcutaneous fat and whole blood of 4 rabbits were collected to isolate the SVFG and APRFE, respectively. Forty-eight rabbits were divided into 4 groups to prepare irradiated skin injury models with 25 Gy for 24 hours; corresponding dose were performed subcutaneously injected into wounds. In group A, the rabbits were treated with 0.3 mL APRFE combined with 1 mL SVFG. In group B, the rabbits were treated with 1 mL SVFG. In group C, the rabbits were treated with 0.3 mL APRFE, and group D was treated with 1 mL normal saline. The wound healing was detected on the 2, 5, 9 and 14 d after intervention. The wounds tissue was cut for hematoxylin and eosin (HE) staining to observe the structure and Masson staining to observe the collagen content. The expression of CD31 in each group was detected by immunohistochemistry (IHC), the protein and mRNA levels of K19, hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), interleukin 8 (IL-8) and interleukin 10 (IL-10) were detected respectively by Western blot (WB) and reverse transcription-polymerase chain reaction (RT-PCR) on 7, 14 and 28 d after intervention. Results: It is revealed that wound healing rates from 5 to 14 d in group A was significantly higher than that of control. The wounds healing rates in group B and C were significantly higher than that of control after 12 d. Masson staining results showed that the collagen content in group A was significantly higher than that of the other 3 groups on the 7, 14 and 28 d. The results of IHC showed that the expression of CD31 in group A was significantly higher than that of the other 3 groups on 7, 14 and 28 d. WB and RT-PCR results showed that relative expression levels of K19, HIF-1α, VEGF, IL-10 in group A were significantly higher than that of the other 3 groups on 7, 14 and 28 d. However, the relative expression levels of IL-8 in group A was significantly lower than that of the other 3 groups on 7, 14 and 28 d. Conclusions: SVFG combined with APRFE can promote the repair of irradiated skin and soft tissue injury by accelerating angiogenesis, promoting collagen synthesis and reducing inflammation.

BACKGROUND:Human adipose-derived stem cells (hASCs) play an important role in regenerative medicine.OBJECTIVE:Exploring the mechanism of Rg1 in the promotion of the proliferation and adipogenic differentiation of hASCs is important in regenerative medicine research.METHODS:To observe ginsenoside Rg1 in promoting the proliferation and adipogenic differentiation of hASCs, Rg1 medium at different concentrations was established and tested using the cell counting kit-8 (CCK-8) assay, oil red O staining, alizarin red, and alcian blue. Compared to the control, differentially expressed genes (DEGs) were screened via DEG analysis, which was carried out in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. To explore the relationship among mRNA, long non-coding RNA (lncRNA) and microRNA (miRNA), we constructed a competing endogenous RNA (ceRNA) network.RESULTS:In this study, Rg1 was observed to promote the proliferation and adipogenic differentiation of hASCs. Additionally, enriched BPs and KEGG pathways may be involved in the promotion process, where FXR1 and Lnc-GAS5-AS1 were found to be regulatory factors. The regulatory network suggested that Rg1 could regulate the adipocytokine signaling pathway and IL-17 signaling pathway via FXR1 and Lnc-GAS5-AS1, which served as the mechanism encompassing the promotion of Rg1 on the proliferation and adipogenic differentiation of hASCs.CONCLUSION:A comprehensive transcriptional regulatory network related to the promotion ability of Rg1 was constructed, revealing mechanisms regarding Rg1's promotion of the proliferation and adipogenic differentiation of hASCs. The present study provides a theoretical basis for optimizing the function of hASCs.

目的 探讨淫羊藿苷(ICA)优化大鼠脂肪干细胞(rASCs)促进超长随意皮瓣存活的作用及机制.方法 选择6周龄雌性健康无特定病原体(SPF)级SD大鼠作为实验动物.提取rASCs并鉴定其多向分化能力及表面标志物.通过蛋白免疫印迹(WB)实验检测不同浓度ICA(0、0.1、1、10μM)对rASCs中血管生成因子[血管内皮生长因子(VEGF)、血小板源性生长因子?BB(PDGF?BB)、成纤维细胞生长因子?2(FGF?2)、胰岛素样生长因子?2(IGF?2)]表达的影响.设置rASCs组(予未处理的rASCs)、ICA+rASCs组(予1μM ICA预处理的rASCs)及空白对照组(予等体积PBS),每组3只大鼠,根据分组在皮瓣蒂部注射相应细胞悬液.于治疗后7、14、28 d评估皮瓣存活情况.治疗后28 d取皮瓣组织行组织学及WB实验,检测组织中微血管密度(MVD)、胶原含量及各血管生成因子的表达情况.结果 rASCs具有成脂、成骨和成软骨分化的能力,CD29及CD44呈高表达,不表达CD45.WB结果提示ICA处理能显著提高rASCs中血管生成因子的表达(P<0.05).动物实验结果显示,与空白对照组比较,rASCs组及ICA+rASCs组治疗后7 d、14 d的皮瓣存活面积比更高(P<0.05);在治疗后28 d,仅ICA+rASCs组的皮瓣存活面积比显著高于空白对照组(P<0.05).组织学实验结果显示,与空白对照组相比,rASCs组和ICA+rASCs组的皮瓣组织结构排列更为紧密,MVD、胶原含量显著提高(P<0.05).WB结果显示,rASCs组和ICA+rASCs组的VEGF、PDGF?BB和FGF?2蛋白表达水平均显著高于空白对照组(P<0.05),且ICA+rASCs组的VEGF、PDGF?BB蛋白表达水平较rASCs组更高,差异有统计学意义(P<0.05).结论 ICA能够提高rASCs血管生成因子的表达水平,这可能是其优化rASCs促进大鼠超长随意皮瓣存活的机制.

Objective To investigate the repair effect of modified autologous platelet-rich fibrin（A-PRF） combined with recombinant human-like collagen mask on female facial skin photoaging. Methods A total of 80 patients with facial skin photoaging were divided into a control group and a treatment group by drawing lots, with 40 cases in each group. Patients in the control group were treated with recombinant human-like collagen mask（Collgene） for external application, on the basis of which those in the treatment group were additionally treated with A-PRF. Both groups were treated for 1 week. The skin pH value, moisture, elasticity, and grease secretion, as well as skin pigmented spots, wrinkles, texture, and pores were compared between the two groups before treatment, 1 week and 1 month after treatment. And the occurrence of adverse reactions from 1 week to 1 month after treatment was observed. Results The facial skin status improved to various degrees in both groups at 1 week and 1 month after treatment, with the improvement in wrinkles, texture, pores, moisture, elasticity, and grease significantly better in the treatment group than in the control group, as indicated by a significant increase in delicacy and gloss, a decrease in fine wrinkles, and subjective sensation of skin moisturization with fullness and elasticity, etc. No adverse reactions occurred in either group during the observation period. Conclusion Using A-PRF combined with recombinant human-like collagen mask to repair female facial skin photoaging can improve the moisture and elasticity of facial skin, while reducing grease and fine wrinkles. It has an obvious repair effect on female facial skin photoaging and is worthy of clinical promotion and application.

随着生活条件和饮食结构的改变,我国糖尿病患者数量逐年增多.1980年的流行病学调查显示,我国糖尿病的患病率约为0.67％[1].随后的40年间,我国糖尿病患者总数不断上升,2021年的数据显示我国糖尿病患者总数已增长至1.4亿例,相较于2011年的9000万例,增幅达56％,位居全球第一,形势严峻[2].

Background:The micro-autologous fat transplantation (MAFT) technique has demonstrated its feasibility in multiple medical fields, such as facial rejuvenation. Advanced platelet-rich fibrin (APRF), an autologous platelet concentrated on a fibrin membrane without added external factors, has shown significant potential for tissue restoration. However, the role of APRF in the modulation of MAFT remains unclear. Here, we aimed to explore the effect of APRF on MAFT.Methods:Adipose-derived stem cells (ASCs) were isolated from human gastric subcutaneous fat and treated with APRF. ELISA assays measured cytokines. The proliferation of ASCs was analyzed by CCK-8 assays. The levels of hypoxia-inducible factor-1α (HIF-1α), heat shock protein 70 (HSP70), insulin like growth factor 2 (IGF-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and vascular endothelial growth factor (VEGF) were measured by ELISA assays, quantitative reverse transcription-PCR (qRT-PCR), and Western blot analysis. The effect of APRF/HIF-1α/VEGF on MAFT in vivo was analyzed in Balb/c nude mice. The BALB/c mice were subcutaneously co-transplanted with fat, APRF, and control shRNA, HIF-1α shRNA, or VEGF shRNA into the dorsal area. The serum and protein levels of the above cytokines were analyzed by ELISA assays and Western blot analysis. Lipid accumulation was measured by Oil Red O staining. The expression of CD34 was assessed by immunohistochemical staining.Results:APRF continuously secreted multiple cytokines, including epidermal growth factor (EGF), FGF-2, insulin like growth factor 1 (IGF-1), interleukin-1beta (IL-1β), interleukin-4 (IL-4), platelet-derived growth factor alpha polypeptide b (PDGF-AB), platelet-derived growth factor beta polypeptide b (PDGF-BB), transforming growth factor-beta (TGF-β), and VEGF. APRF was able to promote the proliferation of ASCs. APRF dose-dependently activated the expression of HIF-1α, HSP70, IGF-2, IL-6, IL-8, and VEGF in ASCs. APRF regulated the paracrine function of ASCs by modulating HIF-1α and VEGF. APRF increased the survival of MAFT by modulating HIF-1α and VEGF in vivo.Conclusions:APRF promotes the paracrine function and proliferation of ASCs and contributes to MAFT by modulating HIF-1α and VEGF. Our findings provide new insights into the mechanism by which APRF regulates MAFT.

Resveratrol (RSV) is known to possess anticancer properties in many types of cancers like breast cancer, in which POLD1 may serve as a potential target. However, the anticancer mechanism of RSV on triple negative breast cancer (TNBC) remains unclear. In the present study, the antitumor effects and mechanism of RSV on TNBC cells were analyzed by RNA sequencing (RNA-seq), which was then verified via cell counting kit-8 (CCK8), immunofluorescence, immunohistochemistry, Western Blot (WB), flow cytometry, and hematoxylin-eosin (HE) staining. According to the corresponding findings, the survival rate of MDA-MB-231 cells gradually decreased as RSV treatment concentration increased. The RNA-seq analysis results demonstrated that genes affected by RSV treatment were mainly involved in apoptosis and the p53 signaling pathway. Moreover, apoptosis of MDA-MB-231 cells induced by RSV was observed to be mainly mediated by POLD1. When treated with RSV, the expression levels of full length PARP1, PCNA, and BCL-2 were found to be significantly reduced, and the expression level of Cleaved-PARP1 as well as Cleaved-Caspase3 increased significantly. Additionally, the mRNA expression of POLD1 was significantly reduced after treatment with RSV, and the protein expression level was also inhibited by RSV in a concentration-dependent manner. The prediction of domain interaction suggested that RSV may bind to at least five functional domains of the POLD1 protein (6s1m, 6s1n, 6s1o, 6tny and 6tnz). Furthermore, after RSV treatment, the anti-apoptotic index (PCNA, BCL-2) of MDA-MB-231 cells was found to decrease while the apoptosis index (caspase3) increased. Moreover, the overexpression of POLD1 reduced the extent of apoptosis observed in MDA-MB-231 cells following RSV treatment. Moreover, animal experimental results showed that RSV had a significant inhibitory effect on the growth of live tumors, while POLD1 overexpression was shown to antagonize this inhibitory effect. Accordingly, this study’s findings reveal that RSV may promote the apoptosis of TNBC cells by reducing the expression of POLD1 to activate the apoptotic pathway, which may serve as a potential therapy for the treatment of TNBC.

In this study, porous polylactic acid/methotrexate (PLA/MTX) scaffolds were successfully fabricated by three-dimensional (3D) printing technology as controllable drug delivery devices to suppress tumor growth. Scanning electron microscopy and energy-dispersive spectrometer confirmed that MTX drug was successfully incorporated into the PLA filament. 3D-printed PLA/MTX scaffolds allow sustained release of drug molecules in vitro for more than 30 days, reducing systemic toxic side effects caused by injection or oral administration. In vitro cytotoxicity assay revealed that PLA/MTX scaffolds have a relatively high inhibitory effect on the tumor cells (MG-63, A549, MCF-7, and 4T1) and relatively low toxic effect on the normal MC3T3-E1 cells. Furthermore, results of in vivo experiments confirmed that PLA/MTX scaffolds highly suppressed tumor growth and no obvious side effects on the organs. All these results suggested that 3D-printed PLA/MTX scaffolds could be used as controllable drug delivery systems for tumor suppression.

AIM:The aim of the present study was to identify the association between tumor grade and liquid-liquid phase separation (LLPS)-related genes, and to generate a LLPS-related gene-based risk index (LLPSRI) as a prognostic tool for hepatocellular carcinoma (HCC).METHODS:Weighted gene correlation network analysis was performed to test whether the LLPS-related gene modules were associated with tumor grade of HCC. The candidate modules were subjected to functional enrichment analysis. We generated a LLPSRI using the expression profiles of the hub genes among the candidate modules in order to identify patients at high risk. Then, the biological characteristics of the high-risk patients were revealed using gene set enrichment analysis. Additionally, an independent external data set was used to validate the LLPSRI.RESULTS:Four gene modules showed a significant positive correlation with tumor grade and involved various cancer-related pathways. Among the hub genes, six were selected to generate the LLPSRI, which was significantly associated with prognosis of HCC patients. The LLPSRI could successfully divide patients with HCC into high- and low-risk groups, and patients in the high-risk group showed shorter overall survival than those in the low-risk group. E2F, MYC, and mTORC1 signaling may be important determinants of survival in the high-risk group. The prognostic value of the LLPSRI was validated with the independent external data set.CONCLUSION:We identified LLPS-related gene modules that are associated with HCC tumor grade. The LLPSRI may be useful as a prognostic marker of HCC, and it may reliably stratify patients into groups at low or high risk of worse survival. Our analysis also suggests that certain biological characteristics of HCC may be associated with high risk of worse survival.

Severe burns are acute wounds caused by local heat exposure, resulting in life-threatening systemic effects and poor survival. However, the specific molecular mechanisms remain unclear. First, we downloaded gene expression data related to severe burns from the GEO database (GSE19743, GSE37069, and GSE77791). Then, a gene expression analysis was performed to identify differentially expressed genes (DEGs) and construct protein-protein interaction (PPI) network. The molecular mechanism was identified by enrichment analysis and Gene Set Enrichment Analysis. In addition, STEM software was used to screen for genes persistently expressed during response to severe burns, and receiver operating characteristic (ROC) curve was used to identify key DEGs. A total of 2631 upregulated and 3451 downregulated DEGs were identified. PPI network analysis clustered these DEGs into 13 modules. Importantly, module genes mostly related with immune responses and metabolism. In addition, we identified genes persistently altered during the response to severe burns corresponding to survival and death status. Among the genes with high area under the ROC curve in the PPI network gene, CCL5 and LCK were identified as key DEGs, which may affect the prognosis of burn patients. Gene set variation analysis showed that the immune response was inhibited and several types of immune cells were decreased, while the metabolic response was enhanced. The results showed that persistent gene expression changes occur in response to severe burns, which may underlie chronic alterations in physiological pathways. Identifying the key altered genes may reveal potential therapeutic targets for mitigating the effects of severe burns.